BioPlex 2200 ANA Screen 多語言支援 CD-ROM 本使用說明手冊 (ICF) 文件為 Adobe PDF 格式, 多語言支援的內容燒錄於 CD-ROM, 可提供下列各種語言 : 英文 德文 法文 西班牙文 義大利文 葡萄牙文 瑞典文及丹麥文 僅供體外診斷使用 In-vitro

Transcription

1 BioPlex 2200 System ANA Screen with MDSS 伯瑞普樂斯抗核抗體篩檢試劑中文仿單 衛署醫器輸字第 號本產品限醫師及醫檢師使用僅供體外診斷使用 聯邦法律規定, 本器材僅限由醫師或經醫師指示進行販售, 或販售至臨床實驗室 ; 僅限醫師或醫師指示使用 本使用說明手冊適用於批號 # 以後的 ANA 抗核抗體試劑組, 以及 BioPlex 2200 軟體 2.0 以上版本 製造廠名稱 : Bio-Rad Laboratories, Inc 製造廠地址 : th Ave NE, Redmond, WA98052, USA 藥商名稱 : 美商伯瑞股份有限公司台灣分公司藥商地址 : 台北市南京東路四段 126 號 3 樓

2 BioPlex 2200 ANA Screen 多語言支援 CD-ROM 本使用說明手冊 (ICF) 文件為 Adobe PDF 格式, 多語言支援的內容燒錄於 CD-ROM, 可提供下列各種語言 : 英文 德文 法文 西班牙文 義大利文 葡萄牙文 瑞典文及丹麥文 僅供體外診斷使用 In-vitro-Diagnostikum Utilisation comme test de diagnostic in vitro Per uso diagnostico in vitro Para uso en diagnóstico in vitro Para uso em diagnóstico in vitro För in vitro-diagnostiskt bruk Til in vitro-diagnostisk brug 參考使用說明手冊 Gebrauchsanweisung beachten Consulter la notice d emploi Consultare le istruzioni per l uso Consulte las instrucciones de uso Consulte as instruções de utilização Läs bruksanvisningen Benyt brugsanvisninger 檢測次數 Anzahl der Tests Nombre de tests Numero di analisi Número de pruebas Número de testes Antal tester Antal tests 製造廠 Hergestellt von Fabriqué par Fabbricato da Fabricado por Fabricado por Tillverkare Fremstillet af 歐洲共同體核准代理人 Bevollmächtigter in der Europäischen Union Représentant agréé dans la Communauté Européenne Mandatario autorizzato per l Unione Europea Representante autorizado en la Comunidad Europea Representante autorizado na Comunidade Europeia Auktoriserad representant i Europeiska gemenskapen Repræsentant i det Europæiske Fællesskab 使用期限 ( 西元年 - 月 - 日 ) Verwendbar bis (JJJJ-MM-TT) Date de péremption (AAAA-MM-JJ) Data di scadenza (AAAA-MM-GG) Usar hasta el (AAAA-MM-DD) Utilizar até (AAAA-MM-DD) Använd före (ÅÅÅÅ-MM-DD) Anvend før (ÅÅÅÅ-MM-DD) 批號 Chargen-Nr. Numéro de lot Numero di lotto Número de lote Número de lote Batchnummer Lotnummer 刺激物 Reizend Irritant Irritante Irritante Irritante Irriterande Lokalirriterende 符合歐洲規定 CE-Konformitätskennzeichnung Conformité aux normes européennes Conformità europea Conformidad europea Conformidade com as normas europeias Europeisk överensstämmelse Europæisk overensstemmelse 溫度限制 Temperaturgrenze Limite de température Limite di temperatura LImite de temperatura Limite de temperatura Temperaturgränser Temperaturgrænse 目錄編號 Katalognummer Numéro de catalogue Numero di catalogo Número de catálogo Número de catálogo Katalognummer Katalognr 內容物 Enthält Contient Contiene Contiene Contém Innehåller Indeholder 版本 Version Version Versione Versión Versão Version Version ANA 抗核抗體試劑組 Reagenzienpack für das ANA-Screening Cartouche de réactifs pour le dépistage d ANA Cartuccia reagenti per lo screening degli ANA Paquete de reactivos para la prueba de detección de ANA Kit de reagentes para despiste de ANA Reagenskassett för ANA-screening Reagenspakke til ANA 抗核抗體 ing 磁珠組 Bead-Set Réactif contenant les billes Set di microsfere Conjunto de micropartículas Conjunto de esferas Mikrosfär-set Perlesæt 樣本稀釋 Probenverdünnungsmittel Diluant échantillon Diluente per campione Diluyente para muestras Diluente de amostras Provdiluent Prøvefortynder 共軛物 Konjugat Conjugué Coniugato Conjugado Conjugado Konjugat Konjugat ii 使用說明 ANA 抗核抗體篩檢試劑

3 BioPlex 2200 ANA Screen 目錄 頁次 效能... 2 摘要與說明... 2 操作原理... 2 試劑內容物... 3 BIO-RAD 可提供的其他必需用品... 3 注意事項 / 警告... 4 檢體收集與處理... 4 試劑配製與儲存... 5 試劑不穩定性與變質指標... 5 程序... 5 A) 品質管理... 5 B) 安裝 / 處理樣本... 6 C) 校正... 6 D) 參考物質的可追溯性... 6 結果判讀準則... 6 計算方法... 6 數據分析... 6 預期結果之選擇... 6 格式 A: 定性篩檢 ( 預留的檢測組 :ANA)... 6 格式 B: 定性與疾病相關性 ( 預留的檢測組 :ANA +)... 6 格式 C: 選擇性抗體結果... 7 程序限制... 7 期望值... 8 盛行率... 8 結果特性... 9 對比測試... 9 ANA 抗核抗體與 ANA Microplate EIA 之前瞻性對比測試... 9 選擇性抗體與 EIA 方法的回溯性對比測試 與 CDC 參考血清之相關性 選擇性抗體與 EIA 方法的前瞻性對比測試 臨床一致性 標靶疾病分析 單一疾病分析 醫療決策輔助軟體 (MDSS) 再現性研究 組內分析 組間分析 線性 WHO Wo/80 dsdna 標準品 dsdna 分析稀釋液 dsdna 分析相關性 交叉反應 干擾物質 附錄 A 附錄 B 參考文獻 商標資訊 E 使用說明 1

4 2 使用說明 ANA 抗核抗體篩檢試劑 BioPlex 2200 ANA Screen 效能伯瑞普樂斯抗核抗體篩檢試劑, 是用來進行人體血清中及 / 或以 EDTA 或肝素處理之血漿中特異抗核抗體 (ANA) 的定性分析篩檢 dsdna 抗體的定量偵測以及 10 種不同抗體檢測法的半定量偵測 (Chromatin, Ribosomal P,SS-A, SS-B, Sm, SmRNP, RNP, Scl-70, Jo-1, 及 Centromere B), 本試劑須搭配合 Bio-Rad BioPlex 2200 系統使用 本檢測系統是用於協助診斷全身性自體免疫疾病 BioPlex 2200 搭配 MDSS 是一項可用來串連患者抗體結果 以及預先設定與下列全身性自體免疫疾病有關檔案的實驗室工具 : 系統性紅斑狼瘡 (SLE) 混和性結締組織疾病 (MCTD) 修格連氏症候群 (SS) 硬皮症 ( 系統性硬化症 ) 以及多發性肌炎 摘要與說明 ANA 抗核抗體篩檢試劑可偵測血清或血漿中具臨床相關性的循環自體抗體, 這些自體抗體可協助診斷全身性自體免疫疾病, 例如 : 系統性紅斑狼瘡 混和性結締組織疾病 未分化型結締組織疾病 (UCTD) 修格連氏症候群 硬皮症 ( 系統性硬化症 ) 皮肌炎 多發性肌炎 類風濕性關節炎(RA) CREST 症候群與雷諾氏症候群 1-4 從歷史上來看, 抗核抗體最常見的檢測為免疫螢光染色法 (IFA), 5 主要利用固定於玻片上的對照細胞株 ( 通常是 HEp-2), 這類細胞含有多達 120 種可用來診斷自體免疫疾病的不同抗原, 當稀釋且含有自體抗體的人體血漿覆蓋於固定在玻片上的細胞時, 抗體會與細胞抗原相結合 通常會利用螢光染劑標示的抗人類免疫蛋白球來偵測這些抗原, 有時候會在患者樣本中偵測到非臨床相關性的自體抗體, 這些可解釋為臨床上的 偽陽性 另外, 也可利用酵素免疫分析法 (EIA) 來進行自體免疫檢測, 6-8 EIA 仰賴常見抗原的混和液來偵測與自體免疫疾病有關的抗體, 而各 EIA 製造商所使用的常見抗原有所不同 進行 EIA 檢測時, 會將稀釋的血漿與結合於固態 ( 最常見使用的是微孔盤 ) 的抗原相結合, 再以與酵素結合的抗人類 IgG 來偵測與微孔盤相結合的自體抗體, 能夠進一步產生色度訊號 當 EIA 技術應用於 ANA 檢測時, 會產生 綜合 訊號, 然而,EIA 檢測法無法從許多抗體的微弱訊號中分辨出單一抗體的強烈訊號, 這是 EIA 檢測法仍會出現偽陽性的風險, 而原因在於其他 IgG 抗體會與固態的非特異性相結合 操作原理 ANA 抗核抗體篩檢試劑採用多重流相免疫分析法, 此方法與傳統 EIA 極為相似, 但可同時偵測及分析試管內的多種抗體 9 於 13 種不同類型的染色磁珠表面塗上一層與系統性自體免疫疾病相關的抗原 (dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B) * BioPlex 2200 系統可將等量的患者樣本 樣本稀釋液以及磁珠試劑混合於反應槽內, 並將混和液培養於 37 C, 經過一次洗滌週期後, 再將與藻紅蛋白 (PE) 相結合的抗人類 IgG 抗體加入染色磁珠內, 並培養於 37 C 接下來的洗滌週期會移除多餘的共軛物, 而磁珠會再懸浮於沖洗用緩衝液中 ; 此時, 磁珠混和液會通過偵測器, 並利用染劑的螢光來分析染色磁珠, 同時透過附著於抗體上 PE 的螢光量, 測量抗原與抗體相結合的數量 最後以相對螢光強度 (RFI) 來計算原始數據 各反應混和液內均有三種額外的染色磁珠 ( 包括 : 內部標準磁珠 (ISB) 血清分析磁珠 (SVB) 以及試劑空白磁珠 (RBB)), 可確認偵測器的反應 血清或血漿是否加入反應槽內, 以及血清或血漿中是否無明顯非特異性結合 如需更多資訊, 請參考 BioPlex 2200 系統的操作手冊 系統的校正是採用 Bio-Rad Laboratories 另外提供的 6 個不同校正液 針對 dsdna, 以 6 個瓶子代表 6 種不同濃度的抗體進行定量校正, 患者樣本的結果以 IU/mL 表示 結果 4 IU/mL 代表 dsdna 抗體呈陰性,5-9 IU/mL 代表呈中間值, 而 10 IU/mL 則代表呈陽性 至於另外 12 種磁珠,4 個瓶子代表以 4 種不同抗體濃度進行半定量校正, 各種抗體的結果以抗體指數 (AI) 呈現,AI 等於 1.0 代表濃度臨界值與趨近 99 來自未罹病族群抗體之數據相同 ; 若結果等於或大於 1.0, 則均代表呈陽性反應

5 BioPlex 2200 ANA Screen 啟動 MDSS 時, 自體抗體結果將與含有超過 1,400 筆血清 / 血漿結果的 MDSS 資料庫進行比對, 這些結果為罹患系統性自體免疫疾病患者與健康成人的檢測結果 ; 若血清或血漿樣本出現一或多個陽性結果, 則該結果將連結至最適當的 MDSS 檔案 得到的疾病相關性, 也有助於判定適當與額外的自體免疫血清檢測 註 :MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 ( 請見結果判讀準則 ) * 在出現 SS-A 60 及 / 或 SS-A 52 的病例中,SS-A 的檢測結果為陽性, 同理, 出現 RNP A 及 / 或 RNP 68 代表 RNP 的檢測結果呈陽性 試劑內容物 ANA 抗核抗體篩檢試劑 ( ) 本試劑含有可進行 100 次檢測的材料 ;ANA 抗核抗體篩檢試 劑亦提供 50 包的規格 ( ),50 包的規格可進行多達 5000 次的檢測 藥瓶說明磁珠組 1 個 10 ml 的藥瓶, 內含覆被核抗原 dsdna dsdna Chromatin Ribosomal P SS-A 60 SS-A 52 SS-B Sm SmRNP RNP A RNP 68 Scl-70 Jo-1 Centromere B 內部標準磁珠(ISB) 血清分析磁珠 (SVB) 以及試劑空白磁珠 (RBB) 的染色磁珠 甘油以及蛋白質穩定劑 ( 牛 ), 混合於 MOPS (3-[N-Morpholino] propanesulfonic acid) 緩衝液中 加入 ProClin 300 (0.3) 苯甲酸鈉(0.1) 與疊氮化鈉 (<0.1) 作為防腐劑 共軛物 樣本稀釋液 1 個 5 ml 藥瓶, 內含小鼠單株抗人類 IgG/ 藻紅蛋白共軛物以及羊抗人類 FXIII/ 藻紅蛋白共軛物, 並混合於磷酸鹽緩衝液中 加入 ProClin 300 (0.3) 與疊氮化鈉 (<0.1) 作為防腐劑 1 個 10 ml 藥瓶, 內含蛋白質穩定劑 ( 牛與小鼠 ), 置於三乙醇胺緩衝液內 加入 ProClin 300 (0.3) 苯甲酸鈉 (0.1) 與疊氮化鈉 (<0.1) 作為防腐劑 BIO-RAD 可提供的其他必需用品說明 ANA 抗核抗體篩檢試劑校正組 :6 個 500µL 藥瓶, 內含覆被核抗原 dsdna Chromatin Ribosomal P SS-A 60 SS-A 52 SS-B Sm SmRNP RNP A RNP 68 Scl-70 Jo-1 以及 Centromere B 的抗體, 置於人體血清中 所有對照液均加入 ProClin 300 (0.3) 與苯甲酸鈉 (0.1) 作為防腐劑 BioPlex 2200 ANA 抗核抗體篩檢試劑對照組 :2 瓶 1.5 ml 陽性對照組內含覆被核抗原 dsdna Chromatin Ribosomal P SS-A 60 SS-A 52 SS-B Sm SmRNP RNP A RNP 68 Scl-70 Jo-1 以及 Centromere B 的抗體, 置於人類血清中, 以及 2 瓶 1.5 ml 陰性對照組 所有對照液均加入 ProClin 300 (0.3) 與苯甲酸鈉 (0.1) 作為防腐劑 ANA 抗核抗體篩檢試劑校正組 :7 個 500µL 藥瓶, 內含覆被核抗原 dsdna Chromatin Ribosomal P SS-A 60 SS-A 52 SS-B Sm SmRNP RNP A RNP 68 Scl-70 Jo-1 以及 Centromere B 的抗體, 加入於去纖維蛋白血漿製成之血清基質中 所有對照液均加入 ProClin 300 (0.3) 與苯甲酸鈉 (0.1) 作為防腐劑 BioPlex 2200 ANA 抗核抗體篩檢試劑對照組 :4 瓶 1.5 ml 陽性對照組內含覆被核抗原 dsdna Chromatin Ribosomal P SS-A 60 SS-A 52 SS-B Sm SmRNP RNP A RNP 68 Scl-70 Jo-1 以及 Centromere B 的抗體, 加入於去纖維蛋白血漿製成之血清基質中, 以及 2 瓶 1.5 ml 陰性對照組, 包含去纖維蛋白血漿製成之血清基質中 所有對照液均加入 ProClin 300 (0.3) 與苯甲酸鈉 (0.1) 作為防腐劑 BioPlex 2200 承載液 :2 個 4 L 玻璃瓶, 內含磷酸鹽緩衝液 (PBS) 加入 ProClin 300 (0.3) 與苯甲酸鈉 (0.1) 作為防腐劑 E 使用說明 3

6 BioPlex 2200 ANA Screen BioPlex 2200 沖洗液 :1 個 10 L 玻璃瓶, 內含磷酸鹽緩衝液與 Tween 20 ProClin 300 (0.3) 與苯甲酸鈉 (0.1) 作為防腐劑 BioPlex 2200 儀器與軟體 (MDSS) 注意事項 / 警告 0.3 ProClin 300 Xi: 刺激物 R43 接觸皮膚可能會造成敏感現象 S 請避免與皮膚接觸 本物質與容器必須以安全方式妥善丟棄 請佩戴適當的手套 1. 體外診斷使用 (IVD) 2. 僅供專業人員使用 3. 所有人類來源的物質均應視為具有感染性, 應以一般生物安全程序並根據 29 CFR 的通則通則防護措施進行處理防護措施進行處理 4. 請勿於處理患者樣本與試劑組之處吸菸或飲食 5. 請勿以口部操作移液管 6. 處理所有試劑與樣本以及操作 BioPlex 2200 系統時, 請穿戴個人防護衣物 7. 請依據國家 地區及 / 或當地的相關法規妥善丟棄所有廢棄物 8. 應以視同生物危害物的處理方式來丟棄或處理含患者樣本或生物產品的廢棄物質 9. 應根據優良實驗室操作規範處理化學試劑 10. 有關更多安全性的資訊以及化學及生物危害的警告, 請參考試劑組及必需品的物質安全資料表 (MSDS) 可向本公司索取物質安全資料表可向本公司索取物質安全資料表 11. 請立即妥善清理所有噴灑出來的液體 ; 生物危害物質的噴濺處必須以有效的消毒劑進行去汙染 ; 請依照規定妥善丟棄所有感染物質有感染物質 12. 請勿使用過期產品進行檢測 ( 保存期限標示於外盒 ) 13. 請勿更換藥瓶與玻璃瓶的瓶蓋與瓶塞, 否則將會造成試劑的交叉汙染 14. 每單位用來製造 ANA 抗核抗體篩檢試劑的人類血清 ( 包括校正液與對照組 ), 均透過 FDA 核准的測試方式進行檢測, 且對 B 型肝炎表面抗原 (HBsAg) 以及 HIV-1 IV-2 與 C 型肝炎病毒抗體不具任何反應 沒有任何檢測方法可完全保證含人類來源物質的產品不含有此等抗原以及其他病原體 根據優良實驗室操作規範 (GLP) 以及 OSHA 法規之規定, 所有人類來源物質均應視為可能感染 B 型肝炎病毒 (HBV) C 型肝炎病毒 (HCV) HIV-1 HIV-2 以及所有其他病原體, 因此在操作 ANA 抗核抗體篩檢試劑 ( 包括 : 試劑組 校正液與對照組 ) 時, 應與處理患者樣本時同樣謹慎 15. 請遵守本手冊內的步驟, 以確保本產品檢測結果的正確性 ; 若出現異常結果, 請與 Bio-Rad 技術服務部門聯絡 16. 請勿混合不同容器內的同樣試劑, 否則可能會造成試劑汙染而影響而影響產品的檢測結果產品的檢測結果 17. 疊氮化鈉可能會與可能會與鉛或銅反應, 形成具成具高度易爆高度易爆性的性的疊氮疊氮化物化物金屬 ; 因此在丟棄液體時, 請以大量大量清水沖洗, 以避免疊氮避免疊氮化物化物累積累積 10 檢體收集收集與處理檢體收集收集注意事項將所有含有人類來源的物質視為具感染性, 並以標準生物安全程序進行處理 檢體類型建議以血清與 EDTA 或肝素處理之血漿作為檢體, 避免溶血 檢體儲存血清或血漿可存放於冰箱 (2-8 C) 內達 7 天, 如欲長期儲存檢體, 請存放於 -20 C 以下 檢體配製請充分混和解凍的檢體, 建議將解凍的檢體進行離心, 以移除所有顆粒物 請避免重複冷凍 / 解凍 ( 最多可重複 3 次 ) 檢體運送所有檢體及其他人類來源檢體, 均必須依照國家與國際規範進行運送 4 使用說明 ANA 抗核抗體篩檢試劑

7 BioPlex 2200 ANA Screen 試劑配製與製與儲存 請勿冷凍 ANA 抗核抗體抗體試劑組試劑組 ANA 抗核抗體篩檢試劑中的試劑均可立即使用 試劑開封使用後 30 天內可保持品質穩定 ; 或可於未開封的情況下儲存於儀器上或冷藏於 2-8 C, 在保存期限期內均可保持品質穩定 試劑超過保存期限後請勿使用 試劑不穩定性與定性與變質指標 請依照標籤上標示的溫度來儲存試劑, 請勿存放超過保存期限 請勿使用任何出現變質現象 混濁或有沉澱物的試劑 ; 請勿使用任何內容物外漏的試劑 程序為取得可靠且一致的結果, 請嚴格遵守本使用說明手冊內的使用說明 ; 請勿自行修改試劑組或患者樣本的處理與儲存條件 關於操作說明 ( 包括 : 校正 品質管制以及 BioPlex 200 系統的維護 ) 的詳盡資訊, 請參見 BioPlex 2200 系統的操作手冊 使用 ANA 抗核抗體篩檢試劑前, 請先確認 BioPlex 2200 系統已開機 試劑組與主體溶液已裝妥, 並且已完成所有必要的維修 有關上述操作資訊, 請參考 BioPlex 2200 系統的操作手冊 任何批次的 BioPlex 2200 系統承載液 BioPlex 2200 系統沖洗液均可交換使用 A) 品質管理針對各試劑組以及每天進行一次的檢測, 請依照 BioPlex 2200 系統的操作手冊正確安裝及處理 ANA 抗核抗體對照組 ANA 抗核抗體對照組包含一個陰性對照品與一個含有本 ANA 抗核抗體試劑組內分析物抗體的多分析物陽性控制組 陽性對照組之設計在於提供陽性結果, 檢測數據會高於各磁珠的臨界值 ; 陰性對照物之設計在於提供陰性結果, 檢測數據會低於各磁珠的臨界值 陰性對照物必須提供陰性結果, 而陽性對照物必須提供陽性結果 註 :ANA 抗核抗體對照組的陰性與陽性對照品, 是用於監測基本的試劑錯誤 ; 陽性對照品無法確保分析臨界值的精準度 請利用所提供的媒介工具 或以手動輸入的方式將陽性對照品的批次數據輸入至 BioPlex 2200 系統的資料庫中 ; 利用藥瓶的條碼辨識對照品後,BioPlex 2200 系統會將對照品的結果與系統資料庫內儲存的批次對照組期望值進行比較 若未取得正確的對照組數值, 將使分析法失效, 且出現程序錯誤 檢體處理不當或試劑變質的情形 註 :ANA 抗核抗體篩檢試劑內某些分析物的陽性對照品, 必須經過稀釋才能達到儲存於 BioPlex 2200 系統資料庫的批次數據 ;BioPlex 2200 系統會自動稀釋這些分析物, 並利用額外的反應槽進行分析 重要 QC 疑難排除 : 在少數情況下, 試劑組內某些分析物可能會出現錯誤的低訊號, 並出現 QC 錯誤 ; 若出現明顯 QC 錯誤, 應進行下列疑難排除步驟 : 1. QC 警告 部分分析分分析物數據過據過低 : 重新進行 QC 檢測 若 QC 警告重複出現, 請移除標示 QC 錯誤結果的試劑組, 且不再使用使用 請向 Bio-Rad 技術服務部門通報疑似訊號過低的試劑組 請使用新的試劑組進行 QC 檢測 若新的試劑組的 QC 結果在可接受的範圍內, 請將遭受影響且出現 QC 警告 數據過低的試劑組丟棄, 請勿使用該次試劑組所取次試劑組所取得的患者結果的患者結果 若新的試劑組仍出現 QC 警告, 請聯絡 Bio-Rad 技術服務部門尋求協助, 以排除問題 所有使用受汙染之試劑組進行檢測的樣本, 均必須重新進行檢測 若儀器上同時有多種 BioPlex 2200 分析的試劑, 則可藉由對照組結果記錄來找出造成 QC 警告 數據過低的試劑組序號 2. QC 警告 部分分析分分析物數據過據過高 : 請重新校正出現 QC 警告 數據過高的試劑組, 並重新進行 QC 提供患者結果前, 請先確認所有分析物的 QC 結果均介於可接受的範圍內 所有使用出現 QC 警告 數據過高進行檢測的樣本, 都必須重新進行檢測 因為試劑組內會自行進行校正, 使用受汙染之試劑組進行檢測的患者樣本仍有效 可依據當地 州立及 / 或聯邦法規或認證要求, 以及貴實驗室的品質管控政策, 對其他對照品進行測試 若對照品的結果超出其預定範圍, 則必須評估所有自上一次可接受之對照品結果之後所取得的檢測結果, 以確認是否對檢測結果造成不良影響 ; 受到不良影響的檢測結果將視為無效, 且這些樣本必須重新進行檢測 E 使用說明 5

8 BioPlex 2200 ANA Screen B) 安裝 / 處理樣本請依照 BioPlex 2200 系統操作手冊的說明, 將樣本置於 BioPlex 2200 系統提供的樣本架上,BioPlex 2200 系統的樣本處理程序為全自動化 有關正確的軟體設定, 請參閱 BioPlex 2200 系統的操作手冊 C) 校正 ANA 抗核抗體校正組必須至少每 14 天一次 每次 2 組或使用新的試劑組批次時進行安裝與分析 針對 dsdna, 請利用 6 點 4PL 曲線擬合來計算定量結果 ; 針對其他分析物, 請利用以 4 個校正品取得的點對點曲線符合來計算半定量結果 如需更多相關資訊, 請參閱 BioPlex 2200 系統的操作手冊 D) 參考物質的可追溯追溯性 ANA 抗核抗體校正組係採用世界衛生組織 (WHO) 的 Wo/80 dsdna 標準品進行 dsdna 校正, 另外, 其他分析物則尚無經認證的標準品可使用 結果判讀準判讀準則計算方法所有結果判讀必須使用的計算方法, 均由 BioPlex 2200 系統軟體自動進行 數據分析除 dsdna 的表達方式為 IU/mL 以外, 各抗體結果的表達方式均為抗體指數 (AI) 在 dsdna 的部分, 若結果 4 IU/mL 為陰性 5-9 IU/mL 為中間值 10 IU/mL 則為陽性 針對其他分析分析, 若結果 < 1.0 AI 為陰性, 等於或大於 1.0 AI 則為陽性 若樣本出現 SS-A 60 及 / 或 SS-A 52, 則結果的表達方式為 SS-A 為陽性 同理, 若樣本出現 RNP A 及 / 或 RNP 68, 則結果的表達方式為 RNP 陽性 dsdna 的線性範圍為 IU/mL, 其他分析分析法的測量範圍則為 AI 根據使用者判斷, 可利用 BioPlex 2200 系統上的醫療決策輔助軟體 (MDSS) 進一步分析以格式 B( 預留的檢測組 :ANA) 或格式 C( 預留的檢測組 :ANA +) 取得的陽性 ANA 結果, 以找出與 MDSS 檔案的潛在相關性 ( 更多資訊請見下一章節 ) MDSS 乃根據 k 最鄰近點 11 (knn) 統計法的原則, 各 未知數 均與預先建立且含有超過 1,400 種具個別特徵之血清 / 血漿的資料庫進行比較 MDSS 的分析結果可歸類為以下整體結果的其中一項 : 陰性 無相關性或與疾病相關 若 MDSS 分析結果落入具疾病相關性的類別中, 則 MDSS 軟體將根據目前分析結果與儲存結果的相似性, 最多建議兩種疾病分類 MDSS 的輸出結果亦有助於決定合適的額外自體免疫血清學檢測 預期結果之期結果之選擇軟體畫面 MDSS 設定 可協助操作者從多種格式中進行選取, 以合乎您特定需求喜好的方式來呈現結果, 此功能需輸入密碼才能使用, 通常實驗室會於安裝儀器時選擇可選取的格式 如需更多資訊, 請參考 BioPlex 2200 系統的操作手冊 格式 A: 定性篩檢 ( 預留的檢測組 :ANA) 在定性篩檢的格式方面, 會根據樣本中是否有 ( 或無 ) 一或多種抗體濃度超過臨界值, 來決定結果為 ANA 陽性或陰性 ;MDSS 未啟動 根據使用者判斷, 可將單一抗體或使者定義含有抗體的檢測組設定為 附加 檢測, 進一步分析以定性篩檢格式取得的陽性 ANA 結果, 並即時呈現結果 如需更多資訊, 請參考 BioPlex 2200 系統的操作手冊 註 : 陽性 ANA 結果代表出現下列一或多種分析物之抗體 :dsdna Chromatin Ribosomal P SS-A 60 SS-A 52 SS-B Sm SmRNP RNP A RNP 68 Scl-70 Jo-1 與 Centromere B 相反的, 陰性 ANA 結果 ( 或 dsdna 中間值結果 ) 代表無任何上述分析物的抗體, 或上述所有分析物抗體的濃度均低於臨界值 格式 B: 定性與疾病相關性 ( 預留的檢測組 :ANA +) 在疾病相關的定性格式部分, 各樣本結果將如同上述方法以陽性或陰性呈現 ; 此外, 會參考 MDSS 資料庫中與未知樣本最接近的疾病狀態血清類型, 以進一步定義陽性結果 以下為標靶疾病的相關性 : 系統性紅斑狼瘡 (SLE) 修格連氏症候群 硬皮症 ( 系統性硬化症 ) 混和性結締組織疾病 (MCTD) 多發性肌炎 6 使用說明 ANA 抗核抗體篩檢試劑

9 BioPlex 2200 ANA Screen MDSS 分析的結果會落入下列整體結果的其中一項 : 整體結果 MDSS 輸出結果 陰性 系統性自體免疫疾病的所有抗體濃度均低於預先設定的臨界值 無相關性 抗體濃度與系統性自體免疫疾病的 MDSS 檔案無相關性 具疾病相關性 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性, 可能為 [ 最多兩種系統性自 體免疫疾病 ] 當 MDSS 根據自體免疫疾病 MDSS 檔案之相關性將結果進行分類時, 會提供最多兩種上述可能的疾病相關性 ( 可能疾病組合的完整清單請見附錄 A) 以下為部分與結果有關的可能案例 : 抗體濃度與自體免疫疾病的 MDSS 檔案具相關性 可能為 SLE 抗體濃度與自體免疫疾病的 MDSS 檔案具相關性 可能為 SLE 或修格連氏症候群 抗體濃度與自體免疫疾病的 MDSS 檔案具相關性 可能為硬化症 格式 C: 選擇性抗體結果在選擇性抗體結果格式中, 只有操作者所選擇的未知樣本抗體結果會出現, 此格式可針對特定樣本選擇單一抗體或一組抗體 ; 實驗室可利用軟體螢幕上的 檢測組設定 預先定義檢測組的組成, 使操作者可選擇符合特定需求的檢測組 舉例來說,SS-A 與 SS-B 可同時進行分析, 也可定義更大的檢測組 以下列檢測組為例, 也可用來取代傳統的 6 項 ENA 檢測 SS-A Scl-70 SS-B Sm RNP Jo-1 此外, 亦可針對額外的個別抗體, 或經使用者定義 且含有過去未曾檢測過之抗體的檢測組來進行即時顯示結果的 附加 檢測 若所選擇的抗體過去已接受過檢測, 則該樣本將被視為重複檢測 如需更多資訊, 請參考 BioPlex 2200 系統的操作手冊 特殊檢測案例 ( 預留檢測組 :ANA 11) 於上述選擇性抗體結果格式下設定單一抗體或一組抗體 或所有單一抗體時,MDSS 不會啟動 然而, 若選擇檢測組 ANA 11( 將所有個別抗體視為一組 ) 時,MDSS 會自動啟動 ; 此外, 抗體與疾病相關性的圖示結果也會啟動 只有在此狀況下 以及至少有一種抗體呈陽性時, 才會出現圖示結果 ( 請見附錄 B) 如需更多資訊, 請參考 BioPlex 2200 系統的操作手冊 註 : 當選擇特定抗體結果時, 可能會出現超出範圍 (OR, Over-Range) 的結果 在 dsdna 的部分, 可先以沖洗液稀釋後再重新進行分析 有關稀釋檢體安裝與分析之稀釋篩檢法的使用, 請參考 BioPlex 2200 系統操作手冊 其他特定抗體則不需要亦不建議進行稀釋 程序限制 ANA 抗核抗體篩檢試劑本身並非自體免疫疾病的診斷方法, 應與其他實驗室檢測結果以及患者的臨床症狀一併考慮 MDSS 本身並非標靶疾病相關性的診斷方法, 應與其他實驗室檢測結果以及患者的臨床症狀一併考慮 看似健康的患者也可能出現陽性 ANA 結果, 12 因此, 檢測結果應與其他實驗室檢測結果以及患者的臨床症狀一併考慮 患者樣本內的免疫複合物或其他免疫球蛋白聚集體, 可能會增加非特異性結合的數量, 進而造成偽陽性結果 13 然而,ANA 抗核抗體篩檢試劑的各項檢測均結合試劑空白磁珠 (RBB), 可用來確認血清或血漿中無明顯的非特異性結合 接受類固醇或免疫抑制劑治療的 SLE 患者, 可能出現陰性檢測結果 14 類風濕風濕性關性關節炎患者可能造成 MDSS 顯示 SLE 相關性 此外, 正在接受抗 TNFα 阻斷劑治療的類風濕性患者, 曾有報告顯示出現 dsdna 與 Chromatin 的抗體 15 基於這些因素, 在判讀類風濕性關節炎患者的 MDSS 相關性時, 應特別謹慎 MDSS 輸出結果為 陰性 或 無相關性 時, 無法完全排除自體免疫疾病的可能性 E 使用說明 7

10 BioPlex 2200 ANA Screen 期望值盛行率下表為兩個群體的 ANA 抗核抗體篩檢期望值 : 正常捐血者 (N=222) 與風濕科診所患者 (N=908) 在 dsdna 的部分, 若結果 4 IU/mL 為陰性 5-9 IU/mL 為中間值 10 IU/mL 為陽性 針對其他分析分析, 若結果 < 1.0 AI 為陰性, 等於或大於 1.0 AI 則為陽性 表 A 正常捐血者 (N=222) 結果 ANA 抗核抗體 1,2 陽性 # () 陰性 # () 中間值 # () 15 (6.8) 207 (93.2) 不適用 dsdna 3 (1.4) 211 (95.0) 8 (3.6) Chromatin 2 (0.9) 220 (99.1) Ribosomal P 0 (0.0) 222 (100.0) SS-A 2 (0.9) 220 (99.1) SS-B 0 (0.0) 222 (100.0) Sm 1 (0.5) 221 (99.5) SmRNP 2 (0.9) 220 (99.1) 不適用 RNP 6 (2.7) 216 (97.3) Scl-70 3 (1.4) 219 (98.6) Jo-1 0 (0.0) 222 (100.0) Centromere B 3 (1.4) 219 (98.6) N/A = 不適用 1) 見下方註釋 2) 根據所有分析物的檢測計算結果 表 B 類風濕性患者 (N=908) 結果 ANA 抗核抗體 1 陽性 # () 陰性 # () 中間值 # () 390 (43.0) 518 (57.0) 不適用 dsdna 119 (13.1) 741 (81.6) 48 (5.3) Chromatin 168 (18.5) 740 (81.5) Ribosomal P 37 (4.1) 871 (95.9) SS-A 173 (19.0) 735 (81.0) SS-B 76 (8.4) 832 (91.6) Sm 60 (6.6) 848 (93.4) SmRNP 103 (11.3) 805 (88.7) 不適用 RNP 112 (12.3) 796 (87.7) Scl (2.5) 885 (97.5) Jo-1 6 (0.7) 902 (99.3) Centromere B 38 (4.2) 870 (95.8) N/A = 不適用 1) 見下方註釋 註 : 陽性 ANA 結果代表出現下列一或多種分析物之抗體 :dsdna Chromatin Ribosomal P SS-A 60 SS-A 52 SS-B Sm SmRNP RNP A RNP 68 Scl-70 Jo-1 與 Centromere B 相反的, 陰性 ANA 結果 ( 或 dsdna 中間值結果 ) 代表無任何上述分析物的抗體 或上述所有分析物抗體的濃度均低於臨界值 8 使用說明 ANA 抗核抗體篩檢試劑

11 結果特性註 : 以下列 4 種方法之一計算本操作手冊中間值能特點章節所使用的 95 信賴區間 BioPlex 2200 ANA Screen 計算方法 條件 95 信賴區間計算間計算方法 一致性與正確性 N 30 參考下列文獻使用的計分方式 : 之相關性 J Sauro 與 JR Lewis( 印刷中 ) 的 以二項式信賴區間預估小量 樣本的完成率 : 比較與建議 於人因工程學會年度會議紀錄 (HFES), 佛羅里達奧蘭多 一致性與正確性 N > 30 CR Blythe 與 HA Still 的兩項式信賴區間, 美國統計協會期 之相關性 刊,1983; 78: [eq. 3.8, p.116] 勝算比 全部 JM Bland 與 DG Altman 的勝算比,BMJ 2000; 320:1468 陽性與陰性概似全部 瓦薩統計計算網站 : 臨床研究計算機 1 比 ; 盛行率 對比測試 ANA 抗核抗體與 ANA Microplate EIA 之前瞻性對比測試採用市售的 ANA Microplate EIA 來評估 ANA 抗核抗體的結果 於 3 個美國臨床檢驗中心檢測共 908 個前瞻性血清樣本, 樣本收集自前往風濕科診所就醫且疑似罹患系統性自體免疫疾病的患者, 結果列於表 C 表 C ANA 抗核抗體與 ANA Microplate EIA (N=908) 陽性 ANA 抗核 1 抗體 陰性 ANA 抗核抗 1 體 合計 陽性 EIA 陰性 EIA 合計 ) 請見前一頁註釋 比較性前瞻測試結果如下 : 陽性一致性 :351/500 = 70.2 (95 CI ) 陰性一致性 :369/408 = 90.4 (95 CI ) 整體一致性 :720/908 = 79.3 (95 CI ) E 使用說明 9

12 BioPlex 2200 ANA Screen 選擇性抗體與 EIA 方法的回溯性對比測試各分析物以 40 個回溯性血清樣本檢測進一步分析 ANA 抗核抗體篩檢試劑的結果, 已知所有樣本為 ANA 陽性, 且下列所有自體抗體有一或多種為陽性 此外, 亦檢測 100 個已知為 ANA 陰性的血清樣本 針對各抗體, 同時以 ANA 抗核抗體篩檢試劑以及市售的 microplate EIA 方法檢測回溯性檢體, 結果列於表 D 表 D ANA 抗核抗體與 EIA: 選擇性抗體 - 回溯性 單一抗體 / 抗體組 dsdna Chromatin Ribosomal P SS-A SS-B Sm SmRNP RNP Scl-70 Jo-1 Centromere B N 123^ * N( 陽性 ) N( 陰性 ) BioPlex 2200 與 EIA 陽性 BioPlex 2200 陽性與 EIA 陰性 BioPlex 2200 與 EIA 陰性 BioPlex 2200 陰性與 EIA 陽性 與 EIA 陽性一性一致性 信賴區間 與 EIA 陰性一性一致 性 信賴區間 整體一體一致性 信賴區間 ^ 排除 16 筆 BioPlex 2200 dsdna 2200 無法判定或 dsdna 不明確之結果 * 排除 2 筆 RNP 不明確之結果 共排除 19 筆 (1 dsdna 2 Chromatin 2 Ribosomal P 1 SS-A 1 Sm 1 SmRNP 1 Scl-7 以及 10 Jo-1) 具重複低血清驗證磁珠 (SVB) 的回溯性研究樣本結果 10 使用說明 ANA 抗核抗體篩檢試劑

13 BioPlex 2200 ANA Screen 與 CDC 參考血清之相關性疾病管制中心 (CDC) 提供一組參考血清檢測劑, 可用來檢測及評估 ANA 抗核抗體篩檢試劑的特性, 結果可用來取得更多有關 ANA 抗核抗體篩檢試劑與盲性 具特性之血清檢測的結果 以上結果不代表 CDC 為 ANA 抗核抗體篩檢試劑背書 結果列於表 E 表 E CDC 參考檢測組特性 樣本 期望值 ANA 抗核抗體 dsdna (lu/ml) Chromatin (Al) Ribosomal P (Al) SS-A (Al) SS-B (Al) Sm (Al) SmRNP (Al) RNP (Al) Scl-70 (Al) Jo-i (Al) Centromere B (Al) CDC-1 同質 /Rim CDC-2 斑點 /La CDC-3 斑點 CDC-4 U1-RNP CDC-5 Sm CDC-6 Nucleolar + + CDC-7 SSA/Ro + + CDC-8 Centromere + + CDC-9 Scl CDC-10 Jo CDC-11 PM/Scl 根據所有分析物之檢測計算結果 註 : 檢測結果不可進行其他統計計算或推斷任何結論 在 dsdna 的部分, 若結果 4 IU/mL 為陰性 5-9 IU/mL 為中間值 10 IU/mL 為陽性 針對其他分析分析, 若結果 < 1.0 AI 為陰性, 等於或大於 1.0 AI 則為陽性 E 使用說明 11

14 BioPlex 2200 ANA Screen 選擇性抗體與 EIA 方法的前瞻性對比測試在 908 個檢測的前瞻性血清樣本中, 以 ANA 抗核抗體檢測對特定自體抗體呈陽性的樣本, 也以相對應的市售 microplate EIA 進行檢測 結果列於表 F 表 F ANA 抗核抗體與 EIA: 選擇性抗體 - 前瞻性 單一抗體 / 抗體組 dsdna Chromatin Ribosomal P SS-A SS-B Sm SmRNP RNP Scl-70 Jo-i Centromere B N 832* BioPlex 2200 與 EIA 陽性 BioPlex 2200 陽性與 EIA 陰性 BioPlex 2200 與 EIA 陰性 BioPlex 2200 陰性與 EIA 陽性 與 EIA 陽性一性一致性 95 信賴區間 與 EIA 陰性一性一致性 95 信賴區間 整體一體一致性 * 95 信賴區間 排除 76 筆 BioPlex 2200 dsdna 無法判定或 dsdna 不明確之結果 排除 29 筆 RNP 不明確之結果 使用說明 ANA 抗核抗體篩檢試劑

15 BioPlex 2200 ANA Screen 臨床一致性標靶疾病分析除了傳統的靈敏度 專一性以及預測值分析外, 也建議使用概似比分析進行自體免疫檢測 16 將表 G 的 ANA 抗核抗體篩檢結果與五 (5) 個標靶疾病相關性進行比較, 以前瞻性方法收集風濕科診所內以美國風濕病學會 (ACR) 或適當疾病分類條件進行診斷之患者的樣本, 針對下列任何標靶疾病相關性進行收集 : 系統性紅斑狼瘡 (SLE) 修格連氏症候群 硬皮症 ( 系統性硬化症 ) 混和性結締組織疾病 (MCTD) 多發性肌炎 表 G 標靶疾病相關性 (N=908) ANA 抗核抗體 陽性陰性合計 標靶 CTD 疾病 所有其他非標靶且無 CTD 合計 靈敏度 : CI 專一性 : CI 整體一致性 : CI 陽性概似比 : CI 陰性概似比 : CI 勝算比 : CI 盛行率 : CI 上述 ( 包括之前與之後 ) 統計計算方法的定義如下 : 在此 靈敏度 : TP/(TP+FN) x 100 專一性 : TN/(FP+TN) x 100 整體一致性 : (TP+TN)/(TP+FN+FP+TN) x 100 陽性概似比 : Sensitivity/(100-Specificity) 陰性概似比 : (100-Sensitivity)/Specificity 勝算比 : (TPxTN)/(FPxFN) 盛行率 : (TP+FN)/(TP+FN+FP+TN) x 100 TP = 真陽性 FP = 偽陽性 TN = 真陰性 FN = 偽陰性 E 使用說明 13

16 BioPlex 2200 ANA Screen 單一疾病分析將 ANA 抗核抗體的結果與五 (5) 的標靶疾病相關性的預測值進行比較, 結果列於下方臨床一致性總整理表 ( 表 H - M) 內, 白色區塊代表與所討論的特定疾病類型具臨床相關性的自體抗體 ; 1,12,14,17 淺灰色區塊代表在特定疾病類型內常觀察到的自體抗體 ; 深灰色區塊代表通常不與特定疾病類型具相關性的自體抗體 患者可能有多項診斷結果, 也可能代表多種疾病類型 系統性紅斑狼瘡 (SLE) 以前瞻性方法收集風濕科診所內以美國風濕病學會 (ACR) 進行 SLE 診斷之患者的樣本, 透過檢測此樣本, 將 ANA 抗核抗體的結果與指定比對的產品進行比較, 針對各抗體同時以 ANA 抗核抗體篩檢試劑以及市售的 microplate EIA 方法檢測檢體 結果列於表 H 表 H ANA 抗核抗體與 EIA: 臨床診斷 -SLE 結果 (N=332) ANA 抗核抗體 dsdnaa Chromatin Ribosomal P SS-A SS-B Sm SmRNP RNPb Scl-70 Jo-i Centromere B BioPlex 2200 與 EIA 陽性 BioPlex 2200 陽性與 EIA 陰性 BioPlex 2200 與 EIA 陰性 BioPlex 2200 陰性與 EIA 陽性 a b 整體一體一致性 95 信賴區間 計算時排除 46 筆 Bioplex dsdna 無法判定以及 EIA dsdna 不明確的結果 計算時排除 15 筆 EIA RNP 不明確的結果 使用說明 ANA 抗核抗體篩檢試劑

17 BioPlex 2200 ANA Screen 主要修格連氏症候群以前瞻性方法收集風濕科診所內以美歐共識規範進行主要修格連氏症候群診斷之患者的樣本, 透過檢測此樣本, 將 ANA 抗核抗體的結果與指定比對的產品進行比較, 針對各抗體同時以 ANA 抗核抗體篩檢試劑以及市售的 microplate EIA 方法檢測檢體 結果列於表 I 表 I ANA 抗核抗體與 EIA: 臨床診斷 主要修格連氏症候群 結果 (N=16) ANA 抗核抗體 dsdna* Chromatin Ribosomal P SS-A BioPlex 2200 與 EIA 陽性 BioPlex 2200 陽性與 EIA 陰性 BioPlex 2200 與 EIA 陰性 BioPlex 2200 陰性與 EIA 陽性 整體一體一致性 信賴區間 * 計算時排除 3 筆 dsdna BioPlex 無法判定以及 EIA 不明確的結果 硬皮症 ( 系統性硬化症 ) 以前瞻性方法收集風濕科診所內以美國風濕病學會 (ACR) 進行硬皮症診斷之患者的樣本, 透過檢測此樣本, 將 ANA 抗核抗體的結果與指定比對的產品進行比較, 針對各抗體同時以 ANA 抗核抗體篩檢試劑以及市售的 microplate EIA 方法檢測檢體 結果列於表 J 表 J ANA 抗核抗體與 EIA: 臨床診斷 - 硬皮症 SS-B Sm SmRNP RNP Scl-7O Jo-i Centromere B 結果 (N=44) ANA 抗核抗體 dsdna Chromatin Ribosomal P SS-A SS-B Sm SmRNP RNP Scl-7O Jo-i Centromere B BioPlex 2200 與 EIA 陽性 BioPlex 2200 陽性與 EIA 陰性 BioPlex 2200 與 EIA 陰性 BioPlex 2200 陰性與 EIA 陽性 整體一致性 信賴區間 E 使用說明 15

18 BioPlex 2200 ANA Screen 混和性結性結締組織疾織疾病 (MCTD) 以前瞻性方法收集風濕科診所內以 Alarcon-Segovia 或 Kahn 標準進行 MCTD 診斷之患者的樣本, 透過檢測此樣本, 將 ANA 抗核抗體的結果與指定比對的產品進行比較, 針對各自體抗體同時以 ANA 抗核抗體篩檢試劑以及市售的 microplate EIA 方法檢測檢體 資料顯示 MCTD 患者體內抗 chromatin 抗體出現機率高, 18 結果列於表 K 表 K ANA 抗核抗體與 EIA: 臨床診斷 -MCTD 結果 (N=16) BioPlex 2200 與 EIA 陽性 BioPlex 2200 陽性與 EIA 陰性 BioPlex 2200 與 EIA 陰性 BioPlex 2200 陰性與 EIA 陽性整體一致性 95 信賴區間 ANA 抗核抗體 dsdna Chromatin Ribosomal P SS-A SS-B Sm SmRNP RNP Scl-7O Jo-i Centromere B 多發性肌炎以前瞻性方法收集風濕科診所內以文獻標準進行多發性肌炎診斷之患者的樣本, 透過檢測此樣本, 將 ANA 抗核抗體的結果與指定比對的產品進行比較, 針對各抗體同時以 ANA 抗核抗體篩檢試劑以及市售的 microplate EIA 方法檢測檢體 註 : 大量資料顯示, 診斷出多發性肌炎的患者體內會出現 Jo-1 的抗體 1-12 結果列於表 L 表 L ANA 抗核抗體與 EIA: 臨床診斷 - 多發性肌炎 結果 (N=12) BioPlex 2200 與 EIA 陽性 BioPlex 2200 陽性與 EIA 陰性 BioPlex 2200 與 EIA 陰性 BioPlex 2200 陰性與 EIA 陽性 ANA 抗核抗體 dsdna Chromatin Ribosomal P SS-A SS-B Sm SmRNP RNP Scl-7O Jo-i Centromere B 整體一致性 信賴區間 使用說明 ANA 抗核抗體篩檢試劑

19 BioPlex 2200 ANA Screen 非標靶與無結締組織疾織疾病以前瞻性方法收集風濕科診所內根據醫療準則未診斷出罹患標靶結締組織疾病之患者的樣本, 透過檢測此樣本, 將 ANA 抗核抗體的結果與指定比對產品進行比較, 針對各抗體同時以 ANA 抗核抗體篩檢試劑以及市售針對各自體抗體的 microplate EIA 方法檢測檢體, 結果列於表 M 表 M ANA 抗核抗體與 EIA: 臨床診斷 非標靶與無結締組織疾病 結果 (N=494) BioPlex 2200 與 EIA 陽性 BioPlex 2200 陽性與 EIA 陰性 BioPlex 2200 與 EIA 陰性 BioPlex 2200 陰性與 EIA 陽性 ANA 抗核抗體 dsdna Chromatin Ribosomal P SS-A SS-B 整體一體一致性 信賴區間 Sm SmRNP RNP Scl-70 Jo-1 Centromere B E 使用說明 17

20 BioPlex 2200 ANA Screen 醫療決策輔助軟體 (MDSS) BioPlex 2200 醫療決策輔助軟體是一種模式辨認演算法, 可透過辨識多項分析結果中相關的診斷模型, 來加強 ANA 抗核抗體檢驗試劑的效果 MDSS 的結果, 相較於其他標靶結締組織疾病的 ACR 疾病分類 文獻或適用的公認醫療準則, 均列於下方表 N-T MDSS 從十一 (11) 個抗體結果中找出接近的模式後, 會提供一或多個可能的疾病相關性 ; 此外,MDSS 亦可顯示抗體濃度與 MDSS 定義的模式不具任何相關性 ( 無相關性 ) 或顯示所有抗體結果均低於預設的臨界值 ( 陰性 ) 共分析 1,130 筆結果, 包括 908 位來自風濕科診所之患者以及 222 位假設無自體免疫疾病之正常捐血者的組合, 所有可能的 MDSS 疾病相關性及相關定義均列於附錄 A 註: 如附錄 A 所示, 所有可能的 MDSS 輸出結果並未在臨床試驗中觀察到 註 : 在某些情況下, 即使同時參考血清學與臨床數據也難以區分 SLE 與修格連氏症候群 19 欲診斷自體免疫疾病的複雜性, 可從一篇近期研究中闡明轉診醫師與最終診斷的一致性僅有 下列 MDSS 臨床結果表所使用的 MDSS 說明定義如下 : 所有抗體均呈陰性 所有系統性自體免疫疾病的抗體均低於預設的臨界值 所有抗體均呈陽性 BioPlex 2200 ANA 的 11 項分析物中, 任何 1 項呈陽性 SLE 系統性紅斑狼瘡 SS 硬化症 MCTD 多發性肌炎無相關性 修格連氏症候群 相同 混和性結締組織疾病 相同 抗體濃度與 MDSS 定義的系統性自體免疫疾病的模式不同 18 使用說明 ANA 抗核抗體篩檢試劑

21 BioPlex 2200 ANA Screen 表 N 為 MDSS 輸出結果與醫師提供之診斷的一致性比例 數據呈現方式為出現一或多種以上陽性抗體患者, 以及具標靶結締組織疾病 (TCTD) 分類患者的疾病一致性比例, 無論為任何抗體反應 疾病一致性的差異為納入所有抗體反應均呈陰性之 TCTD 患者的結果 MDSS 無法針對所有抗體均呈陰性反應的患者提供相關性 表 N MDSS 與疾病分類 :(N=908) 根據規範的疾病分類 ** 標靶結締組織疾病 (TCTD) 系統性紅斑狼瘡 (SLE) 原發性修格連氏症候群 (N) 所有抗體均呈陰性 一或多種抗體呈陽性 (P) 無相關性 MDSS 輸出結果 * 任何 SLE 相關性 修格連氏症候群相關性 任何硬化正相關性 任何 MCTD 相關性 任何多發性肌炎相關性 硬化症 混和性結締組織疾病 (MCTD) 疾病一病一致性 僅出現陽性抗體結果 之患者 (P) 85.3 (186/21 8) 86.7 (13/15) 51.6 (16/31) 81.3 (13/16) 具有 TCTD 疾病分類 之患者 (N) 56.0 (186/33 2) 81.3 (13/16) 36.4 (16/44) 81.3 (13/16) 多發性肌炎 *** (2/6) (2/12) * 有關 MDSS 可能輸出結果的完整清單, 請見附錄 A 註: 如附錄 A 所示, 臨床試驗並未觀察到所有可能的 MDSS 輸出結果 MDSS 輸出結果不包含單獨的修格連氏症候群或 MCTD 的結果 ** 此處的標靶疾病包括符合單一疾病分類的所有患者, 以及符合多種疾病分類的患者, 但原發性的修格連氏症候群為例外 *** 針對這些患者, 多發性肌炎的 MDSS 輸出結果代表僅罹患本疾病未伴隨其他標靶結締組織疾病 E 使用說明 19

22 BioPlex 2200 ANA Screen 在過去, 自體抗體的實驗室測量是根據初步診斷來進行 舉例來說, 抗 Sm 檢測是根據 SLE 的初步診斷而要求進行 而抗 Sm 的陽性結果可支持初步診斷, 下列表 O 為出現特定陽性抗體結果 且醫師的診斷與該抗體一致時,MDSS 輸出結果的一致性 下表顯示, 針對該類樣本,MDSS 相關性與根據公認醫療準則所取得的診斷結果具有良好的一致性 表 O 罹患標靶結締組織疾病且具陽性抗體結果之患者的 MDSS 結果 陽性抗性抗體檢測結果 公認醫療準認醫療準則之則之疾病 * MDSS 輸出結果 ** 一致性 95 信賴區間 dsdna (N = 119) SLE (N = 92) 任何 SLE (N = 87/92 或 87) Chromatin (N = 任何 SLE (N = 112/122 或 SLE (N = 122) 168) 112) Ribosomal P (N = 任何 SLE (N = 29/30 或 SLE (N = 30) 37) 29) SSA (N = 173) SS (N = 15) SS 或 SLE (N = 13/15 或 13) SLE (N = 111) 任何 SLE (N = 106/111 或 106) SSB (N = 76) SS (N = 13) SS 或 SLE (N = 13/13 或 13) Sm (N = 60) SLE (N = 49) 任何 SLE (N = 49/49 或 49) SmRNP (N = 103) MCTD (N = 15) MCTD 或 SLE 13/15 或 (N = 13) RNP (N = 112) MCTD (N = 15) MCTD 或 SLE 13/15 或 (N = 13) Scl-70 (N = 23) 硬化症 (N = 7) 硬化症 ;SLE 或硬化症 (N = 5) 5/7 或 Jo-1 (N = 6)*** 多發性肌炎 (N = 2) 多發性肌炎 (N = 2/2 或 100 2) 硬化症 ;SLE 或 11/12 或硬化症 (N = 12) Centromere (N = 硬化症 (N = 11) ) 任何 SLE (N = SLE (N = 11) 9) 9/11 或 * 此處的標靶疾病包括符合單一疾病分類的所有患者, 以及符合多種疾病分類的患者 本試驗所 使用的公認醫療準則包括由美國風濕協會 (ACR) 美歐共識團體建立的準則 Alarcon-Segovia 或 Kahn 以及多發性肌炎的文獻準則 ** 有關所有 MDSS 可能輸出結果的完整清單, 請見附錄 A *** 註 : 充分文獻顯示, 診斷出罹患多發性肌炎的患者體內會有 Jo-1 抗體 1,12 20 使用說明 ANA 抗核抗體篩檢試劑

23 BioPlex 2200 ANA Screen 針對臨床試驗中面臨的各種標靶結締組織疾病, 除了勝算比 陽性概似比與陰性概似比的計算外, 表 P 與 Q 亦列出具陽性抗體檢測結果的患者數, 以及正確 MDSS 相關性的數據 由於部分 MDSS 輸出結果所含的疾病相關性超過原本欲檢測的疾病相關性, 因此表 P 結果的計算方式是排除輸出結果中具其他疾病的患者, 而表 Q 則是未排除這些患者的計算結果 並非所有罹患標靶結締組織疾病的患者都會出現 BioPlex 2200 ANA 抗核抗體篩檢試劑偵測得到的抗體 表 P MDSS 與依照準則之疾病分類的一致性 ( 不包含具其他 MDSS 相關性之患者 ) 原發性修系統性紅斑混合性結締格連氏症硬化症多發性肌炎依照準則之則之疾病分類狼瘡 (SLE) 組織疾織疾病候群 (N = 44) (N = 12) (N = 332) (N = 16) (N = 16) 陽性抗體檢測結果 MDSS 相關性 勝算比 (OR) OR 95 信賴區間 陽性概似比 (PLR) (PLR) 95 信賴區間 陰性概似比 (NLR) NLR 95 信賴區間 排除後總 N 表 Q MDSS 與依照準則之疾病分類的一致性 ( 包括具其他 MDSS 相關性之患者 ) 原發性修系統性紅斑混合性結締格連氏症硬化症多發性肌炎依照準則之則之疾病分類狼瘡 (SLE) 組織疾織疾病候群 (N = 44) (N = 12) (N = 332) (N = 16) (N = 16) 陽性抗體檢測結果 MDSS 相關性 勝算比 (OR) OR 95 信賴區間 陽性概似比 (PLR) (PLR) 95 信賴區間 陰性概似比 (NLR) NLR 95 信賴區間 總 N E 使用說明 21

24 BioPlex 2200 ANA Screen 某些臨床疾病分類並無 MDSS 相關性的輸出結果, 這些非標靶結締組織疾病應被分類為陰性或無 MDSS 相關性 ; 然而部分案例也曾出現錯誤的 MDSS 相關性, 連結至錯誤標靶結締組織的 MDSS 結果可被分類為 錯誤相關性 所有結果整理於下表內 : 表 R MDSS 與非鏢靶結締組織疾病 (TCTD) 非 TCTD 臨床疾病分類 (N) MDSS 相關性為陰性或無相關性 MDSS 相關性錯誤 錯誤相關性 皮肌炎 僅限 (3/15) 類風濕性關節炎 僅限 * 9 (31/341) 其他 CTD 僅限 (9/45) 無 CTD (16/77) 捐血樣本 ** 4 (8/222) * 31 位僅罹患類風濕性關節炎的患者中, 有 27 位的 MDSS 結果與 SLE 有關 類風濕風濕性關性關節炎的患者可能造成 MDSS 出現 SLE 相關性 ; 此外, 曾發現罹患類風濕性關節炎且正在接受抗 TNFα 阻斷劑的患者, 同時出現 dsdna 以及 Chromatin 的抗體 15 有鑒於此, 應謹慎判讀類風濕性關節炎患者的 MDSS 相關性結果 並請參見程式限制 ** 本試驗中接受檢測之捐血者的臨床狀態為未知 22 使用說明 ANA 抗核抗體篩檢試劑

25 BioPlex 2200 ANA Screen 診斷檢測的傳統評估策略不必然可直接應用於決策支援系統的評估, 因為決策支援系統通常不會只提供 一項答案, 患者可能會有超過一種診斷結果 21 本研究正確比例的定義為 : 具 MDSS 相關性之患者根據 ACR 文獻以及公認醫療準則確實罹患該疾病 表 S 與 T 內的正確比例結果, 應與下列本研究中所觀 察到的疾病盛行率併用 :SLE 29 (332/1130) 修格連氏症候群 1.4 (16/1130) 硬化症 3.9 (44/1130) 混和性結締組織疾病 1.4 (16/1130) 多發性肌炎 1.1 (12/1130) 其他結締組織疾病 36.9 (417/1130) 以及無結締組織疾病 6.8 (77/1130) 註: 下表內的正確相關性數據可能視不同族群患者而 改變 表 S 與任何標靶疾病分類無關的正確相關性 MDSS 輸出結 MDSS# 非標靶疾靶疾病 正確相關性 95 信賴區間 果 # 陰性 (585/719) 無相關性 (57/89) 表 T 與標靶疾病分類有關的正確相關性 MDSS 輸出結 MDSS# 臨床診斷 # 正確相關性 95 信賴區間 果 僅出現 SLE (142/198) SLE 或 SS (35/42) MCTD 或 (30/37) SLE 硬化症 (9/22) SLE 或硬化症 (11/20) 僅出現多發性肌炎 3* (2/3) * 3 位患者中僅有 1 位被診斷出皮肌炎 再現性現性研究 Bio-Radd Laboratories 準備了一個再現性檢測組, 內含 11 種檢測方法 將一或多種陽性患者樣本與 ANA 抗核抗體篩檢試劑中的 13 種分析物 (dsdna Chromatin SS-A 52 SS-A 60 SS-B Sm RNP 68 RNP A SmRNP Centromere Ribosomal P Scl-70 及 Jo-1) 的其中一或多種相互混合, 製作成十種陽性檢測方法 十種檢測方法中, 有五種含有較高濃度的抗體, 而另外五種則含有接近臨界值濃度的抗體 有一種檢測方法中, 所有 13 種分析物均為陰性 ; 另外, 針對三個批次的 ANA 抗核抗體對照組 [1 陽性對照品 (13 種分析物的抗體均呈陽性 ) 1 稀釋陽性對照品以及 1 陰性對照品 (13 種分析物的抗體均呈陰性 )] 進行檢測 於三個不同美國檢測設施進行再現性檢測, 共檢測三個批次的 ANA 抗核抗體篩檢試劑 各檢測單位使用一個批次的 ANA 抗核抗體篩檢試劑評估再現性 提供各檢測單位十一種檢測方法 十一項檢測方法與自體免疫對照組的檢測均以一次 2 組 (x2) 一天 2 次 ( 早上與下午 ) 的方法進行檢測, 共進行十天, 三個檢測單位各使用一個批次的 ANA 抗核抗體試劑組以及一個批次的 ANA 抗核抗體校正組 [2 組 x 2 次 x 10 天 = 40 組 / 檢測方法 / 中心 三個中心的總組數 =120 組 / 檢測方法 ] 依照國家臨床實驗室標準委員會 (NCCLS EP5-A, Vol. 19, No. 2, 第 7 頁 公式 (1) 與第 8 頁 公式 (4)) 進行組內再現性分析以及組間再現性分析 各檢測方法的平均抗體指數 (AI) 標準差 (SD) 以及變異係數 (CV) 均列於下表 針對 dsdna, 各檢測方法結果採平均國際單位 per ml (IU/mL) 標準差 (SD) 及變異係數 (CV) 呈現 表 U 至 Z 為陽性對照組 高陽性檢測方法以及低陽性檢測方法的結果 E 使用說明 23

26 BioPlex 2200 ANA Screen 組內分析表 U 再現性結果 ; 組內分析 研究中心 1 高陽性檢測 低陽性檢測 陽性對照品 高陽性檢測 低陽性檢測 陽性對照品 臨床中心 1 第 1 批 dsdna (IU/mL) Chromatin (AI) Ribosomal P (AI) SS-A 52 (AI) ANA 抗核抗體 - 組內分析 SS-A 60 (AI) SS-B (AI) Sm (AI) SmRNP (AI) RNP A (AI) RNP 68 (AI) Scl-70 (AI) Jo-i (AI) Centromere B (AI) 平均值 SD* CV N= 平均值 SD* CV N= 平均值 SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, 第 7 頁 公式 (1) 表 V 再現性結果 ; 組內分析 - 研究中心 2 臨床中心 2 第 2 批 dsdna (IU/mL) Chromatin (AI) Ribosomal P (AI) SS-A 52 (AI) ANA 抗核抗體 組內分析 SS-A 60 (AI) SS-B (AI) Sm (AI) SmRNP (AI) RNP A (AI) RNP 68 (AI) Scl-70 (AI) Jo-i (AI) Centromere B (AI) 平均值 SD* CV N= 平均值 SD* CV N= 平均值 SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, 第 7 頁 公式 (1) 24 使用說明 ANA 抗核抗體篩檢試劑

27 BioPlex 2200 ANA Screen 高陽性檢測 低陽性檢測 陽性對照品 表 W 再現性結果 ; 組內分析 研究中心 3 臨床中心 3 第 3 批 dsdna (IU/mL) Chromatin (AI) Ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) ANA 抗核抗體 組內分析 SS-B (AI) Sm (AI) SmRNP (AI) RNP A (AI) RNP 68 (AI) Scl-70 (AI) Jo-i (AI) Centromere B (AI) 平均值 SD* CV N= 平均值 SD* CV N= 平均值 SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, 第 7 頁 公式 (1) 組間分析表 X 再現性結果 ; 組間分析 研究中心 1 高陽性檢測 低陽性檢測 陽性對照品 臨床中心 1 第 1 批 dsdna (IU/mL) Chromatin (AI) Ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) ANA 抗核抗體 組間分析 SS-B (AI) Sm (AI) SmRNP (AI) RNP A (AI) RNP 68 (AI) Scl-70 (AI) Jo-i (AI) Centromere B (AI) 平均值 SD* CV N= 平均值 SD* CV N= 平均值 SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, 第 8 頁 公式 (4) E 使用說明 25

28 BioPlex 2200 ANA Screen 高陽性檢測 低陽性檢測 陽性對照品 表 Y 再現性結果 ; 組間分析 研究中心 2 臨床中心 2 第 2 批 dsdna (IU/mL) Chromatin (AI) Ribosomal P (AI) SS-A 52 (AI) ANA 抗核抗體 組間分析 SS-A 60 (AI) SS-B (AI) Sm (AI) SmRNP (AI) RNP A (AI) RNP 68 (AI) Scl-70 (AI) Jo-i (AI) Centromere B (AI) 平均值 SD* CV N= 平均值 SD* CV N= 平均值 SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, 第 8 頁 公式 (4) 高陽性檢測 低陽性檢測 陽性對照品 表 Z 再現性結果 ; 組間分析 研究中心 3 臨床中心 3 第 3 批 dsdna (IU/mL) Chromatin (AI) Ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) ANA 抗核抗體 組間分析 SS-B (AI) Sm (AI) SmRNP (AI) RNP A (AI) RNP 68 (AI) Scl-70 (AI) Jo-i (AI) Centromere B (AI) 平均值 SD* CV N= 平均值 SD* CV N= 平均值 SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, 第 8 頁 公式 (4) 26 使用說明 ANA 抗核抗體篩檢試劑

29 BioPlex 2200 ANA Screen 線性 WHO Wo/80 dsdna 標準品連續稀釋 WHO Wo/80 dsdna 標準品, 以取得分析範圍內的所有 dsdna 濃度 ; 再以 ANA 抗核抗體篩檢試劑分析所有連續稀釋液, 並將結果製成下表 ( 圖 1) 圖 1 WHO Wo/80 標準品 BioPlex 2200 dsdna 結果 (lu/ml) WHO W/o 80 dsdna 標準品 (IU/mI) E 使用說明 27

30 BioPlex 2200 ANA Screen dsdna 分析稀釋液 ANA 抗核抗體篩檢試劑之定量 dsdna 分析的稀釋液 / 線性包括四種含高濃度 dsdna 抗體樣本之檢測, 根據 NCCLS 規範 EP6-A (Vol. 23, No. 16) 連續稀釋樣本, 並以 ANA 抗核抗體篩檢試劑進行分析 結果列於表 AA 表 AA. dsdna 線性結果 樣本 稀釋 dsdna 期望值 BioPlex 2200 dsdna 結果 回收 dsdna 分析相關性以 Wo/80 dsdna 標準品校正 ANA 抗核抗體篩檢試劑, 並將試劑與指定比對產品進行比較 透過檢測 908 個前瞻性族群的樣本以取得相關性 針對低於 25 IU/mL 且包含介於中間等級以及不明確結果的檢測結果 (N=850), 以線性回歸計算出下列統計結果 :Y = 0.05X 以及 R = 針對所有結果, 排除介於中間等級以及不明確的檢測結果 (N=812), 線性回歸計算出下列統計結果 :Y = 0.23X 以及 R = BioPlex 2200 抗 dsdna 的檢測結果與抗 dsdna 預測結果之相關性, 可反映出不同抗體族群需藉由不同的特定分析法進行偵測 使用說明 ANA 抗核抗體篩檢試劑

31 BioPlex 2200 ANA Screen 交叉反應進行交叉分析研究, 以判定來自不同疾病之樣本以及其他潛在干擾因子是否會干擾 ANA 抗核抗體篩檢試劑的檢測結果 評估十種對各種交叉反應物具陽性結果之檢體, 以偵測各檢體是否會與 ANA 抗核抗體篩檢試劑的十一種自體抗體產生潛在的交叉反應 與 ANA 抗核抗體篩檢試劑產生陽性反應的樣本, 也以相對應的市售 microplate EIA 進行檢測 結果顯示, 各種接受評估的疾病狀態樣本不會與 ANA 抗核抗體篩檢試劑的十一種自體抗體產生交叉反應 大部分接受評估的樣本均對各種疾病狀態具高度陽性結果 若特定疾病與 ANA 抗核抗體篩檢試劑的各種分析法的確產生交叉反應, 則該疾病的所有樣本將出現陽性反應 研究顯示, 在各疾病狀態中, 十個樣本中有三到十個樣本會呈陰性 大多數出現陽性結果的樣本, 也會透過適當的市售 microplate EIA 確認為陽性 結果列於表 BB 表 BB 交叉反應 交叉反應 N 方法 dsdna * Chromatin Ribosomal P SS-A SS-B Sm SmRNP RNP Scl-70 Jo-1 Centromere B BioPlex 6 N/A 組織蛋白 EIA 6 N/A NT NT BioPlex ssdna EIA EQ 1 NT 1 BioPlex 類風濕因子 EIA NT NT NT NT NT NT NT NT NT NT NT BioPlex 平滑肌 EIA NT NT NT NT BioPlex 粒腺體 M EIA 0 2 NT 4 1 NT 1 1 NT NT 4 BioPlex 蛋白酶 3 (PR3) EIA NT 0 NT NT NT NT NT NT NT NT 1 BioPlex 髓過氧化物酶 (MPO) EIA NT NT NT NT NT NT 0 抗甲狀腺過氧化 BioPlex 物酶 (TPO) EIA NT NT NT NT NT NT NT NT NT NT 2 BioPlex 抗甲狀腺球蛋白 (TG) EIA 0 0 NT 0 NT NT NT 2 BioPlex 磷脂 EIA 1 3 NT 4 NT 0 2 NT NT 1 NT BioPlex 醇溶蛋白 EIA NT NT NT 1 NT NT NT NT NT NT NT N/A = 不適用 ;EQ = 不明確 ;NT = 未進行測試 * 排除所有不確定的結果 E 使用說明 29

32 BioPlex 2200 ANA Screen 干擾物質干擾物質檢測是根據 NCCLS Protocol 規範 EP7-A (Vol. 22, No. 27) 進行 所有檢測物質中均未觀察到明顯的干擾現象 下列表 CC 內的物質, 均以最高濃度 一次兩組 (2x) 進行單批次檢測 (N=20): 表 CC 干擾物質 物質 濃度 血紅素 < 500 mg/dl 膽紅素 ( 游離 ) < 20 mg/dl 三酸甘油脂 < 3000 mg/dl 蛋白質 ( 總 ) < 12 g/dl 膽固醇 < 500 mg/dl 紅血球細胞 < 0.4 濃縮物 丙種球蛋白 < 2.5 g/dl 維生素 C < 3 mg/dl 30 使用說明 ANA 抗核抗體篩檢試劑

33 BioPlex 2200 ANA Screen 附錄 A 下表為醫療決策輔助軟體 (MDSS) 可能組合的完整清單 # MDSS 文字輸出結果 1 所有系統性自體免疫疾病的抗體濃度均低於預設的臨界值 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 2 抗體濃度與系統性自體免疫疾病的 MDSS 檔案無相關性 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 3 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 4 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為 SLE 或修格連氏症候群 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 5 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為多發性肌炎 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 6 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為硬化症 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 7 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為 MCTD 或 SLE MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 8 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為 SLE 或硬化症 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 9* 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為多發性肌炎或 SLE MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 10* 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為多發性肌炎或 MCTD MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 11* 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為多發性肌炎或修格連氏症候群 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 12* 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為多發性肌炎或硬化症 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 13* 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為 MCTD 或修格連氏症候群 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 14* 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為 MCTD 或硬化症 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 15* 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為硬化症或修格連氏症候群 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 * 註 : 臨床試驗中並未觀察到這些 MDSS 輸出結果 E 使用說明 31

34 BioPlex 2200 ANA Screen 附錄 B 下列為 MDSS 的抗體與疾病相關性的圖示範例 dsdna 的結果通常以 IU/mL 呈現, 轉換成 AI 後, 圖示結果才會與所有抗體濃度的測量範圍軸一致 圖 2. MDSS 結果範例 可能的疾病相關性判讀意見 : 抗體濃度與系統性自體免疫疾病的 MDSS 檔案具相關性 可能為 MCTD 或 SLE MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 實驗室結果 MDSS 相關性 系統性紅斑狼瘡 (SLE) 混和性結締組織疾病 (MCTD) 硬化症 多發性肌炎 修格連氏症候群 抗體濃度與 MDSS 定義的系統性自體免疫疾病的模式不同 抗體指數 圖 3. MDSS 結果範例 無相關性判讀意見 : 抗體濃度與系統性自體免疫疾病的 MDSS 檔案無相關性 MDSS 輸出結果為 陰性 或 無相關性 無法排除自體免疫疾病的可能性 類風濕性關節炎患者可能造成 MDSS 出現 SLE 相關性, 因此應謹慎判讀 RA 患者的 MDSS 相關性 實驗室結果 MDSS 相關性 抗體指數 系統性紅斑狼瘡 (SLE) 混和性結締組織疾病 (MCTD) 硬化症 多發性肌炎 修格連氏症候群 抗體濃度與 MDSS 定義的系統性自體免疫疾病的模式不同 32 使用說明 ANA 抗核抗體篩檢試劑

35 參考文獻 BioPlex 2200 ANA Screen 1. EM Tan. Autoantibodies in Diagnosis and in Identifying Antigens. The Immunologist 1999: 7 (3): A Kavanuagh, R Tomar, J Reveille, DH Solomon and HA Homburger. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigen. Arch Pathol Lab Med 2000; 124 (1): R Tozzoli, N Bizzaro, E Tonutti, D Villalta, D Bassetti, F Manoni, A Piazza, M Pradella and P Rizzotti. Guidelines for the Laboratory Use of Autoantibody Tests in the Diagnosis and Monitoring of Autoimmune Rheumatic Diseases. Am J Clin Path 2002; 117(2): M Golightly and C Golightly. Laboratory diagnosis of autoimmune diseases. Medical Lab Observer 2002(7); ML Astion, MH Wener and K Hutchinson. Autoantibody Testing: The Use of Immunofluorescence and Other Assays. Clin Lab News 2000(7); HA Homburger, YD Cahen, J Griffiths and GL Jacob. Detection of Antinuclear Antibodies: Comparative Evaluation of Enzyme Immunoassay and Indirect Immunofluorescence Methods. Arch Pathol Lab Med 1998; 122(11): BS Reisner, J DiBlasi and N Goel. Comparison of an Enzyme Immunoassay to an Indirect Fluorescent Immunoassay for the Detection of Antinuclear Antibodies. Am J Clin Path 1999; 111: TG Phan, RCW Wong and S Adelstein. Autoantibodies to Extractable Nuclear Antigens: Making Detection and Interpretation More Meaningful. Clin Diag Lab Immunol 2002; 9: RJ Fulton, RL McDade, PL Smith, LJ Kienker and JR Kettman Jr. Advanced multiplexed analysis with the FlowMetrix System. Clin Chem 1997; 43(9): Manual Guide - Safety Management No. CDC-22, Decontamination of Laboratory Sink Drains to Remove Azide Salts. April 30, Atlanta, GA: Centers for Disease Control. 11. A Zlatkis, KY Lee, CF Poole and G Holzer. Capillary column gas chromatographic profile analysis of volatile compounds in sera of normal and virus-infected patients. J Chromatogr 1979; 163(2): WH Reeves and M Satoh. Autoantibodies in Systemic Lupus Erythematosus, in Arthritis and Allied Conditions: A Textbook of Rheumatology, 14th Ed., Ed. William J. Koopman, Lippincott, Williams and Wilkins, Philadelphia, 2001; EM Tan, JS Smolen, JD McDougal, et. al. A Critical Evaluation of Enzyme Immunoassays for Detection of Antinuclear Autoantibodies of Defined Specificities. I. Precision, Sensitivity and Specificity. Arthritis Rheum 1999; 42(3): M Reichlin and JB Harley. Antinuclear Antibodies: An Overview in Dubois Lupus Erythematosus, 5th Ed., Eds. Daniel J Wallace and Bevra H. Hahn, Williams and Wilkins, Baltimore and Philadelphia, 1997; C Eriksson, S Engstrand, K-G Sundqvist, S Rantapää-Dahlqvist. Autoantibody formation in patients with rheumatoid arthritis treated with anti-tnfα. Ann Rheum Dis 2005; 64: A Sturgess and J Edmonds. Improving the effectiveness of autoantibody testing in the clinic. Autoimmunity Reviews 2002; 1: CGM Kallenberg, AA Wouda, MH Hoet and WJ Van Venrooij. Development of connective tissue disease in patients pre- senting with Raynaud s phenomenon: a six year follow up with emphasis on the predictive value of antinuclear antibod- ies as detected by immunoblotting. Ann Rheum Dis 1988; 47: Simón JA, Cabiedes J, Ortiz E, Alcocer-Varela J, and Sánchez-Guerrero J. Anti-nucleosome antibodies in patients with systemic lupus erythematosus of recent onset. Potential utility as a diagnostic tool and disease activity marker. Rheumatology 2004; 43: Isenberg DA. Systemic lupus erythematosus and Sjögren s syndrome: historical perspective and ongoing concern. Arhritis Rheum. 50: Narain S, HB Richards, M Satoh, M Sarmiento, R Davidson, J Shuster, E Sobel, P Hahn, and WH Reeves. Diagnostic accu- racy for lupus and other systemic autoimmune diseases in the primary care setting. Arch Intern Med 2004; 164: Berner ES, Webster GD, Shugermann AA, et. al. Performance of four computer-based diagnostic systems. New England Journal of Medicine 1994; 330: OP Rekvig, M Kalaaji and H Nossent. Anti-DNA antibody subpopulations and lupus nephritis. Autoimmunity Reviews 2004; 3: 1-6. 商標資訊 BioPlex 為 Bio-Rad Laboratories, Inc. 之商標 E 使用說明 33

36 BioPlex 2200 ANA Screen 技術資訊聯絡人 Bio-Rad 提供全天候 24 小時 每週 7 天的技術協助免費服務專線 ; 美國與波多黎各的免付費專線為 BIORAD ( ) 美國境外請聯絡當地的 Bio-Rad 辦公室以尋求協助 Clinical Diagnostics Group 4000 Alfred Nobel Drive Hercules, California Telephone (510) FAX (510) AUSTRALIA, Bio-Rad Laboratories Pty. Ltd. Unit 1 Block Y, 391 Park Road, Regents Park NSW 2143 Phone Telefax AUSTRIA, Bio-Rad Laboratories Ges.m.b.H., Hummelgasse 88/3-6, A-1130 Vienna Phone Telefax BELGIUM, Bio-Rad S.A.-N.V. Begoniastraat 5, B-9810 Nazareth Eke Phone Telefax BRAZIL, Bio-Rad do Brasil, Rua dos Invalidos 212, 5 Andar, Lapa CEP , Rio de Janeiro Phone Telefax CANADA, Bio-Rad Laboratories, Ltd., 2403 Guénette Montreal, Québec H4R2E9 Phone Telefax CZECH REPUBLIC, Bio-Rad spol. s.r.o., Nad ostrovem 1119/7, Prague 4 Phone Telefax CHINA, Bio-Rad China Limited, 18F/D Hai Li Building, No. 88 Da Pu Road, Shanghai Phone Telefax DENMARK, Bio-Rad Laboratories, Generatorvej 8 C, 2730 Herlev Phone Telefax FINLAND, Bio-Rad Laboratories, Pihatorma 1 A, FIN Espoo Phone Telefax FRANCE, Bio-Rad S.A., 3 boulevard Raymond Poincaré Marnes-la-Coquette Phone Telefax GERMANY, Bio-Rad Laboratories GmbH, Heidemannstrasse 164, D Munich Phone Telefax HONG KONG, Bio-Rad Pacific Ltd., Unit 1101, 11/F, DCH Commercial Centre, 25 Westlands Road, Quarry Bay Phone Telefax INDIA, Bio-Rad Laboratories (India) Pte. Ltd., B&B1, Enkay Towers, Vanijya Nikunj, Udhyog Vihar, Phase-V, Gurgaon, Haryana Phone Telefax ISRAEL, Bio-Rad Laboratories Ltd., 14 Homa Street, New Industrial Area, Rishon Le Zion Phone Telefax ITALY, Bio-Rad Laboratories S.r.l., Via Cellini 18/A, Segrate, Milan Phone Telefax JAPAN, Nippon Bio-Rad Laboratories, 7-18, Higashi-Nippori 5-chome, Arakawa-ku, Tokyo Phone Telefax KOREA, Bio-Rad Korea Ltd., B1, Cambridge Building, , Seocho-Dong, Seocho-Gu, Seoul, Phone Telefax LATIN AMERICA, Bio-Rad Latin America, Palmetto Frontage Road, Suite 101, Miami Lakes, Florida Phone Telefax MEXICO, Bio-Rad Laboratorios Mexico, S.A. de C.V., Adolfo Prieto No 1653, Colonia Del Valle, Mexico, D.F. Phone Telefax THE NETHERLANDS, Bio-Rad Laboratories BV, Fokkerstraat 10, 3905 KV Veenendaal Phone Telefax NEW ZEALAND, Bio-Rad New Zealand, 189 Bush Road, Albany, Auckland Phone Telefax NORWAY, Bio-Rad Laboratories, Johan Scharffenbergs vei 91, N-0694, Oslo Phone Telefax POLAND, Bio-Rad Laboratories, Nakielska Str. 3, Warsaw Phone Telefax PORTUGAL, Bio-Rad Laboratories, Rua do Entreposto Industrial, 3-1 Esq., , Amadora Phone Telefax RUSSIA, Bio-Rad Laboratories Ltd., 37/A14 Leningradsky Pr., Moscow Phone Telefax SINGAPORE, Bio-Rad Laboratories (Singapore) Pte. Ltd., 27 International Business Park, #01-02, Phone Telefax SOUTH AFRICA, Bio-Rad Laboratories (Pty) Ltd., 34 Bolton Road, Parkwood, Johannesburg 2193 Phone Telefax SPAIN, Bio-Rad Laboratories S.A., Lopez de Hoyos , Madrid Phone Telefax SWEDEN, Bio-Rad Laboratories A.B., Vintergatan 1, Box 1097, S , Sundbyberg Phone Telefax SWITZERLAND, Bio-Rad Laboratories, Nenzlingerweg 2, CH-4153 Reinach BL Phone Telefax THAILAND, Bio-Rad Laboratories Ltd., 1st & 2nd Floor, Lumpini I Bldg., 239/2 Rajdamri Rd., Lumpini, Pathumwan, Bangkok Phone Telefax UNITED KINGDOM, Bio-Rad Laboratories Ltd., Bio-Rad House, Maylands Ave., Hemel Hempstead, Herts HP2 7TD Phone Telefax E January 使用說明 ANA 抗核抗體篩檢試劑

37 BioPlex 2200 System ANA Screen with MDSS Instructions For Use Federal law restricts this device to sale by or on the order of a physician, or to a clinical laboratory; and use is restricted to, by, or on the order of a physician. This IFU is effective beginning with Lot # of the ANA Screen Reagent Pack and above, and BioPlex 2200 Software Version 4.0 and above. UNITED STATES, Bio Rad Laboratories Clinical Diagnostics Group, Hercules, CA FRANCE, Bio Rad Laboratories, Marnes la Coquette

38 BioPlex 2200 ANA Screen with MDSS Multiple Language CD-ROM This Instructions For Use (IFU) document is provided in Adobe PDF form on a multiple language CD-ROM in the following languages: English, German, French, Spanish, Italian, Portuguese, Swedish and Danish. Caution, consult accompanying documents Achtung, Begleitdokumente beachten Attention, consulter la documentation jointe Attenzione, consultare la documentazione allegata Precaución, consulte los documentos que acompañan al instrumento Atenção, consultar os documentos inclusos Försiktighet: se medföljande dokument Forsigtig, der henvises til den vedlagte dokumentation Number of Tests Anzahl der Tests Nombre de tests Numero di analisi Número de pruebas Número de testes Antal tester Antal tests Manufactured by Hergestellt von Fabriqué par Fabbricato da Fabricado por Fabricado por Tillverkare Fremstillet af Lot Number Chargen-Nr. Numéro de lot Numero di lotto Número de lote Número de lote Batchnummer Lotnummer Authorized Representative in the European Community Bevollmächtigter in der Europäischen Union Représentant agréé dans la Communauté Européenne Mandatario autorizzato per l Unione Europea Representante autorizado en la Comunidad Europea Representante autorizado na Comunidade Europeia Auktoriserad representant i Europeiska gemenskapen Repræsentant i det Europæiske Fællesskab Use by (YYYY-MM-DD) Verwendbar bis (JJJJ-MM-TT) Date de péremption (AAAA-MM-JJ) Data di scadenza (AAAA-MM-GG) Usar hasta el (AAAA-MM-DD) Utilizar até (AAAA-MM-DD) Använd före (ÅÅÅÅ-MM-DD) Anvend før (ÅÅÅÅ-MM-DD) Irritant Reizend Irritant Irritante Irritante Irritante Irriterande Lokalirriterende ANA Screen Reagent Pack Reagenzienpack für das ANA-Screening Cartouche de réactifs pour le dépistage d ANA Cartuccia reagenti per lo screening degli ANA Paquete de reactivos para la prueba de detección de ANA Kit de reagentes para despiste de ANA Reagenskassett för ANA-screening Reagenspakke til ANA screening Temperaure Limit Temperaturgrenze Lte de température Limite di temperatura Límite de temperatura Limite de temperatura Temperaturgränser Temperaturgrænse Catalog Number Katalognummer Numéro de catalogue Numero di catalogo Número de catálogo Número de catálogo Katalognummer Katalognr Contains Enthält Contient Contiene Contiene Contém Innehåller Indeholder BEAD DIL For In Vitro Diagnostic Use In-vitro-Diagnostikum Utilisation comme test de diagnostic in vitro Per uso diagnostico in vitro Para uso en diagnóstico in vitro Para uso em diagnóstico in vitro För in vitro-diagnostiskt bruk Til in vitro-diagnostisk brug Version Version Version Versione Versión Versão Version Version Bead Set Bead-Set Réactif contenant les billes Set di microsfere Conjunto de micropartículas Conjunto de esferas Mikrosfär-set Perlesæt Sample Diluent Probenverdünnungsmittel Diluant échantillon Diluente per campione Diluyente para muestras Diluente de amostras Provdiluent Prøvefortynder Consult Instructions for Use Gebrauchsanweisung beachten Consulter la notice d emploi Consultare le istruzioni per l uso Consulte las instrucciones de uso Consulte as instruções de utilização Läs bruksanvisningen Benyt brugsanvisninger Conjugate Konjugat Conjugué Coniugato Conjugado Conjugado Konjugat Konjugat ii Instructions for Use Manual ANA Screen with MDSS Contains Enthält Contient Contiene Contiene Contém Innehåller Indeholder European Conformity CE-Konformitätskennzeichnung Conformité aux normes européennes Conformità europea Conformidad europea Conformidade com as normas europeias Europeisk överensstämmelse Europæisk overensstemmelse

39 BioPlex 2200 ANA Screen with MDSS Table of Contents Page Intended Use...2 Summary and Explanation...2 Principle of the Procedure...2 Kit Components...3 Additional Required Items, Available from Bio-Rad...3 Precautions/Warnings...4 Specimen Collection and Handling...4 Preparation and Storage of Reagents...5 Indications of Instability or Deterioration of Reagents...5 Procedure...5 A) Quality Control...5 B) Load/Process Samples...6 C) Calibration...6 D) Traceability to Reference Material...6 Guidelines for Interpretation of Results...6 Calculation...6 Data Analysis...6 Selection of Desired Results...6 Format A: Qualitative Screening (Compound Assay: ANAScr)...6 Format B: Qualitative with Disease Association (Reserved Test Group: ANA +)...7 Format C: Selected Antibody Results...7 Limitations of the Procedure...7 Expected Values...8 Prevalence...8 Performance Characteristics...9 Comparative Testing...9 Prospective Comparison of ANA Screen and ANA Microplate EIA...9 Retrospective Comparison of Selected Antibodies to EIA Methods...10 Correlation with CDC Reference Sera...11 Prospective Comparison of Selected Antibodies to EIA Methods...12 Clinical Concordance...13 Targeted Disease Analysis...13 Individual Disease Analysis...14 Medical Decision Support Software (MDSS)...18 Reproducibility Studies...23 Intra Assay...24 Inter Assay...25 Linearity...27 WHO Wo/80 dsdna Standard...27 Dilution of the dsdna Assay...28 Correlation of the dsdna Assay...28 Cross-Reactivity...29 Interfering Substances...30 Appendix A...31 Appendix B...32 References...33 Trademark Information G Instructions for Use Manual 1

40 BioPlex 2200 ANA Screen with MDSS INTeNDeD USe The BioPlex 2200 ANA Screen is intended for the qualitative screening of specific antinuclear antibodies (ANA), the quantitative detection of antibody to dsdna, and the semi-quantitative detection of ten (10) separate antibody assays (Chromatin, Ribosomal P, SS-A, SS-B, Sm, SmRNP, RNP, Scl-70, Jo-1, and Centromere B) in human serum and/or EDTA or heparinized plasma. The test system is used as an aid in the diagnosis of systemic autoimmune diseases. The ANA Screen is intended for use with the Bio-Rad BioPlex 2200 System. The BioPlex 2200 Medical Decision Support Software (MDSS), used in conjunction with the ANA Screen, is an optional laboratory tool that associates patient antibody results with predefined MDSS profiles that have been correlated with the following systemic autoimmune diseases: Systemic Lupus Erythematosus (SLE), Mixed Connective Tissue Disease (MCTD), Sjögren s Syndrome (SS), Scleroderma (Systemic Sclerosis) and Polymyositis. SUMMAry AND explanation The ANA Screen detects the presence of clinically relevant circulating autoantibodies in serum or plasma. These autoantibodies may be useful as an aid in the diagnosis of systemic autoimmune diseases such as Systemic Lupus Erythematosus (SLE), Mixed Connective Tissue Disease (MCTD), Undifferentiated Connective Tissue Disease (UCTD), Sjögren's Syndrome (SS), Scleroderma (Systemic Sclerosis), Dermatomyositis, Polymyositis, Rheumatoid Arthritis (RA), CREST Syndrome, and Raynaud's Phenomenon. 1-4 Historically, the most common test for antinuclear antibodies has been Immunofluorescence Assay (IFA). 5 It uses controlled cell lines (frequently HEp-2) that are fixed on a slide. The cells can contain as many as 120 different antigens used for the diagnosis of autoimmune disorders. When diluted human sera containing autoantibodies are spread over the mounted cells, the antibodies bind to the cellular antigens. Typically, they are then detected by the application of anti-human immunoglobulins, labeled with a fluorescent dye. Sometimes, non-clinically relevant autoantibodies are detected in patient samples and can be interpreted as clinically false positive. Enzyme Immunoassay (EIA) technology can also be employed for autoimmune testing. 6-8 EIA relies upon mixtures of the common antigens to detect antibodies known to be associated with autoimmune diseases. These common antigens vary among EIA manufacturers. In EIA testing, diluted sera are mixed with the antigens bound to a solid phase (most commonly a microtiter plate). Autoantibodies that bind to the plate are then detected with anti-human IgG coupled to an enzyme, that can be utilized to produce a colorimetric signal. EIA technology, when applied to ANA testing, produces a composite signal. However, a strong signal from one antibody is not distinguishable from a number of weak signals to multiple antibodies. There is still a risk of false positives in EIA tests, due to non-specific binding of other IgG antibodies to the solid phase. PrINCIPle of The ProCeDUre The ANA Screen uses multiplex flow immunoassay, a methodology that greatly resembles traditional EIA, but permits simultaneous detection and identification of many antibodies in a single tube. 9 Thirteen (13) different populations of dyed beads are coated with antigens associated with systemic autoimmune disease (dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B).* The BioPlex 2200 System combines an aliquot of patient sample, sample diluent, and bead set reagent into a reaction vessel. The mixture is incubated at 37 C. After a wash cycle, anti-human IgG antibody, conjugated to phycoerythrin (PE), is added to the dyed beads and this mixture is incubated at 37 C. The excess conjugate is removed in another wash cycle, and the beads are re-suspended in wash buffer. The bead mixture then passes through the detector. The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI). Three additional dyed beads, Internal Standard Bead (ISB), Serum Verification Bead (SVB) and a Reagent Blank Bead (RBB) are present in each reaction mixture to verify detector response, the addition of serum or plasma to the reaction vessel and the absence of significant non-specific binding in serum or plasma. Refer to the BioPlex 2200 System Operation Manual for more information. The system is calibrated by either a set of six (6) calibrators (catalog number ) or seven (7) calibrators (catalog number ) supplied separately by Bio-Rad Laboratories. Both ANA Screen calibrator sets contain dsdna. Six (6) different levels of antibody concentrations are used for quantitative calibration, and results for patient samples are expressed in IU/mL. Results of 4 IU/mL are negative, 5-9 IU/mL are indeterminate, and results of 10 IU/mL are reported as positive for dsdna antibody. For the other twelve (12) beads, four (4) vials representing four (4) different antibody concentrations are used for semi-quantitative calibration. The result for each of these antibodies is expressed as an antibody index (AI). An AI of 1.0 indicates an antibody cut-off concentration that corresponds to approximately the 99th percentile of values obtained from a non-diseased population; results of 1.0 or greater are reported as positive. 2 Instructions for Use Manual ANA Screen with MDSS

41 BioPlex 2200 ANA Screen with MDSS When MDSS is activated, the autoantibody results are compared to the MDSS database that contains results for over 1,400 sera/plasma, representing test results from patients with systemic autoimmune diseases and from healthy individuals. If one or more positive results are obtained from a serum or plasma sample, the results are associated with the most appropriate MDSS profiles. The resulting disease associations can also aid in determining appropriate additional autoimmune serological testing. Note: An MDSS output of Negative or No Association does not rule out autoimmune disease (see GUIDELINES FOR INTERPRETATION OF RESULTS). * In cases where either SS-A 60 and/or SS-A 52 are present, results are reported as positive for SS-A. Likewise, when either RNP A and/or RNP 68 are present, results are reported as positive for RNP. KIT CoMPoNeNTS ANA Screen Reagent Pack ( ). The reagent pack contains supplies sufficient for 100 tests. ANA Screen Reagent Packs are also available in an optional 50 pack bulk configuration ( ). The 50 pack bulk configuration contains supplies sufficient for 5000 tests. Vial Bead Set BEAD Conjugate Sample Diluent DIL Description One (1) 10 ml vial, containing dyed beads coated with dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1, Centromere B, Internal Standard (ISB), Serum Verification (SVB), and a Reagent Blank (RBB), with Glycerol and protein stabilizers (bovine) in a MOPS (3-[N-Morpholino] propanesulfonic acid) buffer. ProClin 300 ( 0.3), sodium benzoate ( 0.1) and sodium azide (< 0.1) are added as preservatives. One (1) 5 ml vial, containing murine monoclonal anti-human IgG/phycoerythrin conjugate and sheep anti-human FXIII/phycoerythrin conjugate in a phosphate buffer with protein stabilizers (bovine). ProClin 300 ( 0.3) and sodium azide (< 0.1) are added as preservatives. One (1) 10 ml vial, containing protein stabilizers (bovine and murine) in a triethanolamine buffer. ProClin 300 ( 0.3), sodium benzoate ( 0.1) and sodium azide (< 0.1) are added as preservatives. ADDITIoNAl required ITeMS, AVAIlABle FroM BIo-rAD Description BioPlex 2200 ANA Screen Calibrator Set: Six (6) 500 µl vials, containing antibodies to dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B, in human serum. ProClin 300 ( 0.3) and sodium benzoate (0.1) as preservatives for all calibrators BioPlex 2200 ANA Screen Control Set: Two (2) 1.5 ml vials of Positive Control containing antibodies to dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B, in human serum, and two (2) 1.5 ml vials of Negative Control Serum. ProClin 300 ( 0.3) and sodium benzoate (0.1) as preservatives for all controls BioPlex 2200 ANA Screen Calibrator Set: Seven (7) 500 µl vials, containing human antibodies to dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B, in a human serum matrix made from defibrinated plasma. ProClin 300 ( 0.3), sodium benzoate ( 0.1) and sodium azide (< 0.1) are added as preservatives BioPlex 2200 ANA Screen Control Set: Four (4) 1.5 ml vials of Positive Control containing human antibodies to dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B, in a human serum matrix made from defibrinated plasma, and two (2) 1.5 ml Negative Control vials containing a human serum matrix made from defibrinated plasma. ProClin 300 ( 0.3), sodium benzoate ( 0.1) and sodium azide (< 0.1) are added as preservatives BioPlex 2200 Sheath Fluid: Two (2) 4 L bottles containing Phosphate Buffered Saline (PBS). ProClin 300 (0.03), and sodium azide (< 0.1) are added as preservatives BioPlex 2200 Wash Solution: One (1) 10 L bottle containing Phosphate Buffered Saline (PBS) and Tween 20. ProClin 300 (0.03), and sodium azide (< 0.1) are added as preservatives BioPlex 2200 Instrument and Software G Instructions for Use Manual 3

42 BioPlex 2200 ANA Screen with MDSS PreCAUTIoNS/WArNINgS 0.3 ProClin 300 Xi: Irritant R43: May cause sensitization by skin contact. S : Avoid contact with skin. This material and its container must be disposed of in a safe way. Wear suitable gloves. S56: Dispose of this material and its container at hazardous or special waste collection point. (Human Source Material.) 1. For In Vitro Diagnostic (IVD) Use. 2. For professional use only. 3. Each unit of human serum used in the manufacture of the ANA Screen with MDSS kit (including calibrator and control sets) was tested by FDA accepted methods and found non-reactive for Hepatitis B surface antigen (HBsAg), antibody to HIV-1, HIV-2 and Hepatitis C (HCV). No test method can offer complete assurance that products containing human source materials will be absent of these and other infectious agents. In accordance with good laboratory practice (GLP), all human source material should be considered potentially infectious for Hepatitis B (HBV), Hepatitis C (HCV), HIV-1, HIV-2, and all other infectious agents; therefore, handle the ANA Screen with MDSS kit (including reagent packs, calibrators and control sets) with the same precautions used with patient specimens. It is recommended that these reagents and human specimens be handled in accordance with the Biosafety in Microbiological and Biomedical Laboratories Biosafety Level 2 or other appropriate biosafety practices for materials which contain or are suspected of containing infectious agents. 4. Consider any materials of human origin as infectious and handle them using typical biosafety procedures and Universal Precautions according to 29 CFR Do not smoke, eat, or drink in areas where patient samples and kit reagents are handled. 6. Do not pipette by mouth. 7. Wear personal protective equipment while handling all reagents and samples and while operating the BioPlex 2200 System. 8. Dispose of all wastes in accordance with applicable national, regional and/or local regulations. 9. Waste material containing patient samples or biological products should be considered biohazardous when disposing or treating. 10. Chemical reagents should be handled in accordance with Good Laboratory Practices. 11. Refer to the kit and additional required component Material Safety Data Sheets (MSDS) for more safety information and warnings about chemical and biological hazards. The Material Safety Data Sheets are available at and on request. 12. Clean up all spills immediately and thoroughly. Decontaminate the area for any spills involving biohazardous materials with an effective disinfectant. Dispose of all contaminated materials appropriately. 13. Do not use tests beyond their expiration date. The date is printed on all boxes. 14. Do not interchange vial or bottle caps and stoppers; this will lead to cross-contamination of reagents. 15. Adherence to the protocol specified herein is necessary to ensure proper performance of this product. If aberrant results are obtained, contact Bio-Rad Technical Service. 16. Never mix the contents from different bottles of the same reagent. Doing so may lead to reagent contamination and compromise the performance of the product. 17. Sodium azide may react with lead and copper plumbing to form highly explosive metal azides. On disposal of liquids, flush with a large volume of water to prevent azide build-up. 10 SPeCIMeN ColleCTIoN AND handling Specimen Collection Precaution Consider any materials of human origin as infectious and handle them using typical biosafety procedures. Specimen Type Serum and EDTA or Heparinized plasma are the recommended samples. Avoid hemolysis. Specimen Storage Serum or plasma may be stored under refrigeration (2-8 C) for up to 7 days. For longer storage of samples, keep at -20 C or colder. Specimen Preparation Thoroughly mix thawed specimens; it is also recommended to centrifuge thawed specimens to remove gross particulate matter. Avoid multiple freeze/thaw cycles (up to 3 cycles is acceptable). Specimen Shipping All specimens and other samples of human origin must be shipped in accordance with national and international transportation regulations. 4 Instructions for Use Manual ANA Screen with MDSS

43 BioPlex 2200 ANA Screen with MDSS PrePArATIoN AND STorAge of reagents Do not freeze the ANA Screen reagent Pack. Reagents in the ANA Screen are ready to use. After initial use, the reagents are stable for 30 days, or until the date of expiration when stored unopened on the system or refrigerated at 2-8ºC. Do not use reagents beyond expiration dates. INDICATIoNS of INSTABIlITy or DeTerIorATIoN of reagents Store all reagents at the labeled temperature and do not use past their expiration dates. Do not use any reagents which have any indications of discoloration, cloudiness or precipitation. Do not use any reagents that show any signs of leakage. ProCeDUre In order to obtain reliable and consistent results, strictly adhere to the instructions in this Instructions for Use. Do not modify the handling and storage conditions for kit reagents or patient samples. Operating instructions, including calibration, quality control, and maintenance for the BioPlex 2200 System are further described in the BioPlex 2200 System Operation Manual. Prior to using the ANA Screen, ensure that the BioPlex 2200 System is powered on, loaded with reagent packs and bulk solutions, and that all required maintenance has been performed. Please refer to the BioPlex 2200 System Operation Manual for more information regarding these activities. Any lot numbers of the BioPlex 2200 System Sheath Fluid and BioPlex 2200 System Wash Solution can be interchanged. A) Quality Control As indicated in the BioPlex 2200 System Operation Manual, for each reagent pack once per day testing is performed. Load and process either of the ANA Screen control sets that are available from Bio-Rad (catalog number that contains two (2) control vials, or that contains three (3) control vials). The ANA Screen Control Set includes a negative control as well as multi-analyte positive controls containing antibodies present for analytes within the ANA Screen Reagent Pack. The positive controls are manufactured to give positive results, with values above the cut-off for each specific bead. The negative control is manufactured to give negative results, with values below the cut-off for each specific bead. The negative control must have a negative result, and the positive control must have a positive result. Note: The Negative and Positive Controls of the ANA Screen Control Set are intended to monitor for substantial reagent failure. The Positive Control will not ensure precision at the assay cutoff. Lot specific values for the positive controls are loaded into the BioPlex 2200 System database via the provided media or by manual input. After identifying the control via the barcoded vial, the BioPlex 2200 System compares the control results to the expected lot specific control values stored in the BioPlex 2200 System database. Failure to obtain the appropriate values for controls will invalidate the assay and indicates procedural error, improper sample handling or deterioration of reagents. IMPorTANT qc TroUBleShooTINg: At low frequency, reagent packs may exhibit falsely low signals for certain analytes and generate QC errors. The following troubleshooting steps should be followed when observing the noted QC behavior: 1. qc Warning - low for only some analytes: Repeat QC testing. If the QC Warning repeats, remove the pack with the flagged QC results and do not use. Please call Bio-Rad Technical Support to report the suspected low signal pack. Run QC with a new reagent pack. If QC results are within the acceptable range on the new reagent pack, discard the affected reagent pack with the QC Warning - Low results and do not report patient test results from that reagent pack. If the QC Warning repeats on the new reagent pack, please call Bio-Rad Technical Support for assistance with troubleshooting. Re-test any samples that were tested using the affected reagent pack. If multiple packs for a particular BioPlex 2200 assay are on-board the instrument, the reagent pack (kit) serial number associated with the QC Warning - low results can be determined by viewing the Control Result dialog for the corresponding QC Event. 2. qc Warning - high for only some analytes: Re-calibrate the reagent pack with the QC Warning - high and re-run QC. Verify that QC results are within the acceptable range for all analytes before reporting out patient results. Any samples tested using the pack with the QC Warning - high must be re-tested. Patient samples run on the affected pack are valid due to the fact that a calibration occurred with that pack. Additional controls may be tested in accordance with local, state, and/or federal regulations or accreditation requirements and your laboratory s quality control policy. If a control result is out of its specified range, any test results generated since the last acceptable control results must be evaluated to determine if test results may have been adversely affected. Adversely affected results are invalid, and these samples must be retested G Instructions for Use Manual 5

44 BioPlex 2200 ANA Screen with MDSS B) Load/Process Samples Load samples into the racks provided with the BioPlex 2200 System as indicated in the BioPlex 2200 System Operation Manual. Sample processing on the BioPlex 2200 System is fully automated. Refer to the BioPlex 2200 System Operation Manual for appropriate software setup. C) Calibration The ANA Screen Calibrator Set should be loaded and assayed at minimum in duplicate every 14 days or with each new Reagent Pack lot. For dsdna, a six-point 4PL fitted curve is used to calculate quantitative results. For the other analytes, a point-to-point curve fit using four calibrators is used to calculate semi-quantitative results. Refer to the BioPlex 2200 System Operation Manual for more information. D) Traceability to Reference Material The ANA Screen Calibrator Set is calibrated against the Wo/80 dsdna standard from the World Health Organization (WHO) for dsdna. There are no other certified materials available for the other analytes. guidelines For INTerPreTATIoN of results Calculation All calculations necessary to interpret the results are performed automatically by the BioPlex 2200 System Software. Data Analysis The results for each of the antibodies are expressed as an antibody index (AI), except for dsdna which is expressed in IU/mL. For dsdna, results of 4 IU/mL are negative, 5-9 IU/mL are indeterminate, and results of 10 IU/mL are reported as positive. For the other assays, results of < 1.0 AI are negative and results of 1.0 AI or greater are reported as positive. In cases where either SS-A 60 and/or SS-A 52 are present, results are reported simply as positive for SS-A. Likewise, when either RNP A and/or RNP 68 are present, results are reported simply as positive for RNP. The linear range for dsdna is IU/mL and the measuring range for all other assays are AI. At the user s discretion, positive ANA results obtained with Format B (Reserved Test Group: ANA +) or Format C (Reserved Test Group: ANA 11) may be further analyzed to identify possible associations with MDSS profiles using the Medical Decision Support Software (MDSS) resident on the BioPlex 2200 System (see the following section for more information). The MDSS is based on the principles of the k-nearest neighbor 11 (knn) statistical technique. Each unknown is compared to a pre-established database that contains the results for over 1,400 characterized sera/plasma. Results of MDSS analysis fall into one of the following general outcomes; Negative, No Association, or Association with Disease. When the results of the MDSS analysis fall into the Association with Disease category, the MDSS software will propose a maximum of two disease classifications based upon the similarity of the current analysis to the stored results. The MDSS output can also aid in determining appropriate additional autoimmune serological testing. Selection of Desired Results The software allows the operator to request the customized presentation of results by choosing between several available formats. Access to this section is available via a controlled password and normally the laboratory will make the selection of available formats at the time of installation. Refer to the BioPlex 2200 System Operation Manual for more information. Format A: Qualitative Screening (Compound Assay: ANAScr) In the Qualitative Screening format, results are reported as ANA positive or negative, based on the presence (or absence) of one or more antibodies in concentrations exceeding its assigned cutoff. The MDSS is not activated. At the user's discretion, positive ANA results obtained using the qualitative screening format may be further analyzed by selecting individual antibodies, or a userdefined test grouping containing antibodies, as Add-On test(s) for immediate reporting of results. Refer to the BioPlex 2200 System Operation Manual for more information. Note: A positive ANA result reflects antibodies present for one or more of the following analytes; dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B. Conversely, a negative ANA result (or indeterminate for dsdna) reflects antibodies absent or below the cut-off values for all the above mentioned analytes. 6 Instructions for Use Manual ANA Screen with MDSS

45 BioPlex 2200 ANA Screen with MDSS Format B: Qualitative with Disease Association (Reserved Test Group: ANA +) In Qualitative Format with Disease Association, each sample result is reported as positive or negative as described above. In addition, positive results are further defined with the identification of the disease state sera in the reference database that most closely resemble the unknown sample, as determined by the MDSS. The following are the targeted disease associations: Systemic Lupus Erythematosus (SLE) Sjögren s Syndrome Scleroderma (Systemic Sclerosis) Mixed Connective Tissue Disease (MCTD) Polymyositis Results from the MDSS Analysis fall into one of the following general outcomes: general outcome Negative No Association Association with Disease MDSS output All antibody levels for systemic autoimmune disease are below pre-established cutoffs. Antibody levels show no association with MDSS profiles for systemic autoimmune diseases. Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider [a maximum of two systemic autoimmune diseases]. When the MDSS categorizes an outcome where antibody levels show association with an MDSS profile for a systemic autoimmune disease, the MDSS then suggests a maximum of two of the above mentioned possible disease associations. See Appendix A for a complete list of all possible combinations. The following are some of the possible examples for the reported results: Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider SLE. Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider SLE or Sjögren s syndrome. Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider Scleroderma. Format C: Selected Antibody Results In the Selected Antibody Results format, only antibody results requested by the operator for the unknown samples are reported. In this format, any antibody can be requested individually, or any group of antibodies may be requested for a specific sample. The laboratory may pre-define the test groupings by using the software screen entitled Test Group Setup, allowing the operator to request customized groupings. For example, SS-A and SS-B may be analyzed together. A larger group can also be defined. The grouping below, for example, might be used to replace a traditional 6-test ENA panel. SS-A Scl-70 SS-B Sm RNP Jo-1 Add-On test(s) for immediate reporting of results for additional individual antibodies, or a user-defined test grouping containing antibodies, not previously requested, can also be performed. If the selected antibody has been previously requested, the sample will be treated as a repeated request. Refer to the BioPlex 2200 System Operation Manual for more information. Special Test Case (Reserved Test Group: ANA 11) When one antibody or a small grouping of antibodies, or all individual antibodies, is requested under the Selected Antibody Results Format above, the MDSS is not activated. However, when requesting Test Group ANA 11 (which requests all individual antibodies as a group), the MDSS is automatically activated. In addition, a graphical presentation illustrating the antibodies and disease association is activated. The graphical presentation is only available under this scenario (see Appendix B), and only when at least one antibody is positive. Refer to the BioPlex 2200 System Operation Manual for more information. Note: An Over-Range (OR) result may be generated when results for selected antibodies are requested. For dsdna, samples may be diluted with wash buffer and re-analyzed. Refer to the BioPlex 2200 System Operation Manual for use of the Dilution Screen for loading and analysis of diluted specimens. For other selected antibodies, dilution is not necessary nor recommended. limitations of The ProCeDUre The ANA Screen is not, in and of itself, diagnostic for autoimmune disease and should be considered in conjunction with other laboratory test results and the clinical presentation of the patient. The MDSS is not, in and of itself, diagnostic for the targeted disease associations and should be considered in conjunction with other laboratory test results and the clinical presentation of the patient. Positive ANA may be found in apparently healthy individuals. 12 Therefore, results should be considered in conjunction with other laboratory test results and the clinical presentation of the patient. Immune complexes or other immunoglobulin aggregates present in patient samples may cause increased non-specific G Instructions for Use Manual 7

46 BioPlex 2200 ANA Screen with MDSS binding and produce false positive results. 13 However, the ANA Screen incorporates a Reagent Blank Bead (RBB) with each test that verifies the absence of significant non-specific binding in serum or plasma. SLE patients undergoing steroid or immuno-suppressant therapy may have negative test results. 14 Patients with rheumatoid Arthritis may result in an Sle association from MDSS. Additionally, patients with Rheumatoid Arthritis who are receiving anti-tnfα blockers as part of their therapy have been reported to produce antibodies against both dsdna and Chromatin. 15 For these reasons, MDSS associations from patients with Rheumatoid Arthritis should be interpreted with caution. An MDSS output of Negative or No Association does not rule out autoimmune disease. expected VAlUeS Prevalence Expected values for the ANA Screen test are presented in the following tables for two populations; normal blood donors (N=222), and patients being seen at rheumatology clinics (N=908). For dsdna, results of 4 IU/mL are negative, 5-9 IU/mL are indeterminate, and results of 10 IU/mL are reported as positive. For the other assays, results of < 1.0 AI are negative and results of 1.0 AI or greater are reported as positive. Table A. Normal Blood Donors (N=222) result Positive # () Negative # () Indeterminate # () ANA Screen 1,2 15 (6.8) 207 (93.2) N/A dsdna 3 (1.4) 211 (95.0) 8 (3.6) Chromatin 2 (0.9) 220 (99.1) Ribosomal P 0 (0.0) 222 (100.0) SS-A 2 (0.9) 220 (99.1) SS-B 0 (0.0) 222 (100.0) Sm 1 (0.5) 221 (99.5) SmRNP 2 (0.9) 220 (99.1) N/A RNP 6 (2.7) 216 (97.3) Scl-70 3 (1.4) 219 (98.6) Jo-1 0 (0.0) 222 (100.0) Centromere B 3 (1.4) 219 (98.6) N/A = Not Applicable 1) See note below. 2) Results calculated based on testing of all analytes. Table B. Rheumatology Patients (N=908) result Positive # () Negative # () Indeterminate # () ANA Screen (43.0) 518 (57.0) N/A dsdna 119 (13.1) 741 (81.6) 48 (5.3) Chromatin 168 (18.5) 740 (81.5) Ribosomal P 37 (4.1) 871 (95.9) SS-A 173 (19.0) 735 (81.0) SS-B 76 (8.4) 832 (91.6) Sm 60 (6.6) 848 (93.4) SmRNP 103 (11.3) 805 (88.7) N/A RNP 112 (12.3) 796 (87.7) Scl (2.5) 885 (97.5) Jo-1 6 (0.7) 902 (99.3) Centromere B 38 (4.2) 870 (95.8) N/A = Not Applicable 1) See note below. 8 Instructions for Use Manual ANA Screen with MDSS

47 BioPlex 2200 ANA Screen with MDSS Note: A positive ANA Screen result reflects antibodies present for one or more of the following analytes; dsdna, Chromatin, Ribosomal P, SS-A 60, SS-A 52, SS-B, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1 and Centromere B. Conversely, a negative ANA Screen result (or indeterminate for dsdna) reflects antibodies absent or below the cut-off values for all the above mentioned analytes. PerForMANCe ChArACTerISTICS Note: 95 confidence intervals presented in the Performance Characteristics section of this Instructions For Use were calculated using one of the following four methods as indicated below. Calculation Condition 95 Confidence Interval Calculation Method Agreement and Correct Association Agreement and Correct Association N 30 N > 30 Score Method as described in: J Sauro and JR Lewis (In Press), Estimating Completion Rates from Small Samples using Binomial Confidence Intervals: Comparisons and Recommendations in Proceedings of the Human Factors and Ergonomics Society Annual Meeting (HFES 2005) Orlando, FL CR Blythe and HA Still, Binomial confidence intervals, Journal of the American Statistical Association, 1983; 78: , [eq. 3.8, p.116] Odds Ratio All JM Bland and DG Altman, The Odds Ratio, BMJ 2000; 320:1468 Positive and Negative Likelihood Ratio; Prevalence All Vassar Statistical Computation Website: Clinical Research Calculator 1 Comparative Testing Prospective Comparison of ANA Screen and ANA Microplate EIA Performance of the ANA Screen was evaluated against a commercially available ANA Microplate EIA. A total of 908 prospective serum samples were tested at 3 U.S. clinical testing sites. The samples were collected from patients seen at a rheumatology clinic and suspected of having systemic autoimmune disease. Results can be seen in Table C. Table C. ANA Screen vs ANA Microplate EIA (N=908) Positive ANA Screen 1 Negative ANA Screen 1 Total Positive EIA Negative EIA Total ) See note on previous page. The results of comparative prospective testing demonstrated the following: Positive Agreement: 351/500 = 70.2 (95 CI ) Negative Agreement: 369/408 = 90.4 (95 CI ) Overall Agreement: 720/908 = 79.3 (95 CI ) G Instructions for Use Manual 9

48 BioPlex 2200 ANA Screen with MDSS Retrospective Comparison of Selected Antibodies to EIA Methods Performance of the ANA Screen was further evaluated by testing 40 retrospective serum samples per analyte, all known to be positive for ANA and one or more of the autoantibodies listed below. An additional 100 serum samples known to be negative for ANA were also tested. The retrospective specimens were tested by both the ANA Screen and commercially available microplate EIA methods that were specific for the corresponding autoantibodies. Results can be found in Table D. Table D. ANA Screen vs EIA: Selected Antibodies - Retrospective Antibody/ Antibody group dsdna Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp Scl-70 Jo-1 Centromere B N 123^ * N (Positive) N (Negative) BioPlex 2200 and eia Positive BioPlex 2200 Positive and eia Negative BioPlex 2200 and eia Negative BioPlex 2200 Negative and eia Positive Positive Agreement with eia 95 Confidence Interval Negative Agreement with eia 95 Confidence Interval overall Agreement 95 Confidence Interval ^ 16 BioPlex 2200 dsdna indeterminate or predicate dsdna equivocal results excluded. *2 predicate RNP equivocal results excluded. A total of 19 (1 dsdna, 2 Chromatin, 2 Ribosomal P, 1 SS-A, 1 Sm, 1 SmRNP, 1 Scl-70, and 10 Jo-1) retrospective study samples with repeatedly low Serum Verification Bead (SVB) results were excluded. 10 Instructions for Use Manual ANA Screen with MDSS

49 BioPlex 2200 ANA Screen with MDSS Correlation with CDC Reference Sera The Centers for Disease Control (CDC) provides a reference serum panel, which was tested to evaluate characteristics of the ANA Screen. The results are presented as a means to convey further information on the performance of the ANA Screen with a masked, characterized serum panel. This does not imply an endorsement of the ANA Screen by the CDC. Results can be found in Table E. Table E. Characteristics of CDC Reference Panel Sample expected results ANA Screen dsdna (IU/ml) Chromatin (AI) ribosomal P (AI) CDC-1 Homogeneous/Rim CDC-2 Speckled/La CDC-3 Speckled CDC-4 U1-RNP CDC-5 Sm CDC-6 Nucleolar + + CDC-7 SSA/Ro + + CDC-8 Centromere + + CDC-9 Scl CDC-10 Jo CDC-11 PM/Scl Results calculated based on testing of all analytes SS-A (AI) SS-B (AI) Sm (AI) SmrNP (AI) rnp (AI) Scl-70 (AI) Jo-1 (AI) Centromere B (AI) Notes: There should be no other statistical calculation or inferences drawn from the panel results For dsdna, results of 4 IU/mL are negative, 5-9 IU/mL are indeterminate, and 10 IU/mL are reported as positive For the other assays, results of < 1.0 AI are negative and results of 1.0 AI or greater are reported as positive G Instructions for Use Manual 11

50 BioPlex 2200 ANA Screen with MDSS Prospective Comparison of Selected Antibodies to EIA Methods Of the 908 prospective serum samples tested, samples positive by the ANA Screen for specific autoantibodies were also tested by a corresponding commercially available microplate EIA. Results can be seen in Table F. Table F. ANA Screen vs EIA: Selected Antibodies - Prospective Antibody/ Antibody group dsdna Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp Scl-70 Jo-1 Centromere B N 832* BioPlex 2200 and eia Positive BioPlex 2200 Positive and eia Negative BioPlex 2200 and eia Negative BioPlex 2200 Negative and eia Positive Positive Agreement with eia 95 Confidence Interval Negative Agreement with eia 95 Confidence Interval overall Agreement Confidence Interval * 76 BioPlex 2200 dsdna indeterminate or predicate dsdna equivocal results excluded. 29 predicate RNP equivocal results excluded. 12 Instructions for Use Manual ANA Screen with MDSS

51 BioPlex 2200 ANA Screen with MDSS Clinical Concordance Targeted Disease Analysis In addition to traditional sensitivity, specificity and predictive value analysis, the use of likelihood ratio analysis has been recommended for autoimmune testing. 16 Performance of the ANA Screen was compared against five (5) targeted disease associations with results presented in Table G. Samples were prospectively collected from patients seen in a rheumatology clinic who were diagnosed using American College of Rheumatology (ACR) or appropriate established disease classification criteria for any mention of the following targeted disease associations: Systemic Lupus Erythematosus (SLE) Sjögren s Syndrome Scleroderma (Systemic Sclerosis) Mixed Connective Tissue Disease (MCTD) Polymyositis Table G. Targeted Disease Associations (N=908) ANA Screen Positive Negative Total Targeted CTD Disease All others Non targeted and no CTD Total Sensitivity: CI Specificity: CI Overall Agreement: CI Positive Likelihood Ratio: CI Negative Likelihood Ratio: CI Odds Ratio: CI Prevalence: CI The above (as well as previous and subsequent) statistical calculations are defined as follows: where Sensitivity: TP/(TP+FN) x 100 Specificity: TN/(FP+TN) x 100 Overall Agreement: (TP+TN)/(TP+FN+FP+TN) x 100 Positive Likelihood Ratio: Sensitivity/(100-Specificity) Negative Likelihood Ratio: (100-Sensitivity)/Specificity Odds Ratio: (TPxTN)/(FPxFN) Prevalence: (TP+FN)/(TP+FN+FP+TN) x 100 TP = True Positive FP = False Positive TN = True Negative FN = False Negative G Instructions for Use Manual 13

52 BioPlex 2200 ANA Screen with MDSS Individual Disease Analysis Performance of the ANA Screen was compared against the predicate device in the five (5) targeted disease associations. They are shown in the following set of clinical concordance summary tables (Tables H - M), where the area(s) in white represent autoantibodies that are clinically relevant for the specific disease classification being discussed. 1,12,14,17 The area(s) in light grey represent autoantibodies that are commonly observed for the specific disease classification. The area(s) in dark grey represent autoantibodies that are not commonly associated with the specific disease classification. Patients may have multiple diagnoses and may be represented in several disease classifications. Systemic Lupus Erythematosus (SLE) Performance of the ANA Screen was compared against the predicate device by testing samples prospectively collected from patients seen in a rheumatology clinic who were diagnosed using American College of Rheumatology (ACR) criteria for SLE. The specimens were tested by both the ANA Screen and commercially available microplate EIA methods that were specific for the corresponding autoantibodies. Results can be found in Table H. Table H. ANA Screen vs EIA: Clinical Diagnosis - SLE result (N=332) ANA Screen dsdna a Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp b Scl-70 Jo-1 Centromere B BioPlex 2200 and eia Positive BioPlex 2200 Positive and eia Negative BioPlex 2200 and eia Negative BioPlex 2200 Negative and eia Positive overall Agreement Confidence Interval a 46 Bioplex dsdna indeterminate and EIA dsdna equivocal results are excluded from the calculations. b 15 EIA RNP equivocal results are excluded from the calculations Instructions for Use Manual ANA Screen with MDSS

53 BioPlex 2200 ANA Screen with MDSS Primary Sjögren s Syndrome Performance of the ANA Screen was compared against the predicate device by testing samples prospectively collected from patients seen in a rheumatology clinic who were diagnosed with an American-European Consensus Group criteria for Primary Sjögren s Syndrome. The specimens were tested by both the ANA Screen and commercially available microplate EIA methods that were specific for the corresponding autoantibodies. Results can be found in Table I. Table I. ANA Screen vs EIA: Clinical Diagnosis - Primary Sjögren s Syndrome result (N=16) ANA Screen dsdna* Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp Scl-70 Jo-1 Centromere B BioPlex 2200 and eia Positive BioPlex 2200 Positive and eia Negative BioPlex 2200 and eia Negative BioPlex 2200 Negative and eia Positive overall Agreement Confidence Interval * 3 dsdna BioPlex indeterminate and EIA equivocal results were excluded from the calculations. Scleroderma (Systemic Sclerosis) Performance of the ANA Screen was compared against the predicate device by testing samples prospectively collected from patients seen in a rheumatology clinic who were diagnosed using ACR criteria for Scleroderma. The specimens were tested by both the ANA Screen and commercially available microplate EIA methods that were specific for the corresponding autoantibodies. Results can be found in Table J. Table J. ANA Screen vs EIA: Clinical Diagnosis - Scleroderma result (N=44) ANA Screen dsdna Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp Scl-70 Jo-1 Centromere B BioPlex 2200 and eia Positive BioPlex 2200 Positive and eia Negative BioPlex 2200 and eia Negative BioPlex 2200 Negative and eia Positive overall Agreement Confidence Interval G Instructions for Use Manual 15

54 BioPlex 2200 ANA Screen with MDSS Mixed Connective Tissue Disease (MCTD) Performance of the ANA Screen was compared against the predicate device by testing samples prospectively collected from patients seen in a rheumatology clinic who were diagnosed with an Alarcon-Segovia or Kahn criteria for MCTD. The specimens were tested by both the ANA Screen and commercially available microplate EIA methods that were specific for the corresponding autoantibodies. The high incidence of anti-chromatin antibodies in patients with MCTD has been previously documented. 18 Results can be found in Table K. Table K. ANA Screen vs EIA: Clinical Diagnosis - MCTD result (N=16) ANA Screen dsdna Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp Scl-70 Jo-1 Centromere B BioPlex 2200 and eia Positive BioPlex 2200 Positive and eia Negative BioPlex 2200 and eia Negative BioPlex 2200 Negative and eia Positive overall Agreement Confidence Interval Polymyositis Performance of the ANA Screen was compared against the predicate device by testing samples prospectively collected from patients seen in a rheumatology clinic who were diagnosed with literature criteria for Polymyositis. The specimens were tested by both the ANA Screen and commercially available microplate EIA methods that were specific for the corresponding autoantibodies. Note: The presence of antibodies to Jo-1 in patients diagnosed with Polymyositis has been well documented. 1,12 Results can be found in Table L. Table L. ANA Screen vs EIA: Clinical Diagnosis - Polymyositis result (N=12) ANA Screen dsdna Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp Scl-70 Jo-1 Centromere B BioPlex 2200 and eia Positive BioPlex 2200 Positive and eia Negative BioPlex 2200 and eia Negative BioPlex 2200 Negative and eia Positive overall Agreement Confidence Interval Instructions for Use Manual ANA Screen with MDSS

55 BioPlex 2200 ANA Screen with MDSS Non-Targeted and No Connective Tissue Disease Performance of the ANA Screen was compared against the predicate device by testing samples prospectively collected from patients seen in a rheumatology clinic who were not diagnosed with a targeted connective tissue disease by established medical criteria. The specimens were tested by both the ANA Screen and commercially available microplate EIA methods that were specific for the corresponding autoantibodies. Results can be found in Table M. Table M. ANA Screen vs EIA: Clinical Diagnosis - Non-Targeted and No Connective Tissue Disease result (N=494) ANA Screen dsdna Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp Scl-70 Jo-1 Centromere B BioPlex 2200 and eia Positive BioPlex 2200 Positive and eia Negative BioPlex 2200 and eia Negative BioPlex 2200 Negative and eia Positive overall Agreement 95 Confidence Interval G Instructions for Use Manual 17

56 BioPlex 2200 ANA Screen with MDSS Medical Decision Support Software (MDSS) The BioPlex 2200 Medical Decision Support Software (MDSS) is a pattern recognition algorithm that can enhance the performance of the ANA Screen by identifying associated diagnostic patterns among its multiple assay results. The MDSS results, when compared with disease classification by ACR, literature or appropriate established medical criteria for targeted connective tissue disease, are presented below in Tables N-T. The MDSS can suggest one or more possible disease associations after identifying patterns from the eleven (11) individual antibody results. In addition, MDSS can report that antibody levels show no association with MDSS defined patterns (No Association), or may report that all antibody results are below the established cut-offs (Negative). A total of 1,130 results, a combination of the 908 subjects seen in rheumatology clinics and the 222 normal blood donors presumed to be negative for autoimmune diseases, were analyzed. All possible MDSS disease associations with corresponding definitions are listed in Appendix A. Note: as indicated in Appendix A, not all MDSS outputs were observed in the clinical trial. Note: It is sometimes difficult to distinguish SLE and Sjögren s disease, even when both serological and clinical data are considered. 19 The complexity inherent in diagnosing autoimmune disease is further illustrated in a recent study that demonstrated only a 49 agreement between the referring physician and final diagnosis. 20 MDSS descriptions used in the following MDSS clinical performance tables are defined as follows: Negative for all antibodies All antibody levels for systemic autoimmune disease are below pre-established cutoffs Positive for one or more antibody Any one of the BioPlex 2200 ANA 11 analytes is positive SLE Systemic Lupus Erythematosus SS Sjögren s Syndrome Scleroderma same MCTD Mixed Connective Tissue Disease Polymyositis same No Association Antibody levels show no association with MDSS defined patterns for systemic autoimmune diseases 18 Instructions for Use Manual ANA Screen with MDSS

57 BioPlex 2200 ANA Screen with MDSS Table N presents percent disease agreement of the MDSS output with the diagnosis provided by a physician. Data is presented as percent diseases agreement for patients with one or more positive antibodies and for patients with a targeted connective tissue disease (TCTD) classification, regardless of antibody response. The difference between disease agreements is the inclusion of negative results for all antibodies in the TCTD patients. MDSS does not provide an association with a patient with negative test results for all antibodies. Table N. MDSS vs Disease Classification: (N=908) MDSS output * Disease Classification by Criteria** (N) Negative for all antibodies Positive for one or more antibody (P) No Association Any Sle Association Sjögren s Syndrome Association Any Scleroderma Association Any MCTD Association Any Polymyositis Association Patients with Positive Antibody only (P) Disease Agreement Patients with TCTD Disease Classification (N) Systemic Lupus Erythematosus (SLE) (186/218) 56.0 (186/332) Targeted Connective Tissue Disease (TCTD) Primary Sjögren s Syndrome Scleroderma Mixed Connective Tissue Disease (MCTD) (13/15) 51.6 (16/31) 81.3 (13/16) 81.3 (13/16) 36.4 (16/44) 81.3 (13/16) Polymyositis *** 33.3 (2/6) 16.7 (2/12) * See Appendix A for a complete list of possible MDSS outputs. Note: as indicated in Appendix A, not all MDSS outputs were observed in the clinical trial. Sjögren's Syndrome alone and MCTD alone are not outputs of MDSS. ** Targeted diseases presented include all patients with each disease classification, and patients may have multiple disease classifications, with the exception of Primary Sjögren's Syndrome. ***For these patients, the MDSS outputs suggesting Polymyositis referenced the disorder alone and not in combination with another Targeted Connective Tissue Disease G Instructions for Use Manual 19

58 BioPlex 2200 ANA Screen with MDSS Laboratory measurement of autoantibodies has historically been driven by a presumptive diagnosis. For example, a request for anti-sm would follow from a presumptive diagnosis of SLE. A positive result for anti-sm would be supportive of the presumptive diagnosis. Table O below presents the agreement of the MDSS output when a specific positive antibody result is present and the diagnosis provided by the physician is consistent with the presence of that antibody. The table shows that for such samples, the MDSS associations are in good agreement with the diagnosis by established medical criteria. Table O. MDSS Assignments in Patients with Targeted Connective Tissue Disease and a Positive Antibody Result Positive Antibody Test results Disease by established Medical Criteria* MDSS output** Agreement 95 Confidence Interval dsdna (N = 119) SLE (N = 92) Any SLE (N = 87) 87/92 or Chromatin (N = 168) SLE (N = 122) Any SLE (N = 112) 112/122 or Ribosomal P (N = 37) SLE (N = 30) Any SLE (N = 29) 29/30 or SSA (N = 173) SS (N = 15) SS or SLE (N = 13) 13/15 or SLE (N = 111) Any SLE (N = 106) 106/111 or SSB (N = 76) SS (N = 13) SS or SLE (N = 13) 13/13 or Sm (N = 60) SLE (N = 49) Any SLE (N = 49) 49/49 or SmRNP (N = 103) MCTD (N = 15) MCTD or SLE (N = 13) 13/15 or RNP (N = 112) MCTD (N = 15) MCTD or SLE (N = 13) 13/15 or Scl-70 (N = 23) Scleroderma (N = 7) Scleroderma; SLE or Scleroderma (N = 5) 5/7 or Jo-1 (N = 6)*** Polymyositis (N = 2) Polymyositis (N = 2) 2/2 or Centromere (N = 38) Scleroderma (N = 12) Scleroderma; SLE or Scleroderma (N = 11) 11/12 or SLE (N = 11) Any SLE (N = 9) 9/11 or * Targeted diseases presented include all patients with each disease classification, and patients may have multiple disease classifications. Established medical criteria used in this study include criteria established by the American College of Rheumatology (ACR), American-European Consensus Group, Alarcon-Segovia or Kahn, as well as literature criteria for Polymyositis. ** See Appendix A for a complete list of possible MDSS outputs. ***Note: The presence of antibodies to Jo-1 in patients diagnosed with Polymyositis has been well documented. 1,12 20 Instructions for Use Manual ANA Screen with MDSS

59 BioPlex 2200 ANA Screen with MDSS For each of the targeted connective tissue diseases encountered in the clinical trial, Tables P and Q present the number of patients with a positive antibody test and the number of correct MDSS associations in addition to calculations of Odds Ratio, Positive Likelihood Ratio, and Negative Likelihood Ratio. Since some MDSS outputs contain more disease associations than the disease association under consideration, the results in Table P were calculated by excluding patients with other diseases listed in the output. Table Q presents results where these patients were not excluded. Not all patients with a targeted connective tissue disease produce antibodies that may be detected with the BioPlex 2200 ANA Screen. Table P. MDSS Agreement with Disease Classification by Criteria (excluding patients with other MDSS associations) Disease Classification by Criteria Systemic lupus erythematosus (Sle) (N = 332) Primary Sjögren s Syndrome (N = 16) Scleroderma (N = 44) Mixed Connective Tissue Disease (N = 16) Polymyositis (N = 12) Positive Antibody Test(s) MDSS Associations odds ratio (or) or 95 Confidence Interval Positive likelihood ratio (Plr) (Plr) 95 Confidence Interval Negative likelihood ratio (Nlr) Nlr 95 Confidence Interval Total N after exclusions Table Q. MDSS Agreement with Disease Classification by Criteria (including patients with multiple MDSS associations) Disease Classification by Criteria Systemic lupus erythematosus (Sle) (N = 332) Primary Sjögren s Syndrome (N = 16) Scleroderma (N = 44) Mixed Connective Tissue Disease (N = 16) Polymyositis (N = 12) Positive Antibody Test(s) MDSS Associations odds ratio (or) or 95 Confidence Interval Positive likelihood ratio (Plr) (Plr) 95 Confidence Interval Negative likelihood ratio (Nlr) Nlr 95 Confidence Interval Total N G Instructions for Use Manual 21

60 BioPlex 2200 ANA Screen with MDSS Some of the Clinical Disease Classifications encountered do not have an associated MDSS output. These non-targeted connective tissue diseases should be classified as either Negative or No Association by MDSS. However, in some instances, an MDSS association was incorrectly presented. The MDSS results incorrectly associated with a targeted connective tissue disease can be classified as Incorrect Association. The results are summarized in the following table: Table R. MDSS vs Non-Targeted Connective Tissue Diseases (TCTD) Clinical Disease Classification (N) Negative or No MDSS Associations Incorrect MDSS Associations Incorrect Association Non TCTD Dermatomyositis- only (3/15) Rheumatoid Arthritis- only * 9 (31/341) Other CTD- only (9/45) No CTD (16/77) Blood Donor Samples ** 4 (8/222) * Of the 31 patients with only rheumatoid arthritis, 27 were associated with SLE by MDSS. Patients with rheumatoid Arthritis may result in an Sle association from MDSS. Additionally, patients with Rheumatoid Arthritis who are receiving anti-tnfα blockers as part of their therapy have been reported to produce antibodies against both dsdna and Chromatin. 15 For these reasons, MDSS associations from patients with Rheumatoid Arthritis should be interpreted with caution. See also Limitations of the Procedure. ** The clinical status of blood donors tested in this study was not known. 22 Instructions for Use Manual ANA Screen with MDSS

61 BioPlex 2200 ANA Screen with MDSS Traditional evaluation strategies for diagnostic tests do not always directly apply to the evaluation of decision support systems, because decision support systems often do not provide one answer, and each subject may have more than one diagnosis. 21 The percent correctness is defined for this study as the number of patients with a given MDSS association who also have that disease by ACR, literature, or established medical criteria. The percent correctness results illustrated in Tables S and T should be considered in conjunction with the following prevalence of disease observed in this study: SLE 29 (332/1130), Sjögren s Syndrome 1.4 (16/1130), Scleroderma 3.9 (44/1130), Mixed Connective Tissue Disease 1.4 (16/1130), Polymyositis 1.1 (12/1130), Other Connective Tissue Disease 36.9 (417/1130), and No Connective Tissue Disease 6.8 (77/1130). Note: the Correct Association values presented in the following tables may change in different patient populations. Table S. Correct Association without any Targeted Disease Classification MDSS output # by MDSS # Without any Targeted Disease Correct Association 95 Confidence Interval Negative (585/719) No Association (57/89) Table T. Correct Association with Targeted Disease Classification MDSS output # by MDSS # by Clinical Diagnosis Correct Association 95 Confidence Interval SLE only (142/198) SLE or SS (35/42) MCTD or SLE (30/37) Scleroderma (9/22) SLE or Scleroderma (11/20) Polymyositis only 3* (2/3) * One of these 3 patients was diagnosed with Dermatomyositis. Reproducibility Studies A reproducibility panel, consisting of 11 panel members, was prepared at Bio-Rad Laboratories. Each of ten (10) positive panel members was prepared by combining one (1) or more antibody positive patient samples for one (1) or more of the 13 analytes contained in the ANA Screen (dsdna, Chromatin, SS-A 52, SS-A 60, SS-B, Sm, RNP 68, RNP A, SmRNP, Centromere, Ribosomal P, Scl-70, Jo-1). Five (5) of the ten (10) members had higher levels of the antibodies and five (5) of the ten (10) members had antibody levels near the cutoff. One (1) panel member was negative for all 13 analytes. In addition, three (3) lots of the ANA Screen Control Set [1 positive control (antibody positive for all 13 analytes), 1 diluted positive control, and a negative control (antibody negative for all 13 analytes)] were also tested. Reproducibility testing was performed at three (3) US testing facilities on a total of three (3) lots of the ANA Screen. Each testing facility evaluated reproducibility using one (1) kit lot of the ANA Screen. The eleven (11) panel members were provided to each of the testing sites. Each of the eleven (11) panel members and the Autoimmune Control Set was tested in duplicate (x2) on two (2) runs per day (morning and afternoon) for ten (10) days using one (1) lot of ANA Screen Reagent Pack and one (1) lot of ANA Screen Calibrator Set at each of three (3) sites. [2 times x 2 runs x 10 days = 40 replicates per panel member per site. Total replicates at 3 sites = 120 replicates per panel member.] The data were then analyzed for intra-assay and inter-assay reproducibility according to the National Committee for Clinical Laboratory Standards (NCCLS EP5-A, Vol. 19, No. 2, p7, Eq. (1) and p8 Eq. (4)). The mean Antibody Index (AI), standard deviation (SD), and percent coefficient of variation (CV) for each panel member is presented. For dsdna, the mean International Units per ml (IU/mL), standard deviation (SD), and percent coefficient of variation (CV) for each panel member is presented. Results for Positive Control, High Positive Panel and Low Positive Panel can be found in Tables U through Z G Instructions for Use Manual 23

62 BioPlex 2200 ANA Screen with MDSS Intra Assay Table U. Reproducibility Results; Intra-assay - Site 1 ANA Screen - Intra-assay Clinical Site 1, lot 1 dsdna (IU/ml) Chromatin (AI) ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) SS-B (AI) Sm (AI) SmrNP (AI) rnp A (AI) rnp 68 (AI) Scl-70 (AI) Jo-1 (AI) Centromere B (AI) High Positive Panel Low Positive Panel Positive Control Mean SD* CV N= Mean SD* CV N= Mean SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, Page 7, Equation (1) Table V. Reproducibility Results; Intra-assay - Site 2 ANA Screen - Intra-assay Clinical Site 2, lot 2 dsdna (IU/ml) Chromatin (AI) ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) SS-B (AI) Sm (AI) SmrNP (AI) rnp A (AI) rnp 68 (AI) Scl-70 (AI) Jo-1 (AI) Centromere B (AI) High Positive Panel Low Positive Panel Positive Control Mean SD* CV N= Mean SD* CV N= Mean SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, Page 7, Equation (1) 24 Instructions for Use Manual ANA Screen with MDSS

63 BioPlex 2200 ANA Screen with MDSS Table W. Reproducibility Results; Intra-assay - Site 3 ANA Screen - Intra-assay Clinical Site 3, lot 3 dsdna (IU/ml) Chromatin (AI) ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) SS-B (AI) Sm (AI) SmrNP (AI) rnp A (AI) rnp 68 (AI) Scl-70 (AI) Jo-1 (AI) Centromere B (AI) High Positive Panel Low Positive Panel Positive Control Mean SD* CV N= Mean SD* CV N= Mean SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, Page 7, Equation (1) Inter Assay Table X. Reproducibility Results; Inter-assay - Site 1 ANA Screen - Inter-assay Clinical Site 1, lot 1 dsdna (IU/ml) Chromatin (AI) ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) SS-B (AI) Sm (AI) SmrNP (AI) rnp A (AI) rnp 68 (AI) Scl-70 (AI) Jo-1 (AI) Centromere B (AI) High Positive Panel Low Positive Panel Positive Control Mean SD* CV N= Mean SD* CV N= Mean SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, Page 8, Equation (4) G Instructions for Use Manual 25

64 BioPlex 2200 ANA Screen with MDSS Table Y. Reproducibility Results; Inter-assay - Site 2 ANA Screen - Inter-assay Clinical Site 2, lot 2 dsdna (IU/ml) Chromatin (AI) ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) SS-B (AI) Sm (AI) SmrNP (AI) rnp A (AI) rnp 68 (AI) Scl-70 (AI) Jo-1 (AI) Centromere B (AI) High Positive Panel Low Positive Panel Positive Control Mean SD* CV N= Mean SD* CV N= Mean SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, Page 8, Equation (4) Table Z. Reproducibility Results; Inter-assay - Site 3 ANA Screen - Inter-assay Clinical Site 3, lot 3 dsdna (IU/ml) Chromatin (AI) ribosomal P (AI) SS-A 52 (AI) SS-A 60 (AI) SS-B (AI) Sm (AI) SmrNP (AI) rnp A (AI) rnp 68 (AI) Scl-70 (AI) Jo-1 (AI) Centromere B (AI) High Positive Panel Low Positive Panel Positive Control Mean SD* CV N= Mean SD* CV N= Mean SD* CV N= * NCCLS EP5-A, Vol. 19, No. 2, Page 8, Equation (4) 26 Instructions for Use Manual ANA Screen with MDSS

65 BioPlex 2200 ANA Screen with MDSS Linearity WHO Wo/80 dsdna Standard Serial dilutions of the WHO Wo/80 dsdna Standard were made in order to obtain dsdna concentrations throughout the assay range. The serial dilutions were then assayed by the ANA Screen. Results can be found in the chart below (Figure 1). Figure 1. WHO Wo/80 Standard 250 BioPlex 2200 dsdna Result (IU/ml) y = x R 2 = WHO W/o 80 dsdna Standard ( IU/ml) G Instructions for Use Manual 27

66 BioPlex 2200 ANA Screen with MDSS Dilution of the dsdna Assay Dilution/linearity for the quantitative dsdna assay in the ANA Screen assay consisted of testing four (4) samples with high dsdna antibody levels that were serially diluted following NCCLS protocol EP6-A (Vol. 23, No. 16) and assayed by the ANA Screen. Results can be found in Table AA. Table AA. dsdna Linearity Sample Dilution dsdna expected Value BioPlex 2200 dsdna result recovery Correlation of the dsdna Assay The ANA Screen was calibrated against the Wo/80 dsdna standard and was compared against the predicate device. The correlation was obtained by testing the prospective population of 908 samples. For test results under 25 IU/mL, and where indeterminate and equivocal results were included (N=850), the linear regression gave the following statistical results: Y = 0.05X and R = For all results, and where indeterminate and equivocal results were excluded (N=812), the linear regression gave the following statistical results: Y = 0.23X and R = The correlation between the BioPlex 2200 anti-dsdna results and the predicate anti-dsdna results may reflect the fact that different antibody populations are detected by the respective assays Instructions for Use Manual ANA Screen with MDSS

67 BioPlex 2200 ANA Screen with MDSS Cross-Reactivity A cross-reactivity study was performed to determine if samples from various disease states and other potentially interfering factors interfere with test results when tested with the ANA Screen. A panel of ten (10) specimens positive for each cross reactant were evaluated for possible cross reactivity with the ANA Screen for each of the eleven (11) autoantibodies. Samples that elicited a positive response by the ANA Screen were also tested by a corresponding commercially available microplate EIA. The results demonstrated that the various disease state samples evaluated do not cross react with the eleven (11) autoantibodies in the ANA Screen. Most of the samples evaluated were high positive for each disease state. If a specific disease state did cross react to the various assays in the ANA Screen, all samples for that particular disease state would elicit a positive response. The study demonstrated that for each disease state three (3) to ten (10) samples out of a total of ten (10) were negative. The majority of all samples that did elicit a positive result were also confirmed positive by the corresponding commercially available microplate EIA. Results can be found in Table BB. Table BB. Cross-Reactivity Cross reactives N Method dsdna * Chromatin ribosomal P SS-A SS-B Sm SmrNP rnp Scl-70 Jo-1 Centromere B Histone 10 ssdna 10 Rheumatoid Factor 10 Smooth Muscle 10 Mitochondria M2 10 Proteinase 3 (PR3) 10 Myeloperoxidase (MPO) anti-thyroid Peroxidase (TPO) anti-thryoglobulin (TG) Cardiolipin 10 Gliadin 10 N/A = Not Applicable, EQ = Equivocal, NT = Not Tested. * Indeterminate results were excluded BioPlex N/A EIA 6 N/A NT NT BioPlex EIA EQ 1 NT 1 BioPlex EIA NT NT NT NT NT NT NT NT NT NT NT BioPlex EIA NT NT NT NT BioPlex EIA 0 2 NT 4 1 NT 1 1 NT NT 4 BioPlex EIA NT 0 NT NT NT NT NT NT NT NT 1 BioPlex EIA NT NT NT NT NT NT 0 BioPlex EIA NT NT NT NT NT NT NT NT NT NT 2 BioPlex EIA 0 0 NT 0 NT NT NT 2 BioPlex EIA 1 3 NT 4 NT 0 2 NT NT 1 NT BioPlex EIA NT NT NT 1 NT NT NT NT NT NT NT G Instructions for Use Manual 29

68 BioPlex 2200 ANA Screen with MDSS Interfering Substances Testing for interfering substances was conducted according to NCCLS Protocol EP7-A (Vol. 22, No. 27). No significant interference was observed in any of the substances tested. The following substances, listed in Table CC, were tested (N=20) at maximum levels in duplicate (2x) on one lot: Table CC. Interfering Substances Hemoglobin Substance Bilirubin (unconjugated) Triglycerides Protein (total) Cholesterol Red Blood Cells Gamma-globulin Ascorbic Acid Concentration 500 mg/dl 20 mg/dl 3000 mg/dl 12 g/dl 500 mg/dl 0.4 Concentrate 2.5 g/dl 3 mg/dl 30 Instructions for Use Manual ANA Screen with MDSS

69 BioPlex 2200 ANA Screen with MDSS APPeNDIx A The following is a complete listing of possible combinations used in the Medical Decision Support Software (MDSS). # MDSS Text output 1 All antibody levels for systemic autoimmune disease are below pre-established cutoffs. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 2 Antibody levels show no association with MDSS profiles for systemic autoimmune diseases. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 3 Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider SLE. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 4 Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider SLE or Sjogren s syndrome. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 5 Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider Polymyositis. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 6 Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider Scleroderma. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 7 Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider MCTD or SLE. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 8 Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider SLE or Scleroderma. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 9* Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider Polymyositis or SLE. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 10* Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider Polymyositis or MCTD. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 11* Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider Polymyositis or Sjogren s syndrome. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 12* Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider Polymyositis or Scleroderma. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 13* Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider MCTD or Sjogren s syndrome. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 14* Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider MCTD or Scleroderma. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 15* Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider Scleroderma or Sjogren s syndrome. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. *Note: these MDSS outputs were not observed in the clinical trial G Instructions for Use Manual 31

70 BioPlex 2200 ANA Screen with MDSS APPeNDIx B The following are examples of a graphical presentation illustrating the antibody and disease association activated by the MDSS. The dsdna results, normally represented by IU/mL, are converted into AI in order to graphically represent results using the same measuring range axis for all antibody levels. Figure 2. Example MDSS Results - Possible Disease Association Interpretive Comments: Antibody levels show association with MDSS profiles for systemic autoimmune disease. Consider MCTD or SLE. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. Figure 3. Example MDSS Results - No Association Interpretive Comments: Antibody levels show no association with MDSS profiles for systemic autoimmune diseases. MDSS outputs of Negative or No Association do not rule out autoimmune disease. Patients with Rheumatoid Arthritis may result in an SLE association from MDSS, thus MDSS associations from patients with RA should be interpreted with caution. 32 Instructions for Use Manual ANA Screen with MDSS

71 BioPlex 2200 ANA Screen with MDSS references 1. EM Tan. Autoantibodies in Diagnosis and in Identifying Antigens. The Immunologist 1999: 7 (3): A Kavanuagh, R Tomar, J Reveille, DH Solomon and HA Homburger. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigen. Arch Pathol Lab Med 2000; 124 (1): R Tozzoli, N Bizzaro, E Tonutti, D Villalta, D Bassetti, F Manoni, A Piazza, M Pradella and P Rizzotti. Guidelines for the Laboratory Use of Autoantibody Tests in the Diagnosis and Monitoring of Autoimmune Rheumatic Diseases. Am J Clin Path 2002; 117(2): M Golightly and C Golightly. Laboratory diagnosis of autoimmune diseases. Medical Lab Observer 2002(7); ML Astion, MH Wener and K Hutchinson. Autoantibody Testing: The Use of Immunofluorescence and Other Assays. Clin Lab News 2000(7); HA Homburger, YD Cahen, J Griffiths and GL Jacob. Detection of Antinuclear Antibodies: Comparative Evaluation of Enzyme Immunoassay and Indirect Immunofluorescence Methods. Arch Pathol Lab Med 1998; 122(11): BS Reisner, J DiBlasi and N Goel. Comparison of an Enzyme Immunoassay to an Indirect Fluorescent Immunoassay for the Detection of Antinuclear Antibodies. Am J Clin Path 1999; 111: TG Phan, RCW Wong and S Adelstein. Autoantibodies to Extractable Nuclear Antigens: Making Detection and Interpretation More Meaningful. Clin Diag Lab Immunol 2002; 9: RJ Fulton, RL McDade, PL Smith, LJ Kienker and JR Kettman Jr. Advanced multiplexed analysis with the FlowMetrix System. Clin Chem 1997; 43(9): Manual Guide - Safety Management No. CDC-22, Decontamination of Laboratory Sink Drains to Remove Azide Salts. April 30, Atlanta, GA: Centers for Disease Control. 11. A Zlatkis, KY Lee, CF Poole and G Holzer. Capillary column gas chromatographic profile analysis of volatile compounds in sera of normal and virus-infected patients. J Chromatogr 1979; 163(2): WH Reeves and M Satoh. Autoantibodies in Systemic Lupus Erythematosus, in Arthritis and Allied Conditions: A Textbook of Rheumatology, 14th Ed., Ed. William J. Koopman, Lippincott, Williams and Wilkins, Philadelphia, 2001; EM Tan, JS Smolen, JD McDougal, et. al. A Critical Evaluation of Enzyme Immunoassays for Detection of Antinuclear Autoantibodies of Defined Specificities. I. Precision, Sensitivity and Specificity. Arthritis Rheum 1999; 42(3): M Reichlin and JB Harley. Antinuclear Antibodies: An Overview in Dubois Lupus Erythematosus, 5th Ed., Eds. Daniel J Wallace and Bevra H. Hahn, Williams and Wilkins, Baltimore and Philadelphia, 1997; C Eriksson, S Engstrand, K-G Sundqvist, S Rantapää-Dahlqvist. Autoantibody formation in patients with rheumatoid arthritis treated with anti-tnfα. Ann Rheum Dis 2005; 64: A Sturgess and J Edmonds. Improving the effectiveness of autoantibody testing in the clinic. Autoimmunity Reviews 2002; 1: CGM Kallenberg, AA Wouda, MH Hoet and WJ Van Venrooij. Development of connective tissue disease in patients presenting with Raynaud's phenomenon: a six year follow up with emphasis on the predictive value of antinuclear antibodies as detected by immunoblotting. Ann Rheum Dis 1988; 47: Simón JA, Cabiedes J, Ortiz E, Alcocer-Varela J, and Sánchez-Guerrero J. Anti-nucleosome antibodies in patients with systemic lupus erythematosus of recent onset. Potential utility as a diagnostic tool and disease activity marker. Rheumatology 2004; 43: Isenberg DA. Systemic lupus erythematosus and Sjögren s syndrome: historical perspective and ongoing concern. Arhritis Rheum. 50: Narain S, HB Richards, M Satoh, M Sarmiento, R Davidson, J Shuster, E Sobel, P Hahn, and WH Reeves. Diagnostic accuracy for lupus and other systemic autoimmune diseases in the primary care setting. Arch Intern Med 2004; 164: Berner ES, Webster GD, Shugermann AA, et. al. Performance of four computer-based diagnostic systems. New England Journal of Medicine 1994; 330: OP Rekvig, M Kalaaji and H Nossent. Anti-DNA antibody subpopulations and lupus nephritis. Autoimmunity Reviews 2004; 3: 1-6. TrADeMArK INForMATIoN BioPlex is a trademark of Bio-Rad Laboratories, Inc G Instructions for Use Manual 33

72 Technical Information Contacts Bio-Rad provides a toll free line for technical assistance, available 24 hours a day, 7 days a week. In the United States of America and Puerto Rico toll free BIORAD ( ). Outside the U.S.A., please contact your regional Bio-Rad office for assistance. Bio-Rad Laboratories Clinical Diagnostics Group 4000 Alfred Nobel Drive Hercules, California Telephone (510) FAX (510) Australia, Bio-Rad Laboratories Pty. Ltd., Level 5, 446 Victoria Road, Gladesville NSW 2111 Phone Telefax Austria, Bio-Rad Laboratories Ges.m.b.H., Hummelgasse 88/3-6, A-1130 Vienna Phone Telefax Belgium, Bio-Rad S.A.-N.V. Begoniastraat 5, B-9810 Nazareth Eke Phone Telefax Brazil, Bio-Rad do Brasil, Praia de Botafogo, 440-3rd Floor, Botafogo, RJ CEP , Rio de Janeiro Phone Telefax Canada, Bio-Rad Laboratories, Ltd., 2403 Guénette Street, Montréal, Québec H4R 2E9 Phone Telefax China, Bio-Rad Laboratories Shanghai Ltd., 3rd Floor, #18 Dong Fang Road, Bldg E, Poly Plaza, Pudong, Shanghai, PRC Phone Telefax Czech Republic, Bio-Rad spol. s r.o., Nad ostrovem 1119/7, Prague 4 Phone Telefax Denmark, Bio-Rad Laboratories, Symbion Science Park, Fruebjergvej 3, DK-2100 Copenhagen East Phone Telefax Finland, Bio-Rad Laboratories, Linnanherrankuja 16, FIN Helsinki Phone Telefax France, Bio-Rad, 3 boulevard Raymond Poincaré, Marnes-la-Coquette Phone Telefax Germany, Bio-Rad Laboratories GmbH, Heidemannstrasse 164, D Munich Phone +49-(0) Telefax +49-(0) Greece, Bio-Rad Laboratories M E.P.E, 2-4 Mesogeion Street, Fourth Floor Athens Phone Telefax Hong Kong, Bio-Rad Pacific Ltd., Unit 1101, 11/F DCH Commercial Centre, 25 Westlands Road, Quarry Bay Phone Telefax Hungary, Bio-Rad Hungary Ltd., H-1082 Budapest, Futo street 47-53, Hungary Phone Telefax India, Bio-Rad Laboratories (India) Pvt. Ltd., Bio-Rad House, 86-87, Udyog Vihar Phase IV, Gurgaon, Haryana Phone Telefax Israel, Bio-Rad Laboratories Ltd., 14 Homa Street, New Industrial Area, Rishon Le Zion Phone Telefax Italy, Bio-Rad Laboratories S.r.l., Via Cellini 18/A, Segrate, Milan Phone Telefax Japan, Bio-Rad Laboratories K.K., Tennoz Central Tower 20F, Higashi-Shinagawa, Shinagawa-ku, Tokyo Phone Telefax Korea, Bio-Rad Korea Ltd., 10th Floor, Hyunjuk Building, , Gangnam-gu, Seoul Phone Telefax Mexico, Bio-Rad, S.A., Avenida Eugenia 197, Piso 10-A, Col. Narvarte, C.P Mexico, D.F. Phone +52 (55) Telefax 52 (55) The Netherlands, Bio-Rad Laboratories B.V., Fokkerstraat 2-8, 3905 KV Veenendaal Phone Telefax New Zealand, Bio-Rad New Zealand, 189 Bush Road Unit B, Albany, Auckland Phone Telefax Norway, Bio-Rad Laboratories, Johan Scharffenbergs vei 91, N-0694 Oslo Phone Telefax Poland, Bio-Rad Polska Sp. z o.o., Nakielska Str. 3, Warsaw Phone Telefax Portugal, Bio-Rad Laboratories, Lda., Edificio Prime, Ave. Quinta Grande, 53 Fracção 3B Alfragide Amadora Phone Telefax Russia, Bio-Rad Laboratorii, Business Centre West Bridge, Leningradsky pr-t H.37A Bld. 14, Moscow Phone Telefax Singapore, Bio-Rad Laboratories (Singapore) Pte. Ltd., 27 International Business Park, #01-02 Singapore Phone Telefax South Africa, Bio-Rad Laboratories (Pty) Ltd., 34 Bolton Road, Parkwood, Johannesburg 2193 Phone Telefax Spain, Bio-Rad Laboratories, S.A., C/ Caléndula, 95, Edificio M. Miniparc II, El Soto de la Moraleja, Madrid Phone Telefax Sweden, Bio-Rad Laboratories A.B., Vintergatan 1, Box 1097, S Sundbyberg Phone Telefax Switzerland, Bio-Rad Laboratories AG, Nenzlingerweg 2, CH-4153 Reinach BL Phone Telefax Thailand, Bio-Rad Laboratories Ltd., 1st & 2nd Floor, Lumpini I Bldg., 239/2 Rajdamri Rd., Lumpini, Pathumwan, Bangkok Phone Telefax United Kingdom, Bio-Rad Laboratories Ltd., Bio-Rad House, Maxted Road, Hemel Hempstead, Herts HP2 7DX Phone +44-(0) Telefax +44-(0) G January 2011

73 伯瑞普樂斯抗核抗體篩檢試劑 對照組及校正組 衛署醫器輸字第 號對照組限由醫師或醫檢師使用產品編號 陽性 2 瓶 x 1.5 ml 陰性 2 瓶 x 1.5 ml 效能本對照組是預定用以監控伯瑞普樂斯抗核抗體篩檢試劑整體表現的一種已知濃度的品管物質 摘要及原理使用此對照組可客觀評估其使用方法及使用技術準確性, 同時也是優良實驗室不可或缺的一部分 試劑組成所有的試劑包括含濃度 0.3 ProClin 300 及 0.1 sodium benzoate 之保存劑 陽性對照組含去纖維蛋白原的血漿血清基質並添加來自疾病狀態血漿之已知分析物 陰性對照組含去纖維蛋白原的血漿血清基質 內容物含使用說明及代表性數值 額外使用材料 對照組批號資料庫光碟 儲存及安定性此產品在不開封的狀態儲存於攝氏 2 到 8 度可維持穩定至有效期限 開封後, 在鎖緊蓋子儲存於攝氏 2 到 8 度情況下, 所有分析項目有 60 天的穩定性 步驟此產品的處理與分析方式應視同一般病人的檢體對待, 上機的方式應依循現正使用的儀器, 試藥組或試藥之操作手冊 吸取之前, 讓品管液回溫至室溫 ( 攝氏 18 至 25 度 ) 並緩和地混和以確保均質 使用後請立即更換瓶塞並儲存於攝氏 2 到 8 度 任何廢棄物處置應遵循當地廢棄物管理主管單位的需求 若有任何包裝損壞, 可連絡當地伯瑞業務或技術支援單位 注意事項限制 1. 產品超過有效期限後請勿使用 1. 此產品不設定作為標準液使用 2. 假設有微生物污染的證據或對照組過度混濁, 請將此產品丟棄 2. 本產品僅供使用於 BioPlex 2200, 任何其他的儀器 3. 請勿交互使用瓶蓋, 避免交互汙染 並無被評估 4. 僅限專業人員使用代表性數值 ANA 抗核抗體對照組包含一個陰性對照品與一個含有本 ANA 抗核抗體試劑組內分析物抗體的多分析物陽性控制組 陽性對照組之設計在於提供陽性結果, 檢測數據會高於各磁珠的臨界值, 本平均值是由重複分析而得到並且必須落在相符合的標準差內, 建議每個實驗室應對於每一種參數建立自己的範圍並引用作為指引 ANA 抗核抗體對照組批號資料光碟可以載入所需的資料設定值到分析系統電腦中, 關於此部分請參考系統操作手冊 註 :ANA 抗核抗體篩檢試劑內某些分析物的陽性對照品, 必須經過稀釋才能達到儲存於 BioPlex 2200 系統資料庫的批次數據 ; BioPlex 2200 系統會自動稀釋這些分析物, 並利用額外的反應槽進行分析 校正組 產品編號 瓶 x 0.5 ml 效能本校正組是預定用以監控伯瑞普樂斯抗核抗體篩檢試劑的校正物質 摘要及原理此校正組是使用一組 6 瓶獨特的血清校正液 校正液能在一個試驗系統中建立參考值, 其用於決定取自人類樣本中某物質的存在 試劑組成校正組含去纖維蛋白原的血漿血清基質並添加來自疾病狀態血漿之已知分析物 含濃度 0.3 ProClin 300 及 0.1 sodium benzoate 之保存劑 額外使用材料 校正組批號資料庫光碟 儲存及安定性此產品在不開封的狀態儲存於攝氏 2 到 8 度可維持穩定至有效期限 開封後, 在鎖緊蓋子儲存於攝氏 2 到 8 度情況下, 所有分析項目有 60 天的穩定性 步驟本產品須根據之伯瑞普樂斯抗核抗體篩檢試劑使用說明及 BioPlex 2200 操作手冊一起使用 吸取之前, 讓品管液回溫至室溫 ( 攝氏 18 至 25 度 ) 並緩和地混和以確保均質 使用後請立即更換瓶塞並儲存於攝氏 2 到 8 度 任何廢棄物處置應遵循當地廢棄物管理主管單位的需求 若有任何包裝損壞, 可連絡當地伯瑞業務或技術支援單位 注意事項 限制 1. 產品超過有效期限後請勿使用 1. 此產品不設定作為標準液使用 2. 假設有微生物污染的證據或對照組過度混濁, 請將此產品丟棄 2. 本產品僅供使用於 BioPlex 2200, 任何其他的儀器 3. 請勿交互使用瓶蓋, 避免交互汙染 並無被評估 4. 僅限專業人員使用 代表性數值 結果皆以抗體指標 (AI) 表示, 但 dsdna 除外, 表示單位為 IU/mL 對應每一批號的試劑設定值有一 PDF 檔案包含在隨附於校正組批 號資料光碟中的, 每一個相關的試劑批號都有一獨立的 PDF 檔案隨附於光碟中 校正組的設定是依據 BioPlex 2200 系統中主批校正 組及一個專一的 ANA 抗核抗體試劑 ANA 抗核抗體校正組批號資料光碟可以載入所需的資料設定值到分析系統電腦中, 關於此部分 請參考系統操作手冊 追溯性校正組係採用世界衛生組織 (WHO) 的一級國際標準品 dsdna, 編號 Wo/80 dsdna 所建立 警告生物來源物質, 請當作可能感染物對待當作可能感染物對待 製造此品管物所使用的每個全血提供單位都經過 FDA 所接受的方法測試, 發現對 B 型肝炎表面抗原無反應 無 C 型肝炎抗體 無愛滋病第一與第二型病毒抗體無愛滋病第一與第二型病毒抗體 但此產品也可能含有其它無公認試驗之人類來源的物質但此產品也可能含有其它無公認試驗之人類來源的物質 基於良好實驗室的運作, 所有人類來源的物質都應該認為是有潛在感染性的, 應視同病人檢體的方式小心處理 R43 接觸皮膚可能會造成敏感現象 S24 請避免與皮膚接觸 S37 請佩戴適當的手套 S56 本物質必須以有毒物品方式有毒物品方式妥善丟棄妥善丟棄 製造廠名稱 : Bio-Rad Laboratories, Inc 藥商名稱 : 美商伯瑞股份有限公司台灣分公司 製造廠地址 : th Ave NE, Redmond, WA98052, U.S.A 藥商地址 : 台北市南京東路四段 126 號 3 樓 2011 修定

74 x 1.5 ml 2 x 1.5 ml BioPlex 2200 ANA Screen Control Set english INTENDED USE The BioPlex 2200 ANA Screen Control Set is intended for use as an assayed quality control to monitor the overall performance of the BioPlex 2200 Instrument and BioPlex 2200 ANA Screen Reagent Pack in the clinical laboratory. SUMMARY AND PRINCIPLE The use of quality control materials is indicated as an objective assessment of the precision of methods and techniques in use and is an integral part of good laboratory practices. MATERIALS PROVIDED Reagents: All reagents contain preservatives including ProClin 300 at a concentration of 0.3 and 0.1 sodium benzoate. BioPlex 2200 ANA Screen Positive Controls: Two (2) 1.5 ml vials. The positive controls are provided in a human serum matrix made from defribrinated plasma with added known analyte concentrations derived from human disease state plasma. BioPlex 2200 ANA Screen Negative Controls: Two (2) 1.5 ml vials. The negative controls are provided in a human serum matrix made from defribrinated plasma. Components: One (1) package insert providing instructions for use. One (1) assignment of values sheet. OPTIONAL MATERIALS NOT PROVIDED : BioPlex 2200 ANA Screen Control Lot Data CD-ROM. STORAGE AND STABILITY This product is stable until the expiration date when stored unopened at 2 to 8 C. Once opened, all controls are stable for 60 days when stored tightly capped at 2 to 8 C. PROCEDURE This product should be treated the same as patient specimens and run in accordance with the instructions accompanying the BioPlex 2200 Instrument and the BioPlex 2200 ANA Screen Reagent Pack. Before sampling, allow the control to reach room temperature (18 to 25 C) and gently mix to ensure homogeneity. After each use, promptly replace the cap and return to 2 to 8 C storage. Dispose of any discarded materials in accordance with the requirements of your local waste management authorities. In the event of damage to packaging, contact the local Bio-Rad Laboratories Sales Office or Bio-Rad Laboratories Technical Services. Procedural Precautions: 1. This product should not be used past the expiration date. 2. If there is evidence of microbial contamination or excessive turbidity in the product, discard the vial. 3. Do not interchange vial caps. This may lead to cross contamination of controls. 4. For professional use only. LIMITATIONS 1. This product is not intended for use as a standard. 2. This product is intended for use with the BioPlex 2200 Instrument. Any other use has not been evaluated. ASSIGNMENT OF VALUES The BioPlex 2200 ANA Screen Control Set includes a negative control as well as a multi-analyte positive control containing antibodies present for analytes within the BioPlex 2200 ANA Screen Reagent Pack. The positive control is manufactured to give positive results, with values above the cut-off for each specific bead. The negative control is manufactured to give negative results, with values below the cut-off for each specific bead. The mean values were derived from replicate analyses and should fall within the corresponding standard deviation. It is recommended that an individual laboratory establish its own limits for each parameter and use those provided only as guides. A BioPlex 2200 ANA Screen Control Lot Data CD-ROM is available to load the necessary value assignment data into the instrument. Refer to the Operation Manual for more information regarding this activity. Note: Certain analytes in the BioPlex 2200 ANA Screen positive control must be diluted to achieve the lot specific values, which are loaded into the BioPlex 2200 Instrument database. The BioPlex 2200 Instrument automatically dilutes these analytes and performs the operation using an additional reaction vessel. DEUTSCH VERWENDUNGSZWECK Das BioPlex 2200 ANA Screen Control Set ist als analysiertes Qualitätskontrollmaterial zur Überwachung der Gesamtleistung des BioPlex 2200 Geräts und des BioPlex 2200 ANA Screen Reagent Pack in klinischen Labors bestimmt. EINLEITUNG UND ZUSAMMENFASSUNG Die Verwendung entsprechender Kontrollmaterialien dient der objektiven Beurteilung der Qualität von im Labor durchgeführten Untersuchungen und ist ein unerlässlicher Bestandteil der guten Laborpraxis. GELIEFERTE MATERIALIEN Reagenzien: Alle Reagenzien enthalten Konservierungsstoffe einschließlich ProClin 300 in einer Konzentration von 0,3 und 0,1 Natriumbenzoat. BioPlex 2200 ANA Screen Positive Controls: Zwei (2) Fläschchen mit je 1,5 ml. Die Positivkontrollen werden in einer aus defibriniertem Plasma hergestellten Humanserummatrix geliefert und enthalten bekannte Konzentrationen von Analyten aus dem Plasma erkrankter Patienten. BioPlex 2200 ANA Screen Negative Controls: Zwei (2) Fläschchen mit je 1,5 ml. Die Negativkontrollen werden in einer aus defibriniertem Plasma hergestellten Humanserummatrix geliefert. Beilagen: Eine (1) Packungsbeilage mit Gebrauchsanweisung. Ein (1) Datenblatt mit Wertezuordnungen. IM LIEFERUMFANG NICHT ENTHALTENE FAKULTATIVE MATERIALIEN : BioPlex 2200 ANA Screen Control Lot Data CD-ROM. LAGERUNG UND STABILITÄT Dieses Produkt ist bis zum Verfallsdatum stabil, sofern es ungeöffnet bei 2 C bis 8 C gelagert wird. Nach dem Öffnen sind alle Kontrollen 60 Tage stabil, sofern sie fest verschlossen bei 2 C bis 8 C gelagert werden. TESTDURCHFÜHRUNG Dieses Produkt sollte wie eine Patientenprobe behandelt und in Übereinstimmung mit den Gebrauchsanweisungen für das BioPlex 2200 Gerät und den BioPlex 2200 ANA Screen Reagent Pack verwendet werden. Vor der Messung die Kontrolle auf Raumtemperatur bringen (18 C bis 25 C) und zur Gewährleistung der Homogenität vorsichtig mischen. Nach jedem Gebrauch sofort wieder verschließen und bei 2 C bis 8 C lagern. Die Entsorgung aller Abfälle ist nach den geltenden örtlichen Bestimmungen vorzunehmen. Falls die Verpackung beschädigt ist, nehmen Sie bitte Kontakt zur Bio-Rad Laboratories Niederlassung oder dem Bio-Rad Laboratories Kundendienst auf. Vorsichtshinweise zur Testdurchführung: 1. Dieses Produkt nach Ablauf des Haltbarkeitsdatums nicht mehr verwenden. 2. Bei Anzeichen einer mikrobiellen Kontamination oder einer starken Trübung des Produkts ist das Fläschchen zu verwerfen. 3. DieVerschlüsse der Fläschchen dürfen nichtmiteinander vertauschtwerden. Dies kann zur Kreuzkontamination der Kontrollen führen. 4. Nur zum professionellen Gebrauch. EINSCHRÄNKUNGEN 1. Dieses Produkt ist nicht zur Verwendung als Standard vorgesehen. 2. Dieses Produkt ist zur Verwendung mit dem BioPlex 2200 Gerät bestimmt. Andere Verwendungszwecke wurden nicht evaluiert. WERTEZUORDNUNG Das BioPlex 2200 ANA Screen Control Set enthält eine Negativkontrolle sowie eine Positivkontrolle mit Antikörpern gegen die multiplen Analyte, die im BioPlex 2200 ANA Screen Reagent Pack enthalten sind. Die Positivkontrolle ist dafür ausgelegt, positive Ergebnisse mit Werten oberhalb des Cutoff-Werts für jedes spezifische Bead zu liefern. Die Negativkontrolle ist dafür ausgelegt, negative Ergebnisse mit Werten unterhalb des Cutoff-Werts für jeden spezifischen Bead zu liefern. DieMittelwertewurden aus Analysen von Wiederholproben ermittelt und sollten innerhalb der entsprechenden Standardabweichung liegen. Das Labor sollte für jeden Parameter seine eigenen Grenzwerte festlegen und die vorgegebenenwerte lediglich als Richtwerte ansehen. Über die separat erhältliche BioPlex 2200 ANA Screen Control Lot Data CD-ROM werden die chargenabhängigen Kontrollen- Werte in das Gerätesystem geladen. Weitere Informationen zu diesem Vorgang finden Sie im Benutzerhandbuch. Hinweis: Bestimmte Analyte der BioPlex 2200 ANA Screen Positivkontrolle müssen verdünnt werden, um die chargenspezifischen Werte, die in die Datenbank des BioPlex 2200 Geräts geladen werden, zu erreichen. Das BioPlex 2200 Gerät verdünnt diese Analyte automatisch und verwendet hierzu ein zusätzliches Reaktionsgefäß. français UTILISATION Le BioPlex 2200 ANA Screen Control Set est destiné à être utilisé en tant que contrôle de qualité titré pour surveiller les performances générales de l instrument BioPlex 2200 et du BioPlex 2200 ANA Screen Reagent Pack en laboratoire clinique. INTRODUCTION ET PRINCIPE L utilisation de produits de contrôle de qualité est indiquée à titre d évaluation objective de la précision des méthodes et des techniques utilisées et fait partie intégrante des bonnes pratiques de laboratoire. MATÉRIEL FOURNI Réactifs : Tous les réactifs contiennent des conservateurs, y compris du ProClin 300 à une concentration de 0,3 et 0,1 de benzoate de sodium. BioPlex 2200 ANA Screen Positive Controls : deux (2) flacons de 1,5 ml. Les contrôles positifs sont fournis dans une matrice de sérum humain préparée à partir de plasma défibriné auquel sont ajoutées des concentrations connues d analytes dérivés de plasma humain infecté. BioPlex 2200 ANA Screen Negative Controls : deux (2) flacons de 1,5 ml. Les contrôles négatifs sont fournis dans une matrice de sérum humain préparée à partir de plasma défibriné. Composants : Une (1) notice d utilisation fournissant le mode d emploi. Une (1) feuille d attribution des valeurs. MATÉRIEL FACULTATIF NON FOURNI : BioPlex 2200 ANA Screen Control Lot Data CD-ROM. CONSERVATION ET STABILITÉ Ce produit reste stable jusqu à sa date de péremption lorsqu il est conservé dans son flacon fermé entre 2 C et 8 C. Une fois ouverts, tous les contrôles restent stables pendant 60 jours s ils sont conservés dans leur flacon bien fermé entre 2 C et 8 C. PROCÉDURE Ce produit doit être traité de la même manière que les échantillons patients et analysé conformément au mode d emploi de l instrument BioPlex 2200 et du BioPlex 2200 ANA Screen Reagent Pack. Avant de tester un échantillon, laisser le contrôle revenir à température ambiante (entre 18 C et 25 C) et le mélanger doucement pour assurer son homogénéité. Le reboucher rapidement après chaque utilisation et le remettre au réfrigérateur entre 2 C et 8 C. Éliminer le produit restant conformément aux exigences des organismes locaux de gestion des déchets. Si l emballage est endommagé, contacter le bureau de ventes local ou le service technique de Bio-Rad Laboratories. Précautions relatives à la procédure : 1. Ne pas utiliser ce produit au-delà de sa date de péremption. 2. Si l on constate une contamination microbienne ou une turbidité excessive du produit, jeter le flacon. 3. Ne pas interchanger les bouchons des flacons sous risque de contamination croisée des contrôles. 4. Usage réservé aux biologistes. LIMITES 1. Ce produit n est pas destiné à être utilisé comme un étalon. 2. Ce produit est destiné à être utilisé avec l instrument BioPlex Aucune autre utilisation n a été évaluée. ATTRIBUTION DES VALEURS Le BioPlex 2200 ANA Screen Control Set comprend un contrôle négatif ainsi qu un contrôle positif multi-analytes contenant des anticorps dirigés contre les analytes du BioPlex 2200 ANA Screen Reagent Pack. Le contrôle positif est fabriqué de manière à donner des résultats positifs, avec des valeurs supérieures au seuil pour chaque bille particulière. Le contrôle négatif est fabriqué demanière à donner des résultats négatifs, avec des valeurs inférieures au seuil pour chaque bille particulière. For In Vitro Diagnostic Use In Vitro Diagnosticum Usage In Vitro Per Uso Diagnostico In Vitro Para Uso Diagnóstico In Vitro Utilizar Apenas Em Diagnóstico In Vitro För in-vitro diagnostiskt bruk Til in Vitro diagnosticering European Conformity CE-Konformitätskennzeichnung Conformité aux normes européennes Conformità europea Conformidad europea Conformidade com as normas europeias Europeisk överensstämmelse Europæisk overensstemmelse Temperature Limit Temperaturlimit Limite de température Limite di temperatura Límite de temperatura Limite de temperatura Temperaturgränser Temperaturgrænse Consult Instructions for Use Gebrauchsanweisung beachten Consulter la notice d emploi Consultare le istruzioni per l uso Consulte las instrucciones de uso Consulte as instruções de utilização Läs bruksanvisningen Benyt brugsanvisninger Lot Number Chargen-Nr. Numéro de lot Numero di lotto Número de lote Número de lote Satsnummer Batchnummer Use by (YYYY-MM-DD) Verwendbar bis (JJJJ-MM-TT) Date de péremption (AAAA-MM-JJ) Data di scadenza (AAAA-MM-GG) Usar hasta el (AAAA-MM-GG) Utilizar até (AAAA-MM-DD) Använd före (ÅÅÅÅ-MM-DD) Anvend før (ÅÅÅÅ-MM-DD) Manufactured by Hergestellt von Fabriqué par Fabbricato da Fabricado por Fabricado por Tillverkare Fremstillet af Authorized Representative Bevollmächtigter Représentant agréé Rappresentante autorizzato Representante autorizado Representante autorizado Auktoriserad representant Autoriseret repræsentant Catalog Number Katalognummer Numéro de catalogue Numero di catalogo Número de catálogo Número de catálogo Katalognummer Katalognr. Caution, consult accompanying documents Achtung, Begleitdokumente beachten Attention, consulter la documentation jointe Attenzione, consultare la documentazione allegata Precaución, consulte los documentos que acompañan al instrumento Atenção, consultar os documentos inclusos Försiktighet: se medföljande dokument Forsigtig, der henvises til den vedlagte dokumentation Positive Control Positivkontrolle Contrôle positif Controllo positivo Control positivo Controlo positivo Positiv kontroll Positiv kontrol Negative Control Negativkontrolle Contrôle négatif Controllo negativo Control negativo Controlo negativo Negativ kontroll Negativ kontrol Printed // Gedruckt // Imprimé // Stampato // Impreso // Impresso // Tryckt // Trykt

75 BioPlex 2200 ANA Screen Control Set Les valeursmoyennes ont été dérivées d analyses de répliques et doivent se situer dans l écart type correspondant. Il est recommandé que chaque laboratoire établisse ses propres limites pour chaque paramètre et n utilise celles fournies qu à titre indicatif. Un BioPlex 2200 ANA Screen Control Lot Data CD-ROM est disponible afin de télécharger les données d attribution de valeur nécessaires sur l instrument. Se reporter au manuel d utilisation pour des informations complémentaires concernant cette activité. Remarque : Certains analytes du BioPlex 2200 ANA Screen Positive Control doivent être dilués pour obtenir les valeurs spécifiques d un lot qui sont chargées dans la base de données de l instrument BioPlex L instrument BioPlex 2200 dilue automatiquement ces analytes et exécute l opération dans une autre cuvette réactionnelle. italiano USO PREVISTO Il BioPlex 2200 ANA Screen Control Set è previsto per l uso come controllo di qualità da analizzare per monitorare le prestazioni complessive dello strumento BioPlex 2200 e del BioPlex 2200 ANA Screen Reagent Pack nel laboratorio clinico. RIEPILOGO E PRINCIPIO L uso di materiali di controllo di qualità è utile nella valutazione oggettiva della precisione dei metodi e delle tecniche in uso ed è parte integrante delle buone prassi di laboratorio. MATERIALI FORNITI Reagenti - Tutti i reagenti contengono conservanti, incluso ProClin 300 allo 0,3 e benzoato di sodio (0,1). BioPlex 2200 ANA Screen Positive Controls - Due (2) fiale da 1,5 ml. I controlli positivi vengono forniti in una matrice di siero umano a base di plasma defibrinato addizionata con concentrazioni note di analita derivate da plasma umano proveniente da soggetti malati. BioPlex 2200 ANA Screen Negative Controls - Due (2) fiale da 1,5 ml. I controlli negativi sono forniti in una matrice di siero umano a base di plasma defibrinato. Componenti - Un (1) foglietto illustrativo contenente le istruzioni per l uso. Una (1) scheda contenente i valori assegnati. MATERIALI OPZIONALI NON FORNITI : BioPlex 2200 ANA Screen Control Lot Data CD-ROM. CONSERVAZIONE E STABILITÀ Questo prodotto è stabile fino alla data di scadenza se conservato sigillato a 2-8 C. Una volta aperti, tutti i controlli rimangono stabili per 60 giorni, se conservati a 2-8 C e perfettamente sigillati. PROCEDURA Questo prodotto deve essere trattato analogamente ai campioni dei pazienti e usato attenendosi alle istruzioni che accompagnano lo strumento BioPlex 2200 e il BioPlex 2200 ANA Screen Reagent Pack. Prima di usarlo, attendere che il controllo raggiunga la temperatura ambiente (18-25 C) e miscelarlo con delicatezza per renderlo omogeneo. Dopo ogni utilizzo, richiuderlo immediatamente con il tappo e riportarlo ad una temperatura di 2-8 C. Smaltire i rifiuti in base alle norme in vigore stabilite dalle autorità competenti. Se la confezione presenta danni, rivolgersi all ufficio commerciale o al servizio di assistenza tecnica Bio-Rad Laboratories di zona. Precauzioni procedurali 1. Non usare il prodotto dopo la data di scadenza. 2. Eliminare la fiala se torbida o se presenta segni di contaminazione batterica. 3. Non scambiare tra loro i tappi delle fiale. Ciò può comportare la contaminazione crociata dei controlli. 4. Esclusivamente per uso professionale. LIMITAZIONI 1. Questo prodotto non è previsto per l uso come standard. 2. Il presente prodotto è previsto per l uso con lo strumento BioPlex Non è previsto per impieghi diversi da quelli descritti. ASSEGNAZIONE DEI VALORI Il BioPlex 2200 ANA Screen Control Set include un controllo negativo e un controllo positivo con più analiti contenente gli anticorpi presenti all interno del BioPlex 2200 ANA Screen Reagent Pack. Il controllo positivo è preparato per fornire risultati positivi, con valori superiori al valore di cutoff per ogni microsfera specifica. Il controllo negativo è preparato per fornire risultati negativi, con valori inferiori al valore di cutoff per ogni microsfera specifica. I valori medi sono stati derivati dalle analisi dei replicati e dovrebbero rientrare nella deviazione standard corrispondente. Si consiglia a ciascun laboratorio di stabilire i propri limiti per ciascun parametro e di usare quelli forniti unicamente a scopo indicativo. Il BioPlex 2200 ANA Screen Control Lot Data CD-ROM è disponibile per caricare nello strumento i dati relativi ai valori assegnati necessari. Per ulteriori informazioni al riguardo, consultare il manuale d uso. Nota - determinati analiti presenti nel BioPlex 2200 ANA Screen Positive Control devono essere diluiti per ottenere i valori specifici del lotto, che sono caricati nel database dello strumento BioPlex Lo strumento BioPlex 2200 diluisce automaticamente questi analiti ed esegue l analisi usando una provetta di reazione aggiuntiva. español INDICACIONES El BioPlex 2200 ANA Screen Control Set está diseñado para su uso en laboratorios clínicos como control de calidad analítica para verificar el rendimiento general del instrumento BioPlex 2200 y del BioPlex 2200 ANA Screen Reagent Pack. RESUMEN Y PRINCIPIOS El uso de los materiales de control de calidad está indicado como una evaluación objetiva de la precisión de los métodos y técnicas en uso, y es una parte integral de las buenas prácticas de laboratorio. MATERIAL SUMINISTRADO Reactivos: Todos los reactivos contienen conservantes que incluyen ProClin 300 al 0,3 y 0,1 de benzoato sódico. BioPlex 2200 ANA Screen Positive Controls: dos (2) frascos de 1,5 ml. Los controles positivos se suministran en una matriz de suero humano elaborada con plasma desfibrinado, a la que se han añadido concentraciones conocidas de analito obtenido de plasma de personas enfermas. BioPlex 2200 ANA Screen Negative Controls: dos (2) frascos de 1,5 ml. Los controles negativos se suministran en una matriz de suero humano elaborada con plasma desfibrinado. Componentes: Un (1) prospecto del envase con instrucciones de uso. Una (1) ficha de asignación de valores. MATERIAL OPCIONAL NO SUMINISTRADO : BioPlex 2200 ANA Screen Control Lot Data CD-ROM. ALMACENAMIENTO Y ESTABILIDAD Este producto es estable hasta la fecha de caducidad, siempre y cuando se almacene sin abrir a entre 2 y 8 C. Una vez abiertos, todos los controles son estables durante 60 días si se almacenan bien cerrados a una temperatura de 2 C a 8 C. PROCEDIMIENTO Este producto debe manipularse igual que las muestras de pacientes y usarse de acuerdo con las instrucciones que acompañan al instrumento BioPlex 2200 y al BioPlex 2200 ANA Screen Reagent Pack. Antes del muestreo, deje que el control alcance la temperatura ambiente (entre 18 y 25 C) y mézclelo suavemente para garantizar su homogeneidad. Después de cada uso, coloque el tapón de nuevo inmediatamente y vuelva a almacenarlo a entre 2 y 8 C. Elimine todos losmateriales de desecho de acuerdo con los requisitos establecidos por las autoridades locales enmateria de gestión de residuos. Si el envase está dañado, póngase en contacto con su oficina de ventas o con el departamento de servicio técnico de Bio-Rad Laboratories más cercano. Precauciones procedimentales: 1. Este producto no debe emplearse una vez transcurrida la fecha de caducidad. 2. Deseche el frasco si existen indicios de contaminación microbiana o el producto presenta excesiva turbidez. 3. No intercambie los tapones de los frascos, ya que eso podría ocasionar la contaminación cruzada de los controles. 4. Sólo para uso profesional. LIMITACIONES 1. Este producto no está indicado para utilizarse como patrón. 2. Este producto está indicado para utilizarse con el instrumento BioPlex No se ha evaluado ningún otro uso. ASIGNACIÓN DE VALORES El BioPlex 2200 ANA Screen Control Set incluye un control negativo así como otro positivo, con analitos múltiples, que contiene anticuerpos contra los analitos del BioPlex 2200 ANA Screen Reagent Pack. El control positivo está fabricado para arrojar resultados positivos, con valores por encima del valor discriminatorio para cada micropartícula específica. El control negativo está fabricado para arrojar resultados negativos, con valores por debajo del valor discriminador para cada micropartícula específica. Los valoresmedios se derivaron de análisis de repeticiones y deben estar dentro de la desviación estándar correspondiente. Se recomienda que cada laboratorio establezca sus propios límites para cada parámetro, y que utilice los suministrados solamente como guía. Hay un BioPlex 2200 ANA Screen Control Lot Data CD-ROM disponible para cargar los datos de asignación de valores necesarios en el instrumento. Consulte el manual de funcionamiento para obtener más información sobre este tema. Nota: Ciertos analitos del BioPlex 2200 ANA Screen Positive Control deben diluirse para lograr los valores específicos del lote, que se introducen en la base de datos del instrumento BioPlex El instrumento BioPlex 2200 diluye automáticamente dichos analitos y realiza la operación utilizando un recipiente de reacción adicional. português UTILIZAÇÃO PREVISTA O BioPlex 2200 ANA Screen Control Set destina-se a ser utilizado como um controlo de qualidade analisado, para monitorizar o desempenho global do Instrumento BioPlex 2200 e do BioPlex 2200 ANA Screen Reagent Pack em laboratórios clínicos. RESUMO E PRINCÍPIOS A utilização de materiais de controlo da qualidade está indicada como uma forma de avaliação objectiva da precisão dos métodos e técnicas que estão a ser utilizados, sendo parte integrante das boas práticas laboratoriais. MATERIAIS FORNECIDOS Reagentes: Todos os reagentes contêm conservantes incluindo ProClin 300 numa concentração de 0,3 e benzoato de sódio a 0,1. BioPlex 2200 ANA Screen Positive Controls: dois (2) frascos de 1,5 ml. Os controlos positivos são fornecidos numa matriz de soro humano, produzida a partir de plasma desfibrinado, à qual foram adicionadas concentrações conhecidas das substâncias a analisar obtidas de plasmas de pessoas doentes. BioPlex 2200 ANA Screen Negative Controls: dois (2) frascos de 1,5 ml. Os controlos negativos são fornecidos numa matriz de soro humano produzida a partir de plasma desfibrinado. Componentes: Um (1) folheto informativo com instruções de utilização. Uma (1) folha de atribuição de valores. MATERIAIS OPCIONAIS NÃO FORNECIDOS : BioPlex 2200 ANA Screen Control Lot Data CD-ROM. ARMAZENAMENTO E ESTABILIDADE Este produto mantém-se estável até ao fim do prazo de validade, desde que armazenado não aberto entre 2 e 8 C. Depois de abertos, todos os controlos a analisar se mantêm estáveis durante um período de 60 dias, quando armazenados em frascos bem fechados, entre 2 e 8 C. PROCEDIMENTO Este produto deve ser tratado da mesma forma que as amostras de doentes e analisado de acordo com as instruções anexas ao Instrumento BioPlex 2200 e ao BioPlex 2200 ANA Screen Reagent Pack. Antes da amostragem, deixe o controlo atingir a temperatura ambiente (18 a 25 C) e misture suavemente para garantir a homogeneidade. Após cada utilização, volte a colocar de imediato a tampa e o frasco na refrigeração, entre 2 e 8 C. Elimine os materiais rejeitados de acordo com os requisitos das autoridades locais de tratamento de resíduos. Caso a embalagem se encontre danificada, contacte o Departamento de Vendas local ou a Assistência Técnica da Bio-Rad Laboratories. Precauções relativas ao procedimento: 1. Este produto não deve ser utilizado após o fim do prazo de validade. 2. Se existirem sinais de contaminação microbiana ou turvação excessiva do produto, rejeite o frasco. 3. Não troque as tampas dos frascos. Isto poderá conduzir à contaminação cruzada dos controlos. 4. Apenas para utilização por profissionais. LIMITAÇÕES 1. Este produto não se destina a ser utilizado como um padrão. 2. Este produto destina-se a ser utilizado com o instrumento BioPlex Não foram avaliados outros tipos de utilização. ATRIBUIÇÃO DE VALORES O BioPlex 2200 ANA Screen Control Set inclui um controlo negativo e um controlo positivo para várias substâncias a analisar contendo os anticorpos para as substâncias a analisar presentes no BioPlex 2200 ANA Screen Reagent Pack. O controlo positivo é fabricado para fornecer resultados positivos, com valores acima do valor limite, para cada esfera específica. O controlo negativo é fabricado para fornecer resultados negativos, com valores abaixo do valor limite, para cada esfera específica. Os valores médios foram obtidos a partir de análises de replicados e devem situar-se dentro do desvio padrão correspondente. Recomenda-se que cada laboratório estabeleça os seus próprios limites para cada parâmetro e utilize os limites fornecidos apenas como orientação. Está disponível um BioPlex 2200 ANA Screen Control Lot Data CD-ROM para carregar no instrumento os dados necessários para atribuição de valores. Consulte o Manual de Funcionamento para obter mais informações relacionadas com esta actividade. Observação: Algumas substâncias a analisar existentes no controlo positivo BioPlex 2200 ANA Screen têm de ser diluídas para atingir os valores específicos para o lote, que são introduzidos na base de dados do Instrumento BioPlex O instrumento BioPlex 2200 dilui estas substâncias de forma automática e executa a operação utilizando um recipiente de reacção adicional. svenska AVSEDD ANVÄNDNING BioPlex 2200 ANA Screen Control Set är avsett att användas som en analyserad kvalitetskontroll för att kontrollera total prestanda för BioPlex 2200-instrument och BioPlex 2200 ANA Screen Reagent Pack på det kliniska laboratoriet. SAMMANFATTNING OCH PRINCIP Användningen av kvalitetskontrollmaterial är avsedd som en objektiv bedömning av precisionen i de metoder och tekniker som används, och utgör ett väsentligt inslag i god laboratoriepraxis. MEDFÖLJANDE MATERIAL Reagenser: Samtliga reagenser innehåller konserveringsmedel, däribland ProClin 300 med en koncentration på 0,3 och 0,1 natriumbenzoat. BioPlex 2200 ANA Screen Positive Controls: Två (2) 1,5 ml-flaskor. De positiva kontrollerna levereras i en humanserummatris, som tillverkats av defibrinerat plasma med tillsatta kända analytkoncentrationer som härstammar från humanplasma i sjukdomstillstånd. BioPlex 2200 ANA Screen Negative Controls: Två (2) 1,5 ml-flaskor. De negativa kontrollerna levereras i en humanserummatris som tillverkats av defibrinerat plasma. Komponenter: En (1) förpackningsinlaga med bruksanvisning. Ett (1) blad med värdetilldelning. TILLVALSMATERIAL SOM INTE MEDFÖLJER : BioPlex 2200 ANA Screen Control Lot Data CD-ROM. FÖRVARING OCH HÅLLBARHET Produkten är stabil fram till och med sista förbrukningsdag om den förvaras oöppnad i 2 till 8 C. När förpackningen har öppnats är alla kontroller stabila i 60 dagar om de förvaras med tättslutande lock i 2 till 8 C. PROCEDUR Denna produkt skall hanteras på samma sätt som patientprover och användas enligt anvisningarna som medföljer BioPlex 2200-instrument och BioPlex 2200 ANA Screen Reagent Pack. Låt kontrollen uppnå rumstemperatur (18 till 25 C) före pipettering och blanda försiktigt för att garantera homogenitet. Sätt genast på locket efter varje användning och ställ tillbaka flaskorna för förvaring i 2 till 8 C.

76 BioPlex 2200 ANA Screen Control Set Kasserat material skall hanteras enligt de lokala föreskrifterna för avfallshantering. Om förpackningen är skadad skall du kontakta Bio-Rad Laboratories lokala försäljningskontor eller Bio-Rad Laboratories tekniska service. Procedurmässiga försiktighetsåtgärder: 1. Denna produkt får inte användas efter utgångsdatum. 2. Om det finns tecken på mikrobiell kontaminering eller produkten är starkt grumlig, skall flaskan kastas. 3. Byt inte ut flaskornas lock mot varandra. Det kan leda till kontaminering mellan kontrollerna. 4. Endast för professionell användning. BEGRÄNSNINGAR 1. Denna produkt är inte avsedd att användas som en standard. 2. Denna produkt är avsedd för användning med BioPlex 2200-instrumentet. Ingen annan användning har utvärderats. TILLDELNING AV VÄRDEN BioPlex 2200 ANA Screen Control Set inkluderar såväl en negativ kontroll som en positiv multi-analytkontroll som innehåller antikroppar för analyter i BioPlex 2200 ANA Screen Reagent Pack. Den positiva kontrollen har tillverkats för att ge positiva resultat, med värden över brytpunkten för varje specifik mikrosfär. Den negativa kontrollen har tillverkats för att ge negativa resultat, med värden under brytpunkten för varje specifik mikrosfär. Medelvärdena har erhållits från analyser av replikat och borde falla inom motsvarande standardavvikelse. Vi rekommenderar att varje individuellt laboratorium fastställer sina egna gränser för varje parameter och använder de tillhandahållna gränsvärdena endast som vägledning. En BioPlex 2200 ANA Screen Control Lot Data CD-ROM finns tillgänglig för att ladda in nödvändiga data för värdetilldelning i instrumentet. Se användarhandboken för ytterligare information om denna åtgärd. OBS! Vissa analyter i BioPlex 2200 ANA Screen Positive Control måste spädas för att man skall erhålla de för batchen specifika värden, som är laddade i databasen för BioPlex 2200-instrument. BioPlex 2200-instrumentet späder automatiskt dessa analyter och utför proceduren med ett extra reaktionskärl. dansk ANVENDELSE BioPlex 2200 ANA Screen Control Set er beregnet til anvendelse som en analysekvalitetskontrol til monitorering af BioPlex 2200 Instrument og BioPlex 2200 ANA Screen Reagent Pack samlede ydelse i det kliniske laboratorium. OVERSIGT OG PRINCIP Brugen af kvalitetskontrolmaterialer er indiceret som en objektiv vurdering af præcisionen ved metoder og teknikker, der er i brug, og det er en integreret del af god laboratoriepraksis. MATERIALER, DER MEDFØLGER Reagenser: Alle reagenser indeholder konserveringsmidler, herunder ProClin 300 ved en koncentration på 0,3 og 0,1 natriumbenzoat. BioPlex 2200 ANA Screen Positive Controls: To (2), 1,5 ml ampuller. De positive kontroller leveres i en human serummatrix fremstillet af defibrineret plasma med tilsatte kendte analytkoncentrationer deriveret fra humant plasma i sygdomstilstand. BioPlex 2200 ANA Screen Negative Controls: To (2), 1,5 ml ampuller. De negative kontroller leveres i en human serummatrix fremstillet af defibrineret plasma. Komponenter: En (1) indlægsseddel med brugsanvisning. Et (1) ark med tildeling af værdier VALGFRIE MATERIALER, DER IKKE MEDFØLGER : BioPlex 2200 ANA Screen Control Lot Data CD-ROM. OPBEVARING OG STABILITET Produktet er stabilt indtil udløbsdatoen, når det opbevares uåbnet ved 2-8 C. Når de er åbnet, er alle kontroller stabile i 60 dage, når de opbevares tæt tillukket ved 2-8 C. PROCEDURE Produktet bør behandles på samme måde som patientpræparater og køres i overensstemmelse med vejledningerne vedlagt BioPlex 2200 Instrument og BioPlex 2200 ANA Screen Reagent Pack. Inden prøvetagningen påbegyndes, skal kontrollen nå stuetemperatur (18-25 C), og den blandes forsigtigt for at sikre ensartethed. Efter hver anvendelse sættes låget straks på igen og produktet sættes i køleskab ved 2-8 C. Bortskaf alle kasseredematerialer i overensstemmelsemed kravene fra de lokale renovationsmyndigheder. I tilfælde af beskadigelse af emballagen kontaktes det lokale salgskontor for Bio-Rad Laboratories eller Bio-Rad Laboratories teknisk service. Proceduremæssige forholdsregler: 1. Produktet må ikke anvendes efter udløbsdatoen. 2. Hvis der er tegn på mikrobiel kontamination eller for megen uklarhed i produktet, kasseres ampullen. 3. Ampullågene må ikke ombyttes frit mellem hinanden. Dette kan føre til krydskontamination af kontroller. 4. Kun til erhvervmæssig anvendelse. BEGRÆNSNINGER 1. Dette produkt er ikke beregnet til brug som en standard. 2. Dette produkt er beregnet til brug med BioPlex 2200 instrumentet. Enhver anden anvendelse er ikke blevet evalueret. TILDELING AF VÆRDIER BioPlex 2200 ANA Screen Control Set omfatter en negativ kontrol og en positiv kontrol med flere analytter, der indeholder antistoffer til stede for analytter indeholdt i BioPlex 2200 ANA Screen Reagent Pack. Den positive kontrol er fremstillet for at give positive resultater med værdier over cut-off værdien for hver specifik perle. Den negative kontrol er fremstillet til at give negative resultater med værdier under cut-off værdien for hver specifik perle. Middelværdierne blev deriveret fra replikate analyser og skal falde indenfor den tilsvarende standardafvigelse. Det anbefales, at det enkelte laboratorium fastsætter sine egne grænser for hvert enkelt parameter, samt at det kun anvender de fremsatte grænser som vejledning. En BioPlex 2200 ANA Screen Control Lot Data CD-ROM er tilgængelig til indlæsning af de nødvendige værditildelingsdata i instrumentet. Se brugervejledningen for at få yderligere information om denne aktivitet. Bemærk: Visse analytter i BioPlex 2200 ANA Screen Positive Control skal fortyndes for at opnå de værdier, der er specifikke for partiet, som er indlæst i BioPlex 2200 instrumentets database. BioPlex 2200 instrumentet fortynder automatisk disse analytter og foretager denne handling med en anden reaktionsbeholder. Caution Vorsicht // Attention // Attenzione // Precaución // Cuidado // Försiktighet // Forsigtig Xi IRRITANT Reizend // Irritant // Irritante // Irritante // Irritante // Irriterande ämne // Lokalirriterende english Biological source material. Treat as potentially infectious. Each human donor unit used to manufacture this product was tested by FDA accepted methods and found non-reactive for Hepatitis B Surface Antigen (HBsAg), antibody to hepatitis C (HCV) and antibody to HIV-1/HIV-2. This product may also contain other human agents capable of transmitting infectious disease. In accordance with good laboratory practice, all human source material should be considered potentially infectious and handled with the same precautions used with patient specimens. Contains 0.3 ProClin 300. Risk (R) and Safety (S) Phrases R43 May cause sensitization by skin contact. S24 Avoid contact with skin. S37 Wear suitable gloves. S56 Dispose of this material and its container at hazardous or special waste collection point. Prepared in accordance with requirements for CE Label. deutsch Material biologischer Herkunft. Als potenziell infektiös behandeln. Jede zur Herstellung dieses Produkts verwendete humane Spendereinheit wurde nach FDA-anerkannten Methoden geprüft und erwies sich als nicht reaktiv für Hepatitis-B- Oberflächenantigen (HBsAg), Antikörper gegen das Hepatitis- C-Virus (HCV) und Antikörper gegen HIV-1 und HIV-2. Dieses Produkt kann auch andere humane Substanzen enthalten, die infektiöse Krankheiten übertragen können. In Übereinstimmung mit den Richtlinien der guten Laborpraxis sollten alle Materialien humanen Ursprungs als potenziell infektiös betrachtet und mit der gleichen Sorgfalt wie Patientenproben behandelt werden. Enthält 0,3 ProClin 300 R- und S-Sätze R43 Sensibilisierung durch Hautkontakt möglich. S24 Berührung mit der Haut vermeiden. S37 Geeignete Schutzhandschuhe tragen. S56 Dieses Produkt und seinen Behälter der Problemabfallentsorgung zuführen. Hergestellt gemäß den Anforderungen für die CE-Kennzeichnung. français Produit d origine biologique. Traiter comme s il était potentiellement infectieux. Chaque don de sérum humain contribuant à la fabrication de ce produit a été testé par des méthodes acceptées par la FDA et trouvé négatif pour l antigène de surface de l hépatite B (AgHBs), l anticorps anti-virus de l hépatite C (anti-vhc) et l anticorps anti-vih 1 et 2. Ce produit peut également contenir d autres agents humains capables de transmettre des maladies infectieuses. Conformément aux bonnes pratiques de laboratoire, tous les produits d origine humaine doivent être considérés comme étant potentiellement infectieux et manipulés avec les mêmes précautions que celles utilisées pour les échantillons patients. Contient 0,3 de ProClin 300 Phrases de risques (R) et de sécurité (S) R43 Peut entraîner une sensibilisation par contact avec la peau. S24 Éviter le contact avec la peau. S37 Porter des gants appropriés. S56 Éliminer ce produit et son récipient dans un centre de collecte des déchets dangereux ou spéciaux. Préparé conformément aux exigences d étiquetage de la CE. italiano Materiale di origine biologica. Trattarlo come un prodotto potenzialmente infettivo. Ciascuna unità di donatore umano utilizzata per preparare questo prodotto è stata analizzata con metodi approvati dall ente di controllo statunitense FDA ed è risultata non reattiva per l antigene di superficie del virus dell epatite B (HBsAg), per l anticorpo diretto contro l epatite C (HCV) e per l anticorpo anti-hiv-1/hiv-2. Questo prodotto può anche contenere altri agenti di origine umana in grado di trasmettere malattie infettive. In base a una corretta prassi di laboratorio, tutto il materiale di origine umana deve essere considerato potenzialmente infettivo e trattato con le stesse precauzioni osservate con i campioni dei pazienti. Contiene ProClin 300 allo 0,3 Frasi in materia di rischio (R) e sicurezza (S) R43 Può provocare sensibilizzazione per contatto con la pelle. S24 Evitare il contatto con la pelle. S37 Usare guanti adatti. S56 Smaltire questo materiale e i relativi contenitori in un punto di raccolta rifiuti pericolosi o speciali. Preparato in conformità ai requisiti per l apposizione dell etichetta CE. español Material de origen biológico. Manipúlelo como si fuese potencialmente infeccioso. Todas las unidades procedentes de donantes humanos utilizadas para la fabricación de este producto se analizaron con métodos aceptados por la FDA y se comprobó que no son reactivas a los antígenos de superficie de la hepatitis B (HBsAg), a los anticuerpos contra la hepatitis C (HCV) ni a los anticuerpos contra el VIH-1/ VIH-2. Este producto puede contener también otros agentes de origen humano capaces de transmitir enfermedades infecciosas. En conformidad con las buenas prácticas de laboratorio, todo el material de origen humano debe considerarse potencialmente infeccioso y debe manipularse con las mismas precauciones empleadas con las muestras de pacientes. Contiene ProClin 300 ( 0,3) Frases de riesgo (R) y seguridad (S) R43 Posibilidad de sensibilización en contacto con la piel. S24 Evítese el contacto con la piel. S37 Úsense guantes adecuados. S56 Elimínense esta sustancia y su recipiente en un punto de recogida pública de residuos especiales o peligrosos. Preparado en conformidad con los requisitos de etiquetado de la CE. português Material de origem biológica. Trate como potencialmente infeccioso. Cada unidade de dador humano utilizada no fabrico deste produto foi testada segundo métodos aceites pela FDA, tendo sido considerada não reactiva para o antigénio de superfície da hepatite B (AgHBs), anticorpos contra a hepatite C (VHC) e anticorpos contra VIH-1/VIH-2. Este produto também pode conter outros agentes humanos passíveis de transmitir doenças infecciosas. De acordo com as boas práticas laboratoriais, todos os materiais de origem humana devem ser considerados como sendo potencialmente infecciosos e manuseados com as mesmas precauções empregues no manuseamento das amostras de doentes. Contém ProClin 300 a 0,3 Frases de risco (R) e segurança (S) R43 Pode causar sensibilização em contacto com a pele. S24 Evitar o contacto com a pele. S37 Usar luvas adequadas. S56 Eliminar este produto e o seu recipiente, enviandoos para local autorizado para a recolha de resíduos perigosos ou especiais. Preparado em conformidade com os requisitos do rótulo CE. Svenska Biologiskt källmaterial. Behandla som potentiellt smittsamt. Varje enhet från humana donatorer som använts för att tillverka denna produkt har testats med FDA-godkända metoder och har visat sig icke-reaktiv för hepatit B-ytantigen (HBsAg), antikroppar mot hepatit C (HCV) och antikroppar mot HIV-1/ HIV-2. Denna produkt innehåller kanske även andra humana agenser som kan överföra smittsamma sjukdomar. Enligt god laboratoriepraxis bör allt material av humant ursprung betraktas som potentiellt smittsamt och bör hanteras med samma försiktighetsåtgärder som patientprover. Innehåller 0,3 ProClin 300 Risk- (R) och skyddsfraser (S) R43 Kan ge allergi vid hudkontakt. S24 Undvik kontakt med huden. S37 Använd lämpliga skyddshandskar. S56 Lämna detta material och dess behållare till insamlingsställe för farligt avfall. Beredd enligt kraven för CE-märkning. dansk Materiale af biologisk oprindelse. Behandles som potentielt smitsomt. Hver human donorenhed anvendt til at fremstille dette produkt er testet med metoder godkendt af FDA (USAs regeringskontor for fødevare- og medicinkontrol), og fandtes at være non-reaktiv over for hepatitis B overfladeantigen (HBsAg), antistof mod hepatitis C (HCV) og antistof mod HIV-1/HIV-2. Dette produkt kan desuden indeholde andre stoffer af human oprindelse, som er potentielt smittefarlige. I overensstemmelse med god laboratoriepraksis skal alt materiale af human oprindelse anses som potentielt smittefarligt og håndteres med de samme forholdsregler som ved patientpræparater. Indeholder 0,3 ProClin 300 Risiko- (R) og Sikkerheds- (S) sætninger R43 Kan give overfølsomhed ved kontakt med huden. S24 Undgå kontakt med huden. S37 Brug egnede beskyttelseshandsker under arbejdet. S56 Aflever dette materiale og dets beholder til et indsamlingssted for farligt affald og problemaffald. Præpareret i overensstemmelse med kravene til CE-mærket.

77 Glossary glossar glossaire glossario glosario glossário ordlista ordliste ANALYTES ANALYTE ANALYTES ANALITI ANALITOS SUBSTÂNCIAS A ANALISAR ANALYTER ANALYTTER dsdna dsdna dsdna dsdna dsdna dsdna dsdna dsdna Chromatin Chromatin Chromatine Cromatina Cromatina Cromatina Kromatin Kromatin Ribosomal Protein Ribosomales Potein Protéines ribosomiques Proteina ribosomiale Proteína ribosómica Proteína ribossómica Ribosomalt protein Ribosomal protein SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-B SS-B SS-B SS-B SS-B SS-B SS-B SS-B Sm Sm Sm Sm Sm Sm Sm Sm SmRNP SmRNP SmRNP SmRNP SmRNP SmRNP SmRNP SmRNP RNP A RNP A RNP A RNP A RNP A RNP A RNP A RNP A RNP 68 RNP 68 RNP 68 RNP 68 RNP 68 RNP 68 RNP 68 RNP 68 Scl-70 Scl-70 Scl-70 Scl-70 Scl-70 Scl-70 Scl-70 Scl-70 Jo-1 Jo-1 Jo-1 Jo-1 Jo-1 Jo-1 Jo-1 Jo-1 Centromere B Zentromer-B Centromère B Centromero-B Centrómero-B Centrómero-B Centromer-B Centromer-B TERMS AUSDRÜCKE TERMES TERMINI TÉRMINOS TERMOS TERMER BETEGNELSER Mean Mittelwert Moyenne Media Media Média Genomsnitt Middel Standard Deviation Standardabweichung Écart type Deviazione standard Desviación estándar Desvio padrão Standardavvikelse Standardafvigelse Units Einheiten Unités Unità Unidades Unidades Enheter Enheder UNITED STATES, Bio-Rad Laboratories, Inc., Hercules, CA FRANCE, Bio-Rad 3 boulevard Raymond Poincaré Marnes-la-Coquette Phone: (33) / Fax: (33) english technical Information Contacts Bio-Rad provides a toll free line for technical assistance, available 24 hours a day, 7 days a week. In the United States of America and Puerto Rico, call toll free BIORAD ( ). Outside the U.S.A., please contact your regional Bio-Rad office for assistance. DEUTSCH Technische Unterstützung Bio-Rad bietet Ihnen gebührenfreie telefonische Unterstützung bei technischen Problemen, 24 Stunden am Tag, 7 Tage in der Woche. In den Vereinigten Staaten von Amerika und in Puerto Rico steht Ihnen die gebührenfreie Rufnummer BIORAD ( ) zur Verfügung. Außerhalb der USA wenden Sie sich bitte an Ihre örtliche Bio-Rad-Vertretung. français Pour tous renseignements techniques Bio-Rad a une ligne de téléphone gratuite réservée à l assistance technique, disponible 24 heures par jour, 7 jours par semaine. Depuis les États-Unis et Porto Rico, le numéro gratuit est BIORAD ( ). En dehors des États-Unis, contacter un bureau Bio-Rad local pour de l assistance. italiano Servizio di assistenza tecnica Il servizio di assistenza tecnica Bio-Rad gestisce una linea verde USA di assistenza disponibile ad orario continuato 7 giorni alla settimana. Dagli Stati Uniti e da Portorico, chiamare il numero verde BIORAD ( ). español Contactos para obtener información técnica Bio-Rad ofrece una línea telefónica gratuita de asistencia técnica, disponible 24 horas al día, 7 días a la semana. En Estados Unidos y Puerto Rico, llame al número gratuito BIORAD ( ). Fuera de EE.UU., póngase en contacto con la oficina regional de Bio-Rad si necesita ayuda. português Contactos para informações técnicas A Bio-Rad faculta um número gratuito para assistência técnica, disponível 24 horas por dia, 7 dias por semana. Nos Estados Unidos da América e em Porto Rico, telefone para a linha gratuita BIORAD ( ). 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78 x 0.5 ml BioPlex 2200 ANA Screen Calibrator Set english INTENDED USE The BioPlex 2200 ANA Screen Calibrator Set is intended for the calibration of the BioPlex 2200 ANA Screen Reagent Pack. SUMMARY AND PRINCIPLE The BioPlex 2200 ANA Screen Regent Pack is calibrated using a set of six (6) distinct serum based calibrators. Calibrators are used in a test system to establish points of reference that are used in the determination of the presence of substances in human specimens. MATERIALS PROVIDED Reagents BioPlex 2200 ANA Screen Calibrator: Six (6) 0.5 ml vials. The calibrators are provided in a human serum matrix made from defribrinated plasma with added known analyte concentrations derived from human disease state plasma, and added preservatives including ProClin 300 at a concentration of 0.3 and 0.1 sodium benzoate. Components One (1) package insert providing instructions for use. MATERIALS REQUIRED BUT NOT PROVIDED : BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM Note: Printable PDF files for reagent lot specific calibrator assigned values are included. STORAGE AND STABILITY This product is stable until the expiration date when stored unopened at 2 to 8 C. Once opened, the calibrators are stable for 60 days when stored tightly capped at 2 to 8 C. PROCEDURE This product should be run in accordance with the instructions accompanying the BioPlex 2200 Instrument and BioPlex 2200 ANA Screen Reagent Pack. Before sampling calibrators, allow the vials to reach room temperature (18 to 25 C) and gently mix to ensure homogeneity. After each use, promptly replace the cap and return to 2 to 8 C storage. Dispose of any discarded materials in accordance with the requirements of your local waste management authorities. In the event of damage to packaging, contact the local Bio-Rad Laboratories Sales Office or Bio-Rad Laboratories Technical Services. Procedural Precautions 1. This product should not be used past the expiration date. 2. If there is evidence of microbial contamination or excessive turbidity in the product, discard the vial. 3. Do not interchange vial caps. This may lead to cross contamination of calibrators. 4. For professional use only. LIMITATIONS This product is intended for use with the BioPlex 2200 Instrument. Any other use has not been evaluated. ASSIGNED VALUES The BioPlex 2200 ANA Screen Calibrator Set includes six (6) distinct vials. The results are expressed in antibody index (AI) except for dsdna which is expressed in IU/mL. Reagent lot specific assigned values are included as printable PDF files on each Calibrator Lot Data CD-ROM. For each associated Reagent Pack lot, there is a separate PDF file on the Calibrator Lot Data CD-ROM containing the corresponding assigned values. Calibrator assignment is established using a Master Set of calibrators and a specific lot of BioPlex 2200 ANA Screen Reagent Packs on multiple Bioplex 2200 instruments. A BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM is required to load the necessary value assignment data into the instrument. Refer to the Operation Manual for more information regarding this activity. TRACEABILITY Traceability has been established for dsdna using WHO First International Standard for Anti-double stranded DNA (dsdna), Human Code: Wo/80 (W1065). REFERENCE TEW Felkamp, TBL Kirkwood, RN Maini and LA Aarden. The first International Standard for Antibodies to double stranded DNA. Annals of the Rheumatic Diseases 1988; 47: DEUTSCH VERWENDUNGSZWECK Das BioPlex 2200 ANA Screen Calibrator Set ist bestimmt für die Kalibrierung des BioPlex 2200 ANA Screen Reagent Pack. EINLEITUNG UND ZUSAMMENFASSUNG Der BioPlex 2200 ANA Screen Reagent Pack wurde mit einem Set von sechs (6) verschiedenen Kalibratoren auf Serumbasis kalibriert. In einem Testsystem dienen Kalibratoren zur Bestimmung von Bezugspunkten für den Nachweis von Substanzen in Humanproben. GELIEFERTE MATERIALIEN Reagenzien BioPlex 2200 ANA Screen Calibrator: Sechs (6) Fläschchen mit je 0,5 ml. Die Kalibratoren werden in einer aus defibriniertem Plasma hergestellten Humanserummatrix geliefert und enthalten bekannte Konzentrationen von Analyten aus dem Plasma erkrankter Patienten sowie Konservierungsstoffe, einschließlich ProClin 300 in einer Konzentration von 0,3 und 0,1 Natriumbenzoat. Beilagen Eine (1) Packungsbeilage mit Gebrauchsanweisung. ERFORDERLICHE, IM LIEFERUMFANG NICHT ENTHALTENE MATERIALIEN : BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM Hinweis: Enthält ausdruckbare PDF-Dateien mit reagenzienchargenspezifisch zugeordneten Kalibratorwerten. LAGERUNG UND STABILITÄT Dieses Produkt ist bis zum Verfallsdatum haltbar, sofern es ungeöffnet bei 2 C bis 8 C gelagert wird. Nach dem Öffnen sind die Kalibratoren 60 Tage stabil, sofern sie fest verschlossen bei 2 C bis 8 C gelagert werden. TESTDURCHFÜHRUNG Dieses Produkt sollte in Übereinstimmung mit den Gebrauchsanweisungen für das BioPlex 2200 Gerät und den BioPlex 2200 ANA Screen Reagent Pack verwendet werden. Vor der Messung die Kalibratoren auf Raumtemperatur bringen (18 C bis 25 C) und zur Gewährleistung der Homogenität vorsichtig mischen. Nach jedem Gebrauch sofort wieder verschließen und bei 2 C bis 8 C lagern. Die Entsorgung aller Abfälle ist nach den geltenden örtlichen Bestimmungen vorzunehmen. Falls die Verpackung beschädigt ist, nehmen Sie bitte Kontakt zur Bio-Rad Laboratories Niederlassung oder dem Bio-Rad Laboratories Kundendienst auf. Vorsichtshinweise zur Testdurchführung 1. Dieses Produkt nach Ablauf des Haltbarkeitsdatums nicht mehr verwenden. 2. Bei Anzeichen einer mikrobiellen Kontamination oder einer starken Trübung des Produkts ist das Fläschchen zu verwerfen. 3. Die Verschlüsse der Fläschchen dürfen nicht miteinander vertauscht werden. Dies kann zur Kreuzkontamination der Kalibratoren führen. 4. Nur zum professionellen Gebrauch. EINSCHRÄNKUNGEN Dieses Produkt ist zur Verwendung mit dem BioPlex 2200 Gerät bestimmt. Andere Verwendungszwecke wurden nicht evaluiert. ZUGEORDNETE WERTE Das BioPlex 2200 ANA Screen Calibrator Set beinhaltet sechs (6) unterschiedliche Fläschchen. Die Ergebnisse werden als Antikörper-Index (AI) angegeben, mit Ausnahme von dsdna, welche in IE/mL angegeben wird. Jede Calibrator Lot Data CD-ROM enthält ausdruckbare PDF-Dateien mit reagenzienchargenspezifisch zugeordneten Kalibratorwerten. Die Calibrator Lot Data CD-ROM enthält für jede zugehörige Reagenzienpackcharge eine separate PDF-Datei mit den entsprechenden zugeordneten Werten. Die Zuordnung der Kalibratorwerte erfolgt mithilfe eines Kalibrator-Mastersets und einer bestimmten Charge von BioPlex 2200 ANA Screen Reagent Packs auf mehreren BioPlex 2200 Geräten. Über eine BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM werden die chargenabhängigen Kalibrator-Werte in das Gerätesystem geladen. Weitere Informationen zu diesem Vorgang finden Sie im Benutzerhandbuch. RÜCKVERFOLGBARKEIT Rückverfolgbarkeit für dsdna wurde anhand des internationalen Standards der WHO für Antikörper gegen doppelsträngige DNA (dsdna) Wo/80 (W1065) etabliert. LITERATUR TEW Felkamp, TBL Kirkwood, RN Maini and LA Aarden. The first International Standard for Antibodies to double stranded DNA. Annals of the Rheumatic Diseases 1988; 47: français UTILISATION Le BioPlex 2200 ANA Screen Calibrator Set est destiné à la calibration du BioPlex 2200 ANA Screen Reagent Pack. INTRODUCTION ET PRINCIPE Le BioPlex 2200 ANA Screen Reagent Pack est calibré à l aide d un jeu de six (6) calibrateurs différents à base de sérum. Les calibrateurs sont utilisés dans le cadre d un système de test pour établir des points de référence permettant l évaluation de substances présentes dans des échantillons humains. MATÉRIEL FOURNI Réactifs BioPlex 2200 ANA Screen Calibrator : six (6) flacons de 0,5 ml. Les calibrateurs sont fournis dans une matrice de sérum humain préparée à partir de plasma défibriné auquel sont ajoutées des concentrations connues d analytes dérivés de plasma humain infecté et des conservateurs, y compris du ProClin 300 à une concentration de 0,3 et 0,1 de benzoate de sodium. Composants Une (1) notice d utilisation fournissant le mode d emploi. MATÉRIEL NÉCESSAIRE MAIS NON FOURNI : BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM Remarque : Des fichiers PDF imprimables sont inclus pour les valeurs assignées aux calibrateurs spécifiques aux lots de réactifs. CONSERVATION ET STABILITÉ Ce produit reste stable jusqu à sa date de péremption lorsqu il est conservé dans son flacon fermé entre 2 C et 8 C. Une fois ouverts, les calibrateurs restent stables pendant 60 jours s ils sont conservés dans leur flacon bien fermé entre 2 C et 8 C. PROCÉDURE Ce produit doit être analysé conformément aumode d emploi de l instrument BioPlex 2200 et du BioPlex 2200ANA Screen Reagent Pack. Avant de tester un calibrateur, laisser le flacon revenir à température ambiante (entre 18 C et 25 C) et le mélanger doucement pour assurer son homogénéité. Le reboucher rapidement après chaque utilisation et le remettre au réfrigérateur entre 2 C et 8 C. Éliminer le produit restant conformément aux exigences des organismes locaux de gestion des déchets. Si l emballage est endommagé, contacter le bureau de ventes local ou le service technique de Bio-Rad Laboratories. Précautions relatives à la procédure : 1. Ne pas utiliser ce produit au-delà de sa date de péremption. 2. Si l on constate une contamination microbienne ou une turbidité excessive du produit, jeter le flacon. 3. Ne pas interchanger les bouchons des flacons sous risque de contamination croisée des calibrateurs. 4. Usage réservé aux biologistes. LIMITES Ce produit est destiné à être utilisé avec l instrument BioPlex Aucune autre utilisation n a été évaluée. VALEURS ATTRIBUÉES Le BioPlex 2200 ANA Screen Calibrator Set comprend six (6) flacons différents. Les résultats sont exprimés en taux d anticorps (TA) sauf pour le dsdna qui est exprimé sous forme d UI/mL. Les valeurs assignées spécifiques aux lots de réactifs sont incluses sur chaque CD-ROM des données relatives au lot de calibrateur, sous la forme de fichiers PDF imprimables. Pour chaque lot de cartouches de réactif associé, un fichier PDF distinct est fourni sur le CD-ROM des données relatives au lot de calibrateur contenant les valeurs assignées correspondantes. For In Vitro Diagnostic Use In Vitro Diagnosticum Usage In Vitro Per Uso Diagnostico In Vitro Para Uso Diagnóstico In Vitro Utilizar Apenas Em Diagnóstico In Vitro För in-vitro diagnostiskt bruk Til in Vitro diagnosticering European Conformity CE-Konformitätskennzeichnung Conformité aux normes européennes Conformità europea Conformidad europea Conformidade com as normas europeias Europeisk överensstämmelse Europæisk overensstemmelse Temperature Limit Temperaturlimit Limite de température Limite di temperatura Límite de temperatura Limite de temperatura Temperaturgränser Temperaturgrænse Consult Instructions for Use Gebrauchsanweisung beachten Consulter la notice d emploi Consultare le istruzioni per l uso Consulte las instrucciones de uso Consulte as instruções de utilização Läs bruksanvisningen Benyt brugsanvisninger Lot Number Chargen-Nr. Numéro de lot Numero di lotto Número de lote Número de lote Satsnummer Batchnummer Use by (YYYY-MM-DD) Verwendbar bis (JJJJ-MM-TT) Date de péremption (AAAA-MM-JJ) Data di scadenza (AAAA-MM-GG) Usar hasta el (AAAA-MM-GG) Utilizar até (AAAA-MM-DD) Använd före (ÅÅÅÅ-MM-DD) Anvend før (ÅÅÅÅ-MM-DD) Manufactured by Hergestellt von Fabriqué par Fabbricato da Fabricado por Fabricado por Tillverkare Fremstillet af Authorized Representative Bevollmächtigter Représentant agréé Rappresentante autorizzato Representante autorizado Representante autorizado Auktoriserad representant Autoriseret repræsentant Catalog Number Katalognummer Numéro de catalogue Numero di catalogo Número de catálogo Número de catálogo Katalognummer Katalognr. Caution, consult accompanying documents Achtung, Begleitdokumente beachten Attention, consulter la documentation jointe Attenzione, consultare la documentazione allegata Precaución, consulte los documentos que acompañan al instrumento Atenção, consultar os documentos inclusos Försiktighet: se medföljande dokument Forsigtig, der henvises til den vedlagte dokumentation Calibrator // Level Kalibrator-Level Niveau des calibrateurs Livello calibratore Nivel del calibrador Nível do calibrador Kalibratornivå Kalibratorniveau Printed // Gedruckt // Imprimé // Stampato // Impreso // Impresso // Tryckt // Trykt

79 BioPlex 2200 ANA Screen Calibrator Set On établit la valeur attribuée au calibrateur au moyen d un jeu de calibrateurs de référence et d un lot spécifique de BioPlex 2200 ANA Screen Reagent Packs sur plusieurs instruments BioPlex Un BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM est nécessaire afin de télécharger les données d attribution de valeur nécessaires sur l instrument. Se reporter au manuel d utilisation pour des informations complémentaires concernant cette activité. TRAÇABILITÉ La traçabilité a été établie pour le dsdna en utilisant le premier étalon international de l OMS pour les anticorps anti-adn double brin (dsdna), code humain : Wo/80 (W1065). RÉFÉRENCE TEW Felkamp, TBL Kirkwood, RN Maini and LA Aarden. The first International Standard for Antibodies to double stranded DNA. Annals of the Rheumatic Diseases 1988; 47: italiano USO PREVISTO Il BioPlex 2200 ANA Screen Calibrator Set è previsto per la calibrazione del BioPlex 2200 ANA Screen Reagent Pack. RIEPILOGO E PRINCIPIO Il BioPlex 2200 ANA Screen Reagent Pack viene calibrato mediante un set di sei (6) calibratori differenti basati su siero. I calibratori vengono usati in un sistema di analisi per stabilire i punti di riferimento che verranno successivamente utilizzati per la determinazione della presenza di sostanze nei campioni umani. MATERIALI FORNITI Reagenti BioPlex 2200 ANA Screen Calibrator - Sei (6) fiale da 0,5 ml. I calibratori vengono forniti in una matrice di siero umano a base di plasma defibrinato addizionata con concentrazioni note di analita derivate da plasma umano proveniente da soggetti malati e contenente conservanti, incluso ProClin 300 allo 0,3 e benzoato di sodio (0,1). Componenti Un (1) foglietto illustrativo contenente le istruzioni per l uso. MATERIALI NECESSARI MA NON FORNITI : BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM Nota - Include i file PDF stampabili contenenti i valori assegnati ai calibratori specifici per il lotto di reagenti. CONSERVAZIONE E STABILITÀ Questo prodotto è stabile fino alla data di scadenza se conservato sigillato a 2 8 C. Una volta aperti, i calibratori rimangono stabili per 60 giorni, se conservati a 2 8 C e perfettamente sigillati. PROCEDURA Questo prodotto deve essere usato attenendosi alle istruzioni che accompagnano lo strumento BioPlex 2200 e il BioPlex 2200 ANA Screen Reagent Pack. Prima di usare i calibratori, consentirne la stabilizzazione a temperatura ambiente (18-25 C) e agitarli delicatamente per garantirne l omogeneità. Dopo ogni utilizzo, richiuderlo immediatamente con il tappo e riportarlo ad una temperatura di 2-8 C. Smaltire i rifiuti in base alle norme in vigore stabilite dalle autorità competenti. Se la confezione presenta danni, rivolgersi all ufficio commerciale o al servizio di assistenza tecnica Bio-Rad Laboratories di zona. Precauzioni procedurali 1. Non usare il prodotto dopo la data di scadenza. 2. Eliminare la fiala se torbida o se presenta segni di contaminazione batterica. 3. Non scambiare tra loro i tappi delle fiale. Ciò può comportare la contaminazione crociata dei calibratori. 4. Esclusivamente per uso professionale. LIMITAZIONI Il presente prodotto è previsto per l uso con lo strumento BioPlex Non è previsto per impieghi diversi da quelli descritti. VALORI ASSEGNATI Il BioPlex 2200 ANA Screen Calibrator Set comprende sei (6) fiale differenti. I risultati sono espressi secondo un indice anticorpale (AI, antibody index), eccetto per il dsdna, che è espresso in UI/mL. I valori assegnati specifici per il lotto di reagenti sono inclusi in file PDF stampabili, contenuti su ciascun Calibrator Lot Data CD ROM. Per ciascun lotto associato di cartucce reagenti, esiste un file PDF separato sul Calibrator Lot Data CD-ROM contenente i valori assegnati corrispondenti. Il valore assegnato al calibratore viene stabilito usando un set principale di calibratori e un lotto specifico di BioPlex 2200 ANA Screen Reagent Pack su più strumenti BioPlex Il BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM è necessario per caricare i dati relativi ai valori assegnati nello strumento. Per ulteriori informazioni al riguardo, consultare il manuale d uso. RICONDUCIBILITÀ La riconducibilità per il dsdna è stata stabilita mediante il Primo standard internazionale dell OMS per gli anticorpi anti-dna a doppia elica (dsdna), codice umano: Wo/80 (W1065). RIFERIMENTO BIBLIOGRAFICO TEW Felkamp, TBL Kirkwood, RN Maini and LA Aarden. The first International Standard for Antibodies to double stranded DNA. Annals of the Rheumatic Diseases 1988; 47: español INDICACIONES El BioPlex 2200 ANA Screen Calibrator Set está diseñado para la calibración del BioPlex 2200 ANA Screen Reagent Pack. RESUMEN Y PRINCIPIOS El BioPlex 2200 ANA Screen Reagent Pack se calibra mediante un conjunto de seis (6) calibradores diferentes, preparados a partir de suero. Los calibradores se utilizan en un sistema de análisis para establecer puntos de referencia que se emplean para determinar la presencia de sustancias en muestras humanas. MATERIAL SUMINISTRADO Reactivos BioPlex 2200 ANA Screen Calibrator: seis (6) frascos de 0,5 ml. Los calibradores se suministran en una matriz de suero humano elaborada con plasma desfibrinado, a la que se han añadido concentraciones conocidas de analito obtenido de plasma de personas enfermas y conservantes que incluyen ProClin 300 al 0,3 y 0,1 de benzoato sódico. Componentes Un (1) prospecto del envase con instrucciones de uso. MATERIAL NECESARIO NO SUMINISTRADO : BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM Nota: Se incluyen archivos PDF imprimibles con los valores asignados al calibrador, específicos para cada lote de reactivos. ALMACENAMIENTO Y ESTABILIDAD Este producto es estable hasta la fecha de caducidad, si se almacena sin abrir a una temperatura de 2 C a 8 C. Una vez abiertos, los calibradores son estables durante 60 días, si se almacenan bien cerrados a una temperatura de 2 C a 8 C. PROCEDIMIENTO Este producto debe emplearse de acuerdo con las instrucciones que acompañan al instrumento BioPlex 2200 y al BioPlex 2200 ANA Screen Reagent Pack. Antes de extraer muestras de calibradores, deje que los frascos alcancen la temperatura ambiente (entre 18 y 25 C) y mézclelos suavemente para garantizar su homogeneidad. Después de cada uso, coloque el tapón de nuevo inmediatamente y vuelva a almacenarlo a entre 2 y 8 C. Elimine todos los materiales de desecho de acuerdo con los requisitos establecidos por las autoridades locales en materia de gestión de residuos. Si el envase está dañado, póngase en contacto con su oficina de ventas o con el departamento de servicio técnico de Bio-Rad Laboratories más cercano. Precauciones procedimentales 1. Este producto no debe emplearse una vez transcurrida la fecha de caducidad. 2. Deseche el frasco si existen indicios de contaminación microbiana o el producto presenta excesiva turbidez. 3. No intercambie los tapones de los frascos, ya que eso podría ocasionar la contaminación cruzada de los calibradores. 4. Sólo para uso profesional. LIMITACIONES Este producto está indicado para utilizarse con el instrumento BioPlex No se ha evaluado ningún otro uso. VALORES ASIGNADOS El BioPlex 2200 ANA Screen Calibrator Set incluye seis (6) frascos diferentes. Los resultados se expresan como índice de anticuerpos (IA) salvo el dsdna que se expresa en UI/mL. Los valores asignados, específicos para cada lote de reactivos, están incluidos como archivos PDF imprimibles en el CD de datos del lote de calibradores. En el CD de datos del lote de calibradores se incluye un archivo PDF distinto para cada lote del paquete de reactivos asociado; este archivo contiene los valores asignados correspondientes. La asignación de los calibradores se establece mediante un juego maestro de calibradores y un lote específico de BioPlex 2200 ANA Screen Reagent Packs en varios instrumentos BioPlex Se necesita un BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM para cargar los datos de asignación de valores necesarios en el instrumento. Consulte el manual de funcionamiento para obtener más información sobre este tema. TRAZABILIDAD La trazabilidad para el dsdna se ha establecido mediante el primer estándar internacional de la OMS para el anti-adn bicatenario (dsdna), código humano: Wo/80 (W1065). REFERENCIA TEW Felkamp, TBL Kirkwood, RN Maini and LA Aarden. The first International Standard for Antibodies to double stranded DNA. Annals of the Rheumatic Diseases 1988; 47: português UTILIZAÇÃO PREVISTA O BioPlex 2200 ANA Screen Calibrator Set destina-se a ser utilizado na calibração do BioPlex 2200 ANA Screen Reagent Pack. RESUMO E PRINCÍPIOS O BioPlex 2200 ANA Screen Reagent Pack é calibrado utilizando um conjunto de seis (6) calibradores diferentes à base de soro. Os calibradores são utilizados num sistema de teste para estabelecimento de pontos de referência que são usados na determinação de substâncias em amostras humanas. MATERIAIS FORNECIDOS Reagentes BioPlex 2200 ANA Screen Calibrator: seis (6) frascos de 0,5 ml. Os calibradores são fornecidos numa matriz de soro humano, produzida a partir de plasma desfibrinado, à qual foram adicionadas concentrações conhecidas das substâncias a analisar obtidas de plasma de pessoas doentes, e que contém conservantes, incluindo ProClin 300 numa concentração de 0,3 e benzoato de sódio a 0,1. Componentes Um (1) folheto informativo com instruções de utilização. MATERIAIS NECESSÁRIOS MAS NÃO FORNECIDOS : BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM Observação: São fornecidos ficheiros em formato PDF, que podem ser impressos, com os valores atribuídos aos calibradores, específicos para o lote de reagentes. ARMAZENAMENTO E ESTABILIDADE Este produto mantém-se estável até ao fim do prazo de validade, desde que armazenado não aberto entre 2 e 8 C. Depois de abertos, os calibradores mantêm-se estáveis durante um período de 60 dias quando armazenados, em frascos bem fechados, entre 2 e 8 C. PROCEDIMENTO Este produto deve ser analisado de acordo com as instruções anexas ao Instrumento BioPlex 2200 e ao BioPlex 2200 ANA Screen Reagent Pack. Antes da amostragem dos calibradores, deixe os frascos atingirem a temperatura ambiente (18 a 25 C) e misture suavemente para garantir a homogeneidade. Após cada utilização, volte a colocar de imediato a tampa e o frasco na refrigeração, entre 2 e 8 C. Elimine os materiais rejeitados de acordo com os requisitos das autoridades locais de tratamento de resíduos. Caso a embalagem se encontre danificada, contacte o Departamento de Vendas local ou a Assistência Técnica da Bio-Rad Laboratories. Precauções relativas ao procedimento 1. Este produto não deve ser utilizado após o fim do prazo de validade. 2. Se existirem sinais de contaminação microbiana ou turvação excessiva do produto, rejeite o frasco. 3. Não troque as tampas dos frascos. Isto poderá conduzir à contaminação cruzada dos calibradores. 4. Apenas para utilização por profissionais. LIMITAÇÕES Este produto destina-se a ser utilizado com o instrumento BioPlex Não foram avaliados outros tipos de utilização. VALORES ATRIBUÍDOS O BioPlex 2200 ANA Screen Calibrator Set contém seis (6) frascos diferentes. Os resultados são expressos em índice de anticorpos (IA), excepto em relação ao dsdna, que é expresso em UI/mL. Os valores atribuídos específicos para o lote de reagentes são fornecidos sob a forma de ficheiros em formato PDF, que podem ser impressos, com cada CD-ROM com dados do lote do calibrador. Para cada lote de embalagem de reagente associado, existe um ficheiro em formato PDF separado no CD-ROM com dados do lote do calibrador, que contém os valores atribuídos correspondentes. O valor atribuído ao calibrador é estabelecido utilizando um conjunto principal de calibradores e um lote específico de BioPlex 2200 ANA Screen Reagent Pack em vários instrumentos BioPlex É necessário um BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM para carregar no instrumento os dados necessários para atribuição de valores. Consulte o Manual de Funcionamento para obter mais informações relacionadas com esta actividade. RASTREABILIDADE A rastreabilidade foi estabelecida para o dsdna utilizando o Primeiro Padrão Internacional de Referência da OMS para anti-adn de cadeia dupla (dsdna), código humano: Wo/80 (W1065). BIBLIOGRAFIA TEW Felkamp, TBL Kirkwood, RN Maini and LA Aarden. The first International Standard for Antibodies to double stranded DNA. Annals of the Rheumatic Diseases 1988; 47: svenska AVSEDD ANVÄNDNING BioPlex 2200 ANA Screen Calibrator Set är avsett för kalibrering av BioPlex 2200 ANA Screen Reagent Pack. SAMMANFATTNING OCH PRINCIP BioPlex 2200 ANA Screen Reagent Pack är kalibrerad med ett set av sex (6) olika serumbaserade kalibratorer. Kalibratorerna används i ett testsystem för att fastställa referenspunkter som används vid bestämningen av förekomsten av ämnen i humana prover. MEDFÖLJANDE MATERIAL Reagenser BioPlex 2200 ANA Screen Calibrator: Sex (6) 0,5 ml-flaskor. Kalibratorerna levereras i en humanserummatris som tillverkats av defibrinerat plasma med tillsatta kända analytkoncentrationer, som härstammar från humanplasma i sjukdomstillstånd samt tillsatta konserveringsmedel, däribland ProClin 300 med en koncentration på 0,3 och 0,1 natriumbenzoat. Komponenter En (1) förpackningsinlaga med bruksanvisning. MATERIAL SOM KRÄVS MEN INTE MEDFÖLJER : BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM OBS! Utskrivbara PDF-filer för reagensbatchspecifika kalibratortilldelade värden ingår.

80 BioPlex 2200 ANA Screen Calibrator Set FÖRVARING OCH HÅLLBARHET Produkten är stabil fram till och med sista förbrukningsdag om den förvaras oöppnad i 2 till 8 C. När förpackningen öppnats är kalibratorerna stabila i 60 dagar om de förvaras med tättslutande lock i 2 till 8 C. PROCEDUR Denna produkt skall användas enligt anvisningarna som medföljer BioPlex 2200-instrument och BioPlex 2200 ANA Screen Reagent Pack. Låt flaskorna uppnå rumstemperatur (18 till 25 C) före kalibratorsampling och blanda försiktigt för att säkerställa homogenitet. Sätt genast på locket efter varje användning och ställ tillbaka flaskorna för förvaring i 2 till 8 C. Kasserat material skall hanteras enligt de lokala föreskrifterna för avfallshantering. Om förpackningen är skadad skall du kontakta Bio-Rad Laboratories lokala försäljningskontor eller Bio-Rad Laboratories tekniska service. Procedurmässiga försiktighetsåtgärder 1. Denna produkt får inte användas efter utgångsdatum. 2. Om det finns tecken på mikrobiell kontaminering eller produkten är starkt grumlig, skall flaskan kastas. 3. Byt inte ut flaskornas lock mot varandra. Det kan leda till kontaminering mellan kalibratorerna. 4. Endast för professionell användning. BEGRÄNSNINGAR Denna produkt är avsedd för användning med BioPlex 2200-instrumentet. Ingen annan användning har utvärderats. TILLDELADE VÄRDEN BioPlex 2200 ANA Screen Calibrator Set inkluderar sex (6) olika flaskor. Resultaten anges i antikroppsindex (AI), utom för dsdna som anges i IU/mL. Reagensbatchspecifika tilldelade värden ingår som utskrivbara PDF-filer på varje CD-ROM-skiva med kalibratorbatchdata. För varje tillhörande reagensförpackningsbatch ingår en separat PDF-fil på CD-ROM-skivan med kalibratorbatchdata som innehåller motsvarande tilldelade värden. Värden tilldelas kalibratorerna med hjälp av ett masterset av kalibratorer och en specifik batch av BioPlex 2200 ANA Screen Reagent Packs på flera BioPlex 2200-instrument. En BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM krävs för att ladda in nödvändiga data för värdetilldelning i instrumentet. Se användarhandboken för ytterligare information om denna åtgärd. SPÅRBARHET Spårbarheten har fastställts för dsdna med Världshälsoorganisationens (WHO) första internationella standard för antikroppar mot dubbelsträngat DNA (dsdna), human kod: Wo/80 (W1065). REFERENS TEW Felkamp, TBL Kirkwood, RN Maini and LA Aarden. The first International Standard for Antibodies to double stranded DNA. Annals of the Rheumatic Diseases 1988; 47: dansk ANVENDELSE BioPlex 2200 ANA Screen Calibrator Set er beregnet til kalibrering af BioPlex 2200 ANA Screen Reagent Pack. OVERSIGT OG PRINCIP BioPlex 2200 ANA Screen Reagent Pack kalibreres med et sæt indeholdende seks (6) forskellige serumbaserede kalibratorer. Kalibratorer bruges i et testsystem til at fastlægge referencepunkter, som bruges til bestemmelse af tilstedeværelsen af stoffer i humane præparater. MATERIALER, DER MEDFØLGER Reagenser BioPlex 2200 ANA Screen Calibrator: Seks (6) 0,5 ml ampuller. Kalibratorerne leveres i en human serummatrix, der er fremstillet af defibrineret plasma med tilsatte kendte analytkoncentrationer deriveret fra humant plasma i sygdomstilstand og tilsattekonserveringsmidler inklusiv ProClin 300 ved en koncentration på 0,3 og 0,1 natriumbenzoat. Komponenter En (1) indlægsseddel med brugsanvisning. PÅKRÆVEDE, MEN IKKE MEDFØLGENDE MATERIALER : BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM Bemærk: Pdf-filer til udskrivning indeholdende kalibratortildelte værdier, der er specifikke for hvert reagenslot, er inkluderet. OPBEVARING OG STABILITET Produktet er stabilt indtil udløbsdatoen, når det opbevares uåbnet ved 2-8 C. Når kalibratorerne er åbnet, er de stabile i 60 dage, når de opbevares tæt tillukket ved 2-8 C. PROCEDURE Produktet skal køres i overensstemmelse med vejledningerne vedlagt BioPlex 2200 Instrument og BioPlex 2200 ANA Screen Reagent Pack. Inden prøvetagningen af kalibratorerne påbegyndes, skal ampullerne nå stuetemperatur (18-25 C), og de blandes forsigtigt for at sikre ensartethed. Efter hver anvendelse sættes låget straks på igen og produktet sættes i køleskab ved 2-8 C. Bortskaf alle kasseredematerialer i overensstemmelsemed kravene fra de lokale renovationsmyndigheder. I tilfælde af beskadigelse af emballagen kontaktes det lokale salgskontor for Bio-Rad Laboratories eller Bio-Rad Laboratories teknisk service. Proceduremæssige forholdsregler 1. Produktet må ikke anvendes efter udløbsdatoen. 2. Hvis der er tegn på mikrobiel kontamination eller for megen uklarhed i produktet, kasseres ampullen. 3. Ampullågene må ikke ombyttes frit mellem hinanden. Dette kan føre til krydskontamination af kalibratorer. 4. Kun til erhvervsmæssig anvendelse. BEGRÆNSNINGER Produktet er beregnet til anvendelse med BioPlex 2200 instrumentet. Enhver anden anvendelse er ikke blevet evalueret. TILDELTE VÆRDIER BioPlex 2200 ANA Screen Calibrator Set indeholder seks (6) forskellige ampuller. Resultaterne udtrykkes i antistofindeks (AI) bortset fra dsdna, som udtrykkes i IE/mL. Reagenslotspecifikke tildelte værdier er inkluderet i form af pdf-filer til udskrivning på hver cd-rom med kalibratorlotdata. For hvert associeret reagenspakkelot findes en særskilt pdf-fil på cd-rom en med kalibratorlotdata, som indeholder de tilsvarende tildelte værdier. Kalibratortildeling fastlægges ved hjælp af et mastersæt med kalibratorer og et specifikt lot med BioPlex 2200 ANA Screen Reagent Packs på flere BioPlex 2200 instrumenter. En BioPlex 2200 ANA Screen Calibrator Lot Data CD-ROM er påkrævet til indlæsning af de nødvendige værditildelingsdata i instrumentet. Se brugervejledningen for at få yderligere information om denne aktivitet. SPORBARHED Sporbarheden er blevet fastlagt for dsdna ved hjælp af Verdenssundhedsorganisationens (WHO) første internationale standard for antidobbeltstrenget DNA (dsdna), human kode: Wo/80 (W1065). REFERENCE TEW Felkamp, TBL Kirkwood, RN Maini and LA Aarden. The first International Standard for Antibodies to double stranded DNA. Annals of the Rheumatic Diseases 1988; 47: Caution Vorsicht // Attention // Attenzione // Precaución // Cuidado // Försiktighet // Forsigtig Xi IRRITANT Reizend // Irritant // Irritante // Irritante // Irritante // Irriterande ämne // Lokalirriterende english Biological source material. Treat as potentially infectious. Each human donor unit used to manufacture this product was tested by FDA accepted methods and found non-reactive for Hepatitis B Surface Antigen (HBsAg), antibody to hepatitis C (HCV) and antibody to HIV-1/HIV-2. This product may also contain other human agents capable of transmitting infectious disease. In accordance with good laboratory practice, all human source material should be considered potentially infectious and handled with the same precautions used with patient specimens. Contains 0.3 ProClin 300. Risk (R) and Safety (S) Phrases R43 May cause sensitization by skin contact. S24 Avoid contact with skin. S37 Wear suitable gloves. S56 Dispose of this material and its container at hazardous or special waste collection point. Prepared in accordance with requirements for CE Label. deutsch Material biologischer Herkunft. Als potenziell infektiös behandeln. Jede zur Herstellung dieses Produkts verwendete humane Spendereinheit wurde nach FDA-anerkannten Methoden geprüft und erwies sich als nicht reaktiv für Hepatitis-B- Oberflächenantigen (HBsAg), Antikörper gegen das Hepatitis-C- Virus (HCV) und Antikörper gegen HIV-1 und HIV-2. Dieses Produkt kann auch andere humane Substanzen enthalten, die infektiöse Krankheiten übertragen können. In Übereinstimmung mit den Richtlinien der guten Laborpraxis sollten alle Materialien humanen Ursprungs als potenziell infektiös betrachtet und mit der gleichen Sorgfalt wie Patientenproben behandelt werden. Enthält 0,3 ProClin 300 R- und S-Sätze R43 Sensibilisierung durch Hautkontakt möglich. S24 Berührung mit der Haut vermeiden. S37 Geeignete Schutzhandschuhe tragen. S56 Dieses Produkt und seinen Behälter der Problemabfallentsorgung zuführen. Hergestellt gemäß den Anforderungen für die CE-Kennzeichnung. français Produit d origine biologique. Traiter comme s il était potentiellement infectieux. Chaque don de sérum humain contribuant à la fabrication de ce produit a été testé par des méthodes acceptées par la FDA et trouvé négatif pour l antigène de surface de l hépatite B (AgHBs), l anticorps anti-virus de l hépatite C (anti-vhc) et l anticorps anti- VIH 1 et 2. Ce produit peut également contenir d autres agents humains capables de transmettre des maladies infectieuses. Conformément aux bonnes pratiques de laboratoire, tous les produits d origine humaine doivent être considérés comme étant potentiellement infectieux et manipulés avec les mêmes précautions que celles utilisées pour les échantillons patients. Contient 0,3 de ProClin 300 Phrases de risques (R) et de sécurité (S) R43 Peut entraîner une sensibilisation par contact avec la peau. S24 Éviter le contact avec la peau. S37 Porter des gants appropriés. S56 Éliminer ce produit et son récipient dans un centre de collecte des déchets dangereux ou spéciaux. Préparé conformément aux exigences d étiquetage de la CE. italiano Materiale di origine biologica. Trattarlo come un prodotto potenzialmente infettivo. Ciascuna unità di donatore umano utilizzata per preparare questo prodotto è stata analizzata con metodi approvati dall ente di controllo statunitense FDA ed è risultata non reattiva per l antigene di superficie del virus dell epatite B (HBsAg), per l anticorpo diretto contro l epatite C (HCV) e per l anticorpo anti-hiv-1/hiv-2. Questo prodotto può anche contenere altri agenti di origine umana in grado di trasmettere malattie infettive. In base a una corretta prassi di laboratorio, tutto il materiale di origine umana deve essere considerato potenzialmente infettivo e trattato con le stesse precauzioni osservate con i campioni dei pazienti. Contiene ProClin 300 allo 0,3 Frasi in materia di rischio (R) e sicurezza (S) R43 Può provocare sensibilizzazione per contatto con la pelle. S24 Evitare il contatto con la pelle. S37 Usare guanti adatti. S56 Smaltire questo materiale e i relativi contenitori in un punto di raccolta rifiuti pericolosi o speciali. Preparato in conformità ai requisiti per l apposizione dell etichetta CE. español Material de origen biológico. Manipúlelo como si fuese potencialmente infeccioso. Todas las unidades procedentes de donantes humanos utilizadas para la fabricación de este producto se analizaron con métodos aceptados por la FDA y se comprobó que no son reactivas a los antígenos de superficie de la hepatitis B (HBsAg), a los anticuerpos contra la hepatitis C (HCV) ni a los anticuerpos contra el VIH-1/ VIH-2. Este producto puede contener también otros agentes de origen humano capaces de transmitir enfermedades infecciosas. En conformidad con las buenas prácticas de laboratorio, todo el material de origen humano debe considerarse potencialmente infeccioso y debe manipularse con las mismas precauciones empleadas con las muestras de pacientes. Contiene ProClin 300 ( 0,3) Frases de riesgo (R) y seguridad (S) R43 Posibilidad de sensibilización en contacto con la piel. S24 Evítese el contacto con la piel. S37 Úsense guantes adecuados. S56 Elimínense esta sustancia y su recipiente en un punto de recogida pública de residuos especiales o peligrosos. Preparado en conformidad con los requisitos de etiquetado de la CE. português Material de origem biológica. Trate como potencialmente infeccioso. Cada unidade de dador humano utilizada no fabrico deste produto foi testada segundo métodos aceites pela FDA, tendo sido considerada não reactiva para o antigénio de superfície da hepatite B (AgHBs), anticorpos contra a hepatite C (VHC) e anticorpos contra VIH-1/VIH-2. Este produto também pode conter outros agentes humanos passíveis de transmitir doenças infecciosas. De acordo com as boas práticas laboratoriais, todos os materiais de origem humana devem ser considerados como sendo potencialmente infecciosos e manuseados com as mesmas precauções empregues no manuseamento das amostras de doentes. Contém ProClin 300 a 0,3 Frases de risco (R) e segurança (S) R43 Pode causar sensibilização em contacto com a pele. S24 Evitar o contacto com a pele. S37 Usar luvas adequadas. S56 Eliminar este produto e o seu recipiente, enviando-os para local autorizado para a recolha de resíduos perigosos ou especiais. Preparado em conformidade com os requisitos do rótulo CE. Svenska Biologiskt källmaterial. Behandla som potentiellt smittsamt. Varje enhet från humana donatorer som använts för att tillverka denna produkt har testats med FDA-godkända metoder och har visat sig icke-reaktiv för hepatit B-ytantigen (HBsAg), antikroppar mot hepatit C (HCV) och antikroppar mot HIV-1/HIV-2. Denna produkt innehåller kanske även andra humana agenser som kan överföra smittsamma sjukdomar. Enligt god laboratoriepraxis bör allt material av humant ursprung betraktas som potentiellt smittsamt och bör hanteras med samma försiktighetsåtgärder som patientprover. Innehåller 0,3 ProClin 300 Risk- (R) och skyddsfraser (S) R43 Kan ge allergi vid hudkontakt. S24 Undvik kontakt med huden. S37 Använd lämpliga skyddshandskar. S56 Lämna detta material och dess behållare till insamlingsställe för farligt avfall. Beredd enligt kraven för CE-märkning. dansk Materiale af biologisk oprindelse. Behandles som potentielt smitsomt. Hver human donorenhed anvendt til at fremstille dette produkt er testet med metoder godkendt af FDA (USAs regeringskontor for fødevare- og medicinkontrol), og fandtes at være non-reaktiv over for hepatitis B overfladeantigen (HBsAg), antistof mod hepatitis C (HCV) og antistof mod HIV-1/HIV-2. Dette produkt kan desuden indeholde andre stoffer af human oprindelse, som er potentielt smittefarlige. I overensstemmelse med god laboratoriepraksis skal alt materiale af human oprindelse anses som potentielt smittefarligt og håndteres med de samme forholdsregler som ved patientpræparater. Indeholder 0,3 ProClin 300 Risiko- (R) og Sikkerheds- (S) sætninger R43 Kan give overfølsomhed ved kontakt med huden. S24 Undgå kontakt med huden. S37 Brug egnede beskyttelseshandsker under arbejdet. S56 Aflever dette materiale og dets beholder til et indsamlingssted for farligt affald og problemaffald. Præpareret i overensstemmelse med kravene til CE-mærket.

81 Glossary glossar glossaire glossario glosario glossário ordlista ordliste ANALYTES ANALYTE ANALYTES ANALITI ANALITOS SUBSTÂNCIAS A ANALISAR ANALYTER ANALYTTER dsdna dsdna dsdna dsdna dsdna dsdna dsdna dsdna Chromatin Chromatin Chromatine Cromatina Cromatina Cromatina Kromatin Kromatin Ribosomal Protein Ribosomales Potein Protéines ribosomiques Proteina ribosomiale Proteína ribosómica Proteína ribossómica Ribosomalt protein Ribosomal protein SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 60 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-A 52 SS-B SS-B SS-B SS-B SS-B SS-B SS-B SS-B Sm Sm Sm Sm Sm Sm Sm Sm SmRNP SmRNP SmRNP SmRNP SmRNP SmRNP SmRNP SmRNP RNP A RNP A RNP A RNP A RNP A RNP A RNP A RNP A RNP 68 RNP 68 RNP 68 RNP 68 RNP 68 RNP 68 RNP 68 RNP 68 Scl-70 Scl-70 Scl-70 Scl-70 Scl-70 Scl-70 Scl-70 Scl-70 Jo-1 Jo-1 Jo-1 Jo-1 Jo-1 Jo-1 Jo-1 Jo-1 Centromere B Zentromer-B Centromère B Centromero-B Centrómero-B Centrómero-B Centromer-B Centromer-B TERMS AUSDRÜCKE TERMES TERMINI TÉRMINOS TERMOS TERMER BETEGNELSER Assigned Values Zielwerte Valeurs attribuées Valori assegnati Valores asignados Valores atribuídos Tilldelade värden Tildelte værdier Units Einheiten Unités Unità Unidades Unidades Enheter Enheder UNITED STATES, Bio-Rad Laboratories, Inc., Hercules, CA FRANCE, Bio-Rad 3 boulevard Raymond Poincaré Marnes-la-Coquette Phone: (33) / Fax: (33) english technical Information Contacts Bio-Rad provides a toll free line for technical assistance, available 24 hours a day, 7 days a week. In the United States of America and Puerto Rico, call toll free BIORAD ( ). Outside the U.S.A., please contact your regional Bio-Rad office for assistance. DEUTSCH Technische Unterstützung Bio-Rad bietet Ihnen gebührenfreie telefonische Unterstützung bei technischen Problemen, 24 Stunden am Tag, 7 Tage in der Woche. In den Vereinigten Staaten von Amerika und in Puerto Rico steht Ihnen die gebührenfreie Rufnummer BIORAD ( ) zur Verfügung. Außerhalb der USA wenden Sie sich bitte an Ihre örtliche Bio-Rad-Vertretung. français Pour tous renseignements techniques Bio-Rad a une ligne de téléphone gratuite réservée à l assistance technique, disponible 24 heures par jour, 7 jours par semaine. Depuis les États-Unis et Porto Rico, le numéro gratuit est BIORAD ( ). En dehors des États-Unis, contacter un bureau Bio-Rad local pour de l assistance. italiano Servizio di assistenza tecnica Il servizio di assistenza tecnica Bio-Rad gestisce una linea verde USA di assistenza disponibile ad orario continuato 7 giorni alla settimana. Dagli Stati Uniti e da Portorico, chiamare il numero verde BIORAD ( ). español Contactos para obtener información técnica Bio-Rad ofrece una línea telefónica gratuita de asistencia técnica, disponible 24 horas al día, 7 días a la semana. En Estados Unidos y Puerto Rico, llame al número gratuito BIORAD ( ). Fuera de EE.UU., póngase en contacto con la oficina regional de Bio-Rad si necesita ayuda. português Contactos para informações técnicas A Bio-Rad faculta um número gratuito para assistência técnica, disponível 24 horas por dia, 7 dias por semana. Nos Estados Unidos da América e em Porto Rico, telefone para a linha gratuita BIORAD ( ). Fora dos EUA, contacte os escritórios regionais da Bio-Rad para obter assistência. svenska Kontakter för teknisk information Bio-Rad har en avgiftsfri telefonlinje för teknisk assistans som är öppen dygnet runt, alla dagar i veckan. I USA och Puerto Rico, ring avgiftsfritt till BIORAD ( ). Utanför USA, var god kontakta ett regionalt Bio-Rad-kontor för assistans. dansk Teknisk information Bio-Rad tilbyder en frikaldstelefonlinje for teknisk assistance 24 timer i døgnet, 7 dage om ugen. Inden for USA og Puerto Rico bedes du ringe på frikaldsnummer BIORAD ( ). Uden for USA bedes du kontakte det lokale Bio-Rad kontor for assistance. Per ottenere assistenza negli altri Paesi, rivolgersi all ufficio Bio-Rad di zona. Clinical Diagnostics Group 4000 Alfred Nobel Drive Hercules, California Telephone (510) FAX (510) Australia, Bio-Rad Laboratories Pty. 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