Evaluation Surveillance WYouchun

Evaluation and surveillance of in vitro bio-diagnostic assays in China: 

Evaluation and surveillance of in vitro bio-diagnostic assays in China Wang Youchun MD PhD Director, Division of Cell Biology National Institute for the Control of Pharmaceutical and Biological Products (NICPBP), State Food and Drug Administration (SFDA) China

Contents: 

Contents The procedures of registration for in vitro bio-diagnostic assays Quality control for HIV diagnostic assays in NICPBP’s lab before license Clinical evaluation for HIV diagnostic assays before license Routine Management of HIV diagnostic assays after license including Market monitoring and Batch release

The procedures of registration: 

The procedures of registration

Slide4: 

Organization of State Food and Drug Administration Responsible for GMP inspection Responsible for market monitoring Responsible for licensing

Slide5: 

Organization of Agencies Directly Under SFDA

Slide6: 

Procedures for registration and licensing International Products

The required Dossier : 

The required Dossier Review (the prevalence and burden of the disease, current situation of research and development of such products, prospects for effectiveness and safety, benefit-risk ratio and others) Research data (Antigen, antibody and other materials; Options of manufacturing procedures; Analysis of analytical sensitivity and specificity and others) Requirement for production and quality control The manufacturing documents for three batches Stability data Clinical evaluation data

Quality control for HIV diagnostic assays in NICPBP’s lab before license: 

Quality control for HIV diagnostic assays in NICPBP’s lab before license

The types of HIV assays in China: 

The types of HIV assays in China Kits to detect HIV antibody Sandwich ELISA (the third generation), Rapid assay (Colloidal gold assay), WB Kits to detect HIV antigen To detect P24 Kits to detect HIV antibody and antigen simultaneously Kits to detect HIV RNA qualitative and quantitative assays

Responsibility of NICPBP for HIV diagnostics: 

Responsibility of NICPBP for HIV diagnostics To review the specification To check the technical data To validate the QC test methods To establish reference panels and specification To test the products and issue QC reports To do some clinical evaluation of HIV diagnostics

The procedures for establishment of reference panels: 

The procedures for establishment of reference panels Collecting samples from different population All the samples should be tested with several different kits The candidate panels should be selected according to results The candidate panels should be tested or validated in several different labs with different assays If WHO panels or standards are available, the candidate panels should be calibrated with WHO panels or standards The panels should be approved by Committee of biological standardization, SFDA

Current panel for anti-HIV ELISA: 

Current panel for anti-HIV ELISA 20 negative samples were collected from different population,some are HBsAg positive, some for anti-HCV positive; Among 20 positive samples, some are very strong positive, some weak positive, some middle positive for anti-HIV and two samples are positive for anti-HIV2. The diluted samples were purified anti-HIV gp160 antibody.

Current panel for HIV antibody rapid assays : 

Current panel for HIV antibody rapid assays

Reference panel of HIV-1 RNA: 

Reference panel of HIV-1 RNA Among negative samples, some are positive for HCV RNA,HBV DNA and false positive for anti-HIV; Among positive samples, the copies and genotypes of HIV are different. Diluted sample 1 is genotype AE, Diluted sample 2 is genotype B. The diluted samples are also used as linear analysis.

Reference panel for HIV-1 P24 antigen: 

Reference panel for HIV-1 P24 antigen * For HIV p24 antigen assay; ** for HIV antibody/P24 antigen assay

Slide16: 

Clinical evaluation before license

The basic requirements for clinical evaluation: 

The basic requirements for clinical evaluation Three provincial hospitals or institutes at least The hospitals or institutes should be qualified The staff should be qualified The samples should include different genotypes of HIV At least 10,000 samples from blood donors and 500 positive samples if the assay used for blood screening. For other assays, at least 1,000 samples should be tested for clinical evaluation After testing, each hospital or institute should issue formal reports to center for drug evaluation

Methods to establish HIV negative sample bank: 

Methods to establish HIV negative sample bank Collecting samples The volume of all samples should be more than 50ml Be aliquoted at 0.5ml/vial and stored at -70℃. Avoiding freezeing/thawing cycles Testing the samples with 14 HIV antibody assays and 2 HIV antibody/antigen ELISA assay False positive results were confirmed by Western Blot, P24 antigen and Viral load Caculating specificity andδ value for each assay and comparing the relationship between them

The composition of HIV negative sample bank: 

The composition of HIV negative sample bank 985 samples in HIV negative bank. The correlation coefficient between specificity and δ value is 0.691(P=0.004）

The Methods to establish HIV positive sample bank: 

The Methods to establish HIV positive sample bank Collecting samples from different population infected with HIV The volume of all samples should be more than 50ml Be aliquoted at 0.5ml/vial and stored at -70℃. Avoiding freezeing/thawing cycles Determining HIV genotypes and serotypes Detecting HIV antibody, antigen and viral load Running Western Blot for HIV antibody Analyzing the relationship among different HIV biomarkers

The Composition of HIV positive sample bank: 

The Composition of HIV positive sample bank

Slide22: 

Routine Management of HIV diagnostics

Routine Management of HIV diagnostics: 

Routine Management of HIV diagnostics Market Monitoring SFDA would collect the kits from market or consumers NICPBP would evaluate those kits with current reference panel and issue QC report to SFDA NICPBP entrusted by SFDA inspects the manufactures at any time (flight inspection) Batch release All kits used for screening blood donors must be carried out batch release. Other assays have not been carried out batch release Blood centers must use the kits from batch release

The procedures for batch release: 

The procedures for batch release Manufactures will inform the local drug administration after producing new lot of diagnostic assay Local drug administration will sample the product and collect the lot document. Then send all the samples and document to NICPBP NICPBP will review the document firstly.If the document meets the requirement, NICPBP will test the kit with current reference panel Manufacture can release the product only after getting the qualified report from NICPBP

Results of Batch Release: 

Results of Batch Release

Summary : 

Summary The comprehensive and scientific registration procedure has been established in China The reference panels have been established and improved gradually NICPBP is responsible for quality control and market monitoring All the diagnostic kits used for blood screening must be tested lot by lot by NICPBP The quality of HIV diagnostic assays which are generated in China has been improved gradually