China FDA recently issued a draft guidance document on clinical evaluation basic requirements for clinical exempt IVD reagents, along with a second batch of clinical exempt class II IVD reagents – 130 reagents – to the agency’s directory.
Key provisions in the draft, issued May 24, deal with the clinical evaluation comparison method, sample selection and sample size, the content of the clinical evaluation report and areas that need special attention.
The exempt IVD reagents will still need a clinical performance evaluation based on the assessment of the intended use, interference factors, a comprehensive literature review and other non-clinical-trial elements.
Here are some of the key points from the draft document:
Clinical evaluation comparison method
- Choose approved products that have a good reputation in current clinical application as the predicate reagent. The information for the predicate reagent should include methodology, clinical indications, main performance indicators, traceability of the predicate device, recommended positive parameters, or reference interval etc.
- Choose the reference methodology for the comparative study test, and select the reference laboratory for research. The reference methodology and reference laboratory should have the certification recognized by the China National Accreditation Service for Conformity Assessment.
- Depending on the intended use of the product, applicants can also use patients’ clinical diagnosis, disease progression, efficacy observations and other objective indicators for clinical performance studies.
Sample selection and sample size
- Select clinical samples that cover the intended use and interference factors.
- The sample size for the Class II product should not be fewer than 100. Clinical cases should fully reflect a product’s clinical safety and efficacy.
- The type of samples to be used for the evaluation should be consistent with the type used in the registration application. The comparable sample types are serum and plasma. One of the sample types can be selected for clinical evaluation. If there is no comparable sample type such as serum and urine, they should be evaluated separately.
Basic content of the clinical evaluation report
- The clinical evaluation report should include: the reagent’s generic name, test start date, test completion date, test site, signature of the principal investigator and the seal of the unit, the signature of the person in charge of the statistic and the seal of the unit, the name of the applicant (seal), the applicant’s contact and contact information, and the report date.
- The test sample information should include testing reagents, compared reagents, other reagents used in conjunction with calibration, quality control, dilution, test equipment, etc. Include the specific reagent name, manufacturer, specifications, batch number, expiration date. Equipment should include name, manufacturer, model and so on.
- The evaluation proposal should include background information of the product, purpose of the evaluation, evaluation method, sample size, sample type, crowd selection, disease selection, interference samples, statistical methods and data processing.
- The evaluation results report should include: 1) A description of the implementation of the evaluation proposal, such as the specific sample selection, and the basic testing process; 2) Statistical analysis of the testing data according to the test results, population distribution, disease distribution, interference samples, etc.; 3) For the samples that have unmatched test results in the comparative study, they should be rechecked to analyze the results of the tests. If they do not need to be rechecked, applicants should give a detailed explanation detail; 4) Test conclusions.
- The evaluation data sheet should include at least the following: The sample number, age, sex, tested reagents’ test results, comparative reagent test results, recheck test results (if any), clinical diagnostic information (including interference sample information) etc. The applicant should also provide relevant clinical documents of the tested product and the evaluation documents should reside in the institution itself.
Areas that need special attention.
- The evaluation sample should be traceable.
- The original documents of evaluation samples should include but not be limited to patient sample source, unique and traceable number, age, gender, department, very clear clinical diagnostic information, treatment tracking information (if any) etc.
- Registration changes relating to clinical evaluation should be implemented according to this requirement.
- If the applicant cannot do a clinical evaluation based on the above requirements, they can choose a clinical trial for clinical evaluation.
In summary, although the listed IVDs would be exempt from clinical trials, a clinical evaluation report is still needed. Sponsors would need to assemble a significant amount of data and supporting information to get products approved by the CFDA.
Grace Fu Palma is founder and CEO of Boston-based China Med Device, a firm specializing in commercialization and funding for U.S. medtech companies entering China.