Yes, with limits. 21 CFR 211.84(d)(2) allows a report of analysis from the supplier to be accepted in place of the manufacturer's own testing for purity, strength and quality, provided the manufacturer performs at least one specific identity test on the component and establishes the reliability of the supplier's analyses through appropriate validation at appropriate intervals. EU GMP Chapter 5 (5.35 and 5.36) and ICH Q7 (7.30 and 7.31) take the same position: identity testing of each batch stays with the recipient, and reliance on the certificate rests on a documented supplier evaluation, audits or history, and full analyses at intervals compared against the certificates.
United States: 21 CFR 211.84(d)
The US drug GMP regulation requires each component to be tested for conformity with its written specifications for purity, strength and quality, and then states the exception: in lieu of that testing by the manufacturer, a report of analysis may be accepted from the supplier. Two conditions attach. At least one specific identity test must be conducted on the component by the manufacturer, and the manufacturer must establish the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals.
Paragraph (d)(1) separately requires at least one identity test for each component, using specific identity tests where they exist. Paragraph (d)(3) applies the same structure to containers and closures, with a visual identification replacing the identity test.
European Union: EU GMP Chapter 5, sections 5.35 and 5.36
Chapter 5 of the EU GMP guide makes the finished-product manufacturer responsible for the testing of starting materials described in the marketing authorisation dossier. It may use partial or full results from the approved starting-material manufacturer, but must as a minimum perform identification testing of each batch according to Annex 8 (5.35).
Section 5.36 then sets the conditions for outsourcing that testing. The rationale must be justified and documented. Distribution controls must be such that the results remain applicable to the delivered material. The manufacturer should audit the testing site at risk-based intervals, itself or through a third party. The certificate of analysis from the starting-material manufacturer or supplier should be signed by a designated person with appropriate qualifications and experience, and that signature assures the batch has been checked against the agreed specification. The manufacturer should have appropriate experience with the supplier, including assessment of batches previously received, before reducing in-house testing, and should perform a full analysis at risk-based intervals and compare the results with the supplier's certificate.
ICH Q7 for API manufacturers: sections 7.30 to 7.32
For manufacturers of APIs receiving raw materials, ICH Q7 7.30 requires at least one identity test on each batch of material and allows a supplier's certificate of analysis to be used in place of other tests provided the manufacturer has a system to evaluate suppliers. Section 7.31 asks for adequate evidence, such as past quality history, that the supplier can consistently meet specification; for full analyses on at least three batches before in-house testing is reduced; for a full analysis at appropriate intervals compared with the certificates; and for the reliability of certificates to be checked at regular intervals.
Section 7.32 carves out processing aids, hazardous or highly toxic raw materials and certain other materials, which need not be tested if the manufacturer's certificate shows conformance, with the lack of on-site testing justified and documented.
What this means for the certificate itself
All three frameworks make the certificate carry weight it can only bear if it is a sound document. A certificate that is incomplete, internally inconsistent or looser than the specification it claims cannot support reduced testing, because the reliance is on the supplier's analyses and the certificate is the only evidence of them that travels with the batch.
That gives a concrete reading list for anyone receiving supplier certificates under a reduced-testing arrangement.
- Identity of the material, batch and issuer is complete, so the certificate can be tied to the delivered batch.
- Each test carries a limit and a result, and quantitative tests carry numbers, so the comparison at the periodic full analysis is possible.
- The printed limits are at least as strict as the specification or monograph the certificate claims; a looser printed limit means the supplier's "pass" is against a different standard.
- The signature block identifies a designated person and a date, which EU 5.36(iii) treats as the assurance that the batch was checked.
- Dates are present and consistent, including the retest or expiry date the recipient will need for its own stock control.
What a document review can and cannot do
Reviewing the certificate is not a substitute for the identity test, the supplier audit or the periodic full analysis; the regulations keep those with the recipient. What a structured review does is catch the certificate-level problems early, consistently and with a record: the missing identity field, the "complies" where a number belongs, the limit wider than the monograph, the date that has passed. Those are exactly the faults that make a certificate unfit to carry a reduced-testing decision, and they are far cheaper to find at goods receipt than at a regulatory inspection.
Definitions
- Specific identity test
- A test able to distinguish the material from closely related substances, for example an infrared spectrum compared with a reference, as opposed to a general property such as appearance.
- Starting material
- In EU GMP, any substance used in the production of a medicinal product, excluding packaging materials.
- Reduced testing
- An arrangement under which the recipient performs fewer than the full set of specification tests on incoming batches and relies on the supplier's certificate for the rest, subject to the conditions described above.
Sources
- 21 CFR 211.84, Testing and approval or rejection of components, drug product containers, and closures, U.S. Code of Federal Regulations (eCFR) (paragraphs (d)(1) to (d)(3))
- EudraLex Volume 4, EU Guidelines for GMP, Part I, Chapter 5: Production (revision in operation from 1 March 2015), European Commission (sections 5.35 and 5.36)
- ICH Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (Step 4, 10 November 2000), International Council for Harmonisation (sections 7.30 to 7.32 and 11.44)
Primary sources are cited in preference to summaries. Where a source is licensed (for example a pharmacopoeial monograph) the reference is given and the text is not reproduced.