A certificate of analysis reports data: ICH Q7 11.42 expects it to list each test performed, the acceptance limits and the numerical results obtained. A certificate of conformance reports a conclusion, that the batch meets its specification, without necessarily showing the results behind it. Where a rule allows a supplier's document to stand in for your own testing, it is written around results, so a conformance statement alone does not satisfy it.
What each document is
The difference is data against conclusion. A certificate of analysis reports what was measured: the tests that were run, the limits they were judged against, and the numbers that came out. A certificate of conformance, sometimes called a certificate of conformity or a certificate of compliance, reports a judgement: that the batch meets its specification. It may summarise the tests, and it may not.
Both can be true documents, honestly issued. They answer different questions. The certificate of analysis lets a reviewer form an independent opinion about the batch; the certificate of conformance asks the reviewer to accept someone else's opinion.
Worth naming plainly: ICH Q7 and 21 CFR 211.84 both define what a certificate of analysis should carry, and neither defines a certificate of conformance at all. That absence is the practical point of this article. A document type the rules do not describe cannot be assumed to satisfy them.
What ICH Q7 expects a certificate of analysis to carry
Section 11.40 asks for authentic certificates of analysis to be issued for each batch of intermediate or API on request. Section 11.41 asks for the name of the material including its grade where relevant, the batch number, the date of release, and the expiry or retest date where one has been assigned.
Section 11.42 is the one that separates the two document types. The certificate should list each test performed in accordance with compendial or customer requirements, including the acceptance limits, and the numerical results obtained where results are numerical. A document that omits the limits, or the numbers, or both, is not doing what 11.42 describes.
Section 11.43 adds that certificates should be dated and signed by authorised personnel of the quality unit, and should show the name, address and telephone number of the original manufacturer. Section 11.44 covers the case that causes most trouble in trading chains: where a repacker, agent or broker issues a new certificate, it should name the laboratory that performed the analysis, reference the original manufacturer, and have a copy of the original batch certificate attached.
What the rules accept in place of your own testing
This is where the distinction stops being academic. 21 CFR 211.84(d)(1) requires at least one test to confirm the identity of each component of a drug product, using a specific identity test where one exists. That obligation does not transfer to a supplier under any document.
Paragraph (d)(2) then allows a report of analysis to be accepted from the supplier in place of the manufacturer's own testing for purity, strength and quality, on two conditions: the manufacturer still conducts at least one specific identity test, and the manufacturer establishes the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals. Validating results presupposes results to validate.
The wording is deliberate elsewhere too. Paragraph (d)(3) covers containers and closures, and there the phrase is a certificate of testing, again with a check of the manufacturer's own and a reliability check on the supplier. Neither paragraph provides for accepting a bare statement that the batch conforms.
ICH Q7 7.30 takes the same shape for API manufacture: at least one identity test on each batch of incoming material, after which a supplier's certificate of analysis can stand in for the other tests, provided a supplier evaluation system exists. Section 7.31 puts numbers on that evaluation, expecting full analyses on at least three batches before in-house testing is reduced, a full analysis at appropriate intervals afterwards, and the reliability of certificates checked at regular intervals.
Which one you need, and what to do when you are sent the other
For a batch of an active ingredient, an excipient or any component going into a medicinal product, ask for the certificate of analysis, and treat the conformance certificate as a supplement rather than a substitute. A conformance statement can be a reasonable extra document, for example alongside a shipment where the analytical certificate is also present.
When a conformance certificate arrives on its own, the request back is specific rather than general: the batch certificate of analysis showing each test, its acceptance limit and the result obtained, issued by or traceable to the original manufacturer. Section 11.44 is the reason to name the original manufacturer explicitly. A certificate reissued along a trading chain, with no reference to the laboratory that did the work and no original attached, leaves nothing to check.
There is one exception worth knowing rather than guessing at. ICH Q7 7.32 allows processing aids, hazardous or highly toxic raw materials and certain other special materials to go untested where the manufacturer's certificate of analysis is obtained showing conformance to established specifications, with visual examination of containers and labels and batch numbers recorded. Even there the document named is the certificate of analysis, and the lack of on-site testing has to be justified and documented.
Definitions
- Certificate of analysis
- The batch document described in ICH Q7 11.4: it lists each test performed against compendial or customer requirements, the acceptance limits, and the numerical results obtained, and is dated and signed by the quality unit.
- Conformance to specification
- ICH Q7 glossary, under Specification: that the material, when tested according to the listed analytical procedures, will meet the listed acceptance criteria.
- Certificate of conformance
- A supplier statement that a batch meets its specification. Neither ICH Q7 nor 21 CFR 211.84 defines the term or provides for accepting one in place of a report of analysis.
Sources
- ICH Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (Step 4, 10 November 2000), International Council for Harmonisation (sections 11.40 to 11.44, sections 7.30 to 7.32, and the glossary entry for Specification)
- 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), (d)(2) and (d)(3))
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.
PharmaTrust Team
Written and reviewed by the PharmaTrust team against the primary sources cited above. Corrections are published, never made quietly.
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