Reading a certificate of analysis

A certificate of analysis, or COA, is a short document that carries a lot of weight. It is the statement, by a supplier or a laboratory, that a particular lot of material was tested and what the tests found. Formats vary, and many certificates spend half a page on logos, addresses and boilerplate. Underneath, five fields do most of the work: the lot number, the test method, the measured value, the test date and the signatory. Read those first, and read them against each other.

Lot number

The lot number ties the certificate to the material. It should match the number printed on the container label, the packing list and any other document that came with the shipment, character for character. A certificate that names a different lot, or no lot at all, describes some material, but not this material.

Watch for certificates that cover a range of lots or report “typical values.” A typical-values sheet describes what a product usually looks like. It is a specification summary, not a test result, and it should not be filed as one.

Test method

Each result should name the method used to produce it. That may be a method from a pharmacopoeia, a published standard method, or the laboratory’s own procedure identified by a document number. The method tells you what the number means. A purity figure from HPLC with ultraviolet detection is a statement about the components that method separates and detects. It says nothing about water, residual solvent or inorganic salts, which need their own tests and should appear on their own lines if the specification includes them.

If the method is listed only as “in-house,” with no reference, you cannot tell whether it was validated or what it can see. Under ICH Q2(R2), the guideline on validating analytical procedures, a method used to release material is supported by documented evidence of characteristics such as specificity, accuracy, precision and range. A named method lets you ask for that evidence. An unnamed one leaves nothing to ask about.

Measured value and specification

A result is a number with a unit, reported next to the specification it was judged against. Both halves matter. “Conforms” or “pass” with no number tells you a limit was met but not by how much. A number with no limit tells you what was found but not what was expected.

Check that the units agree between the result and the limit, and that the number of significant figures is consistent with what the method can resolve. Results reported as “not detected” or “less than” should state the detection or quantitation limit they refer to; without it, “not detected” could mean the method was simply not sensitive enough to see anything. A result that sits exactly on a limit, or results that are identical across several different lots, are worth a second look and a question to the issuer.

Test date

The test date says when the material looked like this. It should fall after the date of manufacture and on or before the certificate’s issue date, and the retest or expiry date should be consistent with what is known about the material’s stability. A test date earlier than the manufacturing date, or an expiry date that runs far beyond any stability period the supplier can support, is an internal inconsistency that needs an explanation before the certificate is accepted.

The date also bounds what the certificate can promise. Material that has been stored, shipped and opened since that date may have changed. The certificate describes the lot on the day of testing. The storage and shipping record describes everything since, and the two have to be read together.

Signatory

A certificate should identify the person who reviewed and released the results, by name and role, with a handwritten signature or an equivalent electronic approval. Where records are electronic, regulations such as 21 CFR Part 11 in the United States and EU GMP Annex 11 set out what makes an electronic signature attributable to a specific person and permanently linked to the record it signs.

An unsigned certificate, or one signed only with a department name, has no one accountable for it. If the testing was done by an outside laboratory, the certificate should say which laboratory did it, and the laboratory’s original report should be available on request. Comparing the two is a quick check: the lot, the method, the result and the date should be identical on both, and any difference between them is a question for the issuer before the material is used.