Repackaging, subdivision, and the batch number that changed hands

A certificate of analysis makes claims about a batch. The batch number is therefore not an administrative detail but the entire mechanism by which the document attaches to physical material. If the number printed on the certificate does not appear on the vial — not on the box, not on the invoice, not in the listing, on the vial — then the document is a true statement about a quantity of material that may or may not be the quantity in front of you. This is the first thing the Journal checks and the check most often fails, usually for reasons that are administrative rather than sinister.

The header block: identifying the object

The top of a certificate answers the question, what is this document about. A complete header names the product, gives a catalogue or item number, gives the batch or lot number, states the quantity or fill weight, names the manufacturer and the site, and identifies the customer or order where applicable. Some add a chemical name, a sequence in single-letter code, a molecular formula and a molecular weight, all of which are useful because they let a reader check the theoretical values used elsewhere on the page.

The sequence in particular is worth insisting on. A certificate that prints the one-letter sequence has given a reader the means to calculate the expected mass independently, and therefore to check the identity line. Two of the twenty companies in the Journal’s dossier programme do this as standard. It costs nothing and it converts one line of the document from an assertion into a verifiable claim.

What a header should never do is identify the product only by a trade name. A vial described as a proprietary blend with no chemical identity, no formula and no sequence cannot be checked against anything, and a certificate for such a product is a document about a name. This is a documentary observation rather than an accusation, and the remedy is trivial: print the sequence.

What a batch number is supposed to mean

A batch, or lot, is a defined quantity of material produced in a single process run or a defined series of runs, homogeneous within itself, and identified by a unique code. That definition does real work: it is what makes it meaningful to test a sample and draw conclusions about the whole. If the material identified by one code is not homogeneous — if it was blended from separate syntheses, or filled across several sessions from stock stored differently — then a result on one sample generalises less well than the certificate implies.

In this trade batch codes range from the highly informative to the arbitrary. A code encoding the year, the month, the product and a sequence number tells a reader something and can be checked for internal consistency across documents. A four-digit code with no discernible structure cannot. Neither format is wrong; the difference is whether a reader can detect an anomaly.

The Journal’s dossier programme asks each company how batch codes are constructed and whether one code corresponds to one synthesis, one fill, or one shipment. The answers vary considerably and several companies have not previously been asked. We publish the answers without comment, because a code that identifies a fill session rather than a synthesis is a perfectly reasonable convention as long as a reader knows which convention is in use.

Check the vial, not the box

The single most common documentary failure the Journal encounters is a batch number on the certificate that does not appear on the vial. The variants are instructive. Sometimes the number is on the outer carton and not the vial, which means the connection between document and material depends on the carton having been packed correctly. Sometimes the vial carries a different number entirely, and the certificate corresponds to an earlier lot. Sometimes the vial carries no number at all, in which case the certificate cannot be attached to it by any means.

These situations are not equivalent and none of them is, on its own, evidence of misconduct. Subdivision and repackaging generate new identifiers legitimately, and a reseller filling vials from bulk may reasonably supply the synthesis house’s certificate for the bulk material while assigning its own fill lot. What is not reasonable is leaving the reader to guess which object the document describes, because that guess is exactly what a certificate exists to remove.

The remedy is a single line: a statement of the relationship between the certificate’s lot and the vial’s lot. “Filled from bulk lot X as fill lot Y on date Z” is eleven words and resolves the entire question. Three of the twenty companies in our programme now print something to this effect, two of them after we asked.

Three dates, and the conventions behind them

Date of manufacture is when the material was made. Date of analysis is when the reported tests were performed. Retest date is the date by which the material should be re-examined if it is to continue to be used, and expiry date is the date after which it should not be used at all. The last two rest on different evidence: an expiry date implies stability data supporting the claim over that period, while a retest date implies a policy of re-examination in the absence of such data.

In this market the two are used interchangeably, and the substitution matters. A vial marked with a two-year expiry, where no stability study exists, is carrying a claim its documentation cannot support. The same vial marked with a two-year retest date is carrying a much weaker and entirely defensible statement: we have not established shelf life, so look again by this date. The second is honest and the first is not, and the difference is one word.

What follows for a reader is a specific question to ask: on what basis. A supplier that can point to real-time or accelerated stability data for the sequence in question has something. A supplier that assigned twenty-four months because that is what the form said has something else, and the international framework for setting such limits is explicit about the evidence required.¹

The certificate is a snapshot, and the vial has aged

Every claim on a certificate is indexed to the date of analysis, and everything that has happened to the material since is outside the document. For lyophilised peptides stored cold, dry and dark, the rate of change is slow but not zero: deamidation proceeds even in the solid state at a rate that depends on residual water, oxidation proceeds in the presence of air and light, and aggregation can occur after a temperature excursion that leaves no other trace.²

The practical significance depends on the interval. A certificate dated three weeks before shipment describes material that is, for most purposes, the material in the vial. A certificate dated fourteen months before shipment describes an earlier object. The Journal’s audit of certificates supplied through the dossier programme found a median interval between manufacture and analysis of eleven days, which is reassuring, and a median interval between analysis and the customer receiving the vial of somewhat over four months, which is the number nobody reports.

None of this argues for retesting every vial. It argues for reading the date, which takes two seconds, and for treating purity figures as historical rather than current. It also argues for taking the appearance line seriously, since a change in the cake is one of the few observations a buyer can make that bears on what has happened since the document was written.

How this publication handles certificates

Four rules, arrived at over two years and revised twice. First, we do not cite a purity figure without the method behind it; where a supplier will not supply the method, we report the figure as unverifiable and say who declined. Second, we ask for the underlying laboratory report rather than the certificate, and we record who supplies one. Third, we check the accreditation scope of any laboratory named on a document we intend to rely on. Fourth, we put every documentary finding to the company concerned before publication and print the response in full.

The fourth rule is the one that has changed our coverage most. A substantial majority of the anomalies we find turn out to have mundane explanations: a transcription error, a document forwarded for the wrong lot, a template field left unedited, a scanned copy that lost its metadata. Publishing the finding without the explanation would have produced a series of insinuations rather than a series of corrections, and the corrections are more useful.

The rules also mean we publish less than we could. There are documents in this office that we consider unreliable and have not written about, because the company concerned did not respond and the finding alone would not support a published inference. That is a deliberate trade, and readers who suspect us of excessive caution are welcome to say so at letters@compoundjournal.com, where several already have.

The next piece in this department turns from the document to the institutions that generate it: the four independent testing services this market relies on, what each measures, and the awkward fact that in most cases the party paying for the test is the party being tested. Two of the four advertise in this publication, which is disclosed on our funding page and is stated again wherever the coverage touches them.