Batches, lots and why one vial is not the batch

What is a batch, and what is a lot?

ICH Q7, the good manufacturing practice guide for active ingredients, defines a batch (or lot) as "a specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits" (ICH Q7, Glossary).

US regulations draw a finer line. Under 21 CFR 210.3, a batch is a quantity "intended to have uniform character and quality, within specified limits" and "produced according to a single manufacturing order during the same cycle of manufacture". A lot is "a batch, or a specific identified portion of a batch" (21 CFR 210.3). A lot can be the whole batch or one identified part of it, so one batch can be split into several lots.

ICH Q7 defines a batch number as a unique combination of characters "from which the production and distribution history can be determined". That is the job the code on a vial is meant to do.

How does a peptide get from synthesis to a labelled vial?

A synthetic peptide is usually made and purified as a bulk powder, then dissolved, filled into vials and freeze-dried. Either stage can be split or combined. For the peptide itself, the EMA guideline on synthetic peptides notes that "splitting of batches or combining of sub-batches that are produced in multiple cycles of the same manufacturing steps may be performed at different stages", for example because of equipment capacity, and expects "material traceability from the synthesis steps through the final active substance" (EMA, Guideline on the Development and Manufacture of Synthetic Peptides).

ICH Q7 allows blending of batches only under conditions: each batch must have been "individually tested and found to meet appropriate specifications prior to blending", out-of-specification batches "should not be blended with other batches for the purpose of meeting specifications", and the blend record must trace back to each component batch. In a regulated plant a code is a documented chain. When the code on a vial may be printed by a reseller, you cannot see that chain, and the code is only as meaningful as the process behind it.

Why can one vial not stand for the whole batch?

Because a batch is only expected to be uniform within limits, and because a single measurement has its own uncertainty. Regulated manufacturers deal with this by testing according to a plan, not a single unit. Under 21 CFR 211.165, sampling and testing plans must state "the method of sampling and the number of units per batch to be tested", and acceptance criteria must be adequate to assure that batches meet "appropriate statistical quality control criteria" (21 CFR 211.165). ICH Q7 adds that samples "should be representative of the batch of material from which they are taken" and that the number of containers sampled should rest on a sampling plan.

A buyer, or a testing service, usually has one vial: a sample of size one. It may well be representative, but nothing in a single result shows how much the other vials differ from it.

Measurement adds a second layer. ICH Q2(R2) describes three levels of precision: repeatability, under the same conditions over a short interval; intermediate precision, which captures "different days, different environmental conditions, different analysts and different equipment" within one lab; and reproducibility, "the precision between laboratories" (ICH Q2(R2)). Two vials from the same batch, analysed by two labs, will rarely give identical numbers even if the vials are identical. Lesson 13 looks at how far apart is too far.

So what does one vial actually tell you?

Notice the asymmetry. A failed identity result is strong evidence that something is wrong with how the batch was made or labelled, because a correct process should never put a different molecule in a vial carrying that code. A pass is weaker: it is consistent with a good batch, and with a batch in which most vials are fine and some are not. Purity carries further than amount: if the bulk powder was made and purified once, the HPLC profile of one vial is a fair picture of the powder in all of them (lesson 3, HPLC-UV). Amount depends on each vial's fill, which is why lesson 4 treats small deviations differently from large ones.

How do I check batch codes on my own vials?

1. Read the code on the vial itself, not the box or a sticker added later. Photograph it in good light.
2. Compare character by character with any certificate you are given. A single different digit is a different batch.
3. Check the label amount too. A certificate for a 10 mg vial does not describe a 30 mg vial, even with a similar code.
4. Note the analysis date. A batch analysed long before your purchase may have sold out and been replaced.
5. Look for codes that never change. If every order over a year shows the same code, either the seller has one very large batch or the code is not tracking production. Ask which.
6. Record vials with no code. No code means no thread back to any result. That is useful information about the seller in itself.

The legit checklist includes these questions. When several buyers hold vials with one matching code, a shared test makes sense; the group testing guide covers how that is organised, and the group test splitter works out each buyer's share.

How do public quality surveys handle this?

The World Health Organization's guidelines on medicine quality surveys say "All units of one sample should have the same batch number", each sample is identified by "a unique sample code", and the collection form records the batch or lot number (WHO TRS 996, Annex 7). A survey result is always attached to a batch, never to a brand in general.

The Tested Index follows the same logic. It scores a vendor from several batches, bought anonymously, and requires at least three scored batches in twelve months before giving a grade. Lesson 12 explains why the way each vial was chosen matters, and lesson 16 how the batches are combined.

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