Retain samples for peptide lots: why to keep one, how much and for how long

What a retain sample is for

A retain, also called a reserve or retention sample, is a portion of a lot set aside at receipt and left unopened. ICH Q7 says reserve samples are kept for potential future evaluation of the quality of a batch, not for stability testing. [2] For a research lab buying peptides, that future evaluation usually means one of three things: an independent test after a result looks wrong, evidence in a disagreement with the supplier, or an investigation into which lot was used in which experiment.

Without a retain, every one of those questions has to be answered from material that has already been opened, stored in working conditions and handled many times. A result from that material says little about what arrived.

How regulated rules size and time retains

None of these rules binds a research lab buying for laboratory use, but they show what regulators consider enough. The US drug CGMP rule asks manufacturers to keep a reserve sample of each lot of active ingredient, at least twice the quantity needed for all required tests except sterility and pyrogens, generally for 1 year after the expiration date of the last product lot containing it. Drug product reserves must be stored as labelled, in the marketed container-closure or one with essentially the same characteristics, and representative ones examined visually at least once a year. [1]

ICH Q7 asks API manufacturers to keep enough for at least two full compendial or specification analyses, in the same or a more protective packaging, for 1 year after expiry or 3 years after distribution, whichever is longer; for materials with retest dates, 3 years after the batch is completely distributed. [2] The US GLP rule requires reserve samples from each batch of test article for studies longer than 4 weeks, kept for the period in 58.195, but only while the sample's quality permits evaluation. [3] [4] The OECD GLP principles ask for an analytical sample of each batch for all studies except short-term ones. [5]

How much to keep: a worked example

Size the retain from the tests you would actually order if something went wrong, then double it, which is the logic of both 211.170 and Q7. Bio-Synthesis lists recommended sample amounts for its peptide analyses: at least 0.5 mg for amino acid analysis, 0.2 to 0.5 mg for HPLC purity and at least 0.1 mg for mass spectrometry. [6]

Using the top of each figure, one full set of identity, purity and content tests needs about 0.5 + 0.5 + 0.1 = 1.1 mg. Doubling gives a retain of about 2.2 mg. If the lot arrives as 5 mg vials, the simplest retain is one whole unopened vial, which also keeps the supplier's container and label intact. Confirm amounts with the laboratory you would actually use; requirements differ between laboratories and methods.

Storage and labelling of the retain

Keep the retain in the supplier's sealed container where you can, under the storage conditions on the label or certificate. That mirrors 211.170 and Q7, which tie reserve storage to the marketed or an equivalent packaging. [1] [2] Store it apart from working stock so nobody uses it by mistake, and record where it is.

Seal it so that opening is evident. FDA's sampling manual has investigators seal sample packages so they cannot be opened without evidence of tampering, and notes that they can photograph the seal after applying it in case it is damaged in shipping. [7] A tamper-evident label signed and dated across the closure, plus a photo, does the same job in a lab.

• Label: RETAIN, do not use; product name; supplier; supplier lot; your internal ID; date received; date sealed; initials.
• Location recorded in the inventory log, separate from working stock.
• Seal signed and dated across the closure, photographed.
• Opening allowed only for a recorded reason, with the seal photo and the opener's name logged.

How long to keep it

A retain is only useful while its quality still allows evaluation, which is the limit GLP places on keeping samples. [4] For a research lab, our suggestion is to keep each retain until the later of 1 year after the lot's expiry or retest date, which mirrors 211.170 and Q7, or the closure of any open claim, corrective action request or investigation involving the lot. If the lot was used in work that will be published or submitted, consider keeping the retain until that work is out, as long as the sample remains meaningful.

A one-page retain policy

Adapt the wording; the numbers in brackets are choices for your lab to make.

• Scope: every lot of peptide received for laboratory research.
• Quantity: at least twice the material needed for the identity, purity and content tests we would order, or one unopened unit if smaller units are supplied.
• Timing: set aside at receipt, before any unit of the lot is opened.
• Storage: original sealed container, label storage conditions, separate retain location.
• Labelling and seal: as listed above, with photo stored with the receiving record.
• Access: opened only by [role] for a recorded reason.
• Retention: until the later of [1] year after expiry or retest date, or closure of any open issue involving the lot.
• Disposal: recorded with date, reason and approver, following the lab's chemical waste procedure.