GLP test article characterization: what 21 CFR 58.105 asks of a peptide source

When Part 58 applies

21 CFR Part 58 covers nonclinical laboratory studies that support, or are intended to support, applications for research or marketing permits for FDA-regulated products. [1] It defines a nonclinical laboratory study as in vivo or in vitro experiments in which test articles are studied prospectively under laboratory conditions to determine safety, excluding human studies, clinical studies and animal field trials. [2]

Most exploratory academic work is not run under GLP. The Part 58 definition of a nonclinical laboratory study excludes basic exploratory studies done to find out whether a test article has any potential utility or to determine its physical or chemical characteristics. [2] The question arises when a lab or contract research organisation is asked to run a study whose data will go to FDA, and the peptide comes from a catalogue research supplier. Part 58 defines a batch as a specific quantity of test or control article that has been characterized under 58.105(a), so an uncharacterized lot is not yet a batch in the rule's sense. [2]

What 21 CFR 58.105 requires

The section is short. Each requirement below is paraphrased from the rule. [3]

The OECD GLP principles say much the same

The OECD Principles of Good Laboratory Practice, reproduced as Annex I to EU Directive 2004/10/EC, ask that for each study the identity, including batch number, purity, composition and concentrations of each batch of test item be known, and that stability under storage and test conditions be known for all studies. They also ask for records of characterisation and date of receipt, and for an analytical sample from each batch to be retained for all studies except short-term studies. [4]

Where a typical research-use certificate falls short

Consider a certificate that reports an HPLC purity percentage and an observed mass that matches the expected value. That supports part of identity and one measure of purity. It does not establish strength, meaning how much peptide is in the powder, or composition, meaning the counterion, water and other non-peptide content, and it rarely says how the material was made or how stable it is.

The gaps are not necessarily the supplier's failure; a research-use seller is not selling a GLP test article. They are work the sponsor or testing facility must plan and budget for before the study starts.

Handling, labelling and mixtures

Characterization is only part of the file. 21 CFR 58.107 requires procedures for storage, distribution that avoids contamination, deterioration or damage, identification throughout distribution, and records of receipt and distribution of each batch including the date and quantity distributed or returned. [5] Storage containers must carry the name, code or chemical abstract number, batch number and any expiration date. [3]

If a study design mixes the article with a carrier, 21 CFR 58.113 adds analytical tests of uniformity, periodic concentration checks and stability in the mixture, and requires the earliest expiration date of any component to be shown on the container. [6] How a study prepares any mixture is a protocol matter outside the scope of this guide.

Retention of the characterization file and samples

Characterization data are part of the study's documentation and follow 21 CFR 58.195: the shortest of 2 years after FDA approval of the supported application, 5 years after submission of results, or 2 years after study completion if no application results. Test article samples need only be kept while their quality permits evaluation. [7]

Checklist of documents to obtain or generate

Ask the supplier for the first group before ordering. Plan to generate whatever they cannot supply.

• Certificate for the exact lot to be used, with lot number matching the vial label.
• Identity data with method, for example mass spectrometry with theoretical and observed values.
• Purity data with method and chromatogram.
• Net peptide content or another measure of strength, with method.
• Counterion and water content, or a statement that they were not measured.
• A statement of how the material was synthesized, or a written refusal.
• Stability data or storage-condition evidence, and your plan for periodic analysis.
• Receipt record with date, quantity and condition on arrival.
• Storage container labels meeting 58.105(c).
• Reserve sample set aside at receipt for studies longer than 4 weeks, logged with location.