1What sample management covers.
Every laboratory result depends on the sample behind it. US drug CGMP requires laboratory controls with “scientifically sound and appropriate specifications, standards, sampling plans, and test procedures”, and samples that are representative and adequately identified.¹ Sampling and testing plans must be written procedures that include the method of sampling and the number of units per batch to be tested.²
EU GMP Chapter 6 sets out what a sampling procedure describes:³
- the method of sampling and the equipment to be used;
- the amount to take, and instructions for any sub-division;
- the type and condition of the sample container;
- the identification of the containers sampled;
- special precautions, especially for sterile or noxious materials;
- the storage conditions;
- the cleaning and storage of sampling equipment.
Samples should be representative of the batch, and the sampling plan “should be appropriately justified and based on a risk management approach”.³ For components, the number of containers sampled and the amount taken from each are based on criteria such as component variability, confidence levels, the precision desired, the supplier’s past quality history, and the quantity needed for analysis and for reserve.⁴
2What a sample record must show.
The requirements are spread across several texts. Read together, they describe one record that follows the sample from the container it came from to the result it produced.⁴⁵³⁶
| What the record shows | Source |
|---|---|
| For components, containers and closures, on each sample container: the material, its lot number, the container sampled, the date sampled and the name of the person who collected it | 21 CFR 211.84(c)(5) |
| A mark on each container sampled, showing that samples were removed | 21 CFR 211.84(c)(6) |
| On the sample label: the contents, batch number, date of sampling and the containers sampled, managed to minimise mix-up and protect the sample from adverse storage | EU GMP 6.13 |
| A description of the sample received: its source location, quantity, lot number or other code, the date taken and the date received for testing | 21 CFR 211.194(a)(1) |
| The weight or measure of sample used for each test | 21 CFR 211.194(a)(3) |
| All data from each test, identified to the material and lot tested, with the person who performed it, the dates, and a second person’s review | 21 CFR 211.194(a)(4), (7) and (8) |
| The test record: material, batch, specification and procedure references, results, dates, initials of tester and verifier, a status decision and the equipment used | EU GMP 6.17 |
| A sampling record: batch number, date and place of sampling, the sampling protocol, the containers and materials, any abnormalities, and the name and signature of the inspector who sampled | WHO TRS 929, Annex 4 |
WHO’s sampling guidelines, published in 2005, are written mainly for governmental organisations such as regulators and their inspectorates, quality control laboratories, and customs and police officials, but say some of their general principles may also suit procurement agencies, manufacturers and customers.⁶
3Storage, integrity and retention.
WHO’s guidelines describe how to keep a sample fit for testing.⁶ The container should not interact with the material or allow contamination, and should protect it from light, air and moisture as the material requires; as a rule it should be sealed and preferably tamper-evident. Labels are applied at the time of sampling. The storage container is labelled with details such as the sample type, material name, identification code, batch or lot number, quantity, date of sampling, storage conditions, handling precautions and container number. Sample rooms should be secure and keep the storage conditions the material specifies.
Three rules protect what the sample can show. Where a component has to be sampled from the top, middle and bottom of its container, those subdivisions “shall not be composited for testing”.⁴ Portions of a material that show signs of non-uniformity, such as moist crusts or stratification, should be sampled and tested separately, because pooling them “can mask contamination, low potency or other quality problems”. And samples “should never be returned to the bulk”.⁶
Some samples are kept long after testing. Reserve samples of each active ingredient lot and each drug product batch are covered by 21 CFR 211.170 and, in the EU, by Annex 19.⁷⁸ See what reserve samples are and how long to keep them.
4Samples in nonclinical laboratory studies.
FDA’s Good Laboratory Practice regulations, 21 CFR Part 58, set specific rules for specimens and for the test and control articles given to a test system.⁹
| Requirement | Section |
|---|---|
| Specimens identified by test system, study, nature and date of collection, on the container or accompanying it in a way that precludes error | 58.130(c) |
| For test and control articles, a handling system that ensures proper storage, distribution that precludes contamination, deterioration or damage, and identification throughout | 58.107 |
| Receipt and distribution of each batch of test and control article documented, with the date and quantity | 58.107(d) |
| Reserve samples of each batch of test and control article kept for studies of more than 4 weeks | 58.105(d) |
| Archives for orderly storage and expedient retrieval of specimens, indexed, with a responsible individual and access limited to authorised personnel | 58.190 |
| Specimens kept for the shortest of 2 years after approval, 5 years after submission, or 2 years after the study ends if it is not submitted | 58.195(b) |
Specimens that are relatively fragile and change markedly in storage are kept only as long as their quality affords evaluation.⁹
5How it runs in Seal.
In Seal’s sample management, each sample’s collection, custody, aliquot lineage, reservations and consumption are recorded against it and connected to the experiment, method, result and quality assessment that depend on them. Every custody event keeps who moved the sample, when, from where to where, its quantity and condition. An invalidated result does not restore the material it consumed. In the LIMS, each sample is registered with its material, batch, collection point and required tests, with the method and specification versions assigned before execution.
When a receipt doesn’t match, Seal records the physical container before asserting its sample identity, and keeps an unreadable label unresolved until evidence supports the assignment, as the sample receipt discrepancy guide shows. Neil, Seal’s AI agent, can reconstruct a sample’s chain of custody and mark unrecorded handoffs, and the sample owner assesses any impact on testing.
References
- 121 CFR 211.160, Laboratory controls, General requirements, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ section- 211. 160 (read 6 November 2026) - 221 CFR 211.165, Testing and release for distribution, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ section- 211. 165 (read 6 November 2026) - 3EudraLex Volume 4, Part I, Chapter 6: Quality Control, European Commission, in operation since 1 October 2014. https:/
/ health. ec. europa. eu/ document/ download/ c74c8720- 27bf- 4252- 808f- d65a206a90bb_ en?filename=2014- 11_ vol4_ chapter_ 6. pdf (read 6 November 2026) - 421 CFR 211.84, Testing and approval or rejection of components, drug product containers, and closures, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ section- 211. 84 (read 6 November 2026) - 521 CFR 211.194, Laboratory records, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ section- 211. 194 (read 6 November 2026) - 6WHO guidelines for sampling of pharmaceutical products and related materials, WHO Technical Report Series No. 929, Annex 4, World Health Organization, 2005. https:/
/ cdn. who. int/ media/ docs/ default- source/ medicines/ norms- and- standards/ guidelines/ quality- control/ trs929- annex4- guidelinessamplingpharmproducts. pdf (read 6 November 2026) - 721 CFR 211.170, Reserve samples, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ section- 211. 170 (read 6 November 2026) - 8EudraLex Volume 4, Annex 19: Reference and Retention Samples, C(2026) 4135 final, European Commission, 23 June 2026. https:/
/ health. ec. europa. eu/ document/ download/ 831d392e- bcc4- 4552- 8011- 2b724b8655de_ en?filename=c2026- 4135_ en_ act_ en. pdf (read 6 November 2026) - 921 CFR Part 58, Good Laboratory Practice for Nonclinical Laboratory Studies, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- A/ part- 58 (read 6 November 2026)
AQuestions and answers
Do the US drug CGMP regulations require a chain of custody record?
Part 211 doesn’t use the term, but it requires records of who collected each component sample and when, the source, quantity and lot of each sample tested, the date it was received for testing, and who performed and reviewed each test. FDA’s GLP rules also require receipt and distribution of test and control articles to be documented.
How many containers should be sampled from a delivery?
US CGMP leaves the number to justified criteria: component variability, confidence levels, the precision wanted, the supplier’s quality history and the quantity needed for analysis and reserve. EU GMP asks for a sampling plan justified on a risk management basis.
Can samples from different parts of a container be combined?
Not when the procedure needs top, middle and bottom samples: US CGMP says those subdivisions shall not be composited for testing. WHO also advises sampling portions that show signs of non-uniformity separately, rather than pooling them with the rest, because pooling can mask contamination or low potency.
What must a sample label show?
In the EU, the contents, batch number, date of sampling and the containers sampled. In the US, each sample container from a component, container or closure must identify the material, its lot number, the container it came from, the date it was taken and the person who collected it.
How long must laboratory samples be kept?
It depends on the sample. Reserve samples of active ingredients and drug products follow 21 CFR 211.170 or EU Annex 19, usually until at least a year after expiry. GLP specimens follow the periods in 21 CFR 58.195, and fragile specimens are kept only as long as they can still be evaluated.