Working Procedures in a Pharma QC Laboratory

In short: A QC laboratory should treat every incoming sample the same disciplined way: a written test request, a unique registration number, a label on each container, a visual check against the request, safe storage and a documented hand-over to the testing unit. This article follows WHO’s current good practices for pharmaceutical QC laboratories (2024) and is meant for QC analysts, sample-room staff and QA reviewers.

Where this guidance comes from

The WHO good practices for pharmaceutical quality control laboratories were revised in 2024 and published as Annex 4 of WHO Technical Report Series No. 1052. They replace the earlier version (TRS 957, Annex 1, 2010). Section 6.1 covers sampling and section 6.2 covers incoming samples. The steps below follow those sections, explained in our own words. Your own SOPs and your marketing authorisation or national law decide the exact requirements at your site.

Sampling by the laboratory (WHO TRS 1052 Annex 4, section 6.1)

If the laboratory itself takes samples for later testing:

• Write a sampling SOP that includes a recognised sampling plan, so that the sample is representative of the batch, and steps that keep the chain of custody intact.
• Keep the sampling plan and method available at the place where sampling is done. Where reasonable, base the plan on suitable statistical methods.
• Record the sampling data: the method used, date and time, what the sample is (amount, name, number, which container it came from), who sampled, which tools were used, environmental or transport conditions, the sampling location where relevant, and any deviation from the plan.
• Take samples in a way that avoids contamination, mix-ups and other harm to quality.

For the sampling techniques themselves, WHO refers to its separate guidelines for sampling of pharmaceutical products and related materials. For a worked example, see SOP on sampling of raw materials.

Types of incoming samples (section 6.2)

WHO writes the guidance on sample types and sample portions (paragraphs 6.6 and 6.7) for national quality control laboratories, but the ideas are useful for any laboratory. Samples arrive for one of two purposes:

• Compliance testing: routine control samples, or samples submitted in connection with a marketing authorisation. Agree with the sample provider on a quantity large enough for replicate tests and for a retained portion.
• Investigative testing: suspicious, illegal, falsified or suspected substandard products. Here the laboratory needs documented screening procedures plus confirmatory methods to verify identity. If the content of an identified ingredient is needed, use a suitable quantitative method and, where required, report the result with its measurement uncertainty, especially for borderline results.

WHO also notes that a sample is commonly divided into three roughly equal portions: one for immediate testing, one for confirmation if needed, and one kept in case of dispute. If microbiological testing may be needed, a separate container should be supplied. The chain of custody of each sample should be recorded (who, what, when, where).

Test request

A standard test request form should accompany every sample. In a manufacturer’s own laboratory, the requirements may instead be given in the master production instructions.

The form should capture:

• who supplied the sample and the date of receipt, and the source of the material;
• a full description: composition, INN and brand name where relevant, package and container, dosage form, strength, manufacturer, batch or lot number;
• sample size and the size of the consignment it came from, where relevant;
• reason for the analysis and date of sampling;
• expiry or retest date, if known;
• reference documents and the specification to be used;
• further comments, such as discrepancies or hazards;
• required storage conditions.

Review of the request

Before testing starts, the laboratory should confirm that the quantity is enough for the tests requested, that it has the capability and resources, and that the chosen tests or methods can meet the customer’s need. Resolve any problem with the requester first and keep a record of this review.

Registration and labelling

• Give each sample and its paperwork a unique registration number.
• Use separate numbers for different medicines, dosage forms, batches of the same medicine, and different sources of the same batch.
• Fix a label showing the number on each container, without covering any existing markings.
• Keep a register recording the registration number, the date of receipt and the unit to which the sample was forwarded.

Visual inspection of the received sample

Laboratory staff should check that the labelling matches the test request. Record, date and sign the findings. If there is a discrepancy or visible damage, note it on the test request form straight away and refer the query back to the sample provider.

Storage

Store the sample before testing, the retained sample and any remainder after testing appropriately, under the conditions specified for that sample. Retained samples are covered in section 6.12 of the WHO guide: keep them as required by law or by the requester, in the original packaging, in a quantity that allows at least two re-analyses, and define disposal criteria that follow national law, applicable international recommendations or the requester’s instructions. Our example SOP on handling of laboratory reagents shows how stored materials are controlled in practice.

Forwarding to testing

• The laboratory head (or a designated person) decides which unit tests the sample.
• Accept a verbal request only in an emergency, record all details immediately and obtain written confirmation.
• Unless a computerised system is used, copies of the documents should travel with each numbered sample so the receiving unit can verify its identity, origin and purpose.
• Test as described in the laboratory’s testing procedures (WHO section 6.5).

Records of sample receipt, registration and testing are GMP records. Keep them for at least 1 year after the expiry date of the respective product batch (EU GMP Part I Chapter 4, point 4.11, or 5 years after QP certification if longer; 21 CFR 211.180(a)), and longer if local law or the marketing authorisation requires. See also records maintenance in the QC laboratory.

Frequently asked questions

Why is a unique registration number needed for each batch or source? It prevents mix-ups and lets every result be traced back to one sample, one request and one set of documents.

Can a laboratory start testing on a verbal request? Only in an emergency. All details must be recorded at once and confirmed in writing.

Who decides which unit tests a sample? The laboratory director or a person designated by them.

How much retained sample should be kept? Enough for at least two re-analyses, in its original packaging, unless law or the requester specifies otherwise.

References

1. WHO Expert Committee on Specifications for Pharmaceutical Preparations, Fifty-seventh report, WHO Technical Report Series No. 1052, 2024, Annex 4: WHO good practices for pharmaceutical quality control laboratories (sections 6.1, 6.2, 6.12). Replaces TRS 957, Annex 1 (2010).
2. EudraLex Volume 4, EU GMP Part I, Chapter 4 Documentation, point 4.11.
3. US 21 CFR 211.180(a), General requirements for records.