Good practices in the QC laboratory

A QC laboratory decides whether materials and products are released or rejected, so it works under GMP just like production. The aim is simple: every result must be correct, traceable and defensible years later.

Three sources set the expectations most labs follow. WHO TRS 957 Annex 1, Good practices for pharmaceutical quality control laboratories, is the most detailed and covers management, documentation, equipment, reagents, reference substances, testing and evaluation of results. EU GMP Part I Chapter 6, Quality Control, sets the EU requirements for documentation, sampling, testing and on-going stability. In the US, 21 CFR Part 211 Subpart I (Laboratory Controls) requires scientifically sound specifications, standards, sampling plans and test procedures, calibrated instruments, stability testing and reserve samples.

Good laboratory practice in this guide means GMP for QC labs. It is different from GLP (Good Laboratory Practice) under OECD principles or 21 CFR Part 58, which applies to non-clinical safety studies.

Every material you test needs an approved specification — the list of tests, references to procedures and acceptance criteria — and an approved test procedure that says exactly how to do each test. These come from the marketing authorisation, a pharmacopoeial monograph or both.

Analysts must work from the current, approved version. Compendial methods must be verified under actual conditions of use, and in-house methods validated, before they are used for release testing.

• Check the version and effective date before you start a test.
• Do not deviate from the written procedure. If something cannot be done as written, stop and raise a deviation.
• Record any permitted adjustments (for example within chromatographic allowable changes) and the reason.

A test result is only meaningful if the sample represents the batch. Sampling follows a written procedure stating who samples, how many containers, the method and equipment, the quantity, the containers used and any precautions such as sampling under controlled conditions.

When samples arrive in the lab they are registered, labelled with a unique identifier and stored under the right conditions until testing. Keep sample chain of custody clear: anyone should be able to see who handled the sample and when.

1. 1Receive the sample and check the label against the sampling record.
2. 2Register it in the LIMS or sample register with a unique number.
3. 3Store as specified (for example 2–8 °C, protected from light).
4. 4Issue to the analyst with the specification and test request.
5. 5After testing, return unused sample to controlled storage or dispose of it as per SOP.

Reagents must be of appropriate grade, purchased from approved suppliers and recorded on receipt. Write the date received and date opened on each container. Some reagents, such as ethers that form peroxides or hygroscopic salts, need a shorter in-use period defined in your SOP.

Every solution you make in the lab needs a label and a preparation record. The record lets a reviewer check what went into it; the label lets the next analyst decide whether it is still usable.

An unlabelled bottle is an unknown. Discard it — do not guess what it is.

Before using any instrument, look at its status label. It should show that it is calibrated or qualified and when the next calibration is due. Instruments that are out of calibration, under maintenance or faulty must carry a clear 'out of service' label and must not be used.

Each instrument has a logbook (paper or electronic) recording usage, calibration, maintenance and breakdowns in date order. A good logbook lets an investigator reconstruct exactly what the instrument was doing on any day. The calibration and qualification programme — typically following a risk-based approach such as USP <1058> — defines the checks, frequencies and acceptance criteria for each instrument.

• Do the daily or before-use check (for example the balance performance check) and record it before testing.
• If a calibration fails, label the instrument out of service and assess the impact on results since the last successful calibration.
• Calibration weights, thermometers and buffers must themselves be traceable and in date.
• Log every use: date, analyst, sample or test reference, and any problems.

Analysts may only perform tests they have been trained and qualified for. Training usually starts with reading the SOP, then observing a trained analyst, then performing the test under supervision. Qualification is often confirmed by testing a sample of known result — for example a previously tested batch or a spiked sample — and meeting predefined criteria.

Training records must be current before the analyst performs the test for release. When an SOP is revised, affected analysts are retrained before using the new version. Supervisors should check training status when allocating work.

• GMP and data integrity induction for all staff.
• Technique-specific training (HPLC, dissolution, Karl Fischer, microbiology).
• Periodic refresher training and assessment, as defined in your SOP.

Record everything at the time you do it, in ink or in a validated electronic system, following ALCOA+ principles: attributable, legible, contemporaneous, original and accurate, and also complete, consistent, enduring and available. Corrections are made with a single line, leaving the original visible, with the reason, initials and date.

Every result is checked by a second qualified person before it is reported. The reviewer looks at the raw data, not only the final number: chromatograms and integration, audit trails, system suitability, calculations, instrument and standard status, and whether the procedure was followed. Results outside specification are handled under the OOS procedure — never re-tested or discarded without investigation.

1. 1Check the test was done to the current procedure by a trained analyst.
2. 2Confirm instruments, standards, reagents and columns were in date and recorded.
3. 3Verify system suitability and calculations, including potency and dilution factors.
4. 4Review electronic data and audit trails for unexplained changes or deleted runs.
5. 5Sign and date the review; report the result only after review is complete.

Retention (reserve) samples allow a batch to be re-examined later, for example during a complaint investigation. Typically they are kept for at least one year after the expiry date of finished product, in a quantity sufficient for at least two full tests, stored under the labelled conditions. The exact rules are in EU GMP Annex 19 and 21 CFR 211.170, and your SOP should state them for your products.

The lab also runs the on-going stability programme: samples placed in qualified stability chambers and tested at defined time points to confirm the product stays within specification through its shelf life.

A safe lab is also a better GMP lab: rushing, clutter and improvised set-ups cause both accidents and errors. Read the safety data sheet before using a new chemical and follow the risk assessment for each test.

• Wear a lab coat, safety glasses and suitable gloves; add face protection for corrosives.
• Handle volatile, toxic or flammable solvents in a working fume hood.
• Store acids, bases, oxidisers and flammables separately in suitable cabinets.
• Never pipette by mouth, and never eat or drink in the laboratory.
• Know where the eyewash, safety shower, spill kit and fire extinguishers are.
• Dispose of solvent and chemical waste into labelled, segregated containers.

If a procedure feels unsafe, stop and ask. No result is worth an injury.