SOP for Sampling of Raw Materials

In short: This illustrative SOP outline describes receipt checks, representative sampling, identification, sample labelling, and recordkeeping for pharmaceutical starting materials. Define sampling plans and precautions for each material using its approved specification, risk, supplier controls, and applicable requirements; do not use a generic container-count formula without validation and approval.

1. Purpose and scope

Describe how trained personnel sample received starting materials for testing and retain representative samples. Adapt this template to the site’s approved procedures, material specifications, contamination controls, safety requirements, and applicable law. It does not set universal sample quantities, sample counts, or environmental conditions.

2. Responsibilities

• Stores: receive and identify each consignment, maintain quarantine status and storage conditions, and provide receipt documentation.
• Sampling personnel: verify the consignment, follow the approved sampling plan and precautions, label and secure containers, and record the work.
• Quality Control: define or approve sampling and testing requirements, review results and anomalies, and control sample records.
• Quality Assurance: approve procedures and any justified reduced-sampling programme through the quality system.
• Engineering / EHS: maintain sampling facilities and advise on equipment, containment, and material hazards as assigned.

3. Procedure

3.1 Receipt and readiness checks

Confirm the material name, code, manufacturer, supplier, batch or lot identity, quantity, seal and container condition, receipt record, and required supplier documents against approved records. Keep each batch identifiable and under its established status until disposition. Record damage, mismatched information, unusual appearance, or other discrepancies and refer them for assessment before sampling.

Review the current material specification for storage, handling, safety, sensitivity, required tests, sample quantities, and any special precautions. Check that the sampling location is suitable, clean, and ready; instruments and sampling devices are appropriate and in their required status. Where a controlled booth or room is used, follow its approved operating procedure. These setup checks and operating conditions are example in-house criterion and must be defined for the actual facility.

3.2 Sampling plan

Use a documented plan to identify containers and locations, the sampling device, sample amount, whether samples are individual or composite, and the tests supported by each sample. Ensure the plan preserves batch identity and sample representativeness. WHO GMP for pharmaceutical products (TRS 986, Annex 2, 2014), sections 17.7–17.11, calls for representative samples, written sampling procedures, cleaning (and sterilisation where needed) of equipment before and after use, and sample-container identification including material, lot, container, sample number, sampler, and date.

WHO TRS 986, Annex 2, section 17.14 (2014) states that identity testing should be performed on a sample from each starting-material container. Sampling only a proportion of containers may be accepted where a validated procedure ensures no container was incorrectly labelled; it identifies supplier/manufacturer status, supplier GMP understanding, the manufacturer’s quality system, manufacturing conditions, and intended product use as considerations. WHO also cautions that such a procedure is unlikely to be satisfactorily validated for unknown or unaudited broker sources or materials for parenteral products. Apply the applicable jurisdiction’s requirements and site validation before using reduced sampling.

The imported SOP’s reduced plan of √n + 1 containers, its special case splits, and its alternative full-container sampling rule are example in-house criterion only.

Example in-house criterion (not a pharmacopoeial requirement): the reduced plan above is the site’s in-house formula. WHO’s sampling guideline describes a comparable n = 1 + √N plan, but states that it is not statistically based, should be used only as a guiding principle and with great caution for uniform material from a recognised source, and is not recommended for manufacturers’ control laboratories that must analyse and release each consignment (WHO TRS 929, Annex 4, section 5.1.1). Any reduced sampling plan must therefore be justified, statistically sound and approved in the site’s quality system (for example with supplier qualification and identity testing of each container), and must be documented for each material and market.

3.3 Sample collection and handling

Use clean, suitable devices and sample containers that will not compromise the material. Prevent mix-ups and cross-contamination; sample different materials with dedicated or appropriately cleaned equipment as justified by procedure. Follow additional containment and personal protective measures for hazardous, potent, sensitising, sterile, or otherwise sensitive materials. Collect separate samples when required by the approved plan, such as for identification, complete testing, microbiology, or retention.

For solids, collect from the approved locations within the container using a suitable sampler and transfer the amount specified in the plan. For liquids, use a compatible device and method that supports representative collection without compromising the container or material. Reseal each container promptly and restore its required storage condition. Visual examination for anomalies and the exact sampling technique are example in-house criterion; define them in the controlled material or sampling procedure.

The imported SOP specifies sampling excipients before active materials, separate sterile equipment for microbiological samples, a specified order for gown changes, 70% IPA hand disinfection, and cleaning after each batch. These are example in-house criterion and require confirmation in the site’s contamination-control, safety, and cleaning procedures.

3.4 Labels, samples, and records

Label each sample with enough information to maintain traceability: material, lot, source container, sample identifier, sampling date, and sampler. Record the sampling plan and actual containers sampled, quantities, room or equipment where relevant, storage conditions, observations, deviations, and sample destinations. Transfer samples promptly under specified conditions, particularly where stability or microbiological integrity may be affected. Keep the sampled batch under its required status until the authorised disposition is made.

The source SOP specifies completion of sampling within 15 days of goods receipt, collection of double or fourfold quantities for reserve and microbial samples, and several fixed storage and handling details. These are example in-house criterion.

Example in-house criterion (not a pharmacopoeial requirement): the timings, quantities, splits and storage details above are in-house values; adjust them to the material’s approved specification and the site’s procedures.

3.5 Deviations and equipment cleaning

Document deviations, damaged containers, unexpected material characteristics, sampling interruptions, and equipment issues. Assess potential impact on sample representativeness and material quality before continuing. Clean, dry, sterilise where needed, and store sampling devices according to approved procedures; retain the associated cleaning or status records.

4. Related procedures

See vendor management, sampling and testing of purified water, and cleaning of the QC laboratory.

5. Abbreviations

Frequently asked questions

Must every container of a starting material be sampled?

WHO TRS 986, Annex 2, section 17.14 (2014) describes identity testing of a sample from each container. Sampling a proportion may be accepted under a validated procedure with specified supplier and material considerations; check the applicable local requirements and product risks.

Is √n + 1 a universal sampling formula?

No. The WHO guidance cited here does not prescribe that formula. Use a container-count plan only when its basis is confirmed, validated where required, and approved for the applicable materials and market.

What information belongs on a sample label?

WHO TRS 986, Annex 2, section 17.11 (2014) lists the material name, batch/lot, source container number, sample number, sampler’s signature, and sampling date.

References

• World Health Organization. WHO good manufacturing practices for pharmaceutical products: main principles. WHO Technical Report Series No. 986, Annex 2, 2014, especially sections 17.7–17.14. Official WHO document.
• World Health Organization. WHO guidelines for sampling of pharmaceutical products and related materials. WHO Technical Report Series No. 929, Annex 4, 2005, section 5.1.1 (n plan). WHO publication page.