Who May Perform Sampling in GMP? QA, QC, or Production Personnel?

Introduction

Sampling of raw materials, intermediates, bulk and finished products is a quality-critical GMP activity. It directly impacts product quality, patient safety, and regulatory compliance. The question of who is authorized to perform sampling is not simply an operational matter — it is a regulatory, data integrity, and audit-readiness issue.

1. Regulatory Foundation

• Approved Personnel and Methods
  According to EU GMP (EudraLex Volume 4, Part I, Chapter 1.9):
  “Samples of starting materials, packaging materials, intermediate products, bulk products and finished products are taken by approved personnel and methods.”

• Training and Qualification
  EU GMP Part I (Chapter 2, Personnel) and Part II (Chapter 3, Personnel) state that staff engaged in GMP activities must have the necessary qualifications, practical experience, and receive initial and ongoing training.

• Annex 8 – Sampling Requirements
  EU GMP Annex 8 emphasizes that sampling personnel must undergo initial and continuous training covering:

  • Sampling plans

  • Written sampling procedures

  • Sampling techniques and equipment

  • Risks of cross-contamination

  • Precautions for unstable or sterile substances

  • Importance of visual checks (materials, containers, labels)

  • Recording unexpected or unusual circumstances

• Representativeness and Statistical Basis
  ICH Q7 and WHO guidelines highlight that sampling must be statistically justified and representative of the batch. Sampling plans should specify container numbers, locations (top/middle/bottom), and amounts.

• Chain-of-Custody and Integrity
  FDA guidance stresses that once samples are taken, they must be properly labeled, sealed, transported, and logged to ensure traceability and integrity.

2. Who May Perform Sampling?

Short Answer:

• QA/QC personnel have the primary responsibility and oversight for sampling.

• Production personnel may perform sampling if:

  • They are trained and qualified.

  • Procedures (SOPs) clearly authorize them.

  • QA/QC maintains oversight and final responsibility.

Exceptions:
For high-risk materials (sterile APIs, highly toxic substances, controlled materials, or regulatory witness sampling), only QA/QC or specialized teams should perform sampling.

3. Conditions for Allowing Production Personnel to Sample

Production operators can be authorized to perform sampling only if all conditions below are met:

1. Documented Training and Qualification

   • Specific training in sampling techniques, container handling, contamination control, and documentation.

   • Training records must be maintained and periodically reassessed.

2. Clear SOPs

   • SOPs must define when and how production staff may sample, what materials are covered, and under what supervisory framework.

3. Risk Assessment

   • Sampling permissions must be based on a formal risk assessment considering material type, toxicity, sterility, and potential bias.

4. Independence and Segregation of Duties

   • QA/QC retains approval and oversight, even if production personnel execute sampling.

5. Chain-of-Custody

   • Complete traceability must be maintained from sampling to laboratory receipt, including labeling, sealing, transfer records, and storage conditions.

4. Essential Elements of a Sampling SOP

A compliant Sampling SOP should include:

• Purpose and Scope (materials, stages, personnel authorized)

• Definitions (sample, composite sample, container, etc.)

• Responsibilities (who prepares sampling plans, approves, executes, receives, and archives records)

• Sampling Plan and Statistical Justification (number of containers, amount per container, sampling pattern)

• Methods and Tools (validated techniques, equipment calibration, cleaning requirements)

• Sampling Locations and Quantities (top/middle/bottom; single vs composite samples)

• Controls for Sterile/Unstable Materials (aseptic techniques, cold-chain, protective measures)

• Cross-Contamination Prevention (protective clothing, cleaning order, environmental controls)

• Labeling and Sealing (sample ID, batch number, seal numbers)

• Chain-of-Custody Records (handover forms, signatures, timestamps, photographs if applicable)

• Sample Storage and Retention Periods

• Deviation and Incident Reporting

• Training and Qualification Records

• Change Control for SOP Updates

5. Sampling Plans and Representativeness

• Representative Sampling: Samples must represent the entire batch or container population.

• Sampling Methods: Random sampling, stratified sampling, or statistically justified n/p/r plans.

• Composite vs. Individual Samples: Composite samples may reduce testing burden, but individual container samples should be retained for traceability and investigation purposes.

• Photographic Evidence: Photographs of containers and sampling points are increasingly used to support audit-readiness.

6. Chain-of-Custody & Sample Integrity

To ensure regulatory compliance, chain-of-custody procedures should include:

1. Pre-sampling Verification: Confirm batch, container numbers, and labels.

2. During Sampling: Record sampler name, date, container ID, method reference, seal numbers.

3. Handover: Direct transfer to QC laboratory with signed records.

4. Transport: Sealed containers, cold-chain when applicable, transport logs.

5. Laboratory Receipt: Immediate registration, sample ID assignment, and controlled storage.

6. Retention & Disposal: Retain or destroy according to SOP; destruction requires QA approval.

7. When Production Staff Should NOT Sample

• Sterile or aseptic products requiring specialized aseptic techniques

• Highly potent, hazardous, or controlled substances

• Critical release samples where independence is required

• Regulatory witness sampling (e.g., FDA or customs)

• When representativeness or independence could be compromised

8. Training & Qualification Matrix (Suggested Modules)

• GMP principles & regulatory background (EU GMP Annex 8, ICH Q7)

• Sampling plans & statistical justification

• Sampling tools and techniques

• Cross-contamination prevention & personal protective measures

• Aseptic sampling (if applicable)

• Chain-of-custody documentation and handover procedures

• Deviation handling and unusual event reporting

9. Practical Templates (Examples)

Sample Label Fields (minimum):

• Company name

• Material name

• Batch/Lot number

• Container ID

• Sample ID

• Date/Time

• Sampler Name/ID

• Storage condition

• Seal number

Sampling Record (minimum entries):

• Date/Time

• Location

• Batch/Container IDs

• Sample ID and quantity

• SOP/method reference

• Sampler signature

• QA/QC receiving signature

• Remarks (deviations, unusual circumstances)

10. FAQs

Q: Does production staff sampling violate GMP?
A: No, provided they are trained, qualified, authorized by SOP, and under QA/QC oversight.

Q: Who approves the sampling plan?
A: The Quality Unit (QA/QC) is responsible for preparing, reviewing, and approving all sampling plans.

Q: How long should samples be retained?
A: Retention time depends on material stability, regulatory requirements, and internal risk assessment. SOPs must clearly define retention and disposal procedures.

Conclusion

Sampling is not a simple operational task — it is a critical GMP process with direct regulatory implications. To maintain compliance and audit-readiness, companies should:

1. Document all sampling requirements in SOPs.

2. Ensure training and qualification of all sampling personnel.

3. Establish chain-of-custody systems for sample traceability.

4. Restrict high-risk sampling to QA/QC or specialized personnel.

A robust, well-controlled sampling program not only satisfies regulators but also strengthens overall quality assurance and patient safety.