Who may carry out the sampling?
Question
Should the sampling of medicinal products and active ingredients be carried out by quality control (QC) staff or may production staff also take samples?
Our answer
Medicinal products
The requirements given in the GMP regulations which apply to sampling are described in detail in the following documents:
- EU GMP Guidelines Part I, Chapters 6.11 through 6.14 (C.4.6 Chapter 6 Quality Control)
- EU GMP Guidelines, Annex 8 “Sampling Starting and Packaging Materials” (C.6.8 Annex 8 Sampling of Starting and Packaging Materials),
- 21 CFR 211, especially Subpart I (D.1.2 21 CFR Part 211 Current Good Manufacturing Practice for Finished Pharmaceuticals)
These regulations do not contain an explicit statement as to whether the samplers should or must come from the QC. It is merely pointed out that the personnel need appropriate basic training and continual training, i.e. the personnel must be qualified. This could be checked, for example, on the basis of the training documentation.
However, the procedures for sampling should be approved by QC.
The 21 CFR 211 writes in Sec. 211.160 a):
The establishment of any specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change […] shall be drafted by the appropriate organizational unit and reviewed and approved by the quality control unit.
Active substances
Part II of the EU GMP Guide is relevant for the sampling of active substances, in particular Chapters 7.3, 8.3 and 11.7 (C.5 EU GMP Guide Part II: Basic Requirements for Active Substances used as Starting Materials combined with GMP for APIs: “How to do“ Document by APIC/CEFIC Interpretation of the ICH Q7 Guide). However, also these chapters do not contain any specific information on the actual persons carrying out the sampling.
In the question and answer paper on the ICH Q7 guideline: GMP Guidance for Active Pharmaceutical Ingredients, you will find more detailed explanations on the persons who carry out the sampling and on the responsibility of the QC (GMP Compliance Adviser Chapter E.7.1, Question 2.4):
Question
Does ICH Q7 expect that sampling be performed by the quality unit?
Answer
No. ICH Q7 does not prescribe specifically who should perform the sampling [ICH Q7, Section 2.22]. However, the quality unit has responsibility for reviewing and approving sampling plans [ICH Q7, Section 11.12] and procedures. Sampling should be performed by adequately trained personnel [ICH Q7, Section 3.10] and be appropriately documented as per [ICH Q7, Section 6.52].
Answer from a GMP inspector
Medicinal products
The QC is responsible for the testing of medicinal products. The head of QC has to approve specifications and sampling instructions (EU GMP Guide Part I, Chapter 2.8 iii (GMP Compliance Adviser Chapter C.4.2). The sampling instructions are part of the specifications of starting materials and finished products, respectively (EU GMP Guide Part I, Chapter 4.14 and 4.16, GMP Compliance Adviser Chapter C.4.4).
Chapter 6 of the EU GMP Guide Part I points out that QC is inter alia concerned with sampling and that the QC department should be independent from other departments (GMP Compliance Adviser Chapter C.4.6).
The sampling requirements are described under 6.11 ff. In addition, 6.4 states that QC personnel should have access to production areas for sampling. (The glossary of the GMP Guide defines „production“ as follows: „All operations involved in the preparation of a medicinal product, from receipt of materials, through processing and packaging, to its completion as a finished product.“)
In principle, the QC has to carry out the sampling. In practice, the sampling is often done by production staff. This applies in particular to the samples to be retained during packaging. However, the sampling instructions must be defined by the QC.
Conclusion
The GMP regulations do not specify who may or should carry out the sampling. However, it is clearly defined that responsibility for sampling and sampling plans lies with the QC. In addition, personnel must be appropriately trained and qualified.
In practice, it is therefore possible for appropriately trained production personnel to carry out the sampling. The sampling procedure must be approved by QC.