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PE009-13, the PIC/S guide to GMP for medicinal products

TGA interpretation and expectations for demonstrating compliance

2 January 2018

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Sampling of starting and packaging material (Annex 8)

Reduced sampling of starting materials

It is improbable that reduced sampling and testing would be accepted for:

  • starting materials supplied by intermediaries such as brokers where the source of manufacture is unknown or not audited;
  • starting materials for use in parenteral products.

A validated procedure that would permit less than all containers to be sampled and tested for identification purposes should consider the following:

  • Every container of starting material must be sampled and tested for identity if the supplier is not classified as reliable and is not validated according to Annex 8.
  • For registered medicines, the requirements for sampling active materials do not differ from those for excipients. However, TGA guidance should be consulted for manufacturers of listed medicines.
  • The validation of a supplier cannot be accepted without a regular and adequate assessment. Such validation should comprise a number of actions, which may include all or most of the following:
    1. The use of a questionnaire prepared by the potential customer and completed by the potential supplier, concerning the supplier's operating Quality System
    2. Approval inspection of the potential supplier's operation by the potential customer, or by a third party on their behalf. For example, a sister company located in the same country as the supplier. Reliance on inspection reports of other regulatory authorities by the potential customer is normally not sufficient, unless it can be demonstrated that the inspection covered the specific operations to be used in the processing of materials for the potential customer
    3. A program to evaluate the quality of each shipment of materials on receipt by the customer. In this regard, sampling of powders should be representative of the container contents. For example, sampling from the top, middle and bottom of drums, in the absence of validated sampling positions. Reduced testing programs should be evaluated by the inspector. Sampling by the suppliers should be validated
    4. A program for regular re-inspection of the supplier's operation and for ongoing monitoring of the quality of material supplied, for example, through trend analysis of analytical results, periodic full testing
    5. In the case of active ingredients, the use of brokers as sources should be carefully evaluated. The quality of each batch of material should be confirmed through testing of representative samples

Note: Certification such as a Certificate of Suitability for compliance with Monographs of the European Pharmacopoeia, does not replace an inspection.

Application of √n+1 sampling

Where a validated procedure is established to justify reduced sampling, and scientific and statistical evidence is presented, √n+1 sampling may be justified as applicable.

There are specific provisions for the sampling of materials used in the manufacture of listed complementary medicines as described in the technical guidance on sampling and testing of complementary medicines. Although the principles in this guidance are still applicable, it will be revised where necessary, in consultation with industry, to clarify requirements in the PE009-13 version of the PIC/S Guide to GMP.

The technical GMP guidance for listed complementary medicines are baseline documents, elements of which can also be applied to other listed medicines if justified.

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