Guidance on good manufacturing practice and good distribution practice: Questions and answers | European Medicines Agency

The document ‘guidance on the occasions when it is appropriate for competent authorities to conduct inspections at the premises of manufacturers of active substances used as starting materials’, published as part of the Community procedures, states that it is expected that manufacturing-authorisation holders will gain assurance that the active substances they use are manufactured in accordance with GMP through audit of the active-substance suppliers. Small manufacturers may not have the necessary expertise or resource to conduct their own audits.

Section 5.25 of the GMP guideline requires starting materials to be purchased from approved suppliers and about whom the manufacturer has a particular and thorough knowledge.

An audit conducted by the manufacturing-authorisation holder itself should be integral to the manufacturer’s quality-assurance system and subject to the basic GMP requirements, i.e. conducted by properly qualified and trained staff, in accordance with approved procedures. It should be properly documented. These aspects can be inspected as necessary by the competent authorities.

If a third party is involved, the arrangements should be subject to chapter 7 of the GMP guideline. There should be evidence that the contract-giver has evaluated the contract-acceptor with respect to the aspects described above.

All parties involved should be aware that audit reports and other documentation relating to the audit will be made available for inspection by the competent authorities if requested. This should normally provide sufficient assurance that the results of an audit carried by the third party are credible, thus waiving the need for an audit conducted by the manufacturing-authorisation holder itself. However, it must also be satisfactorily demonstrated that there are no conflicts of interests. Conflicts of interests could arise for example from:

• a commercial relationship between the organisation performing the audit and the organisation being audited;
• a personal conflict on the part of the auditor where he / she has been employed by the organisation being audited in the recent past (i.e. within the last three years) or has a financial interest in it.

This topic should also be addressed in the technical contractual arrangements. Any measures taken by the contract-giver should be documented, e.g. signed undertakings by the auditors.

Similarly, the principles outlined above could be used to allow sharing of audit reports between different manufacturing-authorisation holders using the same active substance supplier, provided that the scope of the audits can be shown to be applicable to the active substances of mutual interest.