GMP-Audits of manufacturers of active substances: Minimum Requirements on Audit Reports and Qualification of Auditors

The European Medicines Agency EMA specifies in one of its questions and answers documents on the GMP guideline under the heading "EU GMP guide part II: Basic requirements for active substances used as starting materials: GMP compliance for active substances" its requirements for active substances. This list of frequently asked questions compiled by the Inspectors Working Group has recently been complemented by the following three questions and answers:

8. "During inspections, why do inspectors sometimes ask to see reports of audits of active substance manufacturers carried out by the medicinal product manufacturer?”

9. "What expectations do inspectors have for the content of reports of audits?"

10. "How should active substance auditors be qualified?"

The answer to question No. 9 on the minimum requirements is especially interesting. The report of the audit of active substances should be sufficient since the requirements on this report are described in an unusual comprehensive and detailed manner. The following points are mentioned by way of example:

• A justification should be recorded for the duration of the audit, especially, if the audit had to be restricted to fewer days on site than initially planned for the scope of the audit. 
• The areas which were not covered by the audit should also be clearly recorded. 
• Auditors should identify and describe the high risk areas specific to the company being audited (for example, cleaning/cleaning validation, possible cross-contamination, sources for unknown impurities, mix-up of materials or products and so on).
• Areas of the site to which access was denied should be recorded. 
• Corrective and preventive actions (CAPAs) as well as the timescales for their completion should be assessed by the auditors to establish whether these are appropriate to the findings. 
• A proposed re-assessment period should be recommended.

EMA’s requirements concerning the qualification of auditors are also clear and precise. No difference is made between contracted auditors and the manufacturing authorisation holder’s own auditors. Auditors are required to

• have sufficient scientific or technical experience for the area to be audited, 
• have undergone a training and assessment programme in the areas that are relevant to the audit. Auditors must also have been trained and assessed in their knowledge and understanding of EU GMP part II and in auditing techniques in general. The training and personal suitability evaluation (assessment) should be fully documented.

With these exceptionally detailed requirements on the quality standards of an audit report of active substances and on the qualification of auditors EMA sets standards that have to be maintained in the future by the numerous Third Party Audit Organisations existing now if they want to survive on the market. Now, GMP auditors have a concrete list of criteria they can use in order to check easily and clearly the quality of audit reports and the qualification of auditors.

You can find the compilation of EMA’s questions and answers on GMP for active substances here.