The specific requirements are described in Part II of the EU GMP guidelines, and are identical to the ICH guidelines used also in US and Japan.
Qualified Persons must confirm that drug substances were manufactured according to GMP as a part of their release of the finished dosage forms.
Marketing authorisation holders must carry out regular (every 2-3 years) audits of all of their drug substance manufacturers and suppliers. Inadequate audit programmes has been cited as a GMP deficiency in a number of regulatory authority inspections.
All manufacturing, packaging and labelling steps, from the introduction of the starting materials through to delivery to the dosage form manufacturer, must be carried out according to the GMP guidelines.
•Other procedures, eg milling, micronising, irradiation etc
•Breaking bulk and repackaging
•Labelling (including simply adding an “imported by” label without opening or sampling the packs)
This is a considerable workload for companies that source drug substances from many suppliers, and in-house Qualified Persons may not have the time to carry out these audits.
Many marketing authorisation holders are resolving this problem by employing contract auditors who have the resource and expertise to cover all areas of the manufacturing process. The EMEA has confirmed that this is acceptable as long as the auditor:
•Has no financial or commercial relationship with the drug substance manufacturer
•Has not been employed by the drug substance manufacturer during the previous three years
•Is contracted to, and instructed by, the drug substance user