Directive 2001/83/EC as amended (Directive 2001/82/EC for veterinary medicinal products) states that manufacturing-authorisation holders are obliged to use, as starting materials, only active substances that have been manufactured in accordance with the detailed guidelines on GMP for starting materials. Thus the legislation puts the responsibility on the manufacturing-authorisation holders using the active substance and does not foresee mandatory routine inspections of active-substance manufacturers.
To provide guidance on how GMP compliance of active-substance manufacturers should be established, guidance documents have been published on this website, including the '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' as part of the Community procedures. This document states that it is expected that manufacturing authorisation holders will normally gain assurance that the active substances it uses are manufactured in accordance with GMP through audit of the active-substance suppliers.
In addition, a number of questions and answers on audits of active-substance manufacturers on this page provide further guidance.
