In detail
Legal basis
The EU legal basis is Article 47 of Directive 2001/83/EC. The principles for medicinal products for human use are laid down in Directive (EU) 2017/1572, and for investigational medicinal products in Delegated Regulation (EU) 2017/1569 based on Regulation (EU) No 536/2014. The European Commission details these principles in the EU GMP Guide, EudraLex Volume 4. In Germany the requirements are implemented mainly through the Ordinance on Medicinal Products and Active Substance Manufacture (AMWHV). Under Section 3(2) AMWHV, Part I of the Guide is used for interpretation for medicinal products, Part II for active substances and Part IV for advanced therapy medicinal products.
Structure of the EU GMP Guide
Part I sets out the basic requirements for medicinal products in nine chapters:
- pharmaceutical quality system, personnel, premises and equipment,
- documentation, production and quality control,
- outsourced activities, complaints and product recall, self-inspection.
Part II applies to active substances, Part III contains GMP-related documents such as the guidance on the Site Master File, and Part IV covers advanced therapy medicinal products. In addition there are annexes on specific topics, such as Annex 1 on the manufacture of sterile medicinal products, Annex 11 on computerised systems, Annex 15 on qualification and validation and Annex 16 on certification by a Qualified Person.
What GMP requires in practice
Directive (EU) 2017/1572 requires manufacturers, among other things, to operate a pharmaceutical quality system, to record and review complaints, to maintain an effective recall system and to carry out repeated self-inspections whose results and corrective actions are documented. Under Section 3(1) AMWHV the quality management system must be fully documented and checked for effectiveness. For imported medicinal products the Directive requires manufacture to standards at least equivalent to those of the EU.
Supervision
Member States verify compliance through repeated inspections of manufacturers holding a manufacturing or import authorisation (Article 3 of Directive (EU) 2017/1572). For investigational medicinal products, Article 63 of Regulation (EU) No 536/2014 also provides for inspections.
In practice at A&O Pharma
A&O Pharma itself operates under a manufacturing authorisation pursuant to Section 13 AMG and runs a GMP-certified laboratory in Itzehoe. Our GxP consulting covers analytical method validation, qualification of equipment and rooms from DQ to PQ, process and cleaning validation, GxP audits and support during regulatory inspections. Day-to-day tasks such as deviations, CAPA, change control and self-inspections are handled by our operational QM/QA support.
GMP & GxP Consulting & QA SupportFrequently asked questions
Where are the GMP rules laid down in the EU?
The principles are set out in Directive (EU) 2017/1572 and, for investigational medicinal products, in Delegated Regulation (EU) 2017/1569. The detailed guidelines are contained in the EU GMP Guide in EudraLex Volume 4.
Which regulation implements GMP in Germany?
Mainly the Ordinance on Medicinal Products and Active Substance Manufacture (AMWHV). Section 3(2) AMWHV refers to Parts I, II and IV of the EU GMP Guide for interpretation.
Does GMP also apply to investigational medicinal products?
Yes. Under Article 63 of Regulation (EU) No 536/2014, investigational medicinal products must be manufactured in line with good manufacturing practice. The details are set out in Delegated Regulation (EU) 2017/1569.
