The GMP guide: a common reference
The GMP guide is intended to serve as a reference for the competent authorities when evaluating manufacturing authorisation applications and when inspecting manufacturers of medicinal products. The GMP principles and the particular guidelines apply to all operations requiring the authorisations provided for in Articles 40 of Directive 2001/83/EC and 13 of Directive 2001/20/EC, as amended.
The guide is divided into four main parts and supplemented with a series of annexes.
- Part I: basic requirements and GMP principles for the manufacture of medicinal products.
The principle set out at the start of each of the chapters highlights the objectives of the chapter concerned in terms of quality management; the text then gives details of the important points that must be considered by the manufacturers when implementing this principle.
- Part II: detailed guidelines on the GMP principles for active substances used as starting materials for medicinal products.
This part was established on the basis of a guideline developed at the level of the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) and published as ICH Q7, applicable to the active pharmaceutical ingredients.
The chapters of parts I and II are supplemented by a number of annexes adding complementary elements in certain more specific areas of activity.
Certain manufacturing processes are concerned by a number of annexes, which apply simultaneously, such as the annexes on sterile medicinal products and radiopharmaceutical products and/or biological medicinal products.
There is also a glossary clarifying certain terms used in the guide.
- Part III: documents clarifying certain regulatory expectations relating to the GMP.
- Part IV: Requirements applicable to medicinal products for innovative therapy, or Advanced Therapy Medicinal Products (ATMP).
On 22 November 2017, the European Commission adopted the New Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products. Since 22 May 2018, this text has applied to all medicinal products authorised and still in the clinical test phase, as well as medicinal products manufactured under the hospital exemption status. This text applies parallelly to that applicable to classical medicinal products pursuant to Article 5 of Regulation (EC) No 1394/2007 and Article 63(1) of Regulation (EU) No 536/2014 for medicinal products in the clinical test phase.
The GMP applicable to commercial medicinal products and still in the clinical test phase only apply to ATMPs if formal reference is made to them.
Throughout the guide, the requirements relating to the quality, safety and effectiveness of the medicinal products covered by the marketing authorisation are assumed to have been systematically respected in all of the measures taken by the holder of the manufacturing authorisation in relation to production, control and release for marketing.
The GMP guide is revised regularly in order to take into account ongoing improvements to practices in the field of quality. This guide in no way restricts the development of new concepts or new technologies, if they are validated and subject to a level of quality management at least equivalent to that defined in this guide.
GMP and CEN/ISO standards
For a number of years, the manufacture of medicinal products has been undertaken in accordance with the GMP guidelines and has not been governed by the European Committee for Standardisation CEN standards and the International Organization for Standardization ISO standards. These standards have however been taken into account, but their terminology has not been used.
It is recognised that methods other than those described in the GMP guide are able to address the principles of quality management.
Notions not covered in the GMP guide
The guide is not intended to address staff security issues for those responsible for manufacturing or aspects associated with respect for the environment. These aspects can be of great importance in the manufacture of certain medicinal products, such as those that are highly active, biological and radioactive. These aspects are addressed by other provisions of Community or national law.
Texts similar to the GMP guide exist for cosmetic products and numerous industrial sectors, such as the agrifood industries, which also employ the terms of good manufacturing practices. These references should not be confused with those applicable to medicinal products. These sectors of activity are not under the responsibility of the FAMHP.