Good Manufacturing Practices - Major developments

06/02/2014
Revision of European Commission Guidelines on Good Manufacturing Practice for Medicinal Products
Today the European Commission has launched the public consultation on the revision of Annex 15: Qualification and Validation.

Stakeholders are invited to comment on this draftpdf(141 KB) by 31 May 2014 at the latest.
Comments should be sent by e-mail to: ADM-GMDP@ema.europa.eu and sanco-pharmaceuticals-D6@ec.europa.eu.

Please consult the privacy statement on this consultationpdf(82 KB).

28/11/2013
Responses to the public consultation on the revision of Annex 16: Certification by a Qualified Person and Batch Release.

23/11/2013
A new version of the Guidelines on good distribution practice (GDP)pdf of medicinal products was published today
The revised guidelines (OJ C 343/1, 23.11.2013)pdf correct factual mistakes in subchapters 5.5 and 6.3, give more explanations on the rationale for the revision and provide a formal date of coming into operation. These guidelines, which replace the guidelines on GDP published in March 2013, are applicable as of 24 November 2013.

08/11/2013
Responses
to the public consultation on draft guidelines on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use.

Gedeon Richter Plc., Merck & Co., Norgine and UCB Pharma SA requested that their responses not be published.

08/11/2013
Responses to the public consultation on draft guidelines on the principles of good distribution practices for active substances for medicinal products for human use.

Gedeon Richter Plc., Merck KGaA, Teva Pharmaceutical Industries Ltd. and UCB Pharma SA requested that their response not be published.

08/11/2013
Responses
to the public consultation on revision of EU Commission guidelines on Good Manufacturing Practice Medicinal Products, Part I, Chapters 3, 5, 6 and 8.

Gedeon Richter Plc. requested that its response not be published.

05/07/2013
Revision of EU Commission guidelines on Good Manufacturing Practice for Medicinal Products
Today the European Commission launched the public consultation on the revision of the Annex 16: Certification by a Qualified Person and Batch Release.
Stakeholders are invited to comment on this draftpdf(150 KB) by 5 November 2013 at the latest. Comments should be sent by email to: ADM-GMDP@ema.europa.eu and SANCO-pharmaceuticals-D6@ec.europa.eu

21/06/2013
The Unites States have been added to the "list of third countries" as regards standards of manufacture and supervision of active pharmaceutical ingredients equivalent to those of the EU. The Commission Decision is herepdf.

05/06/2013
Japan has been added to the "list of third countries" as regards standards of manufacture and supervision of active pharmaceutical ingredients equivalent to those of the EU. The Commission Decision is herepdf.

25/04/2013
Australia has been added to the "list of third countries" as regards standards of manufacture and supervision of active pharmaceutical ingredients equivalent to those of the EU. The Commission Decision is herepdf.

12/04/2013
Importation of active substances for medicinal products for human use

06/02/2013
Guidelines on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use - draft submitted for public consultationpdf(32 KB).

Stakeholders are invited to comment on this draft by 30 April 2013 at the latest. Responses should be sent preferably by e-mail to sanco-pharmaceuticals-d6@ec.europa.eu, or by post to Unit SANCO/D/6, DM24 02/050, BE-1049 Brussels.

06/02/2013
Guidelines on the principles of good distribution practices for active substances for medicinal products for human use - draft submitted for public consultationpdf(45 KB).

Stakeholders are invited to comment on this draft by 30 April 2013 at the latest. Responses should be sent preferably by e-mail to sanco-pharmaceuticals-d6@ec.europa.eu, or by post to Unit SANCO/D/6, DM24 02/050, BE-1049 Brussels.

28/01/2013
Importation of active substances for medicinal products for human use

24/01/2013
Commission Implementing Decision of 23 January 2013 on the assessment of a third country’s regulatory framework applicable to active substances of medicinal products for human use and of the respective control and enforcement activities pursuant to Article 111b of Directive 2001/83/EC of the European Parliament and of the Councilpdf(722 KB) Choose translations of the previous link български (bg) čeština (cs) dansk (da) Deutsch (de) eesti keel (et) ελληνικά (el) español (es) français (fr) italiano (it) latviešu valoda (lv) lietuvių kalba (lt) magyar (hu) Malti (mt) Nederlands (nl) polski (pl) português (pt) română (ro) slovenčina (sk) slovenščina (sl) suomi (fi) svenska (sv)

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24/01/2013
Responses to the public consultation on a concept paper on the implementing act on the requirements for the assessment of the regulatory framework applicable to the manufacturing of active substances of medicinal products for human use (TEVA, the Freie und Hansestadt Hamburg, and the Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten asked not to publish their response).

17/01/2013
Revision of EU Commission guidelines on Good manufacturing Practice Medicinal Products

Today, the European Commission launches the public consultation of the following revised guidelines on good manufacturing practices:
Chapter 3: Premises and Equipmentmsw8(53 KB)
Reasons for changes: The only change is to section 6 as part of the improved guidance on prevention of cross-contamination involving also Chapter 5 and includes reference to a new complementary toxicological assessment guidance.

Chapter 5: Productionmsw8(84 KB)
Reasons for changes: Changes have been made to sections 17 to 20 to improve the guidance on prevention of cross-contamination and to refer to toxicological assessment guidance. Changes were also introduced in sections 26 to 28 on the qualification of suppliers in order to reflect the legal obligation of manufacturing authorisation holders to ensure that active substances are produced in accordance with GMP. The changes include supply chain traceability. Section (33) is inserted to clarify and harmonise expectations of manufacturers regarding the testing of starting materials while section (68) introduces guidance on notification of restrictions in supply.

Chapter 6: Quality Controlmsw8(62 KB)
Reasons for changes:
Inclusion of a new section on Technical transfer of testing methods and other items such as out of specification results.

Chapter 8: Complaints, Quality Defects and Product Recallsmsw8(79 KB)
Reasons for changes:
- To reflect Quality Risk Management principles to be applied when investigating quality defects/complaints and when making decisions in relation to product recalls or other risk-mitigating actions.
- To emphasise the need for the cause(s) of quality defects/complaints to be investigated and determined, and that appropriate preventative actions are put in place to guard against a recurrence of the issue.
- To clarify expectations and responsibilities in relation to the reporting of quality defects to the Supervisory Authority.

Chapter 3 and 5 should be read in conjunction with the draft EMA guideline pdf(170 KB)on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities
Comments and suggestions are invited by 18 July 2013 and should be sent by email to: ADM-GMDP@ema.europa.eu and SANCO-pharmaceuticals-D6@ec.europa.eu

22/11/2012
Commission facilitates importation of pharmaceutical active substances from Switzerland

Switzerland has today been listed as the first third country with standards in the manufacture of active pharmaceutical ingredients equivalent to those of the EU. After a successful assessment, the European Commission concluded that the regulatory framework applicable to active substances exported to the Union from Switzerland, the respective controls and the enforcement activities are equivalent to those of the Union. This means in practice that Switzerland will not have to issue a 'written confirmation' for each consignment of active substance for medicinal product for human use imported into the EU as of 2 July 2013. The 'written confirmation' aims at verifying that the active substance is manufactured in compliance with standards of good manufacturing practices. Being listed by the European Commission or issuing a 'written confirmation' are two possible options introduced by the Falsified Medicines Directive to ascertain the quality of imported active substances.

More information:

06/09/2012
Publication of chapter 1, chapter 7 and Annex 2 of the detailed guidelines of the good manufacturing practices

Today, DG SANCO launches the publication of three revised guidelines:

  • Chapter 1 on Pharmaceutical Quality Systempdf(66 KB)is amended in order to align with the concepts and terminology described in the ICH Q10 tripartite guideline on Pharmaceutical Quality System. The title of the chapter itself is also changed accordingly.
  • Chapter 7 on Outsourced activitiespdf(21 KB)is revised in order to provide updated guidance on outsourced GMP regulated activities beyond the current scope of contract manufacture and analysis operations and in view of the ICH Q10 guideline on the Pharmaceutical Quality System The title of the Chapter has been changed to reflect this.
  • Annex 2 on Manufacture of Biological active substances and Medicinal Products for Human Usepdf(171 KB)is revised as a consequence of the restructuring of the GMP Guide, new manufacturing technology and concepts, the increased breadth of biological medicinal products to include several new product types such as transgenic derived products and the Advanced Therapy Medicinal Products, (ATMPs) together with associated new legislation.

Deadline for coming into operation: 31 January 2013

29/08/2012
Responses to the concept paper submitted for public consultation concerning the Delegated act on the principles and guidelines of good manufacturing practice for active substances in medicinal products for human use
The responses are available here.

25/07/2012
New rules on importing active pharmaceutical ingredients into the EU – information leaflet
An information leaflet on the new rules on importing active pharmaceutical ingredients into the EU is available herepdf(702 KB).

10/07/2012
Template for the 'written confirmation' for active substances exported to the European Union for medicinal products for human usepdf

Importation of active substances for medicinal products for human use - Questions and Answers (version 1.0)pdf(32 KB)

More information >>>

16/04/2012
Public consultation on a draft template for the written confirmation for active substances imported into the European Union for medicinal products for human use.pdf(47 KB)

The responses are available here :

Chongqin Pharmaceutical Research Institute, Dow Corning, Kyongbo, NKF, Qilu, Sandoz and TEVA asked not to publish their response

20/01/2012
Delegated act on the principles and guidelines of good manufacturing practice for active substances in medicinal products for human use - concept paper submitted for public consultation
pdf(35 KB)

Directive 2011/62/EU places an obligation on Member States to take appropriate measures to ensure that manufacturers of active substances on their territory comply with good manufacturing practice ('GMP') for active substances. It also places an obligation on the Commission to adopt, by means of delegated acts, the principles and guidelines of good manufacturing practice for active substances. This concept paperpdf(35 KB) is being released for public consultation with a view to preparing the delegated act on principles and guidelines of good manufacturing practice for active substances in medicinal products for human use.

The responses to the public consultation can be found here

7/12/2011
Implementing act on the requirements for the assessment of the regulatory framework applicable to the manufacturing of active substances of medicinal products for human use - Concept paper submitted for public consultationpdf(52 KB)

Directive 2011/62/EU introduces EU-wide rules for the importation of active substances: According to Article 46b(2) of Directive 2001/83/EC, active substances shall only be imported if, inter alia, the active substances are accompanied by a written confirmation from the competent authority of the exporting third country which, as regards the plant manufacturing the exported active substance, confirms that the standards of good manufacturing practice and control of the plant are equivalent to those in the Union. The requirement of a written confirmation is waived for third countries listed by the Commission in accordance with Article 111b of Directive 2001/83/EC. Article 111b(2) of Directive 2001/83/EC provides that the Commission adopts an implementing measure to apply these requirements. This concept paper is being rolled out for public consultation with a view to preparing this implementing act.

10/05/2011
Publication of the revised Annex 14 of the GMP guidepdf(50 KB) as regards the manufacture of medicinal products Derived from Human Blood or Plasma

Today, the unit in charge of pharmaceuticals launches the publication of the revised Annex 14 of the GMP guide on the manufacture of medicinal products Derived from Human Blood or Plasma
The Annex has been revised in the light of Directive 2002/98/EC and relevant implementing directives setting standards of quality and safety for the collection and testing of human blood and blood components for all uses, including the manufacture of medicinal products.
Deadline for coming into operation: 30 November 2011

19/11/2010
Public consultation of the revised chapter 5 of the GMP laying down the detailed guidelines for production pdf(38 KB)


Today, DG SANCO launches a public consultation of chapter 5 of the good manufacturing practices pdf(38 KB)laying down the detailed guidelines on production. Changes are proposed on the qualification of suppliers of starting material, the supply chain traceability for starting materials and the testing of starting materials.

Comments and suggestions are invited by 28 February 2011 and should be sent by email to: SANCO-gmp@ec.europa.euand ADM-GMDP@emea.europa.eu

9/11/2010
Public consultation of the revised chapter 7 of the GMP laying down the detailed guidelines for outsourcing activities

pdf(18 KB)
Today, DG SANCO launches a public consultation of the revised chapter 7 of the good manufacturing practices on outsourced activities.
Following the ICH Q10 guideline on the Pharmaceutical Quality System, Chapter 7 of the GMP Guide has been revised pdf(18 KB)to provide guidance on outsourced activities beyond the current scope of contract manufacture and analysis operations.

Comments and suggestions are invited by 28 February 2011 and should be sent by email to: SANCO-gmp@ec.europa.euand ADM-GMDP@emea.europa.eu

19/04/2010
Public consultation on Annex 2 of the GMP laying down the guidelines for the manufacture of biological medicinal substances and products for human use
pdf(103 KB)
Today, the unit in charge of pharmaceuticals launches a public consultation on Annex 2 of the good manufacturing practices laying down the guidelines for the manufacture of biological medicinal substances and products for human use.Annex 2 is proposed to be revised as a consequence of the restructuring of the GMP guide, the increased breadth of biological products to include several new product types such as transgenic derived products and the Advanced Therapy Medicinal Products, (ATMPs) together with associated new legislation. Significant changes have also been made as a result of the comments received from the first consultation.

Comments and suggestions are invited by 15 July 2010 and should be sent by email to: adm-gmdp@ema.europa.eu and ENTR-GMP@ec.europa.eu

04/12/2009
Public consultation on part III of the GMP guidelines on the preparation of the site master filepdf(42 KB)

Today, the DG Enterprise launches a public consultation on part III of the good manufacturing practices laying down guidance to manufacturers in preparing site master files.

Comments and suggestions are invited by 31 March 2010 and should be sent by email to: ADM-GMDP@ema.europa.euand ENTR-GMP@ec.europa.eu

16/11/2009
Public consultation on chapter 1 of the GMP laying down the guidelines for Quality Management System

Today, the DG Enterprise launches a public consultation on part I, chapter 1 of the good manufacturing practices laying down the guidelines on Quality Management Systempdf(51 KB). Chapter 1 is proposed to be updated to take into account the principles of “Pharmaceutical Quality System” as described in the ICH Q10 guideline.

Comments and suggestions are invited by 18 February 2010 and should be sent by email to: gmp@emea.europa.eu and ENTR-GMP@ec.europa.eu

16/11/2009
Public consultation on chapter 2 of the GMP laying down the guidelines for Personnel

Today, the DG Enterprise launches a public consultation on part I chapter 2 of the good manufacturing practices laying down the guidelines on Personnelpdf(17 KB). Chapter 2 is proposed to be updated to take into account the principles of “Pharmaceutical Quality System” as described in the ICH Q10 guideline.

Comments and suggestions are invited by 18 February 2010 and should be sent by email to: gmp@emea.europa.eu and ENTR-GMP@ec.europa.eu

22/03/2007
In preparation of a Directive on GMP for certain excipients following Article 46 (f) of Directive 2001/83/EC, as amended by Directive 2004/27/EC, DG Enterprise and Industry asks excipient manufacturers and manufacturers/ importers of medicinal products for human use (excipient users) to contribute to an online consultation on possible impacts of different policy options. Excipient distributors may also participate in this consultation. With the questionnaires for excipient manufacturers and excipient users we also publish the draft "Specific Conditions of the Application of the Principles and Guidelines of GMP for Certain Excipients"pdf(23 KB) as a possible basis for a GMP Directive. Before responding, please carefully read the attached instruction notemsw8(884 KB) . For separate comments to the draft specific GMP conditions please use the template for comments as attached to the instruction note.

Excipient manufacturers and excipient users are asked to respond by 30 July 2007. Small and medium size enterprises are specifically encouraged to contribute to this consultation.

03/05/2006

GMP Annex 7 "Manufacture of Herbal Medicinal Products" : Draft revision for public consultationpdf(28 KB)
The annex has been revised in the light of new GMP requirements for actives substances used as starting materials (GMP Part II). It specifies application of Part II for the manufacture of herbal medicinal products. Additional changes are in particular related to the new Directive 2004/24/EC on traditional herbal medicinal products.

Public comments should be sent to sabine.atzor@ec.europa.eu and gmp@emea.eu.int by 31 July 2006.

20/12/2005
New GMP Annex 19 for Reference and Retention Samplespdf(24 KB)


This new annex to the GMP Guide provides guidance on the taking and holding of reference samples of starting materials, packaging materials and finished products as well as for retention samples of finished products. The annex provides definitions of the terms "reference sample" and "retention sample", which hitherto were often incorrectly considered as synonyms. Updated guidance is also given on the size of reference samples and a consequential change was made to Chapter 6, section 14, of the GMP Guide to maintain consistency (see News on 08/11/2005). Both the revised Chapter 6 and Annex 19 will come into operation on 01 June 2006.

20/12/2005

Revised GMP Part I/ Chapter 8 on Complaints and Product Recallpdf(18 KB)
The revision was made to raise awareness of the possibility that a reported quality defect may be the result of counterfeiting activity and to clarify that the discovery of a counterfeit medicinal product should be reported to the competent authority. These changes are in line with WHO recommendations. The revised Chapter 8 will come into operation on 01 February 2006.

11/11/2005

Draft Amendment to Annex 1 of the GMP guide for public consultationpdf(37 KB) (corrected version)
Following a revision of Annex 1 on the manufacture of sterile medicinal products, which was launched in May 2003, the need for an ongoing discussion on the table providing environmental cleanliness and a number of other aspects to the annex were identified. The results of this discussion are reflected in the draft amendment of the guide. Public comments are invited on the proposal and should be sent to Sabine.Atzor@ec.europa.eu and David.Cockburn@emea.eu.int before 30 April 2006.

8/11/2005

New GMP Provisions for Product Quality Review and On-going Stability Programme:
Revision of GMP Guidelines, Part I Revision ofChapter 1pdf(23 KB) and Chapter 6pdf(33 KB)
Chapter 1 on Quality Management has been revised to include new requirements on Product Quality Review and is now published in a consolidated version. The revised chapter will come into force in January 2006. Although companies should already have most of the information requested available, it is recognised that some time will be necessary to develop and establish a system and associated procedures to implement this new requirement. Therefore, companies performing their first Product Quality Review in 2006 should cover a period of at least 6 months. Subsequent reports should cover a full 12 months' period.
Chapter 6 on Quality Control includes new provisions for an On-going Stability Programme and an update for reference samples and is also published in a consolidated version. The revised Chapter will come into operation on 01 June 2006.

10/10/2005

Restructuring of GMP guide - Revised basic requirements for active substances used as starting materials now public as GMP Part II
The Commission has published the basic requirements for the manufacture of active substances used as starting materials as GMP Part IIpdf(154 KB) replacing the former GMP Annex 18. Compared to Annex 18, the modifications refer to the introduction, indicating that the guide is applicable both for active substances used in the manufacture of human and veterinary medicinal products. The technical requirements remain unchanged compared to the former Annex 18.
A legal provision for the application and publication of GMP Part II is laid down in Article 47 and Article 51 of Directive 2001/83/EC and 2001/82/EC, respectively. Member States shall bring the requirements into force by 30 October 2005 at the latest.
With the implementation of GMP provisions for active substances the GMP Guide was re-structured. The existing basic requirements have now become Part I, the existing annexes remain, except for Annex 18, which has now been withdrawn. For additional information see revisedintroduction to the GMP guidepdf.

10/10/2005

Compilation of Community Procedures on Inspections and Exchange of Information updated to include new EU formats and proceduresmsw8
The updated Compilation includes a revised EU format for the manufacturing authorisation. In addition, the EU inspection report format was updated and the guideline on the preparation of reports under the centralised system revised. A new format for GMP certificates was elaborated. A new procedure on inspection triggers for the conduct of inspections at the premises of manufacturers of active substances used as starting materials was developed jointly with the Member States' authorities. The new September 2004 version of the Compilation was published by the EMEA on behalf of the Commission after the Veterinary Pharmaceutical Committee and the Pharmaceutical Committee had been consulted.
There was a need to update the currently existing manufacturing authorisation and inspection report formats based on practical experiences and the new provisions of Directive 2001/83/EC and of Directive 2001/82/EC, as amended by Directives 2004/28/EC and 2004/27/EC respectively. In addition, the Commission was entitled to publish guidance on the form and content of the GMP Certificate (Articles 47 and 51 respectively).
The new "Guidance on occasions when it is appropriate for competent authorities to conduct inspections at the premises of manufacturers of active substances used as starting materials" was developed in the light of the new obligations of manufactures to ensure the application of GMP for active substances and corresponding inspection provisions for Member States.
The Compilation of Community Procedures is under ongoing development by the EMEA, using Member States' expertise through the Ad Hoc Working Group of GMP inspectors.

17/06/2005

International Conference on Harmonization : ICH Q9 on Risk Management has reached step 2pdf
After having reached step 2 the document ICH Q9 Quality Risk Management is now available as "Note for Guidance on Quality Risk Management" (EMEA/INS/GMP/157614/2005-ICHpdf - transmission to Interested parties May 2005) for public consultation on the Website of the EMEA.
The document is meant to complement GMP guidelines and to support existing and future guidelines published by CHMP and CVMP concerning the quality of medicinal products.

Although developed within ICH the processes, tools and examples are expected to be equally useful in the context of medicinal products for veterinary use. Public comments on this point would be particularly welcome.

Comments should be sent to Sabine.Atzor@ec.europa.eu and in parallel to David.Cockburn@emea.eu.int by 31 August 2005.

- EMEA's inspection website "Compilation of Community Procedures" -EudraLex Volume 4 - Medicinal products for human and veterinary use : Good manufacturing practices

08/03/2005

Concept Papers available for revision of GMP Guide, Sub-Chapter 3.6 on dedicated facilities and Annex 14, defining requirements for medicinal products derived from human blood or plasma.
For further information see the EMEA website on this subject.
Deadline for comments is 30.05.2005 to david.cockburn@emea.eu.int and sabine.atzor@ec.europa.eu.

08/03/2005

Inspections at Manufacturers of Active Substances - Guidance on Grounds (Triggers) for Inspection - for public consultation
The Commission services present a draft of the new 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 materialspdf(34 KB) . Article 111 of Directive 2001/83/EC, as amended by Directive 2004/27/EC, and Article 80 of Directive 2001//82/EC, as amended by Directive 2004/28/EC, include new provisions for inspections in this field. The Ad Hoc Working Group of GMP Inspection Services at the EMEA has developed this guidance as a harmonised approach for inspections under the amended EC legislation.

Please send your comments by 4 April 2005 to sabine.atzor@ec.europa.eu and gmp@emea.eu.int.
After finalisation the document will be published under the Compilation of Community Procedures.

08/03/2005

Detailed GMP guidelines for active substances used as starting materials - public consultation
The Commission presents a draft of the detailed guidelines on the principles of good manufacturing practice for active substances used as starting materials.

The draft revision only affects the introductory text (section1)pdf of the GMP Annex 18pdf, which has been published on the Commission´s website since 2001 implementing the Q7A guideline developed between the ICH partners EC, USA and Japan. No changes to the remaining sections 2-20 of the Annex are currently envisaged.

The Commission would like to emphasise that the document will be equally applicable to the veterinary sector. To take the account of the needs of the veterinary sector, ectoparacitides are excluded from the scope. Specific modifications, where identified for active substances to be used in veterinary medicinal products, can be developed in the GMP annexes 4 and 5 as appropriate.

Changes refer to

The structural implementation in the GMP guide as Part II of the "Basic Requirements" instead of Annex 18. The current "Basic Requirements" of the GMP guide will become Part I in the future. The remaining annexes will supplement both Part I and Part II as appropriate and a programme to review the guidance already given on active substances in annexes 2-7 is being undertaken. EMEA will publish a Concept paper on this shortly.

Section I "Introduction" to the existing Annex 18 (the future Part II of the basic requirements).

Specific exclusion of veterinary ectoparaciticides

Please send your comments by 4 April 2005 to sabine.atzor@ec.europa.eu and gmp@emea.eu.int.

The Commission intends to publish the final version before 30 October 2005. Legal provisions for this guideline are vested in Article 47 of Directive 2001/83/EC, as amended by Directive 2004/27/EC, for human medicinal products and Article 51 of Directive 2001/82/EC, as amended by Directive 2004/28/EC, for veterinary medicinal products.

08/03/2005

Authorisations for manufacturing and import & GMP certificates - form and content for public consultation
The Commission publishes a draft format for the authorisations for manufacturing and importpdf(32 KB) for public consultation. The Ad Hoc Working Group of GMP Inspection Services at the EMEA has developed the draft based on a format developed and published previously within the Compilation of Community Procedurespdf

The second draft document for public consultation refers to the GMP certificatepdf(28 KB) for manufacturers. Within 90 days of an inspection, the competent authorities shall issue such a certificate, if compliance with GMP requirements can be confirmed. Member States will have to implement these provisions by 30 October 2005. The format is based on that used in connection with the Mutual Recognition Agreements and has been adapted for application in all circumstances in which a GMP certificate is issued.

Please send your comments by 4 April 2005 to sabine.atzor@ec.europa.eu and gmp@emea.eu.int.

The Commission intends to publish the final version before 30 October 2005. Legal provisions for the form and content of the authorisation and the certificate of GMP are vested in Article 47 of Directive 2001/83/EC, as amended by Directive 2004/27/EC, for human medicinal products and Article 51 of Directive 2001/82/EC, as amended by Directive 2004/28/EC, for veterinary medicinal products.

15/07/2004

Consultation on a proposal for a new Annex 19 (Reference Samples and Retention Samples) to the EU GMP Guide (Volume 4)
The new annex to the EU GMP Guide provides guidance on the taking and holding of reference samples of starting materials, packaging materials and finished products as well as for retention samples of finished products. The annex provides definitions of the terms "reference sample" and "retention sample", which are often incorrectly considered as synonyms. The guidance is wide ranging in scope and includes the case of multiple manufacturing sites, the position with respect to importers and what should happen when a manufacturing site ceases to operate. Updated guidance is also given on the size of reference samples and a consequential amendment will therefore be necessary to Chapter 6 section 14 of the GMP Guide to maintain consistency. The Pharmaceutical Committee has endorsed the proposal by written procedure. The document is released for a consultation period until 15 January 2005. Comments should be sent to GMP@emea.eu.int and Karin.Krauss@ec.europa.eu.

22/01/2004

GMP - Compilation of Community Procedures on Inspections and Exchange of Information
On behalf of the European Commission the EMEA is now responsible for maintaining and publishing the Compilation of Community Procedures. The Compilation is a collection of GMP inspection-related procedures and forms agreed by the GMP inspectorates of all Member States and designed to facilitate administrative collaboration, harmonisation of inspections and exchange of inspection-related information. EMEA is going to reformat, review and update the procedures and incorporate new additions as soon as possible after they have been agreed.
EMEA's inspection website "Compilation of Community Procedures" 19/12/03 Note to the Members of the GMP Inspectors group - Interpretation of Articles 51(1)b of Directive 2001/83/EC and 55(1)b of Directive 2001/82/EC.pdf(18 KB)
The document outlines the principles of import of medicinal/veterinary medicinal products from 3rd countries and the obligation of retesting of batches.

15/12/2003

"On going Stability - Addition to Chapter 6 to the EU Guide to Good Manufacturing Practice"pdf(80 KB)
The additional text "On going Stability" for Chapter 6 to the EU GMP Guide has been adopted by the Ad hoc GMP inspectors Working Group at their meeting in October 2003. The proposed text provides guidance on ongoing stability monitoring thereby clarifying that ongoing stability monitoring is a Community GMP expectation in line with the GMP requirements of our MRA partners. The Pharmaceutical Committee has endorsed the proposal through written procedure. The document is released for a consultation period until 15 June 2004. Comments should be sent to GMP@emea.eu.int and in parallel to Karin.Krauss@ec.europa.eu.

15/12/2003

"Product Quality Review - Addition to Chapter 1 to the EU Guide to Good Manufacturing Practice"pdf(100 KB)
The additional text "Product Quality Review" for Chapter 1 to the EU GMP Guide has been adopted by the Ad hoc GMP inspectors Working Group at their meeting in July 2003. The proposal arises from the experience of Member States' inspectorates where quality problems with products on the market leading to recall could have been anticipated if the manufacturer/marketing authorisation holder had operated a system for formally reviewing process consistency and trends. The Pharmaceutical Committee has endorsed the proposal through written procedure. The document is released for a consultation period until 15 June 2004. Comments should be sent to GMP@emea.eu.int and in parallel to Karin.Krauss@ec.europa.eu.

27/10/2003

Commission Directive 2003/94/ECpdf , of 8 October 2003, laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use
Replacement of Commission Directive 91/356/EC of 13 June 1991 to cover good manufacturing practice of investigational medicinal products.

03/06/2003

Revision of Annex 1 (Manufacture of sterile medicinal products) to the EU GMP Guide (Volume 4)
The revision of Annex 1 to the EU GMP Guide has been adopted by the Ad hoc GMP inspectors Working Group at their meeting on 28-29 April 2003. The amendments only concern section 3 harmonising where appropriate the environmental standards for clean rooms laid down in the GMP Guide with those laid down in international standards (e.g. EN/ISO 14644-1) together with a minor change to section 20. The remainder of the annex is unchanged. The Pharmaceutical Committee has adopted the revised version at its meeting on 15 May 2003 fixing 1 September 2003 as date for coming into operation.

10/03/2003

"Qualifizierung und Validierung" Choose translations of the previous link Deutsch (de)
The document is the German version of the Annex 15 to the EU GMP Guide with title "Qualification and Validation". The updated version has been provided by Germany (ZLG) and has been agreed by the German "Länder", the German Health Ministry, the German Working Group "Medicinal Gases" and also the Austrian Authorities. Germany has asked us to add this updated version and to remove the old DE version from our website.
EudraLexVolume 4 - Medicinal products for human and veterinary use : Good manufacturing practices

10/03/2003

"Zertifizierung durch eine sachkundige Person und Chargenfreigabe"pdf
The document is the German version of the Annex 16 to the EU GMP Guide with title "Certification by a Qualified person and Batch Release". The version has been provided by Germany (ZLG) and has been agreed by the German "Länder", the German Health Ministry, the German Working Group on "Inspections" and also the Austrian Authorities. Germany has asked us to add this version to the versions (EN, EL, ES, FR, IT, NL) already published on our website.
EudraLexVolume 4 - Medicinal products for human and veterinary use : Good manufacturing practices

10/03/2003

"Parametrische Freigabe" Choose translations of the previous link Deutsch (de)
The document is the German version of the Annex 17 to the EU GMP Guide with title "Parametric Release". The version has been provided by Germany (ZLG) and has been agreed by the German "Länder", the German Health Ministry, the German Working Group on "Inspections" and also the Austrian Authorities. Germany has asked us to add this version to the versions (EN, ES, FR, IT, NL) already published on our website.
EudraLexVolume 4 - Medicinal products for human and veterinary use : Good manufacturing practices

20/11/2002

Consultation on a new proposal for a revision of Annex 1 (Manufacture of sterile medicinal products) to the EU GMP Guide (Volume 4)pdf(122 KB)
The new proposal for a revision of Annex 1 to the EU GMP Guide has been adopted by GMP inspectors at their meeting on 23 October 2002. The amendments have primarily been introduced to harmonise the environmental standards for clean rooms laid down in the GMP Guide with those laid down in international standards (e.g. EN/ISO 14644-1). The Pharmaceutical Committee has endorsed the proposal at its meeting on 13 November 2002. The document is released for a consultation period until 10 January 2003.
Comments should be sent in parallel to GMP@emea.eu.int and to Karin.Krauss@ec.europa.eu

02/05/2002

Modifications to Commission Directive 91/356 of 13 June 1991 laying down the principles and guidelines of good manufacturing practice for medicinal products for human use, as required by Directive 2001/20/ECpdf(105 KB)
Following discussion within the working parties on medicinal products and inspections (Good manufacturing practices and Good clinical practices sectors) modifications to Commission Directive 91/356 are proposed to incorporate the principles and guidelines of good manufacturing practice for investigational medicinal products referred to in Article 13.3 and in the requirements for a manufacturing authorisation referred to in Article 13.1 of the Directive on Good Clinical Practice.
The draft proposal is released for a 3 months consultation period.pdf(105 KB)
Two column informal working documentpdf(138 KB)

21/04/2002

EudraLex Volume 4 : Medicinal products for human and veterinary use : Good manufacturing practices
DE, ES, FR, IT, NL versions of annexes 6, 15, 16, 17 are available

12/04/2002

Publication of Guidance Document on the Implications of the Operational phase of the GMP annexes to the Protocol to the European agreement on Conformity assessment and Acceptance of industrial products (PECA) with European Union associated countriespdf(213 KB)
Following the entry into force of the GMP and Batch certification annex of the PECA agreements with Hungary on 1st December 2001 and Czech Republic on 1st January 2002, the Commission has prepared a document which aims to describe and provide guidance on the key activities which should be undertaken by industry and regulators in the EU
and in an associated country with which a PECA concerning Good Manufacturing Practice (GMP) has entered into force. The content of the manufacturer's certificate of compliance and the batch certificate which must be prepared by the company are described.

22/11/2001

Revision of Good Manufacturing Practices annex 13 to implement directive on Clinical Trials on medicinal products for human use.
Following discussion within the working parties on medicinal products and inspections (Good manufacturing practices and Good clinical practices sectors) the Annex 13 "Manufacture of investigational medicinal products" of the Guide provided by the Commission Directive 91/356/EEC laying down the principles and guidelines of good manufacturing practices (GMP) for medicinal products for human use (Volume 4 - Pharmaceutical legislation - Good manufacturing practices) has been revised in order to implement the "Detailed Guidelines" for the manufacture and the labelling of investigational medicinal products as provided for in Directive 2001/20/EC relating to the implementation of good clinical practice in the conduct of clinical trails on medicinal products for human use.
The draft 1 is released for a 6 months consultation period.
COMMENTS ARE EXPECTED BEFORE 1 MAY 2002 and should be sent to arielle.north@ec.europa.eu

15/10/2001

New version of compilation of Community procedures on inspections and exchange of informationpdf(465 KB)
An updated compilation of administrative procedures for GMP inspections has been prepared.
This compilation updates and replaces document III/5698/94 which had been prepared within the ad hoc group of inspectors and published by the Commission. It includes guidance for inspectors on rapid alerts, exchange of information between inspectorates, batch certificates and a format for a community inspection report.

19/07/2001

ICH guideline published as annex to the EU Guide to Good Manufacturing Practice, Eudralex Volume 4
On 18th July 2001, the Commission adopted a new legislative proposal which introduces a requirement for pharmaceutical manufacturers to use only active substances which have been manufactured according to GMP in the manufacture of medicinal products. Until this comes into force requirements for GMP for active substances and hence the applicability of this guideline will not be mandatory in the EU. However when there are causes for concern, or when required by certain Member States, GMP inspections of active ingredient manufacturers may be carried out by the competent authorities of Member States. In these cases, and in particular when these are performed in the context of an application for a centralised authorisation, it has been agreed that the inspectors of the competent authorities in the EU will inspect against the requirements in this guideline, now published as Annex 18 to the EU guide to Good Manufacturing Practice.
Annex 18pdf
EudraLex Volume 4

12/07/2001

New annexes to the EU Guide to Good Manufacturing Practice, Eudralex Volume 4
Following discussion within the Working party on medicines and inspections, 4 new annexes to Eudralex Volume 4 of the Rules governing medicinal products in the Community have been finalised. Annex 6 is a revision to the current annex on Manufacture of Medicinal gases and should replace current requirements from September 2001. Annex 15 on Qualification and Validation is also due to come into operation In September 2001. Annex 16 concerns the arrangements for Certification by a Qualified Person and Batch Release in the Community and is due to come into operation from January 2002. Annex 17 addresses Parametric Release and is also due to come into operation in January 2002. These annexes will also be translated into the current language versions of Eudralex Volume 4.
Annex 6pdf(139 KB)
Annex 15pdf(136 KB)
Annex 16pdf
Annex 17pdf(124 KB)
EudraLex Volume 4

07/06/2001

Revision of Annex 1 to Volume 4 of The Rules Governing Medicinal Products in the European Union
Following discussion in the EU inspectors' group, Paragraph 42 of Annex 1 to Volume 4pdf of The Rules Governing Medicinal Products in the European Union has been revised to take account of current practices. These changes have necessitated three additional entries in the glossarypdf(27 KB). The changes have been introduced in English into the relevant part of the documents on this web-site. Translations of the changes will be available in the near future and the corresponding edits will be made. The changes are indicated here for your information
(EudraLex Vol 4)
View modificationspdf(59 KB)

06/02/2001

Draft revised version of Annex15 of the GMP: Validation master plan : Design qualification, installation and operational qualification, non-sterile process validation, cleaning validation for information.pdf(131 KB) 26/01/01 Revised Draft of Annex to the Guide to Good Manufacturing Practice for Medicinal Products: Certification by a Qualified Person and Batch Releasepdf(178 KB) (available for comments until 15 March 2001) 25/10/00

Revised Version of Annex 14 - Manufacture of medicinal products derived from human blood or plasma to the EU Guide to Good Manufacturing Practice

27/07/2000

ICH Step 2 Document on GMP for active pharmaceutical ingredients released for consultation

Following discussions within ICH, agreement on a draft ICH Good Manufacturing Practice Guide for Active Pharmaceutical Ingredientspdf(128 KB) has been reached at "Step 2" of the ICH process. The document is now released for public consultation. In order to facilitate the submission and review of comments on this draft guide, two methods for submitting comments have been developed. Interested parties may submit comments to the European Commission either in writing in the normal manner or by downloading a comments templatepdf . Electronic submission of comments is encouraged, since it is anticipated that widespread use of this method will increase the effectiveness of the guidance development process. This document will become an annex to Volume 4 of the Rules Governing Medicinal Products in the European Union.

Please submit comments using the form provided to Gordon.Munro@mca.gov.uk and Emer.Cooke@ec.europa.eu by 30th September 2000.

27/04/2000

Procedure for Handling Rapid Alerts and Recalls Arising from Quality Defects has been agreed by the inspectors group for use within the Community from 1st April 2000. English Versionpdf(123 KB) Choose translations of the previous link français (fr) françaisVersion Françaisepdf(123 KB) Choose translations of the previous link français (fr) français

10/04/2000

A draft text of Annex 17 Parametric Release to the EU Guide to Good Manufacturing Practice was released for consultation on the 7 April 2000. The proposed deadline for comments is September 2000. 31/03/00 Annex 14 Manufacture of medicinal products derived from human blood or plasma to the EU Guide to Good Manufacturing Practice was adopted at the Ad-hoc meeting of the GMP Inspection services on the 11 February 2000. It is expected to come into operation on the 1 September 2000 31/03/00 A draft text of Annex 6 Manufacture of medicinal gases to the EU Guide to Good Manufacturing Practice was released for industry consultation on the 23 March 2000. The Proposed deadline for comments is the 31 August 2000.

17/12/1999

GMP Inspection report - Community format Document
A basic format for the presentation of Good Manufacturing Practice Inspection report in the community has been adopted for use for a trial period of one year. This format is now available in all Community languages.
PDF formatpdf(84 KB) Choose translations of the previous link dansk (da) Deutsch (de) ελληνικά (el) español (es) français (fr) italiano (it) Nederlands (nl) português (pt) suomi (fi) svenska (sv)

Word formatpdfdanskDeutschελληνικάespañolfrançaisitalianoNederlandsportuguêssuomisvenska

9/12/1999

Good Manufacturing Practice for medicinal products - Certification by a qualified person and batch release
A draft annex to the 1997 EU Guide to Good Manufacturing Practice - Eudralex Volume 4 is released for consultationpdf(121 KB) . Comments are expected before May 2000.

30/10/1999

Good Manufacturing Practice - Validation master plan : Design qualification, installation and operational qualification, non-sterile process validation, cleaning validation.
A draft annex to the 1997 EU Guide to Good Manufacturing Practice - Eudralex Volume 4 is released for consultationpdf(273 KB) .

21/10/1999

GMP Inspection reportpdf(124 KB) Choose translations of the previous link dansk (da) Deutsch (de) ελληνικά (el) español (es) français (fr) italiano (it) Nederlands (nl) português (pt) suomi (fi) svenska (sv) - Community format
A basic format for the presentation of Good Manufacturing Practice Inspection report in the community has been adopted for use for a trial period of one year. This format is only available in English versionpdf(85 KB), the other language versions will be available soon. 23/09/99 Community Basic Format for Manufacturing Authorisation. A basic format and contentpdf(124 KB) Choose translations of the previous link dansk (da) Deutsch (de) ελληνικά (el) español (es) français (fr) italiano (it) Nederlands (nl) português (pt) suomi (fi) svenska (sv) for manufacturing authorisations granted by competent authorities in accordance with Article 16 of Council Directive 75/319/EC and Article 24 of Council Directive 81/851/EC has been agreed. This format is now available in all Community languages.

04/02/1999

Inspection and Control of medicinal products - information on the outcome of the expert group meeting on 17 and 18 December 1998.pdf(58 KB) 24/09/98 A revised guideline on Control Authority Batch Release of Vaccines and Blood Products.pdf(75 KB)
In September 1998 the Pharmaceutical Committee approved a revised guideline on Control Authority Batch Release of Vaccines and Blood Products which will replace two 1994 guidelines, one for vaccines and the other for blood products (III/3859/92). It has been drafted by the Network of EU OMCLs responsible for official batch release of vaccines and blood products in consultation with the industry. It will facilitate and improve the transparency of the mutual recognition of official batch release. Annex IId: the Control authority batch release certificate of approval for plasma pools, will be include once it has been finalised (later this year).

03/06/1998

Inspection and GMPpdf(31 KB) . Information on the outcome of the Expert Group on Inspection and Control of medicinal products Meeting 20 March 1998

29/05/1998

GMP for medicinal products derived from human blood or plasmapdf(40 KB) . DG III releases a draft revision of Annex 14 to the EU Guide to Good Manufacturing Practice, comments are requested before 31 August 1998