How to comment on Draft EU GMP Annex 1

News from the European Medicines Agency:

Targeted stakeholders consultation on the revision of annex 1, on manufacturing of sterile medicinal products, of the Eudralex volume 4

Period of consultation

From 20 December 2017 to 20 March 2018.

Objective of the consultation

Annex 1 was first published in 1971, since then it has undergone a number of targeted updates but, until now it has not undergone a full review. This revision is intended to add clarity, introduce the principles of Quality Risk Management to allow for the inclusion of new technologies and innovative processes and to change the structure to a more logical flow. Key changes are:

• Introduction of new sections: scope, utilities, Environmental and process monitoring sections and glossary 
• Introduction of QRM Principles 
• Restructured to give more logical flow 
• Added detail to a number of the previous sections to provide further clarity. 

Acknowledgment

In order to maintain the global alignment of standards, achieving at the same time assurance for the highest quality, the proposed revised version was prepared in cooperation with WHO and PIC/S. The document will be subject to parallel public consultation by WHO and PIC/S.

How to submit your contribution

Please provide feedback using the template enclosed sending it to SANTE-REVISION-ANNEX-1@ec.europa.eu.

They can also be sent by post to Directorate-General for Health and Food Safety, Unit SANTE B/4, BE-1049 Brussels. The subject line of the letter or email should contain the reference "Targeted Public Consultation – Revision of annex 1 of EU GMP Guide".

When submitting your response, please include your name and e-mail address and specify if you are responding as an individual or as a representative of an organisation. If you represent an organisation, please indicate its name and category (company/business; public authority (local, regional, national, international); NGO; patient organisation; other).

If you represent a company, please state whether it falls within the EU definition of a small and medium-sized enterprise (i.e. less than €50 million annual turnover and fewer than 250 employees).

If your organisation is registered in the Transparency Register, please indicate your Register ID number at the beginning of your contribution.

The consultation document

The consultation document can be downloaded here.

The template for comments can be downloaded here.

Contact details

Responsible service: Directorate-General for Health and Food Safety - Unit B4 - Medical Products: quality, safety, innovation.

E-mail: SANTE-REVISION-ANNEX-1@ec.europa.eu

Any queries about the public consultation should be sent to this mailbox.

European and US regulators agree on mutual recognition of inspections

Important news for those who work in organizations that regularly receive both U.S. FDA and European medicines agency inspectors. This has been a long time coming...a new transatlantic agreement is now in place, designed to will help to make better use of inspection capacity and reduce duplication.

This means Regulators in the European Union (EU) and the United States (US) have agreed to recognize inspections of manufacturing sites for human medicines conducted in their respective territories on both sides of the Atlantic.

Here is a press release from the European Medicines Agency (dated March 2, 2017):

Each year, national competent authorities from the EU and the US Food and Drug Administration
(FDA) inspect many production sites of medicinal products in the EU, the US and elsewhere in the world, to ensure that these sites operate in compliance with good manufacturing practice (GMP). Under the new agreement, EU and US regulators will rely on each other’s inspections in their own territories. In future, the need for an EU authority to inspect a site located in the US, or vice versa, will be limited to exceptional circumstances.

The agreement will enable both the EU authorities and the FDA to make better use of their inspection resources to help them to focus on other parts of the world where active pharmaceutical ingredients (APIs) and medicines for the EU or US markets are manufactured. This will ensure that patients can rely on the quality, safety and efficacyof all medicines, no matter where they have been produced. Around 40% of finished medicines marketed in the EU come from overseas and 80% of the manufacturers of APIs for medicines available in the EU are located outside the Union.

In the EU, inspections of manufacturing sites are carried out by national competent authorities from EU Member States. The European Medicines Agency plays an important role in coordinating these activities in collaboration with Member States.

The agreement is underpinned by robust evidence on both sides of the Atlantic that the EU and the US have comparable regulatory and procedural frameworks for inspections of manufacturers of human medicines. Teams from the European Commission, EU national competent authorities, EMA and the US FDA have been auditing and assessing the respective supervisory systems since May 2014, and have worked closely together to reach this agreement.

The agreement is an annex to the EU-US MRA which was signed in 1998 but is not yet implemented. Many provisions of the agreement have already entered into force and others will enter into force on November 1, 2017. By that date, the EU will have completed its assessment of the FDA and the FDA is expected to have completed its assessment of at least eight EU Member States, and will be gradually expanded to all Member States. The text of this agreement is now published on the website of the European Commission’s Directorate General for Trade.

Source: EMA

Posted by Dr. Tim Sandle

EMA Admits Brexit May Cause Significant Disruption

Guido Rasi, Executive Director of the European Medicines Agency (EMA), has conceded that the planned exit of the U.K. from the European Union (EU) could have a major impact on the activities of the EMA.

“The extent of the impact of Brexit on the Agency’s operations and location is uncertain and will depend on the future relationship between the EU and the UK,” he told the EMA’s Management Board. “Depending on the outcome of the negotiations, this could cause significant disruption to the Agency’s operations and business continuity plans will need to be in place.”


As part of its preparedness, EMA will continue carrying out impact assessments to identify the main risks and propose measures to maintain its ability to protect public health, Rasi added.

Speculation about a possible new location for EMA is likely to continue throughout 2017, however. Denmark, Germany, Ireland, Italy and Sweden have expressed a keen interest in accommodating the agency, according to a report in The Guardian newspaper on August 1st, 2016.

Despite the uncertainty caused by the outcome of the U.K. referendum, EMA remains committed to carrying on with its responsibilities as usual, according to Rasi. The Board has adopted a budget of 322 million euros for 2017, a 4.4% increase over the previous year. This is expected to cover the 5.4% increase in its fee-financed workload and will also allow the EMA to focus on priority areas such as antimicrobial resistance, supporting innovation and access to both human and veterinary medicines, increasing and improving regulatory capacity and capability as well as its continued commitment to increased transparency, he stated. The work program is being finalized and will be published by the end of January 2017.

Also, the Board endorsed an extension of the concept of multinational assessment teams to post-authorization assessments. EMA has encouraged the formation of assessment teams not by country but by expertise since 2013, initially for the assessment of new medicines. Following the endorsement by the Board, assessment teams made up of experts from several member states will be able to evaluate applications for extensions of marketing authorizations of existing medicines as of April 2017.

The Board approved the launch of a public consultation to revise the agency’s policy on access to documents. The revision seeks to take account of the experience gained since the current policy came into effect in 2010 and to extend its scope to include both access to documents that relate to human or veterinary medicines as well as to corporate information. The launch of the consultation, including the publication of the consultation documents, is expected in January 2017.

Source: Applied Clinical Trials

New Process Validation Guideline (EMA)

The European Medicines Agency has published the following concept paper ‘Guideline on process validation for finished products -information and data to be provided in regulatory submissions’.

Process validation can be defined as documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes. Continuous process verification has been introduced to cover an alternative approach to process validation based on a continuous monitoring of manufacturing performance. These concepts form the basis of the new guideline.

The guideline is brought into line with ICH Q8, Q9 and Q10 documents and the possibility to use continuous process verification in addition to, or instead of, traditional process validation described in the previous guideline has been added and is encouraged. This guideline does not introduce new requirements on medicinal products already authorised and on the market, but clarifies how companies can take advantage of the new possibilities given when applying enhanced process understanding coupled with risk management tools under an efficient quality system as described by ICH Q8, Q9 and Q10.

The EMA paper can be accessed here.

Posted by Tim Sandle