Worldwide: Impact Of The EU-US Mutual Recognition Agreement On Pharmaceutical Product Inspections

The Mutual Recognition Agreement: An Overview

It has been a long journey for the European Union (EU) and the United States of America (the USA) to reach the current form of the Mutual Recognition Agreement for Good Manufacturing Practice (GMP). From a historical perspective, in 1998 the EU and the USA entered into a Mutual Recognition Agreement (MRA), and while it included provisions concerning current Good Manufacturing Practices (GMPs) for medicines, the relevant annex was never fully implemented. In fact, Article 1.3 of the Annex contained two definitions of "Good Manufacturing Practices" and stated "the US and EC [European Community, now EU] have agreed to revisit these concepts." Since May 2014, regulatory authorities on both sides of the Atlantic have re-energized the initiative to reach an agreement to amend the original sectoral Annex for GMP of the MRA. The updated revised agreement took effect on 1 March 2017 following the signature of the USA and the European Commission, which took place on 19 January 2017 and 1 March 2017, respectively.

A response to the challenges posed by an increasingly global drug supply chain, the purpose of this MRA on GMPs is to allow the US Food and Drug Administration (FDA) and relevant regulatory authorities in the EU to rely on the results of each other's GMP inspections to facilitate cross-border movement of medicines between the two trading partners, and improve oversight of manufacturing facilities.1 The MRA extends the ongoing collaboration and cooperation in relation to various regulated activities between the two regions.

The updated agreement is a result of successful cooperation between the European Commission, the European Medicines Agency, and FDA. The agreement has entered into force, and the recognition of inspections can apply as early as November of 2017 when it is expected that the EU will have completed its assessment of the FDA. FDA is also expected to have completed its assessment of at least eight EU Member States by that time, and will progressively expand that effort to all EU Member States.

A Joint Sectoral Committee will monitor the implementation of the GMP MRA and has authority to amend the GMP annex in certain respects, such as to update the products within the scope of the MRA or adopt technical and administrative arrangements for effective implementation.2

Once the GMP annex takes effect, it will impact the following principal areas:

  • exchange of information between the FDA and regulatory authorities in the EU;
  • trade of medicinal products and their constituent ingredients between the regions; and
  • GMP inspections.

Products Currently Covered by the MRA at this Time

The MRA applies to post-approval products and, to an extent, pre-approval products for human and veterinary products. Appendix 3 contains an indicative list of the products covered by the MRA and includes the following3 :

  • investigational products (clinical trial material);
  • marketed finished pharmaceuticals for human use (including homeopathic products and herbal products which are regulated as medicines by the EU and FDA);
  • marketed biological products such as vaccines for human use, plasma derived pharmaceuticals, therapeutic biotechnology-derived products, and allergenic products;
  • intermediates (for the EU) and in-process materials (for the USA);
  • active pharmaceutical ingredients or bulk drug substance; and
  • veterinary products.

These products are covered by the MRA to the extent that they are regulated by the authorities of both regions. However, human blood, human plasma, human tissues and organs, and veterinary immunologicals are excluded from the MRA.

Conditions for Mutual Acceptance of Inspections

Mutual recognition of GMP inspections and official GMP documents will not take place until both parties have assessed the regulatory authorities in the other region. The MRA is based on the guiding principle of equivalence, which is defined to mean that the regulatory system under which an authority operates is sufficiently comparable to assure that the process of inspection and the ensuing official GMP documents will provide adequate information to determine whether respective statutory and regulatory requirements of the authorities have been fulfilled. In the context of the MRA, equivalence does not require that the respective regulatory systems have identical procedures.

In order to determine whether to recognize an authority under the MRA framework, FDA and EU national competent authorities are subject to reciprocal assessments against the following agreed criteria set out in Appendix 4:

  • the legal authority to inspect against a standard for GMP;
  • the legal authority to manage conflict of interest in an ethical manner;
  • the ability to evaluate risks and mitigate them;
  • appropriate regulatory oversight of manufacturing facilities within its jurisdiction;
  • availability of sufficient resources;
  • availability of trained and qualified inspectors with the skills and knowledge to identify manufacturing practices that may lead to patient harm; and
  • availability of the tools necessary to take action to protect the public health arising from poor quality drugs or medicinal products.

Appendix 4 also establishes a procedure for assessment of EU authorities by FDA. Under this procedure, each EU Member State authority must submit a "capability assessment package" containing a variety of information (which FDA may modify on a case-by-case basis), such as inspection reports, standard operating procedures, and a conflicts of interest questionnaire. FDA then has 70 days from the date on which it receives a translation of all requisite information to make an initial capability determination. The Appendix further specifies that FDA will "dedicate two capability assessment teams" and will therefore conduct assessments of two Member State authorities at any given time.

Since the FDA is the only regulatory authority in the USA, the EU's task is less onerous and is targeted for completion by 1 July 2017. FDA will have to assess the regulatory authorities in all 28 EU Member States, which is scheduled for completion in accordance with the timelines in Appendix 5. Specifically, Appendix 5 sets out the following schedule for FDA to complete assessments:

  • 1 November 2017: eight assessments
  • 1 March 2018: four additional assessments
  • 1 June 2018: two additional assessments
  • 1 December 2018: six additional assessments
  • 15 July 2019: eight additional assessments4

Nonetheless, both regions have the right to suspend recognition of a recognized authority in an objective and reasoned manner.5 Once the assessment process is complete, each region will recognize pharmaceutical inspections and accept "official GMP documents" issued by a recognized authority of the other region for manufacturing facilities located in its territory, unless there is indication of material inconsistencies or inadequacies in an inspection report, quality defects identified in the post-market surveillance, or other specific evidence of serious concern in relation to product quality or consumer safety. 6

Processing, packaging, testing, and sterilizing facilities, including contract facilities performing these functions located in the USA and the EU, are all subject to the MRA.

Acceptance 7 of official GMP documents issued by a recognized authority of the other party for manufacturing facilities located outside the territory of the issuing authority is at the discretion of each region, and the MRA allows them to individually determine the terms and conditions under which it accepts such documents.

FDA does not routinely inspect all manufacturing facilities for investigational products during the conduct of clinical studies, although a pre-approval inspection is routinely conducted as part of the review of the approval application. In the EU, sites which manufacture investigational products are susceptible to GMP inspection given that the GMP requirements for such products are now aligned with that of marketed products. The updated agreement now allows regulatory authorities to carry out inspections of sites engaged in the manufacture and control of pre-approval products at the request of another.8

Mechanism for Greater Information Sharing

The MRA contemplates that regulatory authorities of one region may request official post-approval GMP documents from the other. If they consider it necessary to do so, they can ask the other region to conduct a new inspection.

Regulatory authorities of the two regions are required to inform and consult each other on proposals to introduce new controls or for changes to existing technical regulations or significant changes to pharmaceutical inspection procedures, and to provide the opportunity for the other region to comment on such proposals.

A database will be established to facilitate the exchange of official GMP documents and other information relating to the inspection of a manufacturing facility, as well as information concerning any confirmed reports relating to GMP non-compliance, corrective actions, recalls, rejected import consignments, and other regulatory and enforcement problems for products covered by the MRA.

In addition, both regions are required to maintain a system to alert the regulatory authorities of quality defects, recalls, counterfeit, or falsified products or potential serious shortages and other problems concerning quality or non-compliance with GMP, which could necessitate additional controls or suspension of the distribution of the affected products.

Notwithstanding the foregoing, the MRA permits each region to retain the right to inspect a manufacturing facility in the territory of the Party. However, it is expected that the exercise of such rights will ultimately be exceptional.

Possible Effect of Reducing Trade Barriers

In the EU, the Qualified Person (who is personally responsible for certifying batch release, including importation testing of product batches from outside of the EU) will be relieved of the responsibility of verifying that medicinal products have been manufactured in accordance with GMP prior to authorizing batch release of products onto the market, provided that the following conditions are met:

  • the equivalent controls were carried out in the US;
  • the product was manufactured in the US; and
  • each batch/lot is accompanied by a batch certificate issued by the manufacturer certifying that the product complies with requirements of the marketing authorization and signed by the person responsible for releasing the batch/lot.

For the US, while initially FDA will have to expend resources to determine whether a foreign regulatory authority is a "capable authority," once this determination has taken place, FDA will be able to focus its resources on nations where drug manufacturing has greatly increased, and prior inspections have suggested risk-based prioritization, such as India and China. According to FDA, over the last 5 years about 40 percent of FDA's drug inspections were performed in the EU. Under the new framework, a regulatory authority conducting its own inspection of a manufacturing facility in the territory of another party to the Annex should become an "exception to the normal practice.9

Impact of 'Brexit'

The United Kingdom's (UK) eventual departure from the EU is likely to take the UK outside the scope of this MRA, given that MRA is an agreement between the two trading blocs. FDA has indicated that once the UK has finalized the terms on which it will leave the EU under Article 50 of the EU Treaty, the FDA and the Medicines and Healthcare products Regulatory Agency acting on behalf of the UK licensing authority will re-examine existing commitments between the two countries and, if necessary, renegotiate any existing agreements. FDA did not comment on what the USA position would be if new commitments or agreements are required to implement an MRA with the UK separately. This may present uncertainty about the possible cross-border movement of pharmaceutical products between the USA and the UK post-Brexit.

*Bethan Jones contributed to this Advisory. She is a graduate of the University of Pennsylvania Law School employed at Arnold & Porter Kaye Scholer LLP. Ms. Jones is not admitted to the District of Columbia Bar.


1 Article 2.

2 Article 14.

3 Veterinary products may be included to the extent that they are added to the list by the Joint Sectoral Committee pursuant to Article 20.

4 While FDA has not provided insight regarding when these assessments will take place, since May 2014, FDA and the EU have been working together through the Mutual Reliance Initiative to "evaluate the way they each inspect drug manufacturers" and assess "the risk and benefits of mutual recognition of drug inspections." As part of this initiative, FDA has observed more than 12 audits of drug inspectorates across the EU.

5 Article 13.

6 Article 8.

7 Acceptance of an official GMP document means to rely on the factual findings in such a document.

8 Article 11.

9 Article 18.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on

Click to Login as an existing user or Register so you can print this article.

In association with
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Check to state you have read and
agree to our Terms and Conditions

Terms & Conditions and Privacy Statement (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

Use of

You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these terms & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use or performance of information available from this server.

The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.

Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

If you do not want us to provide your name and email address you may opt out by clicking here .

If you do not wish to receive any future announcements of products and services offered by Mondaq by clicking here .

Information Collection and Use

We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to with “no disclosure” in the subject heading

Mondaq News Alerts

In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

Log Files

We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

Surveys & Contests

From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to

Correcting/Updating Personal Information

If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to

Notification of Changes

If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

How to contact Mondaq

You can contact us with comments or queries at

If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at and we will use commercially reasonable efforts to determine and correct the problem promptly.