Will Transatlantic Regulatory Cooperation Meet Expectations?

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Pharmaceutical Technology Europe

Pharmaceutical Technology Europe, Pharmaceutical Technology Europe-11-01-2010, Volume 22, Issue 11

There has been increasing cooperation between the EMA and the FDA in recent years, and this looks set to continue in the future.

Since 2003, there has been a growing level of interaction between the European Medicines Agency (EMA) and the FDA.1–3 With Europe and the US representing the two largest pharmaceutical markets in the world, cooperation between the agencies has several potential benefits. In particular, the increased sharing of information and opinions regarding medicines will result in better and faster information exchange regarding the safety of products being used in the US and vice versa. If unnecessary differences in regulations (with their associated costs) can be avoided, this would also offer huge benefits to industry. For instance, it may be possible to use similar documentation for submissions to both agencies; indeed, the EMA and the FDA already offer a common application for Orphan Drug Status. There are also practical steps that have been taken; for example, previously European phone numbers could not be entered electronically into the editable fields on the US form! More harmonisation among global regulatory requirements would also help encourage more innovative medicines to be brought to market because sponsors feel that meeting regulatory standards in one region will help them develop their products in another.

Regulatory cooperation also benefits the agencies themselves because they can share experiences and learn more about one another's internal workings. This may also help to avoid duplication of work; for example, the FDA's oncology review team already holds monthly teleconferences with their EMA counterparts to discuss a range of ongoing activities, such as meetings with sponsors, regulatory decisions and even staff exchanges.4 These forums involve the exchange of documents such as minutes from internal agency meetings and important regulatory letters.

In 2007, the two agencies also chaired a Transatlantic Administrative Simplification Workshop, which featured participation from the heads of individual EU member state regulatory bodies and the US.5 The objective was to simplify regulations wherever possible, provided that they did not involve any changes to existing legislation and as long as they maintained (or increased) public safety standards. Given the wide range of activities carried out by the agencies, it was necessary to classify the areas to be targeted under four general themes: quality and inspections; pharmacovigilance; scientific collaboration; and guidelines, format harmonisation and electronic submission. Following the 2007 meeting, a formal Coordination Committee has been established, which consists of a representative from the EC, the EMA and the FDA. They hold regular teleconferences and carry out yearly reviews of the confidentiality exchange agreements. A follow-up meeting was held in September 2009 when the agencies formalised formats, scales and time periods for information exchange.

Other cooperative initiatives between the agencies are also underway. In September 2010, the EMA and FDA announced that an existing programme to allow both agencies to exchange confidential information as part of their regulatory and scientific processes was to be extended indefinitely.1,2 The new arrangement encompasses areas such as scientific advice to sponsors, orphan drug designation, paediatric drug development, and GMP and GCP inspection planning and reports. Marketing authorisation procedures are also covered, as well as any changes to marketing authorisations and postmarketing surveillance.

Differing standards?

Although the two agencies have upped their level of cooperation and share many similar roles, it is important to remember that they remain very different organisations. Whereas the FDA is a unified regulatory agency, the EMA is an administrative organisation that relies on the agencies in individual member states to carry out the functions required. Consequently, whereas the FDA has its own staff for certain roles (site inspections, etc.), the EMA will turn to the agencies in individual member states for such support, which means that EMA decision-making can be influenced by the working culture of the personnel being used from the supporting agencies.6 It is also quite possible that the same data package can generate different opinions from the EMA and the FDA; indeed, a frequent complaint of companies is this perceived divergence in scientific opinions, which makes the process of putting together a development programme that will generate data to satisfy both agencies difficult (and costly).

As part of their cooperative agreement, the agencies now offer voluntary parallel scientific advice, whereby FDA and EMA assessors provide their views on scientific issues during the development phase of new products. However, this move has not fully satisfied companies. Following the advice procedure, both the EMA and the FDA retain their individual regulatory decision-making authority regarding drug development issues, which means that the advice of each agency may still differ after the joint discussion.

Agency criticisms

In the US, there has been criticism from the pharma industry that the FDA is more conservative than the EMA when it comes to approvals. The FDA has flatly denied this accusation, despite a recent slowdown in product approvals, with some FDA officials adding that the analysis of their decision-making is flawed because it places too much emphasis on the absolute numbers of approvals in the US compared with previous years. In contrast, they believe greater attention should be paid to the quality of the applications themselves.7,8

The pharma industry's criticism of the FDA is ironic because the agency frequently finds itself under fire from the US media and the public for being too "industry-friendly". For example, the agency has recently been criticised for having approved Pfizer's Mylotarg (gemtuzumab) for acute myeloid leukaemia (AML) based on preliminary data.9 Mylotarg had been approved under the FDA's accelerated approval regulations, but was withdrawn from the market by Pfizer earlier this year following disappointing results from ongoing trials, as well as safety concerns. This type of criticism is a worry for the FDA, which has been trying to rebuild its reputation with the US public following the scandal surrounding Vioxx (rofecoxib) in 2004.10

Meanwhile in Europe, the EMA also faces much criticism and is often touted as not being as efficient and as transparent as its US counterpart. According to a report issued in 2007, over the period 2000 to 2005, of the 71 drugs approved by both agencies, 47 were approved more quickly by the FDA than by the EMA.11

As with the FDA, the EMA has also received criticism over the way it has handled product approvals. In May 2010, a Lancet editorial attacked the EMA for not releasing additional safety information on Roche's acne drug Accutane (isotretinoin).12 The EMA initially responded by stating that it was under no obligation to release serious adverse reaction reports; however, following intervention from the European Ombudsman, the EMA decided to comply.13


Moving forward, both the EMA and the FDA will have their work cut out for them regarding their intent to provide parallel scientific advice to companies. Because of limitations in resources, both agencies say they intend to concentrate on breakthrough drugs or important safety issues in areas that have been identified as "clusters of interest".14 The process will be voluntary and is generally expected to be initiated at the request of a sponsor. However, with the decision-making processes of both agencies having been called into question on occasions, finding a balance between the two systems may be problematic for the agencies. For compounds at an early stage of development, companies also worry whether the advice will still be valid by the time the product is ready for a formal regulatory application. A separate issue is how the cooperative efforts of the EMA and the FDA will be perceived by the public. Industry critics — already unconvinced by the rigour of the approval processes currently in existence — may feel that companies are being given an easier ride through joint regulatory measures.

The author says...

At present, both agencies are under fire regarding the approval of GlaxoSmithKline's Avandia (rosiglitazone).15,16 While the FDA has been criticised for not having enough resources to have conducted a thorough evaluation of the trial results, the EMA has been described as being too reliant on data summaries provided by the companies marketing the products. In September 2010, the EMA recommended suspension of Avandia's marketing authorisation in the EU, whereas in the US, the FDA decided to significantly restrict the drug's use.


In the future regulatory environment, there will be increased cooperation between the EMA and the FDA, and this is set to provide numerous benefits. At present, various projects focusing on different areas of drug regulation are underway to generate specific recommendations on how the cooperative measures will work in practice. A further development has been an exchange staff programme — the FDA has had a permanent representative in the EMA office in London (UK) since 2009 and the EMA adopted a similar approach earlier this year by placing a representative at the FDA headquarters in Maryland (USA).

Despite the progress being made, however, the agencies will need to ensure that they gain the support of both the pharma industry and the public. Only in this way will the true benefits of collaborative regulatory measures be realised.


1. European Medicines Agency, "European Medicines Agency and U.S. Food and Drug Administration extend confidentiality arrangements indefinitely" (2010).


2. European Medicines Agency, "Statement of authority and confidentiality commitment from the European Medicines Agency not to publicly disclose non-public information shared by the United States Food and Drug Administration" (2010).


3. European Medicines Agency, "Partners & networks: Regulators outside the EU: United States of America" (2010).


4. EuroPharma Today, "FDA and EMEA: Minding the Gap" (2009).


5. European Medicines Agency, "Transatlantic Administrative Simplification Action Plan Implementation report — 2009" (2009).


6. R. Lane, "Similarities and Differences between CMC Information required for EU IMPD CTA and US IND" (2008).


7. Biopharma Today, "Is FDA More Conservative Than EMEA? FDA Says No; Investors Weigh In" (2009).


8. Europharma Today, "FDA Not More Conservative Than EU, Jenkins Says; Investors Not Convinced" (2009).


9. Business Week, "Pfizer Withdraws Drug After Deaths, No Proven Benefit (Update1)" (2010).


10. New York Times, "FDA Official Admits 'Lapses' on Vioxx" (2005).


11. Eye on FDA, "The EMEA and the FDA" (2009).


12. The Lancet, "European Medicines Agency — more transparency needed" (May 2010).


13. European Ombudsman, "Ombudsman welcomes release of adverse reaction reports by the European Medicines Agency " (2010).


14. European Medicines Agency, "General principles EMEA — FDA Parallel scientific advice"


15. Financial Times, Pharmaceuticals: Perils for pill pushers (2010).


16. Pharma Times, "End of the road for Avandia: halted in EU, restricted in USA" (2010).