The FDA's new direction

As the world's largest pharmaceutical market, the US is frequently targeted by companies for initial drug launches, and this means bending over backwards to convince the FDA that the product is safe and effective. As such, the FDA has a tremendous task on its hands in reviewing the huge amount of regulatory dossiers it receives as submissions, as well as ensuring the safety of products that have already reached the market.

Faiz Kermani

In meeting its regulatory commitments, the FDA can find itself increasingly at odds with pharma companies, which are under pressure to launch as many drugs as possible and to grow their businesses from sales of these products. As the new political administration, under President Barack Obama, has promised a new direction for US healthcare,¹ it is inevitable that the FDA will undergo significant change. However, although the agency and pharma have often been at loggerheads, it is the criticism of the general public regarding failings in drug safety that will have a greater impact on the future of the FDA.

A reorganization of the regulatory body will have huge implications for the pharmaceutical and biotech industries operating in the US, and will also influence activities in other markets because of the growing interactions between the FDA and its foreign counterparts. In particular, the next few months at the agency will be of great interest to all firms planning drug launches because the regulatory landscape could be about to be revolutionized.

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The blame game

There is internal debate within the pharma industry concerning its productivity and innovation in R&D. Year by year, new drug output has steadily declined, despite continuing unmet medical need in a number of important disease areas. The global pharma industry continues to increase its investment in R&D — with an estimated spend of $70 billion (51.7 billion) in 2007² — but the performance of the sector in translating this investment into innovative products remains questionable. Critics of the pharma industry have argued that companies rely too heavily on line extensions and working on new formulations of existing products rather than concentrating their efforts on true innovation in R&D. This has led to companies submitting weaker regulatory dossiers, which in turn has restricted the number of drugs reaching the market.

Some companies have blamed regulatory agencies, such as the FDA, for the decline in new drugs on the market. In 2007, the FDA approved 65 original new drug applications (NDAs), the least since 1999.³ Furthermore, the ratio of NDAs approved to NDAs submitted has dropped from the 76% level of 2006 to less than 60%.⁴ Many companies believe that the FDA has been excessively bureaucratic, which has slowed the review process.⁵ One 2008 media report claimed that 15 additional new drugs could have been on the national market if the FDA had been more efficient in conducting its reviews.⁵ The FDA has a target of meeting 90% of its new drug approval timelines for review, but although full 2008 performance data have not yet been released, the agency has already indicated that it is unlikely to reach this goal.⁶

Despite these criticisms, the FDA insists it has not changed the way in which it approaches regulatory review. Recently, an agency spokesman stated that the rate of NDA approvals to submissions remained steady at approximately 80% from 1997 through to 2005³ — although independent media reports have cited a decline after this period.⁴

FDA decisions under scrutiny

The FDA is in a tricky position because its role is primarily to safeguard the public rather than support the pharma industry in launching its drugs. Ironically, it frequently comes under attack in the US media for being too close to pharmaceutical companies and the agency has faced a media onslaught regarding the approval of some drugs whose safety risks eventually outweighed their benefits following launch. One of the most damaging episodes for the FDA was Merck's COX2 inhibitor Vioxx (rofecoxib), which was withdrawn from the market after being linked to an increase in the risk of heart attacks and strokes. In 2005, FDA representatives admitted administrative lapses regarding Vioxx in front of a Senate committee.⁷

New leadership, new implications

As a government agency, the operational aspects of the FDA are often not appreciated by the public or the pharma industry. To meet the demands of its regulatory role, the agency requires sufficient resources and strong leadership — both have been in short supply in recent years, but it looks as if Obama may change this.

The US media have reported that Dr Margaret A. Hamburg, a former New York City health commissioner, is set to be the agency's new head, with Dr Joshua Sharfstein, the health commissioner of Baltimore, serving as her deputy. These proposed appointments have been well received, with many among the public believing that they will keep the agency independent from the pharma industry, but also give it the required direction to meet its difficult challenges.

The change in leadership will primarily affect the US market, but it will also have an international influence — as one of the world's leading regulatory agencies, the FDA's thinking has a profound impact on shaping regulatory policy overseas. For example, it has a critical role in the efforts to promote greater regulatory harmony between different world regions through the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH regularly brings together the regulatory authorities of the US, Europe and Japan, and experts from the pharmaceutical industry in these three regions to discuss scientific and technical aspects of product registration.

What does this mean for Europe?

Despite the perception of having different regulatory processes, the FDA works closely with the EMEA in a number of key areas and holds regular bilateral meetings. Since 2003, the two agencies have had a confidentiality agreement in place that allows them to exchange information as part of their regulatory processes at both pre and postapproval stages. The agreement also has provisions to allow the exchange of staff between the two agencies. Another development is an initiative to develop a common application for orphan designation of medicines to simplify the process of obtaining orphan status for medicines developed for rare diseases.

All the signs indicate that the FDA will be increasing its cooperation with the EMEA within the coming years. Ensuring this cooperation improves standards will be part of the remit of the new leadership at the FDA. At the 2008 Transatlantic Economic Council meeting, the two agencies agreed to pool resources to become more effective at a global level.⁸ With many APIs manufactured outside the US and Europe, maintaining control over standards can be difficult. The FDA and EMEA hope to achieve increased regulatory vigilance by undertaking joint inspections of foreign facilities.

Many regulatory agencies in emerging markets also look to the FDA for guidance. For example, in early 2008, representatives of the FDA held talks with their counterparts in India regarding the provision of assistance to create an equivalent of the agency in the country. In November 2008, the FDA set up an office in China, its first foreign location. China's State Food and Drug Administration already has a number of agreements in place regarding information exchange with the FDA.

The impact will be global

The FDA plays a vital role in regulating the US pharmaceutical market and its cooperation with international agencies influences the market at a global level. In recent years the agency has struggled to live up to public and industry expectations because of poor resourcing and uncertain leadership. With a new head of the FDA expected to be formally announced, it is likely the agency will receive the direction it needs to meet its future regulatory challenges.

References

1. "Barack Obama and Joe Biden's plan to lower health care costs and ensure affordable, accessible health coverage for all" (2008). www.barackobama.com

2. Business Insights, "The Pharmaceutical Market Outlook To 2018: Key Threats And Opportunities For Big Pharma And Its Responses To Them" (2008). www.marketresearch.com

3. J. Schmidt, USA Today (2008). www.usatoday.com

4. E. Silverman, PharmaLot (2007). www.pharmalot.com

5. MedHeadlines, "FDA Criticized for Slow Approvals but Allows 21 New Drugs This Year" (2008). http://medheadlines.com

6. M. Perrone, Drug Discovery & Development (2009). www.dddmag.com

7. G. Harris, TheNew York Times (2005). www.nytimes.com

8. N. Taylor, In-Pharma Technologist (2008). www.in-pharmatechnologist.com