Harnessing the Power of Regulatory Science


Applied Clinical Trials

Applied Clinical TrialsApplied Clinical Trials-03-01-2010
Volume 0
Issue 0

To successfully bring a drug to market and keep it there requires the skills of regulatory scientists.

Outside the regulatory affairs department, there is often little understanding of the exact job functions of the regulatory scientist. Yet, their competence is essential to achieving success in dealing with regulatory agencies. The role requires a combination of expertise from evidence-based medicine, pharmacology, pharmacokinetics, statistics, law and medical ethics, chemistry, and regulatory toxicology.

In addition, the regulatory scientist needs to blend these skills and feel at ease in interacting with those in other departments so that the company submits a strong application to the regulators. They must also be capable of dealing directly with those in the regulatory agency on behalf of their company, which requires excellent presentation and diplomacy skills. And at all times, the regulatory scientist needs to be aware of the changing nature of the regulatory environment and be able to advise what needs to be done for their company to respond to these changes.

Since the future of a company's compounds depend heavily on how well these personnel are able to deal with counterparts on the agency side, it is not surprising that there is a constant demand for those with experience in regulatory science. In a 2008 survey by PriceWaterhouse-Coopers, 66% of U.S. company respondents stated that boosting their internal regulatory expertise had improved their relationship with FDA.1

R&D Expenditure by Function

Nevertheless, many companies struggle to find the right individuals to fill these important roles. In small companies, the problem is particularly acute and this can have a negative impact on their survival, since regulatory science is intrinsically tied to product strategy and approval. At any stage, regulatory scientists must be able to provide guidance on the level of information required by external agencies to support the conduct of proposed trials and to quantify the risks associated with providing a different data package to that expected by regulatory bodies.

It should also be noted that just because a company has a well-staffed regulatory department doesn't guarantee instant success. Despite some criticism being levelled at regulators, there is a view that pharma is also to blame for the instances of failed approvals and drug withdrawals.2

A surprising outcome of the 2008 PriceWaterhouseCoopers survey was that half of respondents often failed to incorporate FDA feedback into their drug development programs.1 This was an unusual finding since the majority of companies reported that guidance meetings with FDA were helpful in advancing the drug development process. Conversely, a few respondent companies stated that FDA changed its guidance position and did not provide them with reasonable scientific reasons for doing so. Such outcomes were partly linked to staff turnover at the agency.

Rather than speculating the situation, companies should turn to regulatory scientists who can evaluate what has occurred and advise on whether the agency did indeed change its guidance and, if so, why it might have done so.

Agency liaisons

Early contact with regulatory agencies in seeking scientific guidance is generally considered invaluable for companies. Regulatory scientists should actively seek to build a good relationship with agencies early on in development programs so that they can gain input on a range of issues, on an ongoing basis. Many agencies do offer guidance papers, but these only serve as current thinking on an issue and the opinions expressed are not binding. Companies should determine whether there are mechanisms that allow them to consult the agency all through the development process.

FDA itself has highlighted the benefits of consultation, although it also points out that this is very labor-intensive for the agency. In 2005, FDA received over 2400 requests for formal meetings with industry regarding products in development.3 In a 2006 retrospective analysis, FDA specifically highlighted the positive impact on first-cycle approval rates for companies that consulted with it before beginning the final phase of human testing (end of Phase II). FDA data show that during this period, 52% of companies that held a meeting with the FDA at the end of Phase II trials received approval during the first review cycle, but that this was only 29% for those who had not arranged such meetings.3

Internal vs. external specialists

Employing the services of external, independent regulatory specialists can be a powerful way of bringing objectivity to projects as the external specialist will integrate the Target Product Profile (TPP) with regulatory science for their client's benefit. The external specialists should be well versed in guidance procedures and must ensure that there is frequent contact with the regulators so that any agency staff changes are factored into how the company should proceed with previous direction from the agency.

Since externally-based regulatory science organizations deal much more frequently with regulatory agencies on behalf of a wide client base, they can often build up a more realistic picture of what is expected for a product. In contrast, regulatory staff within a pharmaceutical company might become overly biased due to expectations for the product from those around them. The frequent interaction with regulatory agencies also means that external regulatory specialists often build up good professional relationships with reviewers. For small companies with limited expertise and a lack of funds to hire additional staff on a permanent basis, external regulatory scientists provide a vital support role.

In addition, external regulatory scientists tend to work concurrently with numerous agencies in different world regions across various projects, whereas their pharmaceutical company counterparts are often limited to select markets for a set number of products. This allows external regulatory scientists great insight into the nuances of the decision-making within regulatory agencies. Companies accustomed to dealing with a particular regulatory agency, such as FDA, can find that proposed submissions to other countries can dramatically alter the regulatory strategy and the time involved in gaining approval. In such instances, external regulatory scientists can also provide extra value by training company staff in order to broaden their international regulatory expertise.

Despite the potential benefits of employing the services of an external regulatory scientist, care should be taken in selecting whose advice to follow. Furthermore, it is impossible for any one individual to be fully versed in all global regulations and so the services of more than one regulatory scientist are frequently necessary. Initially, it is advisable to gain the viewpoints of a number of external regulatory scientists to determine who can provide the company with the best value. Evaluating their credentials and verifying their track record is also essential, particularly with respect to the area of regulatory specialization required. Poor advice from an external regulatory scientist could prove fatal to a company, particularly a small one with limited experience in the area. For larger companies, in-house regulatory scientists should be able to gauge how much additional value the external party can bring to the project.

Regulatory scientists are already having an impact on the way in which sponsors deal with the postmarketing environment. Rather than relying solely on preapproval trials and the drug approval process, companies are realizing that they must invest in appropriate pharmacovigilance measures to monitor their products for safety upon use by the general population.4 Thus, company managers must appreciate that the regulatory scientist is of immense value beyond simply dealing with regulators and regulations.

Globalization and new challenges

Ensuring a wide international presence has become a critical feature of the current strategy of pharmaceutical companies. Global rollout of new drugs is necessary to maximize revenue through the rapid penetration of available markets, and over the past 10 years this process has become a priority. The standard of improvement in this regard is illustrated by Pfizer's Viagra (sildenafil), which became available in 60 countries within two years of its first launch in 1998. In comparison, it took Pfizer nine years to get Norvasc (amlodipine), first launched in 1990, into 60 countries.5 Advancing beyond the core markets of the U.S., Europe, and Japan is considered crucial to the future of the pharmaceutical industry, since by 2012 it is predicted that 40% of global growth in sales will come from emerging markets.6

For regulatory scientists, a degree of international knowledge has always been part of the job, as they needed to follow developments from the International Conference of Harmonisation (ICH). ICH involves industry and agency representatives from the U.S., Europe, and Japan meeting regularly to review the requirements for product registration and agree upon common principles and standards, which should apply during drug development. However, regulatory scientists now face pressures in interpreting regulatory guidelines from a range of emerging markets.

Two key emerging markets that the pharmaceutical industry has invested heavily in are China and India. Interestingly, the regulators in both these countries have sought discussions with FDA in how best to develop expertise at their agencies for new demands from multinational companies.7-9 In January 2008, U.S. Health and Human Service (HHS) secretary Michael Leavitt and FDA Commissioner Andrew Von Eschenbach visited India. Public statements indicated that much of the discussions with the Indian Minister of Health and Family Welfare, Anbumani Ramadoss, centered on regulatory issues. Specifically, the talks included assistance to create an equivalent of the FDA in India.

The ever-growing amount of cross talk between international regulatory agencies should not be underestimated. Regulatory questions that arise with an agency on one side of the world frequently appear elsewhere. For example, FDA and the EMEA have had a confidentiality agreement in place to share information since 2003.10 Similarly, since December 2007, FDA has had an information sharing agreement with China's State Food and Drug Administration.11 Regulatory scientists should understand how such agreements are developed between agencies and their implications.


For new medicines to reach the market, and thereby address patient's medical needs, a better understanding of regulatory science by company personnel is not only recommended but should be considered essential.

All companies have much to gain from investing in this area as they do with other parts of the drug development process. Improving internal regulatory resources should be a priority, but companies must also not be afraid to consult external regulatory specialists for an objective viewpoint. Furthermore, they must keep in close contact with their counterparts at regulatory agencies and proactively monitor changes in the global regulatory environment.


1. PriceWaterhouseCoopers, Improving America's Health IV (2007), http://www.pwc.com/gx/en/pharma-life-sciences/pharmaceutical-industry-thought-leadership.jhtml.

2. A. Johnson and R. Winslow, Drug Makers Say FDA Safety Focus Is Slowing New-Medicine Pipeline, National AIDS Treatment Advocacy Project (2008), http://www.natap.org/2008/newsUpdates/070308_03.htm.

3. FDA, Report Demonstrates Benefits of Earlier Meetings with FDA to Make Drug Review Process More Efficient (2006), http://www.fda.gov/bbs/topics/news/2006/NEW01312.html.

4. PriceWaterhouseCoopers, Pharmacovigilance Seen as Complementing Pre-Approval Testing (2007).

5. G. Lewis, IMS Health, Over the Horizons Conference, London, October 2000.

6. D. Fuscaldo, Big Pharma Turns to China, India to Test Drugs, Fox Business (2008), http://www.foxbusiness.com/story/big-pharma-turns-china-india-test-drugs.

7. "US wants FDA inspectors stationed in India," The Times of India, March 19, 2008, http://timesofindia.indiatimes.com/World/USA/US_wants_FDA_inspectors_stationed_in_India/articleshow/2880547.cms.

8. K. Barnes, FDA considering Establishing Indian Presence, In-Pharma Technologist (2008), http://www.in-pharmatechnologist.com/news/ng.asp?n=82658-fda-india-china-inspection.

9. Mike Leavitt's blog, Chennai, India (January 7, 2008).

10. EMEA, Confidentiality arrangements concluded between the EU (EC and EMEA) and the US FDA/DHHS (2003), http://www.emea.europa.eu/pdfs/general/direct/internationalcoop/EMEA-FDAconfidentialityimplement%20.pdf.

11. HHS, New Agreement Will Enhance the Safety of Drugs and Medical Devices Imported From the People's Republic of China (2007), http://www.hhs.gov/news/facts/drugsmedical.html.

Charles H. Davis, RAC, is Vice President, Regulatory Science, for Abingdon Life Sciences, Inc., 5963 LaPlace Ct., Suite 107, Carlsbad, CA 92008, email: cdavis@abingdoncorp.com.

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