The Big Shift

Pharmaceutical Executive

Pharmaceutical Executive, Pharmaceutical Executive-01-01-2010, Volume 0, Issue 0

Pharma must confront regulatory and marketing challenges in a global competitive environment.

The worldwide economic downturn, the contentious debate over national healthcare reform, and important changes on the regulatory front have all taken tolls on biomedical research and new drug development. Luckily, the new year brings optimism on both fronts. Healthcare reform legislation will either become law or die a painful death. The new team heading up the Food and Drug Administration will be firmly established and eager to implement new policies and programs. Pharma companies will be consolidating operations following major industry upheavals. And all will be watching the following trends shaping drug development in 2010.

Jill Wechsler

Going Global

The rising importance of overseas markets for drugs and medical products, along with pressure to cut production and research costs at home, is driving pharma overseas. Marketers are becoming established in China, India, and other newly industrialized nations that will be major markets within the next five years. Astra-Zeneca recently announced plans to outsource production of active pharmaceutical ingredients to Asia, and Novartis is investing $1 billion in R&D in China.

A presence in developing countries means more investment in new treatments for malaria, tuberculosis, and other neglected diseases. FDA is encouraging such efforts, and is likely to do more under its public health–oriented commissioner Margaret Hamburg. The agency supports development of new tuberculosis treatments to replace ineffective old therapies, and is promoting a priority review voucher program to stimulate industry R&D in tropical conditions. To better monitor the growing volume of pharmaceutical imports and foreign clinical trials, FDA is establishing overseas offices and doubling the number of foreign inspections it conducts each year. Collaboration between FDA and European regulatory authorities to conduct joint inspections and share information could expand from APIs to other areas.

Invigorating Vaccines

The battle against infectious disease has spurred worldwide investment in vaccine development and production; this surge is slated to continue. Global funding of a vaccine to combat the H1N1 influenza pandemic has financed construction of new vaccine manufacturing facilities in the US and abroad. Vaccines to combat malaria and TB are in clinical trials, and scientists remain optimistic about moving forward with a long-sought preventive to HIV infection. Novel antigens are in the works; an anti-smoking vaccine is moving into late-stage testing; and scientists continue to seek therapeutic vaccines for cancer and other conditions.

Ensuring Drug Quality

Longer supply chains and rising imports raise questions about the ability of drug manufacturers to document the quality and safety of drug products. Because FDA can never check all the thousands of products and ingredients coming into the US, it expects manufacturers to do more to ensure that contractors and suppliers have a commitment to quality, and that products and ingredients are routinely monitored and inspected. The aim is to prevent future adulteration crises, such as contaminated heparin and products with melamine.

An electronic drug registration and listing system was fully implemented in 2009, and should make it easier for FDA to identify and track products. Industry also could gain from a long-promised FDA guidance on reducing the volume of manufacturing supplements that require preapproval—an initiative designed to provide more predictability for companies contemplating improvements in manufacturing processes.

Safety Over All

FDA continues to implement provisions in the FDA Amendments Act of 2007 (FDAAA), designed to ensure the appropriate use of approved medicines through the product life cycle. FDAAA has authorized postapproval label changes when new safety issues arise, along with penalties for manufacturers that fail to conduct agreed-upon post-marketing studies. There are mandates for more extensive listing of clinical trials and study results on the ClinicalTrials.gov Web site, and for Risk Evaluation and Mitigation Strategies (REMS) governing postmarket prescribing and surveillance. FDA has approved REMS for more than 50 products, and is formulating a REMS for the entire class of extended-relief opioid medicines in order to provide continued access for patients suffering from chronic pain, while also curbing inappropriate prescribing, unintentional overdosing, and intentional abuse.

Sponsors, health professionals, and patient groups will be watching closely to see how well these programs prevent drug safety problems, and whether these efforts support more FDA flexibility in approving somewhat risky new products. Internally, FDA is bolstering its safety assessment capabilities. A Safety First program in the Center for Drug Evaluation and Research (CDER) seeks to clarify responsibilities for pre- and postapproval drug safety assessments. The agency's Sentinel Initiative aims to detect medical product safety problems more effectively through an electronic monitoring system linked to healthcare databases. Sentinel eventually should detect emerging safety problems in real time and identify patient subgroups experiencing adverse events.

FDA's Safe Use initiative, which commissioner Hamburg announced in November, aims to build partnerships with other components of the nation's healthcare system to ensure that medicines are used safely and appropriately. FDA plans to collaborate with other government agencies and healthcare providers to address situations that lead to medication errors and inappropriate prescribing.

IT Adoption

These programs require access to electronic health information systems, a prominent goal of national health reform. Earlier economic stimulus legislation aimed to spur e-health development by providing $19 billion to support adoption of electronic health records by doctors and hospitals and to develop standards and systems supporting electronic health information exchange, including e-prescribing. Electronic databases promise to accelerate detection of drug adverse events and to streamline data collection from clinical trials and population studies.

At the same time, broader access to personal health information has generated demands for stronger protections against unauthorized disclosure of patient records. The concern for the biomedical research community is that privacy issues could limit access to patient information needed for pre-clinical and postapproval studies. Research experts are exploring alternative models for health surveillance and assessment based on the data-sharing capabilities of electronic information systems, approaches that may gain more attention in coming months.

Personalized Medicine and CER

E-health systems also are critical for developing personalized, or individualized, therapies and the diagnostics needed to determine who may benefit or experience harm from more targeted treatments. The shift to personalized medicine requires access to personal health data to recruit research subjects who meet genetics-based enrollment criteria, and to identify those individuals who should—or should not—receive a treatment based on specific genotype. Long-promised FDA guidance on developing personalized medicine and diagnostics could give the field a welcome push.

Researchers also will be tapping health system databases to assess health outcomes and to compare the risks and benefits of medical products. Federal agencies are funding a number of comparative effectiveness research (CER) projects with an eye to assessing a broad range of medical treatments and strategies. Pharma companies seek limits on government-funded studies that compare one drug to another and focus on cost issues, but more CER will inevitably highlight comparative prices as well as health benefits.

More Disclosure

"Transparency" is a recurrent theme in health reform and regulatory matters. Efforts to lower drug prices could require broader disclosure of manufacturer rebates and discounts negotiated by payers and health plans. Congress further seeks to shed more "sunshine" on drug company payments to physicians to reduce industry influence on prescribers.

More transparency in FDA regulatory decisions also is on the horizon. Commissioner Hamburg established a high-level transparency task force last June to identify ways to better inform the public about FDA operations—and enhance agency credibility in the process. The panel, headed by deputy commissioner Joshua Sharfstein, is examining whether FDA should be able to disclose more information about drug applications filed with the agency; what kind of emerging safety information should be disclosed and when; and whether early communication about ongoing safety reviews would be beneficial or raise needless concerns. The panel will issue a report in the coming year on what information FDA should be able to release on its own, and what changes require new regulations or legislation.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com