Issues and Opportunities Challenge Biotech Manufacturers

After a year of considerable turmoil in Washington policy and regulatory circles, there is optimism that healthcare coverage and requirements for medical product development will gain some clarity in the coming months. National health reform legislation either will become law in some form, or die. The new team heading up the US Food and Drug Administration will be firmly established and eager to implement new policies and programs. These developments will shape a number of key trends and developments in 2010 of importance to biotech manufacturers.

Jill Wechsler

PRODUCTION GOES GLOBAL

International funding of a vaccine to combat the H1N1 influenza pandemic has spurred construction of new vaccine manufacturing facilities in the US and abroad, and that trend is not likely to diminish. Manufacturer interest in expanding sales in newly industrialized nations has spurred worldwide support for research on new vaccines and for treatments for malaria, tuberculosis (TB), and neglected tropical diseases, along with investment in foreign manufacturing facilities and new vaccine production and testing methods. Vaccines to combat malaria and TB are in clinical trials, and scientists remain optimistic about moving forward with the long-sought vaccine to prevent HIV infection. An anti-smoking vaccine is moving into late-stage testing, while scientists continue to seek therapeutic vaccines for cancer and other conditions.

The FDA is supporting such efforts, particularly development of new TB treatments to replace ineffective old therapies and to help counter a resurgence in drug-resistant TB strains. And to better monitor the growing volume of food items and medical products imported to the US, the FDA is establishing overseas offices and doubling the number of foreign inspections it conducts each year. New legislation to overhaul food safety would further expand FDA inspections of food facilities in the US and abroad. In addition, the FDA is partnering with European regulatory authorities to share inspection information and conduct joint inspections of foreign active pharmaceutical ingredient producers, an initiative that could expand if beneficial.

QUEST FOR QUALITY

Longer supply chains and rising imports raise questions about the ability of drug manufacturers to ensure the quality and safety of biomedical therapies. Because the FDA can never check all of the thousands of products coming into the US, the agency expects manufacturers to do more to ensure that contractors and suppliers have a commitment to quality, and that they are routinely monitored and inspected. The aim is to prevent future adulteration crises, such as those involving heparin, melamine, and DEG-contaminated glycerin in medical products.

Along these lines, the FDA's Center for Drug Evaluation and Research (CDER) continues to emphasize the importance of manufacturer Quality by Design (QbD) and risk management systems to ensure drug quality. CDER officials are evaluating a QbD review pilot and launching a similar initiative for biotech therapies. Additional efforts to harmonize quality standards are under discussion. An electronic drug registration and listing system was fully implemented this past year and should make it easier for the FDA to identify and track products and manufacturing facilities.

ENSURING SAFETY

The FDA also is involved in multiple initiatives to encourage the safe use of medicines. The FDA Amendments Act of 2007 (FDAAA) authorizes post-approval label changes when new safety issues arise and action against manufacturers that fail to conduct agreed-on post-marketing studies. There are mandates for more extensive listing of clinical trials and study results on the ClinicalTrials.gov public web site and for Risk Evaluation and Mitigation Strategies (REMS) governing post-market prescribing and surveillance. The FDA has approved REMS for almost 90 products and is developing a REMS for the entire class of extended-relief opioid medicines. Manufacturers will be watching to see how well these programs detect and prevent drug safety problems and if that encourages FDA reviewers to approve products that raise some safety concerns.

Internally, the FDA is bolstering its safety assessment efforts through several initiatives. CDER's Safety First program is integrating oversight of drug safety issues by clarifying responsibility for pre- and post-approval drug safety assessment and strengthening safety-related policies and procedures. The agency's Sentinel Initiative is developing an electronic system for monitoring medical product safety. And the FDA's Safe Use initiative aims to build partnerships with other components of the healthcare system to ensure that medicines are used safely and appropriately. The FDA plans to partner with other government agencies and with healthcare providers to address situations that lead to medication errors and inappropriate prescribing.

IT ADOPTION

The Sentinel System requires access to electronic health information systems, a prominent goal of health reform efforts. Medical record databases offer a way 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, which may stymie research and treatment.

PERSONALIZED MEDICINE AND COMPARATIVE RESEARCH

Health information systems also are critical for the development of personalized, or individualized, medicine and the diagnostics needed to determine who may benefit or experience harm from certain therapies. The shift to more targeted treatment requires access to personal health data to recruit research subjects who meet increasingly specific genetic-based enrollment criteria, and to identify those individuals who should—or should not—receive a treatment based on specific genotype.

Researchers also will be tapping health system databases to assess 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. The industry seeks limits on federal funding of studies that compare one drug to another and focus on cost comparisons, but more CER will inevitably highlight comparative prices as well as health benefits.

PRICES AND PATHWAYS

Whatever the outcome of health reform legislation, the high prices of many biotech therapies will remain in the spotlight. Both Wall Street analysts and patient advocates have documented record increases in wholesale drug prices this past year, at a time when inflation was declining. The studies exposed manufacturers to charges of jacking up revenues in anticipation of tighter legislative controls on pharmacy spending.

Such developments will continue to build support for greater access to generic drugs, including follow-on biologics (FOBs). Congress is poised to establish a regulatory pathway for bringing biosimilars to market. There is general agreement among generics makers and innovator firms on FDA regulatory standards and clinical testing requirements, but strong disagreement on patent issues: pharmaceutical and biotech companies successfully pushed for 12-years exclusivity on FOBs which has infuriated generics makers. Manufacturers on all sides will be assessing how these requirements will shape the development of biosimilar products.

MORE DISCLOSURE

Transparency is a recurrent theme in health reform and regulatory matters. Efforts to lower the prices of biomedical treatments have built support for broader disclosure of manufacturer rebates and discounts negotiated by payers and health plans. Congress seeks to further shed light on industry payments to physicians as a way to reduce commercial influence on prescribers.

Manufacturers also face more transparency in FDA regulatory decisions and pending drug applications. Commissioner Margaret Hamburg established a high-level FDA transparency task force last June to identify ways to better inform the public about FDA operations. The panel headed by Deputy Commissioner Joshua Sharfstein is examining the viability of disclosing information about applications filed with the agency, what kind of emerging safety information should be disclosed and when, and whether early communication about ongoing safety reviews of foods and medical products would be beneficial or raise unnecessary concerns about a product. The panel will issue a report in the coming year on what information the FDA should be able to release on its own and what changes require new regulations or legislation.

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, jwechsler@advanstar.com