PUBLIC POLICY
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Sidebar:
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Panel Discussion Information
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Thursday, October 4 10:00–10:45 A.M. |
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Chair: Bradley Merrill Thompson Member of the Firm Epstein Becker & Green PC |
- Regulatory challenges caused by the regulatory, cultural, business, technological, and legal differences among the biotechnology, medical device, and pharmaceutical industries.
- Working with Washington regulators to develop cohesive policy when the affected industries are fragmented and insular.
- Regulatory schemes for coping with a wide variety of potential types of convergence.
- Dealing with FDA’s regulatory systems and cultures, which vary tremendously among biotechnology products, medical devices, and pharmaceuticals.
Regulatory Context
The term combination product is defined in the Federal Food, Drug, and Cosmetic Act as encompassing regulated medical products that constitute a combination of a drug, device, or biologic (21 CFR 3.2(e)). FDA defines three distinct types of combination products.
- Single-entity. A product comprised of two or more regulated components that are physically, chemically, or otherwise combined or mixed as a single entity.
- Kits. Two or more separate products packaged together (e.g., drug and device products).
- Cross-labeled products. Products provided separately but intended for use together where both are required to achieve the intended use and where cross-labeling is needed.
When it comes to regulating this emerging class of products, part of the challenge arises from the wide variety of technologies and finished products that are currently being developed. Medical devices themselves vary from the simple Class I tongue depressor to the Class III pacemaker. But when looking at combination products, that variation can easily be magnified 100-fold. The regulatory scheme has to be appropriate for that degree of variation.
Consequently, combination products bring together entities and regulatory frameworks that are usually distinct from one another. A given combination product may require expertise from any or all of FDA’s centers—the Center for Biologics Evaluation and Research (CBER), Center for Drug Evaluation and Research (CDER), or Center for Devices and Radiological Health (CDRH).
Similarly, manufacturers may need to sort out the submission path for a combination product, which may require something other than the usual frameworks employed by the reviewing centers, such as new drug applications (NDAs), biologic license applications (BLAs), premarket approval applications (PMAs), and so on.
Combination Product Drivers
Whatever the nature of such combination products may be, they constitute a product class of growing clinical and economic importance to the healthcare industry.
A number of factors are driving companies to investigate the potential for developing combination products. From a clinical point of view, the appeal of combination products results from the desire of healthcare professionals to enhance patient outcomes with regard to both safety and effectiveness. Their hope is that novel combination products will be able to overcome or avoid the systemic effects and toxicities caused by many current treatments, which often restrict the number of patients who can be considered for those therapies. Following this line of thinking is driving product developers in the direction of methods for localized delivery, targeting, and individualized therapy.
Economic factors are also driving the trend toward combination products. In recent years, the amount of time and money required to develop a new drug has risen significantly. Consequently, there has been a corresponding decrease in pharma industry productivity. Meanwhile, limits on the life of drug patents have not increased, forcing pharma companies to recoup all of their expenses—and their profit—in a relatively short period. Faced with such a difficult economic picture, many drug companies have sought to disperse their financial risk by collaborating with other firms—including companies from outside the drug sector.
Areas of active exploration among life sciences companies include tissue engineering, microelectromechanical systems (MEMS), biomaterials, gene and protein delivery, targeted medicine, and new routes for delivering drugs. Each of these areas offers the potential for collaborative efforts to produce combination products of various types.
Practical Challenges and Opportunities
The need to regulate combination products has forced FDA’s nearly autonomous component centers to work with one another in ways that could not have been imagined a decade ago. But the gradual emergence of regulatory schemes appropriate for such products has raised questions about whether FDA and industry have a clear understanding of the direction of the trend toward convergence. Complicating this challenge is the fact that, unlike drugs and devices by themselves, the degree of innovation in convergent technologies is a multiple of the innovation in either area alone.
The agency’s Office of Combination Products (OCP) offers help in this regard, but the office is still relatively new and has limited resources. Now directed by Joanne R. Less, PhD, who was formerly associate director for clinical research at CDRH, OCP has a daunting task. The different industries that it serves have very different perspectives and priorities, leaving the office to weigh its options and make difficult choices. By statute, OCP must perform the following duties.
- Assign review responsibilities for combination products.
- Ensure timely and effective premarket review.
- Establish consistent and appropriate postmarket regulation.
- Conduct dispute resolution (timeliness versus substance).
- Review and update guidance, agreements, and practices.
- Compile reports to Congress.
- Serve as resource to sponsors and review staff.
Because OCP is thinly staffed, industry has an opportunity to fill the gaps by helping to generate ideas for novel regulatory approaches; contributing research; sharing regulatory, scientific and practical knowledge; and providing feedback about OCP proposals.
For its part, OCP leadership has indicated that the office is interested in hearing from, and working with, industry. Opportunities for close collaboration exist, and industry can begin by providing input on OCP’s current initiatives in the following areas.
Good manufacturing practices. In the near future, FDA expects to issue a proposed rule on good manufacturing practices (GMPs) for combination products. A likely theme of the rule will be the requirement that combination product manufacturers must satisfy both sets of applicable GMP regulations (e.g., those for both drugs and devices). Manufacturers may choose an ‘umbrella’ system under which to operate, but it must meet the requirements of both sets of applicable GMP regulations.
Adverse incident reporting. FDA is expected to issue a proposed rule to establish postmarket safety reporting requirements for adverse incidents involving combination products.
Cross-labeling. As a follow-up to the May 2005 public meeting on cross-labeling, OCP is planning a new public meeting to discuss its strawman proposal, which is due to be released soon.
Combination product modifications. OCP has compiled a draft guidance on premarket submissions for modifications to combination products. However, the office is still considering how to implement its suggestions, and the release date of the guidance document is uncertain.
