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MedImmune supports the establishment of a regulatory pathway for the approval of biosimilars in the U.S. that ensures patient safety, product efficacy and continued incentives for biotechnology innovation.

Background

“Biologics” are complex medicines that are reviewed and approved by the U.S. Food & Drug Agency (FDA) under the provisions of the Public Health Service Act (PHSA) for use in the United States. The “biological standard” for approval requires demonstration that a biologic is “pure, potent, and safe” and that its manufacturing facility is designed to assure the product continues to be pure, potent, and safe. The recent passage of the Patient Protection and Affordable Care Act (PPACA) established a foundation for biosimilars to enter the U.S. marketplace. While the PPACA created a general framework, the law also provides FDA authority to establish rules and guidance that will govern the specific requirements and procedures for reviewing and approving biosimilars.

The terms “biosimilars” (also called “follow-on biologics”) refer to products that are intended to copy previously-approved, innovator biologics and are submitted for approval based on similarity to the innovator product. Biosimilars are fundamentally different from small molecule generic drugs, which are virtually identical versions of innovator products and can readily be characterized by comparison of the exact chemical composition to the innovator product. As such, even without clinical trials to show safety and efficacy, generic drugs are usually designated to be “therapeutically equivalent” with the innovator drug and therefore interchangeable under FDA generic regulations. Conversely, while a biosimilar may be similar to an innovator product, it currently cannot be proven to be identical based on the current state of science. Thus, there are unique and inherent characteristics of biologics that must be considered as FDA establishes a regulatory pathway for biosimilars:

• Biologics are manufactured using live cells and biologics, such as monoclonal antibodies manufactured by MedImmune, are larger and more complex than small molecule drugs.
• Biologics are more difficult to characterize using laboratory techniques and have a more complex manufacturing process.
• Every biologic is different – even slight differences between biosimilars and innovator biologics, including their manufacturing processes, can result in meaningful differences in the safety and efficacy profile of the products.

What we believe

We support a regulatory pathway for biosimilars that is based on patient safety, product efficacy and continued incentives for innovator companies to invest in the development of novel, life-changing biologic medicines. We believe a biosimilars pathway should ensure:

• Appropriate rigorous scientific standards and a robust regulatory review process;
• A determination that biosimilars demonstrate the purity, potency and safety of innovator biologics as proven through human clinical trials and post-market surveillance; and
• Implementation of effective innovator regulatory exclusivity and patent enforcement provisions.

Below is a detailed look at our position:

Patient Safety
Because of the complexities of biologics, we believe that patient safety must be paramount when evaluating the approval of biosimilars. The introduction of biosimilars into the marketplace must ensure the current purity, potency, and safety standards established for innovator products by FDA. In addition, because the manufacturing process can have a significant impact on a biologic’s structure and activity, a regulatory pathway should ensure a rigorous inspection and control process for the manufacture of biosimilars that is similar to the innovator product standards

Clinical Trials
We believe that all biosimilars applicants should be required to conduct clinical trials that demonstrate sufficiently similar product safety, efficacy and immunogenicity relative to the innovator product. Non-clinical methods of characterizing complex biotechnology drugs have not matured to the point where they can substitute for clinical studies. Therefore, to ensure patient safety, it is essential for biosimilar sponsors to demonstrate product safety and efficacy by testing their product in adequate and well-controlled clinical studies. Furthermore, immunogenicity testing in human subjects, an integral part of biologics drug development, is critical to help measure potential adverse immune response to the biosimilar product. Immunogenicity has been associated with allergic or anaphylactic reactions, as well as reduction in efficacy or autoimmunity. We believe the FDA should issue molecule-by-molecule guidance for clinical trials required for biosimilars to account for the particular characteristics of the product.

Post-Market Risk Management Programs
We believe that biosimilars, once approved, should have FDA-approved risk management plans to ensure the products are rigorously monitored for post-market safety and immunogenicity. If biosimilars are approved with less clinical data than innovator biologics, the FDA should ensure that longer-term post-marketing outcomes for biosimilars remain similar to those with the innovator product.

Interchangeability/Substitution
We do not support interchangeability between an innovator biologic and a biosimilar product. Current regulations allow small molecule generic drugs to be designated as “therapeutically equivalent” and dispensed interchangeably with innovator products without physician’s knowledge. Because biosimilars are not identical to innovator biologics, they should not be deemed therapeutically equivalent and dispensed interchangeably for innovator biologics absent clinical trials that adequately demonstrate such interchangeability.

Unique Naming and Product Identification
Because biosimilars are similar to innovator biologics (rather than identical), we believe biosimilars should have a unique common name to distinguish themselves for prescribing, dispensing and pharmacovigilance purposes. In the interest of patient safety, it is critical that any adverse events be accurately traced to the actual product administered so that the manufacturer can take immediate remedial actions.

Patent Rights
Strong patent protection is the cornerstone of preserving incentive for biologics innovation, and a biosimilars approval pathway must establish a fair, transparent and effective system for all parties to quickly resolve any patent disputes.

Incentives for Innovation
Because biologics generally have substantial research, development and manufacturing periods and costs, a significant period of non-patent data exclusivity for innovator biologics must be provided to maintain an environment that fosters discovery of new and innovative biotechnology therapies. Although patent protection is important, this alone may be insufficient to protect the substantial investment made by innovators. For example, a biosimilar may be similar enough to an innovator biologic to receive regulatory approval, but different enough to circumvent the innovator’s patents. We support the provisions in PPACA that provides a base 12-year period of data exclusivity for innovator biologics plus an additional 6 months for pediatric studies.

Next Generation Improved Biologics
We support measures that protect investment in improvements to innovator biologics through extension of data exclusivity and intellectual property protections. This will help encourage continued investment and discovery of enhanced versions of previously-approved biologics that are safer, more effective, easier to administer and more capable of meeting patient needs. Modifications such as changes in amino acid sequences involve fundamental changes to a biologic’s molecular structure, and generally require clinical trials to gain regulatory approval. The vital, step-by-step process for advancing these medicines is dependent upon continued incentives for next generation biologics.

Conclusion
As new, innovative biologics and biosimilars enter the marketplace, AstraZeneca and MedImmune believe patient safety and product efficacy are of utmost importance. As a result, we support the development of a regulatory pathway for biosimilars that is based on patient safety, product efficacy and incentives for innovation. We will continue to monitor policy discussions and proposed regulations as the FDA moves forward in establishing a biosimilars pathway, and share our expertise and views where appropriate.

Download POSITION ON BIOSIMILARS (PDF, 34KB)