Biopharmaceuticals have demonstrated unparalleled advances for the treatment of cancer, immune diseases, and other common medical conditions, and are the fastest growing segment of the pharmaceutical industry today. Worldwide sales of these agents are expected to increase to more than $167 billion annually by 2015.

Biosimilars (also called follow-on biologics) are similar to brand name biopharmaceuticals. Their introduction in the United States is expected to improve the affordability of costly biopharmaceutical therapies, leading to cost savings of up to 40% compared to their innovator products. The potential profits for biosimilar manufacturers are huge.

In anticipation of patent expirations for a significant number of costly biopharmaceuticals, the Food and Drug Administration (FDA) has proposed an abbreviated pathway for the approval of biological products that are “highly similar” (i.e., biosimilar) to, or interchangeable with, a biological product.


The United States has established strict scientific standards and legal mechanisms for granting FDA approval for generic versions of prescription medications. Generic medications are approved on the basis of abbreviated applications, demonstrating that they are the same in structure as, and bioequivalent to, a previously approved product. Importantly, nonclinical and clinical data are not usually required for generics’ approval. Is this approach applicable to the approval process for biosimilars?


Should an abbreviated regulatory approval pathway for biosimilars be allowed?


  • The manufacturing process for biopharmaceuticals is extremely complex, costly, and time-consuming—even more so than for the development and commercialization of typical prescription medications.
  • According to the FDA, for a biosimilar to receive approval, there must be “no clinically meaningful differences between the biological product and the reference product in safety, purity, or potency.”
  • Furthermore, approval of a biosimilar is based on evidence from a variety of sources that may involve structural analyses, functional assays, animal studies, and human studies.
  • The FDA has the discretion to determine if and when some of these requirements are not needed.


Unlike traditional, chemical-based prescription drugs, biologics are large molecule drugs derived from proteins. Due to the complexity of biologics, a product can only be made that is similar, not identical. As part of the Affordable Care Act (ACA), Congress established an abbreviated approval pathway for biosimilars.

Unlike small molecule drugs, whose structure can usually be completely defined and entirely reproduced, proteins are more complex and are unlikely to be structurally identical to a reference product. Because even minor structural differences can significantly affect a protein’s safety, purity, and potency, just how “similar” a biosimilar is compared to the original biopharmaceutical becomes critical. This seems to indicate that rigorous clinical studies, such as those required for approval of a new biopharmaceutical, are needed. Each claimed indication for a biosimilar should be established by indication-specific clinical trials unless there is a solid scientific rationale to justify extrapolation of the clinical safety and efficacy data from one indication to another.

There also exists much debate as to what exactly will be required by FDA for a biosimilar to demonstrate proof of interchangeability. According to a draft FDA guidance, companies can apply for an interchangeability designation for a biosimilar. However, the guidance goes on to say that it would be “difficult” for applicants “as a scientific matter to establish interchangeability utilizing the initial biopharmaceutical new drug application.” The provision that biosimilars can extrapolate results across patient populations further compounds just how interchangeable a biosimilar may or may not be. With interchangeability defined for all biosimilars as a class, and not on a product-specific basis, the effect of very small differences in the manufacturing process and testing in humans could introduce additional risks and unknown adverse effects.

Finally, in addressing the issue of market exclusivity, an application for the approval of a biosimilar may not be submitted to the FDA for 4 years after the approval of the innovator product. This is significantly shorter than the 12-year exclusivity period permitted for prescription drugs. In light of the effects of the current “patent cliff” and the much higher costs associated with the development and commercialization of a biopharmaceutical, the consequences of reducing market exclusivity by 8 years will inevitably impact innovation and the willingness of a biotech organization to invest in research and development for much needed biopharmaceuticals.


There is little disagreement that biosimilars will save patients, insurance companies, and the government billions of dollars each year. However, an abbreviated regulatory approval pathway for biosimilars should not be allowed.

Although the generic drug paradigm has been in place for several decades, it is generally recognized that the paradigm will not work for biologically derived drugs.

In terms of public safety, the FDA should require more—not less—testing of biosimilars. The term “interchangeability” as used by the FDA is too general and does not apply to all biosimilars. The FDA needs to develop product-specific definitions of interchangeability to ensure that a biosimilar can produce the same effect as the original biopharmaceutical without increasing potentially harmful side effects.

In terms of reducing the period of market exclusivity of biopharmaceuticals to 4 years, there appears to be no reason other than to reduce the cost of biosimilars for the government, and more pointedly, for insurance companies. Biopharmaceuticals cost more, are more difficult to produce, and require more time to reach the marketplace. If anything, lengthening the period of market exclusivity past the 12-year mark may be appropriate.

For more information on this issue, contact the Kulkarni Law Firm.