A key component of the Patient Protection and Affordable Care Act (PPACA) of 2010 has just been released with little fanfare. One of the most significant provisions in the law gives the Food and Drug Administration (FDA) the authority to regulate biosimilars, which are attempts to replicate some of the most complex medicines known as biologics. These advanced medicines treat serious medical conditions including cancer, multiple sclerosis, and rheumatoid arthritis. Last week, the FDA provided draft guidance that will eventually lead to the introduction of biosimilars in the U.S.

To date, there are no biosimilars in the U.S. market because they were considered “too complex” to include in the 1984 Hatch-Waxman legislation, which regulates the generic drug industry in America. In recent years the European Union, Canada and several other jurisdictions have made biosimilar versions of biologic products available for sale, and the United States is currently following suit.

The Unique Nature Of Biotech Medicines

In formalizing its “biosimilars pathway,” the FDA has sought input from patient groups, academics, physicians and industry. Regulating biotech medicines is an immense task. Whereas most pharmaceuticals primarily treat the symptoms of a disease, biologics can be manipulated to target the underlying mechanisms and pathway of a disease.

Additionally, unlike traditional chemical compounds, biologics are complex, large molecules that are genetically engineered from living cells or organisms by programming a cell line to produce a desired protein in a highly controlled environment. Because biosimilars do not utilize the same living cell line, production process, or raw material as the innovator drug, they can never be made “identical” to the innovator biologics. This matters because small differences in molecules can result in major differences in the drug’s clinical efficacy and safety.

The draft guidance is an important step forward in expanding access to existing biological therapies and will be refined in the coming months. The FDA has opted for a “totality of the evidence” approach, encouraging biosimilar developers to submit analytical data, which will then be evaluated to determine if further animal or human testing is needed. In every case, the FDA has stated that it will require additional clinical studies when a manufacturer requests its biosimilar to be deemed “interchangeable.” In some states, this additional designation will allow the biosimilar to be automatically substituted by a practicing pharmacist for the reference product, without even notifying the treating physician. As a practicing physician, I am deeply concerned about the possibility that I may be unaware that my patient has been switched from the medicine that we in consultation decided was best.

What The Final Guidance Should Include

As the guidance is finalized, it’s important that the FDA’s data requirements for the approval of a biosimilar as well as a designation of ‘interchangeability’ reflect that a biosimilar is similar to, but never identical to its innovator biologic. And because a biosimilar is not a “copy and paste” of the original biologic medicine, they must include appropriate measures to ensure patient safety including at a minimum:

  • The requirement of robust clinical and nonclinical measures to approve any biologic and biosimilar medicine;
  • The assurance that every product will be traceable by way of robust pharmacovigilance systems in place prior to approval of any biosimilar products;
  • The requirement of unique names for all biologic medicines;
  • The requirement of transparent product labels that reflect the trials conducted on that specific product, not on the reference product;
  • The assurance that patients and their physicians have the ability to decide a course of treatment that may not be altered by the pharmacist or others without the consent of the treating physician and the patient, or at a minimum being notified at the time of a product substitution;
  • In addition to the necessary clinical evidence required by statute, the recognition that similarity between the reference product and its interchangeable biologic product(s) may change over time as a result of manufacturing or environmental changes impacting one or more products. This potential divergence post-approval must be addressed by U.S. regulators before labelling a biosimilar ‘interchangeable’.

The release of the draft guidance was an important first step for the introduction of biosimilars into the U.S. Ultimately the agency’s decision to treat each application as unique and refrain from a one-size-fits-all approach is good for patients. Lower cost medicines are extremely important especially in these difficult economic times, but the FDA has always put patient safety above all else and it is reassuring to know that the biosimilar pathway will not be an exception.