Biosimilars: Pharmacist Self-Education Is Key to Drug Safety and Efficacy

Top-selling biologics and potential biosimilars were the topic of an educational session at the 2015 APhA meeting in San Diego, CA. The 2010 Affordable Care Act paved the way for FDA approval of biosimilars. With many blockbuster biologics’ patents expiring, pharmacists can expect change, and potentially, lower costs.

It is important that pharmacists educate themselves so they can properly inform patients about the safe and effective use of biosimilars, according to copresenter James Stevenson, PharmD, FASHP, of the University of Michigan.

Biologics’ issues are unique compared with those of simple molecules. With biologics’ living cell culture sources, comparatively high molecular weights, complex folding, variable stability, and immunogenic properties (which create antibodies or neutralizing products), stakeholders have been concerned that demonstrating true interchangeability would be impossible.

Hence, the FDA uses the word biosimilars to describe the entities that are as close as possible to the reference drug. The FDA’s goal is to ensure that if patients switch between innovator and biosimilar products, they have no adverse clinical consequences. In short, pharmacists can confidently substitute a true biosimilar for a brand name product and know that it is “unlikely to have clinically differences in safety and efficacy,” according to copresenter Edward Li, PharmD, MPH, BCOP, University of New England.

Dr. Li emphasized that the process for determining biosimilarity is a lot more complex than for determining the “bioequivalence” of a generic drug.

The FDA has formulated requirements for establishing biosimilarity and interchangeability, allowing biosimilars makers to use different formulations, delivery devices, or containers. Their product’s strength must be identical to the innovator’s product. They may apply for licensure for routes of administration that the innovator had approved, and only the indications the innovator had approved.

Dr. Li told attendees, “I think that’s where a lot of confusion comes in, [people ask] what if they are not comparable? Well, if they are not comparable, they won’t be biosimilars.”

The FDA has developed a robust regulatory pathway for biosimilars using an abbreviated approval pathway. The goal is to avoid replicating unnecessary and costly clinical trials, and allow smaller-scale direct comparisons and extrapolation. For each biosimilar, the FDA will tailor approval requirements based on the specific agent’s unique history, indications, and clinical experience.

As these are very different products than small molecule drugs, the FDA was careful to create a robust pathway for biosimilar approval. “It’s very appropriate that the FDA has been cautious,” Dr. Stevenson said.

Much of the US biosimilar approval process was informed by the European biosimilar approval and practice experience, according Dr. Stevenson. He noted that Europe has 15 approved so far. Thorough analytical characterization is the critical component of approvability.

So far, there have been no signs that these approved products are less safe than their branded counterparts. “There has not been a single one that has had to be removed from market,” Dr. Stevenson said.

Dr. Li noted that interchangeability and pharmacovigilance are unresolved issues, and the specifics of how postmarketing data will be documented are still being refined. Looking ahead, it will be critical for pharmacists to correctly attribute the safety signals. “Our role for pharmacovigilance is this—when we report an adverse event, we need to report the correct manufacturer of the product the patient received,” he said.

Pharmacists can expect to see biosimilar insulins, growth hormones, monoclonal antibodies, and many more products entering the market. Some workplace concerns include differentiating biologics in computer order entry systems, and addressing these agents in medication reconciliation.

Dr. Stevenson told attendees that pharmacists need to stay abreast of their own state’s legislation on this issue, especially as it pertains to prescriber preference, labeling, and record-keeping.