December 2019 Advisor – Biosimilars 101

Key Points

  • Biologics are large molecule products, such as proteins or monoclonal antibodies, with inherent variations that make them impossible to replicate.
  • Biosimilars are defined by the FDA as “biological products that are highly similar to and have no clinically meaningful differences from an existing FDA-approved reference product.”
  • An interchangeable product is defined by the FDA as a “biosimilar product that meets additional requirements outlined by the Biologics Price Competition and Innovation Act.”

Background

Biological medications have become a large part of medical treatments in recent years. As more biological medications enter the market, cost has become an increasing concern. Unlike the traditional small molecule drugs, biologics are large molecule products, such as proteins or monoclonal antibodies, with inherent variations that make them impossible to replicate. This means that creating an identical generic product is not possible, so instead products that are considered biosimilar are used. Both biosimilars and generic drugs are less costly versions of their brand name reference products. Biosimilars are biological products whereas generic drugs are traditional small molecule products.

Biosimilar vs Interchangeable vs Generic vs Authorized Generic

Generic medications are defined by the FDA as a “medication created to be the same as an existing approved brand-name drug in dosage form, safety, strength, route of administration, quality, and performance characteristics.” Generic drugs use the same active ingredients and must be shown to be both pharmaceutically equivalent and bioequivalent, which means it will work the same way in the body as the brand-name drug. The main differences that occur between generic drugs and their brand-name counterparts are differences in excipients used and the manufacturing process. Pharmacists are able to substituted generic drugs for brand-name drugs without consulting the prescriber. Authorized generics are the actual brand-name drug sold under a generic label. A list of authorized generics can be found on the FDA website.

Biosimilars are defined by the FDA as “biological products that are highly similar to and have no clinically meaningful differences from an existing FDA-approved reference product.” It is important to note that only minor differences are allowed between the biosimilar and its reference product. These minor differences are only acceptable if they occur in clinically inactive components of the biosimilar. Safety, purity, and potency must be demonstrated through additional human studies to prove there is no clinically meaningful difference in safety and efficacy of the product. An interchangeable product is defined by the FDA as “a biosimilar product that meets additional requirements outlined by the Biologics Price Competition and Innovation Act.” These additional requirements include more in depth testing to show safety and efficacy in any given patient and when alternating or switching between products. Depending on state laws, this designation could potentially allow Pharmacists to substitute interchangeable products for reference products without consulting the prescriber. As of now, no biosimilar has been designated as interchangeable.

Approval Process

Generic drug approval is done through an abbreviated new drug application (ANDA) which shows that the generic product uses the same active ingredient, and is both pharmaceutically equivalent and bioequivalent to the brand-name product. No additional animal or clinical trials are required for generic drug approval, which allows for lower pricing.

Biosimilar drug approval is done through a biosimilar product application. Data submitted with the application must show that the biosimilar is safe, effective, and highly similar to the reference product. This data often consists of animal studies assessing toxicity, and smaller clinical studies assessing things such as immunogenicity, pharmacokinetics, and pharmacodynamics to demonstrate safety, purity, and potency. Similar to generics, manufacturers of biosimilars can avoid having to do large expensive clinical trials, which allows for lower pricing. Post marketing surveillance is the same for both small molecule drugs and biologics.

In May of 2019, the FDA finalized the guidance document on interchangeable product approval. This guidance provides manufacturers with clearer information on what is needed to gain interchangeable status approval.

Nomenclature

The FDA released a guidance update in March of this year for nonproprietary naming of biological products. Newly licensed biological products will continue to include the core name and a four-character suffix that carries no meaning. No change will be made to the names of biological products already on the market.

Staying Up-to-Date

  • The “Purple Book” lists all biological reference products along with any biosimilar and interchangeable products licensed by the FDA under the Public Health Service Act. This resource is similar to the “orange book” which lists approved drug products and their therapeutic equivalents.
    • The “purple book” is updated periodically and can be accessed on the FDA website.

References:

  1. U.S. Food & Drug Administration. Biosimilar and interchangeable products [Internet]. 2017 Oct 23. [cited 2019 Oct 15]. Available at: https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products
  2. U.S. Food & Drug Administration. Biosimilar development, review, and approval [Internet]. 2017 Oct 10. [cited 2019 Oct 15]. Available at: https://www.fda.gov/drugs/biosimilars/biosimilar-development-review-and-approval
  3. U.S. Food & Drug Administration. Generic drugs: questions & answers [Internet]. 2018 Jun 1. [cited 2019 Oct 17]. Available at: https://www.fda.gov/drugs/questions-answers/generic-drugs-questions-answers
  4. U.S. Food & Drug Administration. FDA listing of authorized generics [Internet]. 2019 Oct 1. [cited 2019 Oct 17]. Available at: https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/fda-listing-authorized-generics
  5. U.S. Food & Drug Administration. Purple book: lists of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations [Internet]. 2019 Oct 8. [cited 2019 Oct 17]. https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/purple-book-lists-licensed-biological-products-reference-product-exclusivity-and-biosimilarity-or
  6. Pharmacy Times. FDA issues final guidance on pathway for interchangeable biologics [Internet]. 2019 May 10. [cited 2019 Oct 17]. Available at: https://www.pharmacytimes.com/news/fda-issues-final-guidance-on-pathway-for-interchangeable-biologics
  7. Davio, Kelly. FDA releases guidance on biologic, biosimilar, and interchangeable biosimilar naming conventions [Internet]. 2019 Mar 7. [cited 2019 Oct 17]. Available at: https://www.centerforbiosimilars.com/news/fda-releases-guidance-on-biologic-biosimilar-and-interchangeable-biosimilar-naming-conventions
  8. U.S. Food & Drug Administration. Guidance for industry: post marketing safety reporting for human drug and biological products including vaccines. 2001 Mar. [cited 2019 Oct 19]. Available at: https://www.fda.gov/media/72504/download
About the author

PharmD, PGY-1 Pharmacy Practice Resident

Leave a Reply

Keep updated on COVID-19 by entering our secure Member's Portal.ENTER HERE >