Biosimilars: How the Approval Process Differs from a Standard ANDA

September 9, 2020

Biosimilars, by their very nature, are different from generic drugs. The core difference is that generic drugs are chemically synthesized, while biosimilars are grown in complex living systems. Because of this difference, generic drugs are reviewed and approved under the abbreviated new drug application (ANDA) pathway and biosimilars are reviewed and approved under the 351(k) pathway.


The Generic Drug Application Process

Generic drugs are reviewed and approved under the Food, Drug and Cosmetic Act. A generic drug product is one that is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics, and intended use. Once approved, a Sponsor may manufacture and market the generic drug, providing a safe, effective, and lower cost alternative to the brand-name drug it references.

An ANDA contains data that provides for the review, and ultimately the approval, of a generic drug product. When developing a generic drug and preparing an ANDA submission, a Sponsor’s main responsibility is to show that their drug product is bioequivalent to the innovator product. Essentially, the active ingredient of the generic drug must be identical to the innovator product as proven by a bioequivalence study.

Generic drug applications are referred to as “abbreviated” because they are not required to include preclinical (animal) or clinical (human) data other than the bioequivalence study to establish safety and effectiveness. Instead, the Sponsor must scientifically demonstrate that its product performs in the same manner as the innovator product.

One of the ways that Sponsors do this is by measuring the time it takes for the active ingredient in the generic drug to reach the bloodstream in healthy volunteers. This demonstration of “bioequivalence” gives the rate and amount of absorption, or bioavailability, of the generic drug, which can then be compared to that of the innovator drug. To be approved by the FDA, the generic version must deliver the same amount of active ingredient into a patient's bloodstream in the same amount of time as the innovator drug.

The Biosimilar 351(k) Pathway

A biosimilar product is a medicine that is similar to an already-approved biologic medicine, which includes vaccines, blood and blood components, allergenics, somatic cells, gene therapies, tissues, and recombinant therapeutic proteins. Biologics and their biosimilars are created from natural sources (human, animal, or microorganism), and they can be composed of sugars, proteins, nucleic acids, or complex combinations of these substances. In some instances, they may even be living entities, such as cells and tissues.

Biologics and biosimilars are reviewed and approved under the Public Health Service (PHS) Act. Unlike with generic products, the FDA requires a biosimilar to be highly similar, but not identical to the reference product. Additionally, a biosimilar also must demonstrate no clinically meaningful differences in efficacy, safety, and potency with its reference product. The 351(k) pathway is considered to be “abbreviated” because the amount of safety and efficacy data needed for a biosimilar to be approved by the Agency is usually less than the amount needed to approve the original biologic.

Biosimilar Sponsors must demonstrate biosimilarity primarily from nonclinical analyses in an approach that includes an examination of the structure and functional nature of the biosimilar molecule. Every biologic has a unique and complex molecular structure; a biologic can’t be made by simply placing molecules like amino acids in a pot and stirring it. Each molecule must be placed in a precise location to form the correct molecular structure.


Biosimilar Interchangeability

A 2018 guidance on biosimilar interchangeability issued by the FDA states that a product granted an interchangeable designation is expected to produce the same clinical result as the reference product in any patient without impacting safety or efficacy. Although automatic substitution laws and requirements for notifying physicians may vary at the state level, the FDA designation of interchangeability means that the biologic product may be considered to be automatically substituted by a pharmacist without intervention of the prescribing provider.

To date, no biosimilar has received the interchangeable designation, which means that a biosimilar may not be automatically substituted when filling a prescription for a biologic.


Follow the Right Path

When seeking the review and approval of a biosimilar, it is critical that a Sponsor follow the correct approval path. Biosimilars are governed by the PHS Act, which means that Sponsors must follow the abbreviated 351(k) pathway. Prior to the existence of this pathway, the FDA had to treat every biosimilar as if it were a brand-new biologic drug. Far from being a shortcut, the 351(k) pathway is a process through which the FDA can efficiently assess the nature of a biosimilar and approve it for use by the public. Consequently, the amount of time and money a Sponsor must invest in the approval process is significantly less than what is necessary to get an innovator biologic approved.


ProPharma Group Can Help Get Your Product Approved by FDA

Are you in the process of developing a generic or biosimilar product? Do you need to submit an ANDA or 351(k) submission to the FDA? ProPharma Group can help you achieve successful outcomes with the Agency regardless of where you are in the development/approval process.  To learn more about our services and how we can help you, contact us today.


6 Compliance Tips to get FDA Approval for Your Pharmaceutical Project

FDA Approval Process Overview The Food and Drug Administration (FDA), as part of the United States (US) Department of Health and Human Services, is the regulatory agency responsible for the review,...

November 3, 2020

Why Drug Approvals Are Never Slam Dunks

It's the FDA, Not the NBA Aside from being a spectacular thing to watch, the slam dunk is the highest percentage shot a basketball player can take. The likelihood of getting the ball in the basket is...

April 2, 2012

GRAS List Substances: Background and Misconceptions

Although it is widely known that the acronym GRAS stands for “Generally Recognized as Safe”, many individuals believe that GRAS substances have been rigorously reviewed for safety and approved for...