What are Biosimilar Drugs, Interchangeability, Exclusivity, Substitution, and Approval Process? | Rachael Olsufka, PharmD | RxEconsult

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Interchangeability, Exclusivity, and Substitution of Biosimilar Drugs Category: Rheumatoid Arthritis & Inflammatory Conditions by - September 11, 2014 | Views: 70745 | Likes: 2 | Comment: 0  

What is a biosimilar drug?

The FDA defines a biosimilar drug as, “A biological product that is highly similar to a US-licensed reference biological product notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.”  A reference product is an original biologic approved after submission of an NDA and BLA. In simple terms, to meet the FDA definition of “biosimilar” a product must:

  • Be a biologic product (i.e., synthesized from a living organism)
  • Have the same route of administration, dosage form, and strength as the reference product
  • Work by the same mechanism as the reference product
  • Be highly similar to the reference product (apart from minor differences in inactive ingredients)
  • Not show any clinically meaningful differences in the reference product in safety, purity, and potency

What is the difference between a biologic and a small-molecule medication?

To understand what a biosimilar medication is it is necessary to understand the differences between biologics and small-molecule medications. Biologic medications originate from living cells or organisms and include vaccinations, blood components, and antibody medications. Examples of biologic medications include Humira (an antibody for rheumatoid arthritis), Lantus (insulin for diabetes), and Herceptin (antibody for breast cancer). Small-molecule medications are not created from living cells. They are synthesized from chemical processes in a laboratory. Examples of medications classified as small molecules include aspirin, Lipitor, and Plavix. Compared to small molecules, biologics are generally very large in size (up to 1000 times the molecular weight of small molecules). To put this into perspective, Genentech has equated this difference in size and weight (for example, 21 atoms for aspirin versus ~25,000 atoms for an antibody) to a 20-pound bicycle and a 30,000-pound jet.

Owing to their natural origin and because they are proteins, biologic medications are more sensitive to manufacturing processes than small-molecule medications. Temperature, stability, and other external environmental factors can quickly compromise the integrity of the final product. This makes it difficult to consistently reproduce the same product each time it is made (especially on a large scale production). This also accounts for why biologic medications are usually injected instead of taken orally. For example, a common technique for manufacturing biologics is to insert DNA into a bacterium and allow the bacterium to replicate the DNA and create the protein of specific interest. The protein will later be isolated and purified to create the desired medication. This example differs greatly from small-molecule synthesis where a chemist, not a bacterium or other living organism, synthesizes the compound of interest by performing numerous chemical reactions. Although small molecules are also sensitive to the same environmental factors that can compromise the quality of the final product, a biologic product can undergo up to 250 tests during the manufacturing process to ensure quality compared to up to 50 for a small-molecule.

An additional difference between biologics and small molecules is in their regulatory approval pathway. While both biologics and small molecules are filed under an NDA, a biologic must also file for a BLA. This licensure ensures that the standards of manufacturing high quality, safe, and effective products are met. Biologics failing to file a BLA will not receive an approved NDA, which means no drug approval.

Next: Biosimilars vs Generic

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