Drugs vs. Biologics - What is the Difference?

Drugs

  • typically a smaller chemical structure than biologics
Aspirin Molecule - Simple
  • typically manufactured through chemical synthesis, which means that it is made by combining specific chemical ingredients in an ordered process.
  • generally have well-defined chemical structures, and a finished drug can usually be analyzed to determine all its various components
  • a drug manufacturer can change the manufacturing process extensively and analyze the finished product to establish that it is the same as before the manufacturing change.

Biologics

  • very large, complex molecules, proteins or mixtures of molecules
Protein - Vastly Complex
  • manufactured in a living system such as a microorganism, or plant or animal cells
  • it is difficult, and sometimes impossible, to characterize a complex biologic by testing methods available in the laboratory, and some of the components of a finished biologic may be unknown
  • for biologics, “the product is the process.” Because the finished product cannot be fully characterized in the laboratory, manufacturers must ensure product consistency, quality, and purity by ensuring that the manufacturing process remains substantially the same over time.

Additional Biologics Info

  • The living systems used to produce biologics can be sensitive to very minor changes in the manufacturing process. Small process differences can significantly affect the nature of the finished biologic and, most importantly, the way it functions in the body. To ensure that a manufacturing process remains the same over time, biologics manufacturers must tightly control the source and nature of starting materials, and consistently employ hundreds of process controls that assure predictable manufacturing outcomes.
  • Process controls for biologics are established separately for each unique manufacturing process/product, and are not applicable to a manufacturing process/product created by another manufacturer. These process controls may also be confidential to the original manufacturer. Therefore, it would be difficult or impossible for a second manufacturer to make the “same” biologic without intimate knowledge of and experience with the innovator’s process.

Generic Drugs vs. Follow-on Biologics (Biosimilars)

Generic Drug Manufacturing

To be approved as a generic, a drug must have the same active ingredient, strength, dosage form, and route of administration as the reference drug, and it must also be “bioequivalent.” This means that generic drugs are the same chemically as their innovator counterparts and that they act the same way in the body.

Biosimilar Manufacturing (not really possible)

FDA has stated that it has not determined how interchangeability can be established for complex proteins.  More here

Historically, FDA has permitted interchangeability only when two products are “therapeutic equivalents.” However, when the follow-on manufacturer establishes a new manufacturing process, beginning with new starting materials, it will produce a product that is different from and not therapeutically equivalent with that of the innovator (i.e. the end product is different). Due to the complexity of biologics, the only way to establish whether there are differences that affect the safety and effectiveness of the follow-on product is to conduct expensive and time-consuming clinical trials.