Understanding Biologic Substitutions – New Tool Available!

The FDA publishes two lists of approved drugs:

• The Orange Book – Approved Drug Products with Therapeutic Equivalence Evaluations
• The Purple Book – Approved Biological Products including Biosimilar and Interchangeable products

Biologic products are found in the Purple Book and are not described in familiar terms like “brand“, “generic”, or “AB rated” as found in the Orange Book. The FDA’s Purple Book lists each product as a Reference Product, Biosimilar, or Interchangeable. Review the Purple Book terminology below:

Reference Product is the original biological product approved through a 351(a) BLA (Biologic Licensing Application)

• Think of these products like brand drugs in the FDA Orange Book
• Cannot be substituted for other Reference Products without prescriber approval

Biosimilar products are approved through an abbreviated 351(k) BLA

• Think of these products like B-rated generic drugs in the FDA Orange Book
• Cannot be substituted for Reference Products without prescriber approval

Interchangeable products have been deemed interchangeable with a reference product after going through additional switching studies and approved under a 351(k) BLA

• Think of these products like A-rated generic drugs in the Orange Book
• CAN be substituted for respective Reference Products without contacting the prescriber if state law permits

Unbranded biologic products are approved under the Reference Product’s 351(a) BLA

• Think of these products like authorized generics in the Orange Book
  • CAN be substituted for the Reference Product without prescriber approval or regard to state law
  • Considered by the FDA to be equivalent to its brand name biological product because it is the same product as the brand name under the same BLA, just with a different label
  • Is not different in strength, dosage form, route of administration, or presentation
  • NOT separately identified in the Purple Book

PAAS Tips:

• Pharmacy level substitution of a reference product is only allowed if one of the following scenarios is applicable:

• identified as interchangeable AND your state pharmacy practice law allows
  • Ex: Semglee® can be substituted for Lantus® due to 351k interchangeable status

• an unbranded biologic with the same BLA number as the reference product
  • Ex: Semglee® (BLA 761201) can be freely substituted with its unbranded biologic Insulin glargine-yfgn (BLA 761201)

• an unbranded biologic with the same BLA number as an interchangeable biosimilar
  • Ex: Insulin glargine-yfgn (BLA 761201), an unbranded biologic of Semglee® (BLA 761201), can be substituted for Lantus (BLA 021081) because Semglee® has 351(k) interchangeable status to Lantus and therefore its unbranded biologic (insulin glargine-yfgn) can also be freely substituted

• See FDA Purple Book to determine interchangeability status of a particular biologic drug
  • FDA has more detailed definitions on the Purple Book website.
  • There is also a frequently asked question section that discusses unbranded biologics (FAQ #11).
• State pharmacy laws may limit biologic interchangeability, but this does not apply to unbranded biologics. Review your state laws (reference) or  contact your state Board of Pharmacy.
• If you are ever in doubt about whether products may be substituted
  • Utilize PAAS National^®’s® new tool titled Understanding Biologic Substitutions for a stepwise process on substitutability
  • Call the prescriber to obtain approval – do not forget to document with a clinical note
  • Contact a PAAS Expert
• Review the September 2022 Newsline article, NCPDP Updates DAW Code Definitions to Encompass Interchangeable Biosimilars
• Review the FDA’s Curriculum Materials for Health Care Degree Programs | Biosimilars