Generic Drugs Flashcards
Definition: Generic Drug
A generic drug is identical–or bioequivalent–to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use.
Legal Basis for Generic Drugs
Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Amendments)
Amended the FD&C Act
Established a statutory generic drug approval process with section 505(j) for post-1962 drugs
Created an abbreviated mechanism for approval of the generic copies without pre-clinical or clinical testing
Clinical criteria based on bioequivalence
FDA List of Approved Drugs
Basic Generic Drug Requirements
Same active ingredient(s)
Same dosage form
Same strength
Same route of administration
Same intended use
Inactive ingredients already approved in a similar NDA
How are Generics Approved: ANDA
505(j) application is an Abbreviated New Drug Application (ANDA)
Generic drug applications contain information to show that the proposed product is identical in active ingredient, dosage form, strength, route of administration, labeling, quality, performance characteristics and intended use to a previously approved product - the reference listed drug (RLD)
Submit to the Office of Generic Drugs (OGD)
Must be submitted electronically (eCTD)
Has an associated User Fee (GDUFA)
User Fees have been used to help clear the backlog of applications
What ergulation applies to Generic Drugs
Described in Regulations (21 CFR §314.92)
Reviewed by separate group at FDA (Office of Generic Drugs)
Application form
Basis for application
Must indicate the Reference Listed Drug (RLD) for which applicant is seeking approval
Patent certification and exclusivity statements
Key element
Proposed labeling
CMC information
Bioequivalence data –both in vitro and in vivo
Equivalences in Generic Drugs
Pharmaceutical (Chemical) Equivalence
Bioequivalence (Biological Equivalence)
Therapeutic (Clinical) Equivalence
In FDA Practice
Pharmaceutical Equivalence + Bioequivalence
= Therapeutic Equivalence
Pharmaceutical Equivalents
Drug products with following three criteria
Same active ingredient(s)
Same dosage form and route of administration
Same strength or concentration
Pharmaceutically equivalent drug products may differ in characteristics such as
shape
release mechanism
labeling (to some extent)
scoring
excipients (including colors, flavors, preservatives)
Bioequivalence
Must be pharmaceutical equivalents
Must display comparable bioavailable and meet criteria for bioequivalence
rate and extent of absorption is the same
statistical criteria for equivalence
The FDA requires the bioequivalence of a generic product to be between 80% and 125% of the innovator product
This does not mean that generic drugs must be exactly the same (“pharmaceutical equivalent”) as their innovator product counterparts, as chemical differences may exist
Generic drug marketing occurs…
After the patent has expired
After patent and exclusivity protection ends, or patent owner waive its right
The generic company certifies the brand company’s patents are either invalid, unenforceable or will not be infringed
For drugs which have never held patents
And
FDA requirements are met
Label will be based on the Reference Listed Drug (RLD) or Innovator label
“The Orange Book”
The Orange Book lists all FDA approved drug products (NDAs, OTCs and ANDAs)
Published annually (with supplements) by FDA
Update monthly in on-line version
All FDA approved drug products listed (NDAs, OTCs and ANDAs)
Identifies what is the RLD
Provide patent and exclusivity expiration dates
Therapeutic Equivalence codes
Identifies what is the RLD
‘A’ prefix – substitutable
‘B’ prefix – inequivalent, NOT substitutable
Authorized Generics
Authorized generics (AG’s): Generics sold under license from the patent holder to discourage generic competition
AG’s are not affected by the 180-day exclusivity period as they fall under the patent holder’s original drug application
AG’ submission can be done “overnight” via the NDA annual report
What are Biosimilars?
A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an FDA-approved biological product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product.
Only minor differences in clinically inactive components are allowable in biosimilar products.
Legal Basis for Biosimilars
The Affordable Care Act (aka “ObamaCare”) was signed into law on March 23, 2010.
In it was the Biologics Price Competition and Innovation (BPCI) Act which was set up to do the same things as the Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Act) did - including establishes an abbreviated pathway for the approval of biological products that are “highly similar” (i.e., biosimilar) to, or interchangeable with, the reference biological product.
The abbreviated Biologics License Application or aBLA is required for Biosimilars
There are also modifications to agency interactions for biosimilars.
Differences between Biosimilars and Generic drugs
Generic drugs are usually chemically synthesized while biological products, including biosimilars, are generally manufactured from living sources.
Because the active ingredients of generic drugs generally are smaller and simpler, they are usually easier to copy.
Biologics generally cannot be copied exactly, because the product (e.g., monoclonal antibody) contains a mix of many slight variations of a given protein that occurs during its production from living sources, which introduces inherent variation.
FDA Review of Biosimilars
As part of the approval process for both reference products and biosimilars, FDA assesses a biosimilar manufacturer’s strategy to control for the pattern and degree of variations between different lots to help ensure consistent safety and effectiveness.
Manufacturers must demonstrate that their proposed biosimilar product has similar variations compared to the reference product and that their product has no clinically meaningful differences in terms of safety and effectiveness. Compared to the reference product, the effect of the biosimilar is the same, dosing is the same, and administration is the same.
Sponsor must include in the BLA
An adequate clinical PK comparison, and PD comparison if relevant, between the proposed biosimilar and reference product.
An assessment of immunogenicity for the proposed biosimilar product.
A comparative clinical study in patients cancontribute to the totality of the evidence supporting biosimilarity.
“The Purple Book”
NOT an actual book – never was!
It includes the following information about biological products:
The date on which the product was licensed under section 351(a) of the PHS Act.
Whether FDA evaluated the product for reference product exclusivity.
Whether the product has been determined to be biosimilar to or interchangeable with a reference product (i.e., a previously licensed biological product).
To facilitate use of Purple Book information, biosimilar products and interchangeable products are grouped under the reference product to which biosimilarity or interchangeability was demonstrated
