The scope of this blog to give the overview of Drug approval process in US.
The regulatory agency of USA is FDA which has two bodies: CBER and CDER.
CBER stands for Centre for biological evolution and Research and CDER stands for Centre for drug evaluation and research. CBER agency deals with biological product whereas CDER deals with drugs and biological both. In general the drug (chemical) approval process in US can be divided into four parts, they are:
- Supplemental new drug application
- Abbreviated new drug application
- Petitioned ANDA
- and New drug application
Abbreviated new drug application (ANDA): It follows the 505 b (j) pathway. Proposed drug candidate must be same with respect to following attributes compared to Reference listed drug (RLD). List-1
- Active ingredient,
- Dosage strength,
- Dosage form,
- Route of administration
- Inactive ingredients
As per FDA, “A Reference Listed Drug (RLD) is an approved drug product to which new generic versions are compared to show that they are bioequivalent.”
Bio-equivalence studies (to check rate and extent of absorption) are conducted to ensure that proposed product is bio equivalent to RLD. Safety and efficacy studies are not required. Certain differences in inactive ingredients are permissible. Few differences in the inactive ingredients are allowed in ophthalmic, Parenteral and otic formulations. Preservative buffer and antioxidants can differ from the RLD parenteral formulation. These excipients are called exception excipient. The difference in the excipient should not have any effect on safety and efficacy of drugs.
Supplemental new drug application: This application follows the 505(b2) pathways. It can be chosen if a proposed drug candidate has to undergo any of the changes mentioned in list-1. In addition to this, if any switch to OTC product from prescription or any new combination of drugs, are evaluated, then it follows 505 b(2) pathway. If any change in active ingredients as new salt formulation or complex, then FDA can consider it for 505 b(2) pathways .
Petitioned ANDAs (submitted and approved under § 505(j)): As per the FDA: “A petitioned ANDA is a type of ANDA for a drug product that differs from the RLD in its dosage form, route of administration, strength, or active ingredient (in a product with more than 1 active ingredient), and for which the FDA has determined, in response to a suitability petition under § 505(j)(2)(c), that safety and efficacy studies are not necessary for the proposed drug product.”
In short, applicants apply for 505 b(2), but FDA determines that safety and efficacy studies are not needed and drug product is reviewed under petitioned ANDA.
NDA (New Drug application): This pathway is used for new chemical entity which has not been approved by the FDA. Rigorous pre-clinical and clinical studies (Phase I to Phase III) are required to establish PK-PD profile, safety and effectiveness of the drug candidate before submission to FDA.
For better understanding about Drug approval process in different countries you can refer following blogs:
The Drug approval process in EU:
Drug Approval Process in China
Generic Products Approval Pathways: Paragraph Certification I, II, III, and IV:
Drug Approval Process in India
https://www.sternekessler.com/news-insights/publications/505b2-drug-approval-pathway-potential-solution-distressed-generic-pharmahttps://www.fda.gov/media/124848/download https://www.finnegan.com/en/insights/summary-of-fda-guidance-on-determining-whether-to-submit-an-anda-or-a-505b2-application.html https://www.sternekessler.com/news-insights/publications/505b2-drug-approval-pathway-potential-solution-distressed-generic-pharma