U S Food and Drug Administration: Overview of drug approval
03 Oct 2018
After the discovery of a lead compound, the process of bringing a new drug into the market is termed as the drug development process and includes preclinical studies, clinical studies and regulatory approval for marketing the product.
Different countries have different regulatory acts and rules under which regulatory approval is given to a drug.
Legal Framework in US
The drug approval process in the US is regulated by the Food and Drug administration (FDA). The FDA has rules mentioned under 505 of section V of the Food, Drug, and Cosmetic Act (FD&C Act), which must be satisfied by the new compound. Section 505(b)(2) and 505(j) were added to the FD&C Act in 1984 as Hatch-Waxman Amendments.
Three main pathways are provided by the US regulators for the submission of application for the approval of a drug:
505(b)(1) is the most expensive and time consuming process. This application is only for the new drug application or NDA and provides market exclusivity for 5 years. Application requires a large amount of data to support safety and efficacy of the drug. Safety and efficacy is evidenced with preclinical and clinical studies.
505(b)(2) application is a NDA submitted under section 505(b)(1) of the Act which is approved under section 505(c). This pathway applies for the registration of the compound with similar active ingredient which relies to an extent on published literature. This application provides market exclusivity for 3-5 years.
Ideal 505(b)(2) candidates include:
“An applicant should submit a 505(b)(2) application if approval of an application will rely to any extent on published literature. If the applicant has not obtained a right of reference to the raw data underlying the published study or studies, the application is a 505(b)(2) application; if the applicant obtains a right of reference to the raw data, the application may be a full NDA”.
This is for the generic copies of the innovator’s drugs which are already approved termed as Abbreviated New Drug Application(ANDA). For this application, no clinical or preclinical studies are required in most of the cases; only bioavailability/ bioequivalence (BA/BE) studies are required to show bioequivalence of the generic with the innovator’s drug. Market exclusivity of 180 days is provided to companies who are the First To File (FTF) ANDAs.
For biosimilar products, manufacturers need to submit a 351(k) biologics license application (BLA). BLA includes the information regarding analytical studies, animal studies, and a clinical study demonstrating efficacy and safety of the biologic.
Source: USFDA guidelines
- 505(b)(1) NDA
1. Drugs with new indications
2. Drugs with changes in dosage form, strength, formulation, dosing regimen or route of administration
3. New combination products
4. Pro-drugs of an existing drug
5. In some cases, drugs with new active ingredients
- 505(j) ANDA
- 351(k) biologics license application