For a better understanding of the generic drug approval, one must be clear about the drug development process. Once a new compound has been identified in the laboratory,it undergoes the drug development process before it can be marketed for public use.
The entire drug development process can be summarized in a series of steps:
Drug Development Steps:
- PreclinicalTesting
- Investigational New Drug Application (IND).
- Clinical Trials
- New Drug Application(NDA)
- Approval
Investigational New Drug Application (IND)
After completing preclinical testing, a company files an IND with the U .S. Food and Drug Administration (FDA) to begin to test the drug in people. The IND application is the result of a successful preclinical development program. The IND is also the vehicle through which the innovator advances to the next stage of drug development known as clinical trials (human trials) .
New Drug Application (NDA)
Following thecompletion of all three phases of clinical trials, a company analyzes all of the data and files an NDA with FDA if the data successfully demonstrate both safety and effectiveness.
The NDA contains all of the scientific information that the company has gathered. NDAs typically run 1 00,000 pages or more. By law, FDA is allowed six months to review an NDA.
Approval
Once FDA approves an NDA, the new medicine becomes available for physicians to prescribe. A company must continue to submit periodic reports to FDA, including any cases of adverse reactions and appropriate quality-control records. For some medicines,FDA requires additional trials (Phase IV) to evaluate long-term effects.
Hatch-Waxman Act
In 1984, Congress enacted Hatch-Waxman with the intent, to open up the market for products that were previously patent protected.
The legislative intent of Hatch- Waxman was to balance the competing policy interests of manufacturers of brand-name drugs and those of the generic trade group.
The intention was to maintain inducements necessary for the brand companies to research and develop new therapies, and enable lower cost generic products to reach the market.
Hatch-Waxman allowed generic manufacturersto file an Abbreviated New Drug Application (ANDA).
The ANDA requires the generic company to demonstrate that its product is “bioequivalent” to a referenced NDA’s brand name product.
Proof of bio-equivalence for a drug is much easier to establish than the requirements for an NDA: i.e.,the active (not inactive) ingredients must be proven “bioequivalent” by performing tests(plasma level data/urinary excretion data/IVIVIC). Thus,ANDA is a far less expensive process than filing an NDA.
The ANDA must reference the NDA of the patented drug listed in the Approved Drug Products with Therapeutic Equivalence Evaluations, which is generally known as the “OrangeBook.” The Orange Book provides a list of the applicable patents to licensed drugs.
In order to reference an NDA, the generic manufacturer must file one of four alternative certifications provided for under Hatch-Waxman:
- The FDA shall approve any ANDA making Paragraph I and II certification.
- The FDA can only approve an ANDA with a Paragraph III Certification after all patent(s) in the NDA have expired.
- The FDA has to review the Paragraph IV certification where the generic manufacturer must notify the innovator manufacturer that it is filing a Paragraph IV certification with its ANDA. This may result into a Paragraph IV challenge by the innovator company.(see fig. below)
180 Day Exclusivity
The Hatch- Waxman act provides the incentive of 180 days of market exclusivity for the first company to file an ANDA with paragraph IV certification for a product.
The FDA may not approve additional ANDAs for a period of 180 days commencing from the first commercial marketing of the first-to-file product.
References:
1)Authorized Generics: Antitrust Issues and the Hatch-Waxman Act (available from--http://www.fenwick.com/docstore/Publications/IP/Authorized_Generics.pdf
2) Saigal N. et al, USFDA Generic Approval Process,Indian J.Pharm. Educ. Res.; Jul-Sept, 2009:232-238. available from the internet at:http://www.ijperonline.com/archives/IJPER_43_3_2009.pdf
( A very nice review article regarding the generic drug approval process, very simply explained. A must read for those who are interested in this.)
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