Wednesday, March 29, 2006

An overview of Hatch-Waxman Act

Pre-Hatch-Waxman Regulatory Environment
In 1962, Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act added a proof-of-efficacy requirement to new drug approvals. Before that time, the FDA approved drugs on safety parameters only. As a result all drug products approved between 1938 and 1962 (for safety only) were reviewed through the Drug Efficacy Study Implementation program to evaluate efficacy. Even today all brand-name companies are required to prove that new drugs are safe and effective for FDA approval. To prove this, brand-name companies are required to conduct human clinical trials and submit the results to the FDA with their New Drug Application (NDA). Those seeking to market a generic version of a post-1962 brand-name drug also had to perform their own safety and efficacy studies, much like the brand name companies. Hence due to the high costs involved few generic companies were interested in launching products in the US. As a result by 1984, the FDA estimated that there were approximately 150 brand-name drugs whose patents had expired for which there was no generic equivalent available. Another factor complicating generic drug approval concerned the timing of when generic companies could perform their clinical tests. Even if a generic manufacturer gets access to the innovator clinical data making copies of a pharmaceutical product is not simple. Sourcing active ingredients, performing bio-equivalence studies, assuring quality, putting together a dossier, establishing patient information leaflets and going through the regulatory process can take 2-3 years. Manufacturing adds on another 3-6 months. Before Hatch-Waxman was enacted, a generic company could not begin the required FDA approval process until the patents on the relevant brand-name product had expired. Consequently, patent protection was extended by 2-3½ years beyond the intended period. Thus, at that time, FDA’s generic approval process coupled with the patent law, in effect, discouraged generic entry and extended the term of the brand-name company’s patent protection. Not only the generic companies but also the brand-name pharmaceutical companies faced problems. The discovery and development of new drug is expensive and time consuming. To spur this investment, as well as to recoup investments made, brand name companies obtain patent protection to, prior to FDA approval of the drug product, to exclude others from making, using, or selling an invention for a number of years. Thus, the effective terms of many patents were shortened due to the time required for the FDA to ensure the safety and efficacy of the brand-name company’s drug product.
The Hatch-Waxman Act: Congress passed the Hatch-Waxman Act to address the following issues:
  1. Cut generic approval costs: Rather than requiring a generic manufacturer to repeat the costly and time consuming NDA process, the act permitted the companies to file an Abbreviated New Drug Application (“ANDA”). Thereby allowing the generic applicants to rely on the brand-name company’s trade secret data to demonstrate the safety and efficacy of their products.
  2. Early-Experimental-Use-Doctrine: In the 1984 case of Roche Products v. Bolar Pharmaceutical Company, the US Court of Appeals for the Federal Circuit, held that a generic drug manufacturer's use of a drug under patent to develop information needed for market authorization was an act of patent infringement. This resulted in a pseudo patent extension for the innovator, since ANDA applicants had to wait until the patent expired prior to commencing any drug development activities. The so-called "Bolar Amendment,” embodied in 35USC §271(e) (1) of the patent law, and passed as part of the Hatch-Waxman Act, reversed the court's decision in the Roche v Bolar case and provided that “[I]t shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention...solely for uses reasonably related to the development and submission of information [to support a market approval to the FDA].” This provision allows generic manufacturers sufficient lead time to develop, perform necessary testing, and to seek US regulatory approval so they can be ready to launch their products upon expiration of a listed patent covering the innovator product.
  3. Compensate brand-name companies for the patent time lost in obtaining FDA approvals. Brand name companies were now allowed to obtain patent term extension as a measure of compensation of the patent time lost due to long regulatory approval process. The Act also introduced the concept of Market Exclusivity in the Federal Food, Drugs and Cosmetic Act. This was done to provide innovators with a minimum period of monopoly and protection against generic entry.

Thus the Hatch-Waxman Act balanced an expedited FDA approval process to speed generic entry with patent term extension and Market Exclusivity to ensure incentive for continues innovation. The Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Amendments) added two new provisions to the Federal Food, Drug, and Cosmetic Act. Section 505(b)(2) : Hybrid New Drug Application (Changes to an Approved Drug)Section 505(j) : Abbreviated New Drug Application (Copy of Approved Drugs)

Abbreviated New Drug Application, 505(j) Filing

What is a Generic Drug? As per the U.S FDA, a generic drug product is the same as a brand name or a Reference Listed Drug (RLD) product, in dosage, safety, strength, how it is taken, quality, performance, and intended use. By law, a generic drug product must contain the identical amounts of the same active ingredient(s) as the brand name product. Before approving a generic drug product, FDA requires many rigorous tests and procedures to assure that the generic drug can be substituted for the brand name drug.

RLD (Reference Listed Drug): A Reference Listed Drug is an approved drug product to which generic versions are compared to show that they are bioequivalent. All RLD’s are listed in the FDA's list of Approved Drug Products with Therapeutic Equivalence Evaluations also known as the Orange Book. A drug company seeking approval to market a generic equivalent must refer to the Reference Listed Drug in its Abbreviated New Drug Application (ANDA). By designating a single reference listed drug as the standard to which all generic versions must be shown to be bioequivalent, FDA hopes to avoid possible significant variations among generic drugs and their brand name counterpart.

Definition of an Abbreviated New Drug Application (ANDA): It contains data that, when submitted to FDA's Center for Drug Evaluation and Research, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product. Generic drug applications are called "abbreviated" because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness. Instead, a generic applicant must only scientifically demonstrate that its product is bioequivalent (i.e., performs in the same manner as the innovator drug). Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective and a low cost alternative to the public. At the time of filing an ANDA the applicant must certify the clause under which he wishes to file the application and hence issue a certificate in this regard: Para I filing : This certification is made when the ANDA applicant is aware that there may be a patent in force that may cover the RLD, but that the NDA holder has for whatever reason decided not to list the patent with the agency. If an ANDA applicant makes a Paragraph I certification, the FDA may approve its application immediately, as long as the FDA determines that the ANDA otherwise meets the approval requirements; or Para II filing : A Paragraph II certification is appropriate when there is a patent listed in the Orange Book, but it has expired. The ANDA applicant simply certifies that the patent has expired, and provides the patent number and the date the patent expired. An ANDA application containing such a certification is eligible for immediate effective approval if the ANDA applicant has otherwise met the FDA approval requirements; or Para III filing : A Paragraph III certification acknowledges that there is a listed patent on the RLD that has not expired and that the ANDA applicant does not plan to market its product prior to the expiration of the patent. In this instance, the law precludes the FDA from approving the application until the patent has expired; or

Para IV filing : An application containing a Paragraph IV certification signifies that the ANDA applicant plans to challenge one or more of the listed patents. The ANDA holder hence claims that the patent is invalid, unenforceable, or will not be infringed by the manufacture, use, or sale of the generic product. A generic applicant makes a Paragraph IV certification only when its intent is to market the drug product prior to the expiration date of the patent.

This article is submitted by Ashish Mohan, Dept. of Pharmaceutical Management, NIPER, Mohali, India (


  1. nice & informative read

  2. Anonymous9:57 PM

    too gud, simple and very informative.thanq very much