HATCH-WAXMAN ACT & 505 (b)(2) Application

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What is Hatch-Waxman act?



It is the popular name for Drug Price Competition and Patent Term Restoration Act, 1984. It is considered as the landmark legislation which established the modern system of generic drugs in USA. Hatch-Waxman amendment of the federal food, drug and cosmetics act established the process by which, would be marketers of generic drugs can file Abbreviated New Drug Application (ANDA) to seek FDA approval of generic drugs. Paragraph IV of the act, allows 180 day exclusivity to companies that are the "first-to-file" an ANDA against holders of patents for branded counterparts.



In simple words “Hatch-Waxman act is the amendment to Federal, Food, Drug and Cosmetics act which established the modern system of approval of generics through Abbreviated New Drug Applications (ANDAs)”



Significant results due to Hatch-Waxman act-

  • Prior to the Hatch and Waxman act the generic drug manufacturer had to do the entire clinical trials. After the passage of Hatch and Waxman act the generic drug manufacturer had to only prove bioequivalence of generic drug to the innovator drug by showing that the generic drug is 80-125% bioequivalent to the innovator drug.

  • The time and cost involved for getting the generic drug into the market was significantly reduced.

  • Low cost quality, safe and effective generic drugs were available to the patients.

  • Since 1984, over 10,000 generic drugs have entered the market, and generics accounted for close to 50 percent of prescriptions filled (as on august 1, 2003).

  • Billions of dollars in health care costs are being saved annually.



Patents and Exclusivity



Generic drug approval process isn’t less complicated as it involves patent and exclusivity issues. If any New Molecular Entity (NME) is approved, it is granted a exclusivity period of 5 years, which could be extended to 3 more years for supplements requiring clinical trials.



Patent Certifications



As per the Hatch and Waxman act, generic drug and 505 (b) (2) applicants should include certifications in their applications for each patent listed in the “Orange Book” for the innovator drug. This certification must state one of the following:

  • (I) that the required patent information relating to such patent has not been filed (Para I certification);

  • (II) that such patent has expired (Para II certification);

  • (III) that the patent will expire on a particular date (Para III certification); or

  • (IV) that such patent is invalid or will not be infringed by the drug, for which approval is being sought(Para IV certification).

A certification under paragraph I or II permits the ANDA to be approved immediately, if it is otherwise eligible. A certification under paragraph III indicates that the ANDA may be approved when the patent expires.



A paragraph IV certification, however, begins a process in which the question of whether the listed patent is valid or will be infringed by the proposed generic product may be answered by the courts before the expiration of the patent. Under the current regulations, the ANDA applicant who files a paragraph IV certification to a listed patent must notify the patent owner and the NDA holder for the listed drug that it has filed an ANDA containing a patent challenge. Until the effective date of FDA’s final rule, all patents submitted and listed in the Orange Book that are the subject of a paragraph IV certification require notice to the NDA holder and patent owner. The notice must include a detailed statement of the factual and legal basis for the ANDA applicant’s opinion that the patent is not valid or will not be infringed.



The submission of an ANDA for a drug product claimed in a patent is an infringing act if the generic product is intended to be marketed before expiration of the patent. Accordingly, the ANDA applicant who submits an application containing a paragraph IV certification may be sued for patent infringement. If the NDA holder or patent owner files a patent infringement suit against the ANDA applicant within 45 days of the receipt of notice, FDA may not give final approval to the ANDA for at least 30 months from the date of that notice. This 30-month stay will delay approval of the generic drug product unless the court reaches a decision earlier in the patent infringement case or otherwise orders a longer or shorter period for the stay.



180 Day Exclusivity



The Hatch-Waxman Amendments provide an incentive of 180 days of market exclusivity to the “first” generic applicant who challenges a listed patent by filing a paragraph IV certification and thereby runs the risk of having to defend a patent infringement suit.



The statute provides that the first applicant to file a substantially complete ANDA containing a paragraph IV certification to a listed patent will be eligible for a 180-day period of exclusivity beginning either from the date it begins commercial marketing of the generic drug product, or from the date of a court decision finding the patent invalid, unenforceable or not infringed, whichever is first.



180 Day Exclusivity could be granted to more than one applicant. The recent example is- 180 day exclusivity was granted to Ranbaxy and Watson Laboratories for marketing generic version of Lipitor (Atorvastatin calcium).



Keywords: Drug price competition and patent term restoration act-1984, ANDA, generics,180 day exclusivity, 80-125% bioequivalence,  505 (b) (2) application,  Para I certification, Para II certification, Para III certification, Para IV certification.







What is a 505 (b) (2) application?



An application submitted under section 505(b)(1) of the Federal Food, Drug and Cosmetics act for a drug for which one or more of the investigations relied on by the applicant for approval of the "application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted"



In simple words “505 (b)(2) application is a type of NDA for which one or more investigation relied on by applicant for approval were not conducted by/for applicant and for which applicant has not obtained a right of reference”



Section 505(b)(2) was added to the Food, Drug and Cosmetics act by the Drug Price Competition and Patent Term Restoration Act of 1984 (popularly known as Hatch-Waxman Amendments).



What type of information can an applicant rely on?

  • Published literature

  • The agency's finding of safety and effectiveness of an approved drug.

What kind of application can be submitted as a 505(b)(2) application?

  • New chemical entity (NCE)/new molecular entity (NME)

  • Changes to previously approved drugs



Examples of changes to approved drug products for which 505(b)(2) application should be submitted

  • Change in dosage form.

  • Change in strength

  • Change in route of administration

  • Substitution of an active ingredient in a formulation product

  • Change in formulation

  • Change in dosing regimen

  • Change in active ingredient

  •  New combination Product

  • New indication

  • Change from prescription indication to OTC indication

  • Naturally derived or recombinant active ingredient

  • Bioequivalence



What can't be submitted as 505(b)(2) applications?

  • An application that is a duplicate of a listed drug and eligible for approval under section 505(j) (ANDA)

  • An application in which the only difference from the reference listed drug is that the extent to which the active ingredient(s) is absorbed or otherwise made available to the site of action is less than the listed drug

  • An application in which the only difference from the reference listed drug is that the rate at which its active ingredient(s) is absorbed or otherwise made available to the site of action is unintentionally less than that of the listed drug

Advantages of 505 (b)(2) application-

  • A 505(b)(2) application may itself be granted 3 or 5 years of exclusivity

  • Time-consuming , costly and duplication of clinical studies can be eliminated

  • A 505(b)(2) application may be eligible to qualify for orphan and/or paediatric drug exclusivity

Challenge-

  • 505(b)(2) application may be delayed due to patent or exclusivity protections covering an approved product

I found a useful link which is provided below, wherein you could get  useful information on differences between 2 types of NDA and ANDA, examples of medication approved under 505 (b)(2) application , Q & A related to 505 (b)(2) application, learning assessment etc


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