The document discusses the Hatch-Waxman Act and its role in facilitating generic drug approvals in the US. It introduced the Abbreviated New Drug Application (ANDA) process which allows generics to piggyback on the clinical trial data of branded drugs. The Act also established the Orange Book database which lists drug patents. Generic companies can file ANDAs with certifications (Paras I-IV) regarding the patents. Para IV filings are the most complex and involve claims of non-infringement or patent invalidity, often leading to litigation between generic and branded companies. The Act aimed to balance increased generic competition with incentives for continued drug innovation.

1. P. ILANANGAIIP CONSULTANTALTACIT GLOBALCHENNAI PARA I, PARA IV, ORANGE BOOK

2. INTRODUCTIONAs the world moves closer to the concept of a 'global village' by reduction and elimination of trade barriers, new challenges crop up. A case in point is the market for Generic Drugs (Drugs which are free from patent protection or not covered under patents). It was felt that since 95% of the drugs being marketed in India were generics, introduction of a new IPR regime would not affect prices. Rather it was felt that the benefits were more-Indian Companies could license out new technologies and also tap global markets for their products. Indian Pharmaceutical companies enjoyed two 'homegrown' advantages viz. much cheaper manufacturing facilities and world-class medicinal chemistry skills. contd..

3. Prior to 1962, as per Federal Food, Drug and Cosmetic Act, all application for registration were examined on the basis of the safety profile. But for manufacturing of generic, there were also the requirement of the clinical data to prove efficacy. Then after, Kefauver- Harris amendment was done in FDC Act in the year of 1962. As per this amendment, proof of efficacy was also required along with the safety profile. contd..

4. To overcome the drawback of Kefauver- Harris amendment, in year of 1984, Drug Price Competition and Patent Term Restoration act was implemented in FDC act, also known as Hatch-Waxman act."The Hatch-Waxman Act is an act dealing with the approval of generic drugs and associated conditions for getting their approval from the Food and Drug Administration (FDA), market exclusivity, rights of exclusivity, patent term extension and Orange Book Listing."contd…

5. THE ACT WAS ENACTED BY THE FOLLOWING OBSERVATIONS:There were no generic drugs in market for 150 off patent drugs. Manufacturers were not interested to manufacture cheaper generic versions because of stringent regulatory procedures.Drug companies were not interested to waste time and money on clinical trials of generic drugs, because of fewer profits from those cheaper generics and more stringent regulations. The Hatch-Waxman Act focused these issues and proposed many changes and started the generic drugs approval procedure as Abbreviated New Drug Application (ANDA), for the purpose of market authorization.

6. ORANGE BOOKEach holder of an approved new drug application (NDA) must list pertinent patents it believes would be infringed if a generic drug were marketed before expiration of these patents. The FDA maintains a list of such patents in its publication, Approved Drug Products with Therapeutic Equivalence Evaluations commonly known as Orange Book. Purpose: To make generic pharmaceutical firms aware of patents protecting brand-name drugsAll patents that claim a new drug, or some method of using this drug are listed in the Orange Book. contd..

7. Electronic Orange Book (EOB) is updated daily providing product information for new generic drug approvals. Daily generic updates provide the consumer with the current list of approved generic products which is important for substitution purposes. The EOB content includes:New Drug Application (NDA) approvals. NDA application numbers are preceded with “N”Abbreviated New Drug Application approvals (ANDA or Generic). Generic application numbers are preceded with “A”.

8. GENERIC DRUGSA generic drug is a drug which is produced and distributed without patent protection. The generic drug may still have a patent on the formulation but not on the active ingredient.A generic must contain the same active ingredients as the original formulation.Generics are considered (by the Food and Drug Administration (FDA)) identical in dose, strength, route of administration, safety, efficacy, and intended use.The costs of these generic drugs are so low that many developing countries can easily afford them.For example, Thailand has imported millions of doses of a generic version of the blood-thinning drug Plavix (used to help prevent heart attacks), at a cost of 3 US cents per dose from India, the leading manufacturer of generic drugs.Generic drug companies may also receive the benefit of the previous marketing efforts of the brand-name drug company, including media advertising, presentations by drug representatives, and distribution of free samples.

9. GENERIC DRUGS CAN BE LEGALLY PRODUCED FOR DRUGS WHERE:1) the patent has expired, 2) the generic company certifies the brand company's patents are either invalid, unenforceable or will not be infringed, 3) for drugs which have never held patents, or 4) in countries where a patent(s) is/are not in force.

10. FILING FOR GENERIC DRUGSWho can file?Any person could file an ANDA for a drug approved under § 505(b) of the Federal Food, Drug, and Cosmetic ActRequirementsSame active ingredientSame conditions of use (labeling)Same dosage formSame strengthSame route of adminBioequivalentPatent Certification

11. FOUR POSSIBLE CERTIFICATIONS[PARAS]The generic approval process is called Abbreviated New drug Application (ANDA). While filing an ANDA, the generic company has to choose one of the following four options (referred to as paras) A Para I filing is made when the innovator has not made the required patent information in the Orange Book. A Para II filing for the launch of a generic drug is made when the drug is already off patent. A Para III filing is made when the patent for the product exists but the generic company wants to enter the markets after the date of patent expiry passes. A Para IV filing is made when the ANDA applicant believes its product or the use of its product does not infringe on the innovator's patents listed in the Orange Book or where the applicant believes such patents are not valid or enforceable.

12. PARA IV FILINGDrugs are necessity in ailments. But sometimes the drug prescribed may be costly and may not be affordable for patients. In such a scenario, generic companies manufacturing the same costly drugs at affordable price are a boon for the patients. But this involves infringement of patents of the innovator. To serve the patients with affordable drugs, several companies have adopted the route of Para IV filings.

13. PROCESSIn all the generic filings, the FDA has 180 days to deem the generic application complete and accept it for review, or incomplete and reject for filing.In case of Para I and Para II filing, once the application is deemed complete, it is simply processed for approval. In case of Para III the application is processed for approval, however its approval status depends upon the products patent expiry. Apparently Para IV filings are the most lucrative, tedious, time consuming and expensive of the above.

15. Large pharmaceutical companies often spend millions of dollars protecting their patents from generic competition. Apart from litigation, companies use other methods such as reformulation or licensing a subsidiary (or another company) to sell generics under the original patent. Generics sold under license from the patent holder are known as authorized generics. They are not affected by the 180 day exclusivity period as they fall under the patent holder's original drug application.

16. Prime example isSimvastatin (Zocor), a popular drug created and manufactured by U.S. based pharmaceutical Merck & Co., which lost its US patent protection on June 23, 2006. India-based Ranbaxy Laboratories (at the 80 mg strength) and Israel-based Teva Pharmaceutical Industries (at all other strengths) received 180 day exclusivity periods for Simvastatin; due to Zocor's popularity, both companies began marketing their products immediately after the patent expired. However, Dr. Reddy's Laboratories also markets an authorized generic version of Simvastatin under license from Zocor's manufacturer, Merck & Co.; some packages of Dr. Reddy's Simvastatin even show Merck as the actual manufacturer and have Merck's logo on the bottom.

17. Drug makers in Para IV LitigationHoffman – La Roche has slapped a lawsuit at Indian generic drug maker Orchid Chemicals & Pharmaceuticals Ltd. over a newly issued patent for Roche's blockbuster osteoporosis drug Boniva. The US Patent was issued (US Patent 7410957 - Method of treatment using bisphosphonic acid) on August 12, 2008 and Orchid had filed an ANDA (Abbreviated New Drug Application) with the USFDA under Para IV of the Hatch-Waxman Act. Interestingly, Orchid was sued in September last year over the alleged infringement of another patent of Boniva by Roche. Orchid was accused of infringing US Patent 7192938 (US Patent Issued on March 20, 2007) following its paragraph IV ANDA submission to manufacture a generic version of Boniva.

18. AstraZeneca blocks Sun Pharma's Para IV filing on NexiumAstraZeneca filed two separate cases against Sun Pharma. The MNC seeks to block Sun Pharma from selling an intravenous (IV) version of Nexium ,a medicine for ulcer (esomeprazole magnesium), its largest selling drug, in the US before 2014. Approved by the US Food and Drug Administration (FDA) in 2005, Nexium's patents are valid in the US till 2014. With global sales of close to $5 billion (Rs 22,907 crore), the drug had sales of $2.84 billion (Rs 13,011 crore) in the US market in 2009.

19. CONCLUSIONThe Hatch-Waxman act act has changed the scenario of pharma industry by providing various provisions for generic as well as branded drug manufacturer and also helped to make available low cost drug therapy.

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