Wednesday, March 29, 2006
- 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.
- 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.
- 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 (firstname.lastname@example.org)
Tuesday, March 28, 2006
Saturday, March 25, 2006
Thursday, March 23, 2006
Monday, March 20, 2006
Saturday, March 18, 2006
Thursday, March 16, 2006
Targeting Para IV
To recap, in February 2004, AstraZeneca filed a patent infringement lawsuit against Andrx Corp. in the United States District Court for the District of Delaware as a result of a Paragraph IV certification letter submitted by Andrx concerning its intent to manufacture and sell generic form of Toprol-XL in the 50 mg dose form in US. Again, in July 2004 AstraZeneca filed a second patent infringement against Andrx Corp. in the same District Court following the Andrx’s notification that it had filed ANDA under paragraph IV with USFDA for seeking approval to market generic form of Toprol-XL 50 mg dose form. Astra advocated that Andrx infringes its patents covering Toprol-XL. In the same year, AstraZeneca also filed a lawsuit in the District Court for the District of Delaware against generic manufacture, Eon Labs, for patent infringement following the Eon’s move for market approval of generic form of Toprol-XL for all dose forms under paragraph IV. Moreover, later in the same year, AstraZeneca filed legal proceedings against KV Pharmaceutical Co. in the District Court for the Eastern District of Missouri this time following the KV’s notification regarding ANDA submission under paragraph IV for market approval of generic form of Toprol-XL 50 mg dose form. Earlier to this AstraZeneca filed a suit in May 2003 against KV Pharmaceutical Co. for patent infringement by the 200mg dose form of Toprol-XL and again in August 2003 for patent infringement by the 100 mg dose form. Pre-trial Discovery All of these pending patent litigations later consolidated for pre-trial discovery purposes and motion practice in the U.S. District Court for the Eastern District of Missouri, which do not include a jury. A pre-trial discovery means that a party to a lawsuit should not be surprised by its adversary on the day of trial, and therefore has the right to full discovery, prior to trial, of all relevant evidence, including documents (broadly defined to include virtually every tangible and intangible form of record keeping) and witness testimony related to the matter at issue in the litigation. In other words, each party to the suit attempts to “discover” relevant or pertinent facts. However, in this trial consideration was of the validity and enforceability of two AstraZeneca patents (US Patent No. 5,081,154 and 5,001,161) relating to active ingredient (metoprolol succinate per se) and composition of Toprol-XL (extended release tablet of metoprolol succinate) and to determine whether the defendants in the case infringe those patents. Both ‘154 and ‘161 patent were due to expire in September of 2007.
Tuesday, March 14, 2006
Sunday, March 12, 2006
In December 2004, Shire even after receiving notification that Colony Pharmaceuticals has submitted an ANDA with FDA seeking approval to market generic Adderall XR of 5mg, 10mg, 15mg, 20mg, 25mg and 30mg strengths prior to the expiration dates of the ‘819 and ‘300 patents, decided not to sue it.
On October 20, 2005 Shires announced that it has filed yet another lawsuit against Barr and Impax for infringement of U.S. Patent No. 6,913,768 in the U.S District Court of the Southern District of New York in response of an ANDAs filed by Barr and Impax. The ‘768 patent was issued to Shire on July 05, 2005. This case, however, does not effect the ongoing litigations in the Southern District of New York between Shire and Barr involving ‘819 and ‘300 patents which later consolidated in December 2003 and scheduled to go to trial in January 2006. In January 2006, Shire and Impax settled all pending patent litigation concerning Adderall XR under an agreement that Impax will be permitted to market generic Adderall XR in the United States no later than January 01, 2010 and will pay Shire a royalty from those sales. In certain conditions, such as launch of another generic version of Adderall XR, Impax may be permitted to enter the market as Shire’s authorized generic. No payments to Impax are involved in the settlement agreement.
Friday, March 10, 2006
Allergan filed the first lawsuit in the U.S District Court for the District of Delaware contending that Alcon’s proposed brimonidine 0.15% product infringes Allergan’s orange book listed US Patent Nos. 6,673,337 and 6,641,834. Both ‘337 and ‘834 patent are valid up to July 2021 and January 2022 (with pediatric exclusivity). The lawsuit was in response to a New Drug Application (NDA) filed by Alcon under section 505(b) (2) of the Federal Food, Drug and Cosmetic Act seeking approval for marketing generic brimonidine tartrate ophthalmic solution 0.15% product in the United States. Alcon’s product received tentative Food and Drug Administration (FDA) approval on 28th February 2005, but final approval was withheld pending resolution of the litigation.
The second lawsuit was filed in the U.S. District Court for the District of California alleging infringement of U.S Patent Nos. 6,166,012 and 6,492,361 directed to self-preserved antibiotic products. Alcon believes this lawsuit was intended to target its leading ophthalmic ocular antibiotic Vigamox (0.5% moxifloxacin HCl ophthalmic solution).
Thursday, March 09, 2006
The lawsuit was filed in response of an abbreviated new drug application (ANDA) filed under Para IV certification by Ivax with Food and Drug Administration (FDA) seeking approval for generic version of Nexium in the US prior to the expiration of the five AstraZeneca orange book listed patents: 5,714,504; 5,877,192; 6,369,085; 6,428,810; and 6,875,872. The expiration dates for these patents range from 2014 through to 2019.
Earlier in November 2005, AstraZeneca also sued Ranbaxy for willfully infringing AstraZeneca’s patents protecting Nexium and filed a lawsuit in response of an ANDA submission for esomperazole magnesium delayed-release capsules under Para IV certification with Food and Drug Administration (FDA). The lawsuit was filed in the same District Court.