Sometimes you win; sometimes you lose – especially when you're a generic drug maker!!!
Statutory and regulatory background
The Food and Drug Administration (FDA) regulates the pharmaceutical industry. The Federal Food Drug and Cosmetic Act (FFDCA) is the statute that governs the manufacture and distribution of drugs and medical devices.
A drug which goes off patent is called a generic drug. Such drugs when marketed without a brand name are called generic generics and when sold with brand names are called branded generics.
Ordinarily, a company seeking to market a pioneer drug must complete a New Drug Application (NDA). Preparing an NDA consists of conducting studies and gathering data that prove the drug's safety and efficacy. An NDA is also required to contain a list of any patents that cover the pioneer drug, as well as any patents that cover a specific use for the drug. The FDA then publishes all patent information that a pharmaceutical company submits regarding a pioneer drug in a publication titled Approved Drug Products with Therapeutic Equivalence Evaluations, commonly referred to as the "Orange Book."
In 1984, Congress enacted the Hatch-Waxman Amendments to the FFDCA, which simplified the process for FDA approval of generic drugs. Under the Amendments, applicants who wish to market generic versions of pioneer drugs may file an Abbreviated New Drug Application (ANDA) which relies on the FDA's previous determination that the pioneer drug is safe and effective. Thus, the generic drug manufacturer need not submit new safety and effectiveness studies. One requirement of the ANDA is that for each patent applicable to the pioneer drug, the ANDA applicant must certify whether the generic drug would infringe that patent, and if not, the reasons why it would not.
To satisfy this requirement, an ANDA applicant may certify that
1. the required patent information has not been filed,
2. the patent has expired,
3. the patent has not expired, but will expire on a particular date, or
4. the patent is invalid or will not be infringed by the drug for which the ANDA applicant seeks approval.
If an ANDA applicant makes a certification under clause IV (commonly referred to as a "paragraph IV certification") and the pioneer patent holder brings suit within 45 days, the FDA must delay its approval of the ANDA until the earlier of 30 months or the date of a court decision finding the patent invalid or not infringed.
The first applicant to file an ANDA containing a paragraph IV certification is known as a "first filer" and is eligible for a 180-day exclusivity period during which it is entitled to have the sole generic version of the pioneer drug on the market. This exclusivity period is calculated from the earlier of
1) the date of the first commercial marketing of the generic drug by the first filer, or
2) the date of a court decision declaring the patent at issue invalid or not infringed.
Any subsequent ANDA filer must wait until the expiration of the first filer's 180-day exclusivity period before receiving FDA approval of its ANDA.
Story starts
On January 15, 1999, Teva Pharmaceuticals USA, Inc. filed an ANDA seeking approval to market generic quinapril hydrochloride tablets with paragraph IV certification, asserting that the 4,743,450 patent was invalid.
In response, Warner-Lambert Company, (Pfizer's predecessor-in-interest) filed suit in the United States District Court for the District of New Jersey on March 2, 1999, which was within 45 days of Teva's paragraph IV certification. As the first filer, Teva is entitled to the 180-days exclusivity period, which commence on the date it first commercially markets its generic quinapril hydrochloride or the date on which a court declares the 450 patents invalid.
The 450 patents is directed to stabilized compositions of a class of non-sulfhydryl Angiotension Converting Enzyme (ACE) inhibitors. It states that certain additives have a stabilizing effect on the composition. It mentions the following ACE inhibitors that can be used in the invention: "enalapril, quinapril, or indolapril, their corresponding free acids or pharmaceutically acceptable acid addition or base salts thereof."
On October 2, 2003, the District Court of New Jersey held that Teva infringes the 450 patent and granted summary judgment in favor of Pfizer on the ground that the 450 patent is not invalid by reason of the failure of the Warner-Lambert inventors to call the Merck Vasotec product to the examiner's attention. Nor is the 450 patents invalid by reason of anticipation or obviousness. [Warner-Lambert Co. v. Teva Pharms. USA, 289 F.Supp.2d 515, 545 (D.N.J.2003)].
The FDA approved Teva's ANDA on May 30, 2003 and besides Teva, nine other companies also filed ANDAs seeking approval to market generic quinapril hydrochloride between January 2001 and May 2003.
ANDA applicants are:
1. Geneva Pharmaceuticals, Inc;
2. Andrx Pharmaceuticals, Inc.;
3. Par Pharmaceuticals, Inc.;
4. Ivax Pharmaceuticals, Inc.;
5. Mutual Pharmaceutical Company, Inc.;
6. Ranbaxy Pharmaceuticals Inc.;
7. Amide Pharmaceutical, Inc.;
8. Mylan Pharmaceuticals Inc.; and
9. Torpharma.
Meanwhile, Ranbaxy’s abbreviated new drug application (ANDA) for Quinapril HCl tablets also got the final approval from the US FDA. Since, Teva had the six months marketing exclusivity under para IV filing, Ranbaxy entered into a supply and distribution agreement with Teva whereby Ranbaxy will manufacture and supply the product to Teva and Teva will distribute the product. The agreement was the result of Teva’s relinquishment of its right to a 180-day period of marketing exclusivity for Quinapril HCl tablets. One of the clause of the agreement included that Ranbaxy would fully indemnify Teva for all patent infringement claims relating to Ranbaxy's Quinapril tablets.
After Teva started marketing the Ranbaxy’s generic version, Pfizer filed patent infringement lawsuit against Teva and Ranbaxy on Jan. 28, 2005 and US District Court of New Jersey granted the preliminary injunction halting sales of generic version of the Accupril.
Pfizer strategically initiated litigation against Teva and Ranbaxy in connection with their ANDAs in an interesting manner. Two years ago, when Ranbaxy filed an ANDA for quinapril hydrochloride, Pfizer did not sue to obtain automatic thirty-months stay at that time. Rather, Pfizer waited until after the commercial launch of the generic to litigate.
“Mylan’ and “Par” have also launched their generic Quinapril HCL but why Pfizer did not opt to sue them is another issue. Pfizer also sued Apotex (Torpharm) and subsequently withdrew the case to frustrate (moot) the Defendants suit filed by Apotex. Therefore, Apotex is also withholding market entry.
Ranbaxy has now stated that they are going on appeal and that they are reasonably confident to succeed at the Appeal Court.
(The author is the Legal Associate with Gopakumar Nair Associates).