Exclusivity 505 NDAs

Drugs Under Patent. This book [77] is a cross-referenced listing of over 2500 drugs covered in the United States under patent law and marketing exclusivity provisions of the Waxman-Hatch Act. Eight indexes provide market and patent status information by company, trade name, generic name, expiration date, dosage form, exclusivity code, patent number, and NDA number. Updated annually, this book is available commercially. 

Prior to the Mova court of appeals decision on April 14, 1998, the FDA had granted the 180-day exclusivity to 3 generic applicants for dmg products covered by 3 NDAs. In each case, a court had decided that the patent was invalid or not infringed such that the generic applicant had successfully defended the patent litigation suit. Each of these grants of the 180-day... 

It is important to note that generic drug products can be developed and approved more quickly than innovator drugs, because clinical trials are not typically required. A 505(b)(1) or 505(b)(2) NDA holder may delay approval of an ANDA due to patent or exclusivity considerations, however. These issues, however, while described briefly later, are beyond the scope of this chapter. 

The most common way to switch a product is for a manufacturer to submit an sNDA, because the NDA owner might obtain 3 years of market exclusivity if the supplement is supported by new clinical investigations (other than bioavailability studies), conducted or sponsored by the applicant, that are essential to approval of the application or supplement [92] that is, FDA will not approve (but will accept the filing of) a 505(b)(2) NDA or an ANDA before the expiration of 3 years from the date of the approval of the first applicant s NDA or sNDA. A second manufacturer, however, may... 

In addition, the formal granting of the three-year patent exclusivity requires the formal notification of the original patent holder of the approval of a 505(b)2 NDA. 

Unlike a full NDA for which the sponsor has conducted or obtained a right of reference to all the data essential to approval, the filing or approval of a 505(b)(2) application may be delayed due to patent or exclusivity protections covering an approved product. Section 505(b)(2) applications must include patent certifications described at 21 CFR 314.50(i) and must provide notice of certain patent certifications to the NDA holder and patent owner under 21 CFR 314.52. 

Because of the Abbreviated nomenclature in the ANDA title and because of the often shortened form of the NDA represented by the 505(b)2 NDA, there has been some confusion between the two applications. Perhaps the ANDA should have been called the Abbreviated Generic Drug Application form it is appropriate only as an application for a manufacturing variant of an approved (via an NDA) new drug, presumably off patent or exclusivity. The... 

One of the key provisions the FDA worked into the regulations was the protection of the holder of the application. For holders of NDAs that have been approved under these provisions, FDA will grant 7 years market exclusivity. Section 527 of the Act notes ... 

The sponsor receives 7 years exclusivity if their NDA remains unique for the product, and if no significant improvements are instituted by a competitor. 

One thing to remember is that although there may be exclusivity to an orphan product granted an NDA, there is no exclusivity to the orphan designation itself thus, two competitors may be pursuing an NDA for the same indication. If the products are sufficiently similar, the first one with an NDA will be the one with exclusivity. Unless the competitor can show that his product is unique and different from the other product, he will be denied an NDA. If the two products can be shown to be significantly different from each other, both... 

It should also be noted that if the sponsor receives NDA approval and then is not able to provide sufficient supply, he might lose exclusivity. He can either consent to let other applications be filed, or the director may decide to grant approval to other applications. FDA may withdraw exclusivity even if other applications are not pending. Once withdrawn, exclusive approval may not be reinstated for the drug (4). 

Medical/clinical reviewers, often called medical officers, are almost exclusively physicians. In rare instances, nonphysicians are used as medical officers to evaluate drug data. Medical reviewers are responsible for evaluating the clinical sections of submissions, such as the safety of the clinical protocols in an IND or the results of this testing as submitted in the NDA. Within most divisions, clinical reviewers take the lead role in the IND or NDA review and are responsible for synthesizing the results of the animal toxicology, human pharmacology, and clinical reviews to formulate the overall basis for a recommended agency action on the application. 

Whereas Phase 1, 2, and 3 studies are conducted prospectively using subjects or patients whose entrance into the study depends on strict inclusion and exclusion criteria. Phase 4 studies employ mainly observational, rather than exclusionary, study designs. Postmarketing surveillance and any additional studies requested by the regulatory agency as conditional approval of the NDA are conducted during Phase 4. 

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