Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

An Approach to Abbreviated New Drug Applications (ANDA) and Question based Review (QbR) ***

Jörg Schneidereit (Abschlußjahr: 2008)

Language: English

In the United States, generic marketing authorization applications are filed by so called "Abbreviated New Drug Applications (ANDA)". The application is called abbreviated because results from (pre-)clinical safety and efficacy studies are usually not required. Instead, reference is made to the data on file for an already approved reference drug.
The current regulatory framework for generics in the United States is governed by the Drug Price Competition and Patent Term Restoration Act of 1984, more commonly known as the Hatch-Waxman Act, and the Medicare Prescription Drug Improvement & Modernization Act (MMA) of December 2003. The legal basis for the filing of an ANDA is laid down in section 505(j) of the Food, Drugs & Cosmetics Act.

After introduction of the United States legal system and regulatory authority the specific terms and requirements related to the filing of an Abbreviated New Drug Application are discussed within this thesis.
An ANDA is usually submitted for a drug product that is the same as a drug product previously approved by the FDA. The approved drug product, usually an innovator drug, when referred to in a generic application, is called the Reference Listed Drug.
According to the Regulation the term "same as" means the drug product and the Reference Listed Drug shall contain identical active ingredients, be identical in dosage form, strength, route of administration, and shall have identical conditions of use.

Provisions of the Hatch-Waxman Act protect the innovator drug products by market exclusivity and patent term restoration. Consideration, consequently, is given to patent certification requirements. In case a patent exists that claims the drug, drug product, or method of use the applicant is requested to file a patent certification with regard to the patent status. The different types of patent certifications are discussed. By submitting a so called Paragraph IV Certification the applicant challenges the patent assuming that the latter is invalid, unenforceable or will not be infringed. Inclusion of a Paragraph IV Certification permits the Applicant to file its ANDA 4 years after approval of a new chemical entity, that is 1 year before actual expiry of the 5 year exclusivity.

The submission of an ANDA containing a Paragraph IV Certification is an infringing act and, therefore, may be followed by a patent infringement litigation. In such cases, the FDA will delay the approval of the ANDA up to 30 months for pending resolution of lawsuit. As part of the thesis the availability and termination of the 30-month stays is discussed considering statutory amendments and current guidance.

As provided by the Food, Drugs & Cosmetics Act, the first generic applicant to submit an application containing a Paragraph IV Certification is eligible to an incentive of 180 days of generic exclusivity. This exclusivity, commonly known as "180-day exclusivity", protects the first-to-file applicant, whose ANDA contains a Paragraph IV Certification, from competition by subsequent generic applicants referring to the same Reference Listed Drug. This thesis elucidates FDA's previous interpretations of the statute regarding 180-day exclusivity, it explains the latest statutory amendments and current guidance.

A separate section is given to discussion of the content and format of an Abbreviated New Drug Application. Information considered helpful in the compilation of Modules 1, 2, 3 and 5 is provided. Requirements for electronic submission in eCTD format are outlined.

Finally, attention is paid to the new Pharmaceutical Quality Assessment System called Question based Review (QbR), which is the requested format for the Quality Overall Summary in Module 2.3 since the beginning of 2007. Development and rationale of the QbR are described in the context of the cGMPs for the 21st century Initiative. The design of the QbR is discussed and an evaluation of achievements is proposed.

Pages: 48