The FDA recently issued draft guidance in the Federal Register setting forth the circumstances in which the FDA will refuse to receive an ANDA. [Guidance for Industry ANDA Submissions] The draft guidance is subject to a 30-day public comment period.

The 21-page FDA Guidance seeks to improve the quality of ANDA submissions and allow efficient review by the FDA by providing recommendations to generic companies. In 2012 the FDA refused to receive 9.4% of the ANDA’s submitted.

The impact of refusal of an ANDA can be significant in the context of Paragraph IV litigation. An applicant can fail to qualify for first-to-file status if the FDA refuses to receive an ANDA, losing out on the exclusive right to sell the generic and potentially millions of dollars.

Generally, if the FDA refuses to receive an ANDA, the applicant can withdraw the ANDA, amend to correct the deficiencies, or take no action. If the applicant amends the ANDA, it is considered to be a new filing received on the date the amendments were submitted. The FDA Guidance also explains that the FDA will allow an applicant to maintain its original filing date if the FDA determines that the ANDA contains fewer than 10 minor deficiencies and the applicant corrects the deficiencies within 5 business days.

The FDA Guidance describes various circumstances that will result in the refusal to receive an ANDA, including issues relating to formatting, payment, active pharmaceutical ingredient drug master file, chemistry, manufacturing and control, and bioequivalence .

On the patent front, the FDA Guidance addresses Section viii carve-outs. A Section viii carve-out is a strategy a generic can use to avoid litigation on method-of-use patents listed by the brand company in the Orange Book. With this approach, the generic submits a Section viii statement certifying that the generic does not seek approval to market the drug for the uses claimed by the method-of-use patents listed in the Orange Book.
The FDA Guidance cautions that a generic attempting a Section viii carve-out strategy must ensure that the proposed labeling is consistent with the Section viii statement and not include patented uses in the label. If the FDA determines that such uses are described, it will ask the applicant to revise its labeling or withdraw the patent statement. If the applicant fails to do so within five business days, the FDA will refuse to receive the ANDA.

Although the FDA Guidance is a draft, it notes that it describes the FDA’s current thinking on the topics covered. Generic companies in the process of filing an ANDA should review the FDA Guidance carefully to avoid refusal by the FDA.