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From Health Law Daily, February 6, 2015

FDA finally takes action to implement a 2003 law affecting generic and 505(b)(2) drug applications

By Harold M. Bishop, J.D.

After only 12 years of waiting, the FDA has proposed regulations designed to implement portions of Title XI of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) (P.L. 108-173), which amended provisions of the federal Food, Drug & Cosmetic Act (FDC Act) relating to the approval of abbreviated new drug applications (ANDAs/generic applications) and Section 505(b)(2) new drug applications (NDAs). It was hoped by some that the Proposed rule would be published on the 10 year anniversary of the MMA, which did not happen (Proposed rule, 80 FR 6801, February 6, 2015).

Background. Title XI of the MMA (Access to Affordable Pharmaceuticals) was designed to address Federal Trade Commission concerns that anticompetitive strategies may delay access to generic drugs by  limiting the availability of 30 month stays of approval on 505(b)(2) drug applications and ANDAs that are otherwise ready to be approved by the FDA, and by establishing conditions under which a first ANDA applicant would forfeit the 180-day exclusivity period because the approval of subsequent ANDAs would no longer be blocked.

A 505(b)(2) application, named for section 505(b)(2) of the FDC Act (21 U.S.C. §355(b)(2)), is a NDA that must contain full reports of investigations of safety and effectiveness, and where at least some of the information required for approval comes from studies not conducted by the applicant and for which the applicant has not obtained a right of reference or use (such as published literature or an FDA finding of safety and effectiveness for one or more listed drugs).

An ANDA is an application for a duplicate (or generic version) of a previously approved drug that is submitted under the abbreviated approval pathway described in section 505(j) of the FDC Act (21 U.S.C. §355(j)). An ANDA must contain information to show that the proposed product is the same as a previously approved drug with respect to active ingredient, dosage form, route of administration, strength, labeling, and conditions of use, among other characteristics.

The 505(b)(2) application and ANDA approval pathways were enacted as part of the Drug Price Competition and Patent Term Restoration Act of 1984 (P.L. 98-417) (Hatch-Waxman Amendments). The Hatch-Waxman Amendments were part of a Congressional effort make available more low cost generic drugs by combining a generic drug approval procedure with new incentives for drug development in the form of marketing exclusivity and patent term extensions.

Rationale. The FDA hopes that its proposed regulations will reduce unnecessary litigation, reduce delays in the approval of 505(b)(2) drug applications and ANDAs that are otherwise ready to be approved, and provide business certainty to both brand name and generic drug manufacturers. The proposed regulations would also codify current FDA practice and thereby promote transparency.

Is more to come? It is thought by the industry that this Proposed rule is only the opening salvo of changes to come.  A second Proposed rule will likely deal with forfeiture of 180-day exclusivity eligibility.

Some highlights of the proposed provisions follow.

Submission of patent information. The Proposed rule would revise submission of patent information requirements for: (1) patents that claim the drug substance or drug product and meet the requirements for patent listing on that basis; (2) drug substance patents that claim only a polymorph of the active ingredient; and (3) certain new drug application (NDA) supplements. The Proposed rule also would clarify requirements for the submission of information related to patents that have been reissued by the Patent and Trademark Office. In addition, the proposal would codify the FDA’s long-standing requirement that the NDA holder’s description of the patented method of use required for publication in the Orange Book must contain adequate information to assist FDA and 505(b)(2) and ANDA applicants in determining whether a listed method-of-use patent claims a use for which the 505(b)(2) or ANDA applicant is not seeking approval.

Timing of submission of patent information. The proposal would: (1) describe the FDA’s current practice with respect to listing patent information that has not been submitted to FDA within 30 days after patent issuance; (2) expand the category of untimely filed patent information to include certain amendments to the NDA holder’s description of the approved method(s) of use claimed by the patent, if such changes do not relate to a corresponding change in approved labeling or are submitted more than 30 days after such labeling change; and (3) establish that the submission date of patent information provided by an NDA holder after approval would be the earlier of the date on which Form FDA 3542 is date-stamped by the Office of Generic Drugs Document Room or officially received electronically by FDA.

Correction or change of patent information. The FDA is proposing to improve its response to challenges to the accuracy or relevance of submissions of patent use code information to the agency. In addition, the FDA proposal would expressly require the correction or change of patent information by the NDA holder if: (1) the patent or patent claim no longer meets the statutory requirements for listing; (2) the NDA holder is required by court order to amend patent information or withdraw a patent from the list; or (3) the term of a listed patent is extended under patent term restoration provisions.

Notice of paragraph IV certification—Timing. The FDA is proposing to revise its regulations to clearly delineate the two limitations on the time frame within which notice of a paragraph IV certification (named for the Hatch Waxman Amendments contained in 21 U.S.C. §355(j)(2)(A)(vii)(IV)) can be provided to the NDA holder and each patent owner: (1) the date before which notice may not be given (which reflects the FDA’s long-standing practice); and (2) the date, established by MMA, by which notice must be given. The FDA is also proposing administrative consequences for ANDA applicants who fail to send notice of paragraph IV certification within the statutory time frame established by the MMA. Under the proposal, the date the ANDA was submitted would be deemed to be delayed by the number of days by which the time frame was exceeded, which may result in the applicant losing eligibility for 180-day exclusivity.

Notice of paragraph IV certification—Content and methods. The proposal would revise the content of notice of a paragraph IV certification to incorporate requirements added by the MMA and to expand the acceptable methods of sending notice of a paragraph IV certification beyond registered or certified mail to include “designated delivery services.”

Amended patent certifications. The Proposed rule would: (1) clarify the requirements for a 505(b)(2) or ANDA applicant to amend a paragraph IV certification after a judicial finding; (2) clarify the circumstances and time frame in which a 505(b)(2) or ANDA applicant must submit an amended patent certification after an NDA holder has withdrawn a patent and requested removal of the patent from the Orange Book; (3) codify the FDA’s  current practice of not removing a withdrawn patent from the list until the FDA has determined that no first applicant is eligible for 180-day exclusivity or such exclusivity is extinguished, and exempting 505(b)(2) applicants from providing or maintaining a certification to withdrawn patents; (4) clarify an applicant’s current patent certification obligations with respect to a reissued patent; and (5) expressly codify the current requirement for a 505(b)(2) or ANDA applicant to submit a patent certification to a newly issued patent that claims the listed drug or an approved method of use.

Patent certification requirements for amendments or supplements. The FDA proposal would clarify and augment the patent certification requirements for amendments and supplements to 505(b)(2) applications and ANDAs to ensure that changes to the drug product that could be protected by patent are accompanied by a new patent certification.

Limitation on submission of certain amendments and supplements. The Proposed rule would codify its current interpretation of the MMA’s prohibition on submitting an amendment or a supplement to seek approval of “a drug that is a different drug” than the drug identified in the original 505(b)(2) application; or “a drug referring to a different listed drug” than the drug cited as the basis for ANDA submission.

505(b)(2) applications. The proposal would require a 505(b)(2) applicant to identify a pharmaceutically equivalent product, if already approved, as a listed drug relied upon, and comply with applicable regulatory requirements.

Date of approval. The Proposed rule would: (1) describe, in a more detailed manner, the timing of approval of a 505(b)(2) application or ANDA based on the patent certifications or statements submitted by the 505(b)(2) or ANDA applicant; (2) revise the regulations to reflect the MMA’s limitation on multiple 30-month stays of approval of a 505(b)(2) application or an ANDA containing a paragraph IV certification to certain patents submitted to FDA on or after August 18, 2003; (3) clarify that the statutory 30-month stay begins on the later of the date of receipt of notice of paragraph IV certification by any owner of the listed patent or by the NDA holder who is an exclusive licensee; and (4)  codify the MMA’s amendments that clarify the type of court decisions in patent litigation that will terminate a 30-month stay and lead to approval of a 505(b)(2) application or ANDA that is otherwise eligible for approval.

Notice of commercial marketing. The Proposed rule would update the regulations to reflect the MMA provisions that modify the types of events that can trigger the start of the 180-day exclusivity period. Under the proposals, a first ANDA applicant would be required to notify the FDA within 30 days of the date of first commercial marketing of the drug product.  If the first applicant fails to do so, the FDA would deem the date of first commercial marketing to be the date of the drug product’s approval.

Notice of court actions or documented agreements. The Proposed rule would expand the scope of documentation that an applicant must submit to the FDA regarding patent-related court actions and documented agreements. This would ensure that the FDA is promptly advised of information that could affect the timing of approval of a 505(b)(2) application or ANDA.

Comments on the Proposed rule may be submitted to the FDA through May 7, 2015.

MainStory: TopStory AntitrustNews FDCActNews DrugBiologicNews GenericDrugNews HatchWaxmanNews PrescriptionDrugNews RiskNews SafetyNews

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