Health Law Daily A decade in the making, drug makers get establishment rules
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Wednesday, August 31, 2016

A decade in the making, drug makers get establishment rules

By Anthony H. Nguyen, J.D.

After a decade of comments and reviews, in order to improve management of drug establishment registration and drug listing requirements, the FDA will require electronic submission of the registration and listing information, unless waived in specific circumstances. The Final rule describes the situations in which owners or operators of establishments at which drugs are manufactured or processed must register with the FDA, as well as list the drugs manufactured or processed. In addition, the Final rule makes changes to the National Drug Code (NDC) system to support implementation of the electronic prescribing provisions of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) (P.L. 108-173). The Final rule is effective on November 29, 2016, with compliance dates for various aspects set from one to two years after the effective date (Final rule, 81 FR 60169, August 31, 2016).

The changes also align the FDA’s regulations governing drug establishment registration and listing with federal Food, Drug, and Cosmetic Act (FDC Act) Section 510 (21 U.S.C. § 360), as amended by the Food and Drug Administration Amendments Act (FDAAA) (P.L. 110–85) and the Food and Drug Administration Safety and Innovation Act (FDASIA) (P.L. 112–144).

Significant aspects of the Proposed rule not finalized include: (1) a requirement that the FDA, not registrants, develop NDCs for assignment to listed drugs; and (2) a requirement that the NDC appear in human-readable form on the label of each listed drug and provisions that would have defined the appropriate NDC for that purpose.

Background. In the Federal Register of August 29, 2006, (71 FR 51276), the FDA proposed to amend its regulations governing drug establishment registration and drug listing in 21 C.F.R. Part 207. After the Proposed rule was published, the FDAAA was adopted into law and amended FDC Act Sec. 510(p) to require electronic submission of drug establishment registration and listing information, unless the FDA waived the requirement in individual cases. In June 2009, the FDA published a guidance titled "Providing Regulatory Submissions in Electronic Format—Drug Establishment Registration and Drug Listing" to assist manufacturers in this regard.

The FDASIA made further changes to the FDC Act and required that: (1) annual registration of establishments takes place during the period beginning on October 1 and ending on December 31; and (2) the information registrants supply for annual registration include a unique facility identifier (UFI) for the establishment and include a point-of-contact email address.

Distribution. To prevent confusion, the FDA replaces the term "bulk drug substance" with the more descriptive term "active pharmaceutical ingredient."Consistent with the FDAAA and current practice, the drug listing requirements are applicable to finished drug products and to active pharmaceutical ingredients (APIs) alone or together with one or more other ingredients. The establishment registration and listing obligation rests with persons who manufacture, repack, relabel, or salvage drug products and does not require persons who act only as private label distributors of drug products to register establishments or list drugs. Private label distributors are permitted to submit drug listing information as agents acting on behalf of persons who manufacture, repack, relabel, or salvage drug products.

The FDA also clarifies how it defines commercial distribution, noting that it disagreed with comments that "a transfer of drugs from a contract manufacturer to another contracting party should not qualify as commercial distribution." The agency stressed that including such an exemption would interfere with its ability to track drugs and establishments for inspection. Instead the FDA revised the definition of "commercial distribution" to exclude internal or interplant transfers of drugs, including active pharmaceutical ingredients, other unfinished drugs, and finished drug products, as well as between registered establishments under common ownership and control. The exclusion would address common practices of specialized manufacturing at different registered establishments under common ownership and control.

Registration. The establishment registration number identifies establishments for inspection by the FDA. Generally an establishment registration number is assigned to each establishment of each manufacturer, repacker, relabeler, or salvager after the initial registration, when such activities begin. The FDA Establishment Identifier (FEI) is the number assigned by the agency as the establishment registration number.

Under the Final rule, the establishment registration number and the UFI are two distinct numbers. The FDA will continue to assign an FEI as the establishment registration number after an establishment is registered for the first time. The Final rule requires registrants to submit the establishment registration number, which is currently the FEI. First time registrants will not have such number and are instead required to submit a registration number at the time of the first annual review, if not sooner.

Several adjustments are also made to the timing and substance of the submission of information to register a drug establishment and list of drugs manufactured, repacked, relabeled or salvaged at the establishment.

Drug codes. The FDA noted that it received several comments on the format of the NDC, and various parties expressed concern about the impact of any potential changes in the NDC format on various systems using NDCs. Based on these concern, the FDA will allow 10- or 11-digit NDCs, consistent with a longstanding statement in the statute, and also expand the NDC labeler code from five to six numeric characters when the available five-character code combinations are exhausted. The Final rule also includes formatting requirements for registrants to follow when formulating their own proposed NDCs and provides for alternatively formatted NDCs in certain instances and offers an explanation on how a labeler code can be obtained.

MainStory: TopStory FinalRules FDCActNews DrugBiologicNews GenericDrugNews LabelingNews PrescriptionDrugNews

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