FDA Finalizes New Regulations for Drugmakers a Decade After First Proposal

Regulatory NewsRegulatory News | 30 August 2016 |  By 

After a decade of consideration, the US Food and Drug Administration (FDA) on Tuesday finalized new regulations governing drug establishment registration and drug listing for foreign and domestic firms, though the agency stopped short of finalizing several provisions that commenters took issue with.

The new rule, expected to take effect in 90 days, includes amendments that reorganize, modify and clarify FDA regulations on who must register establishments and list human drugs, active pharmaceutical ingredients (APIs), biological products and animal drugs.

The more than 200-page final rule requires the electronic submission of the registration and listing information, unless waived in certain circumstances, and describes not only how but when owners or operators of drug manufacturers must register their establishments with FDA and list the drugs they manufacture or process. In addition, the rule makes a couple of changes to the National Drug Code (NDC) system.

The rule also includes in-depth responses to 92 of the more than 200 comments that were submitted to FDA, with clarifications on the agency’s current thinking.


Since the 1962 Kefauver Harris amendments to the Food Drug & Cosmetics Act (FD&C Act), drug manufacturers have been required to register their establishments with FDA annually.

The registration identifies establishments for inspection by FDA and provides FDA with an updated list of what drugs are manufactured where.

Major Provisions

In addition to requiring new electronic submissions, the final rule makes clear that the establishment registration and listing obligation rests with the people who manufacture, repack, relabel or salvage drug products (definitions of salvage, repack and relabel are included in the rule).

But FDA notes that the rule does not require persons who act only as private label distributors of drugs to register establishments or list drugs, but allows them to submit drug listing information as agents acting on behalf of those who manufacture, repack, relabel or salvage drugs.

The amendments also make several adjustments 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.

FDA notes that the final rule also updates “longstanding regulatory provisions governing FDA disclosure of drug registration and listing information, stating that with certain exceptions, establishment registration and drug listing information is generally available for public disclosure.”

What Wasn’t Included

However, the final rule does not include certain aspects of the proposed rule that were opposed by many who submitted comments, FDA explains.

“Features of the proposed rule that have not been finalized include most significantly: (1) A requirement that FDA, not registrants, develop national drug codes (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,” the agency says.

National Drug Codes

FDA notes that it received several comments on the format of the NDC, and many expressed concern about the impact of any changes in the NDC format on various systems that track and use NDCs.

The agency says it is “sensitive to these concerns” and Section 207.33(b) of the final rule “specifies the format of an NDC recognized by FDA. The final rule necessarily includes more specifications than did the proposed rule concerning NDC formatting because under the final rule, registrants, not FDA, develop their own proposed NDCs, and they must all meet certain formatting parameters. The final rule states, for example, that the NDC is 10 or 11 digits to preclude the submission of longer NDCs.”

FDA says it allows for 10- or 11-digit NDCs, consistent with a longstanding statement in the statute, and that FDA will expand the NDC labeler code from five to six numeric characters when the available 5-character code combinations are exhausted. The final rule also includes formatting requirements for registrants to follow when formulating their own proposed NDCs, and it allows for alternatively formatted NDCs for certain HCT/Ps and offers an explanation on how a labeler code can be obtained.

And to accommodate for the possibility of alternatively formatted NDCs in bar codes, the statute is amended in this final rule to allow FDA's center directors to approve additional standards or formats for bar codes.

Other Responses of Note

Commenters, meanwhile, asked FDA to clarify how the content of labeling differs from package inserts and final printed labeling.

FDA explains the nitty gritty of the terms: “In defining the term ‘content of labeling,’ for human drugs, we use the phrase ‘prescription drug labeling’ (instead of ‘package insert’ or ‘professional labeling’) to mean FDA-approved labeling for prescription drug products described in §§ 201.56, 201.57, and 201.80. For human prescription drugs that are subject to section 505 of the FD&C Act or section 351 of the PHS Act, content of labeling is defined as the content of the prescription drug labeling. For human OTC drugs, content of labeling is not defined in these terms; it includes ‘all text, tables, and figures including the drug facts labeling required by § 201.66.’ For animal drugs, ‘content of labeling’ is defined to mean labeling that accompanies the drug that is necessary to enable safe and proper administration of the drug. This would generally include package inserts and final printed labeling.”

The final rule also revises the regulations to state that FDA will accept establishment registration or listing information submitted by a private label distributor if it is acting as an authorized agent for an establishment that manufactures, repacks, relabels, or salvages drugs. It also revises the statute to specify that registrants must review and update registration information between 1 October and 31 December each year.

Digging even more into the weeds of the final rule, FDA clarifies how it defines commercial distribution, telling industry commenters: “We disagree with the suggestion that a transfer of drugs from a contract manufacturer to another contracting party should not qualify as commercial distribution. Such an exemption would interfere with FDA's ability to track drugs and establishments for inspection. However, by revising the definition of ‘commercial distribution’ to exclude internal or interplant transfers of drugs, including active pharmaceutical ingredients, other unfinished drugs, and finished drug products, between registered establishments under common ownership and control, we have reduced the drug listing burden generally. This exclusion accommodates the common practices of specialized manufacturing at different registered establishments under common ownership and control. This practice often results in multiple internal and interplant transfers of these materials prior to marketing, which we do not consider commercial distribution for registration and listing purposes.”

Compliance Dates

For drug products currently subject to part 207, the electronic submission requirement was largely implemented via 2009 electronic registration and listing guidance (74 FR 26248), FDA says. But upon the effective date of this final rule (90 days after 31 August 2016), FDA expects continued electronic submission of registration and listing information in accordance with the electronic registration and listing guidance and with the new § 207.61.

“This applies to newly submitted registration and listing information as well as updates to information previously submitted. FDA will accept waiver requests in accordance with § 207.65 of this final rule upon its effective date,” FDA says.

Two years after the effective date of this final rule (90 days after 31 August), FDA also says it intends to remove from its current electronic database establishment registration and listing information submitted in the past on paper and not updated with a more recent electronic submission.

“The purpose of this removal is to purge outdated information from our database, such as information registrants failed to update after discontinuing a drug product or closing an establishment,” FDA says. Other compliance dates are listed on pages 116 through 118 of the final rule.

Requirements for Foreign and Domestic Establishment Registration and Listing for Human Drugs, Including Drugs That Are Regulated Under a Biologics License Application, and Animal Drugs



© 2023 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy