Proposed Rule Could Alter Current FDA Regulation of Fixed-Combination Drugs

January 7, 2016

Last month, the Agency released a proposed rule regarding FDA regulation of fixed-combination drugs. More specifically, the Agency is suggesting that its requirements for prescription fixed-combination drugs be modified "to apply the regulations to both prescription and nonprescription fixed-combination and co-packaged drugs and combinations of active ingredients under consideration for inclusion in an over-the-counter (OTC) monograph." In its announcement, the FDA stated that the proposed revisions are being made in an effort to "harmonize the requirements for prescription and nonprescription products and make them consistent with long-standing Agency policy."

If finalized, the proposed rule "would apply to both prescription and OTC fixed-combination and co-packaged drugs that are subject to approval under a new drug application (NDA) under section 505 of the FD&C Act (21 U.S.C. 355), or a biologics license application (BLA) under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262), and to combinations of active ingredients under consideration for inclusion in an OTC monograph in accordance with part 330." Additionally, the rule will "not apply to individual natural-source drugs, which are drugs derived from natural raw materials, even though those drugs may contain multiple ingredients derived from the same source."

21 CFR 300.53

Proposed section 300.53 of Title 21 of the Code of Federal Regulations outlines the "requirements for combinations of active ingredients under consideration for inclusion in an OTC monograph and prescription and OTC fixed-combination and co-packaged drugs." The proposed section states that two or more active ingredients can be combined to produce a fixed-combination or co-packaged drug or included in an OTC monograph as a combination when two or more of the following requirements are met:

Section 300.53(a)

  1. Mandates that each active ingredient contribute to the effect(s) of the combination, enhance either the safety or the effectiveness of another active ingredient, or reduce the abuse potential of another active ingredient.
  2. Asserts that "the dosage of each active ingredient (amount, frequency of administration, and duration of use) must be such that the combination is safe and effective and provides rational concurrent therapy."

Section 300.53(b)

  1. Directs applicants and ‘interested persons' (people seeking to change an existing OTC monograph) who are pursuing approval of a combination to state the intended use of each active ingredient included in the [combination] product.
    • "This requirement ensures that the therapeutic purpose of all active ingredients, even those that might not be considered active ingredients in other contexts, is claimed."
  2. Requires applicants and interested persons to provide sufficient evidence, demonstrating that the product(s) in reference meet the requirements of section 300.53(a), above.

21 CFR 300.60

The Agency acknowledges that "there are some products for which it would be infeasible or medically unreasonable or unethical to meet the requirements of this proposed rule." As such, proposed section 300.60 of the Code of Federal Regulations would award FDA with the authority to grant a waiver of some or all of the requirements listed above. FDA would be able to grant a waiver "for products that contain a subset of the components contained in a natural-source drug or a product that has already received a waiver under the proposed rule." In addition, the proposed rule declares that FDA has the authority to waive any of section 300.53's requirements depending on the evidence that is presented.

FDA seeks to obtain comments, concerns, and any other feedback on the proposed rule. Interested individuals may submit comments either electronically (here) or by mail, hand delivery, or courier (paper delivery) by March 22, 2016.

Are you in the process of developing a prescription or OTC fixed-combination or co-packaged product that may be effected by this regulation? Do you already have one on the market? We can help ensure that you are compliant with all applicable regulation. To learn more about our services and how we can help you achieve a successful outcome with FDA, contact us today.


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