OTC Drug Irradiation Rule Exposed As Unnecessary In FDA Regulatory Review

US FDA proposes to repeal regulation that, since 1955, has required an NDA or ANDA for any drug product sterilized by irradiation, including drugs that otherwise would be marketed under an OTC monograph. It notes the Trump administration's order that federal agencies identify and potentially eliminate any unnecessary rules and regulations.

US FDA estimates that eliminating its premarket approval requirement for irradiated OTC drugs would generate between nearly $400,000 and more than $2m in one-time cost savings to the industry.

Since 1955, FDA has included provisions in multiple rules requiring an approved new drug application or abbreviated NDA for any drug product sterilized by irradiation, including drugs that otherwise would be marketed under an OTC monograph. The agency on Sept. 11 published a notice of a proposed rule to repeal that requirement.

Cutting the regulation would mean OTC drugs sterilized by irradiation that are generally recognized as safe and effective and compliant with all applicable regulatory requirements can be marketed legally without an NDA or ANDA. Currently, only  the monograph for ophthalmic drug products incorporates a sterility condition, though drugs marketed under other monographs could be irradiated (see box below).

FDA's Center for Drug Evaluation and Research states in the notice, slated for Sept. 12 Federal Register publication, that the eliminating the "unnecessary preparation and review of a pre-market drug application" for OTC monograph drugs that are irradiated "will generate an estimated one-time cost savings that range from about $395,000 to $2,076,000."

CDER also estimates annual net cost savings over 10 years of $50,000 to $280,000 at a 7% discount rate or $40,000 to $240,000 with a 3% discount rate.

Considering "an infinite horizon," CDER estimates that the change would benefit one firm every 10 years and the present value of net cost savings are $830,000 to $4.37m with a 7% percent discount rate and $1.58m to $8.3m with a 3 percent discount.

Monograph But NDA, Too

The majority of OTC drugs available in the US are marketed under FDA's OTC monograph, which sets dosages, formulations and indications for certain ingredients that all firms authorized by FDA to manufacture drugs sold in the US can use.

Sterilization generally is not a condition specified in OTC monographs and the

monograph for ophthalmic drug products is the only one that incorporates a sterility condition.

However, while products available under other OTC monographs are not required to be sterile, manufacturers may choose to sterilize some types including consumer and health care antiseptics, In 2013, FDA asked manufacturers to voluntarily revise topical antiseptic labels to indicate whether a product is manufactured as a sterile product

Other OTC drugs available in the US are allowed on the market through FDA's premarket approval process that requires a firm to submit to the agency a new drug application with data and other information, sometimes from clinical trials, showing an ingredient's safety and efficacy history and that it can be used safely by consumers without the intervention of a physician or other health care professional.

Ingredients that previously have not been available OTC in the US, almost always ingredients that have been available Rx-only, can be proposed for nonprescription distribution in an NDA to FDA. Generic equivalents of OTC ingredients marketed under NDAs can be approved through abbreviated NDAs.

The center also estimates that the industry's one-time costs linked to the proposed change will be $120 to $150, though it does not state how those savings will be realized.

The Consumer Healthcare Products Association supports the proposal. “Repealing the old and cumbersome regulation that requires NDAs/ANDAs for OTC products that are sterilized by irradiation – but which are otherwise GRAS/E – is a meaningful change that would help to reduce the burden on manufacturers and regulators, enabling products to get to market faster for consumers,” CHPA said in a statement.

Hunt For Unnecessary Regulations

CDER gives multiple reasons for the proposal. One is that FDA no longer concludes that drugs sterilized by irradiation are necessarily new drugs as the technology of controlled nuclear radiation for sterilization of drugs is well understood and OTC monograph drugs must be manufactured in compliance with the agency's good manufacturing practices requirements.

"Appropriate and effective sterilization of drugs, including by irradiation, is adequately addressed by the [current] GMP requirements. Repealing the irradiation regulation would eliminate a requirement that is no longer necessary, and will not diminish public health protections," CDER states.

GMP requirements relevant to to irradiation include ensuring that sterile drug products are free of objectionable microorganisms ensure and that irradiation or any other sterilization processes do not have a detrimental effect on a drug product’s identity, strength, quality, purity or stability. Additionally, FDA's GMP inspections include checking records firms are required to maintain on drug product manufacturing, including sterilization processes.

Another reason for the change is an executive order President Trump issued soon after his inauguration in 2017 that federal agencies review their rules and regulations to identify and potentially eliminate any that are unnecessary. (Also see "Trump Order Reducing Regulation Might Imperil FDA Good Guidance Practices" - Pink Sheet, 30 Jan, 2017.)  "As part of this initiative, FDA is proposing to repeal the irradiation regulation as specified in this rule," according to FDA's notice.

CDER also notes a third reason for the proposal: a 2014 citizen petition from the Wood Burditt Group LLC requesting elimination of the irradiation regulation. The center responded to Wood Burditt in 2014 acknowledging receipt of the petition and in 2015 to state that the agency had not resolved its request.

FDA first indicated its intent to act on Wood Burditt's petition while also carrying out the White House's regulation-cutting order in the spring 2017 semiannual Unified Regulatory Agenda. The agency's list included for the first time a statement on proposing a rule to revoke the irradiation regulation; the statement included a target date of March 2018 for publishing a proposed rule. The next semiannual agenda for federal agencies published in fall 2017 also included a statement on a rule to revoke the irradiation regulation with the same target gate. However, the target date for the proposal was changed in the spring 2018 agenda to May 2018. (Also see "Generic Labeling Rule Defies Predictions, Remains In FDA's Long-Term Pipeline" - Pink Sheet, 25 Jul, 2017.) From the editors of the Tan Sheet.