FDA proposes rule for difficult-to-compound drugs, drug categories

The US Food and Drug Administration (FDA) is proposing the creation of two lists of drugs or drug categories that are difficult to compound under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act), as well as criteria for inclusion on the lists.

FDA’s proposed rule would implement sections 503A and 503B of the FD&C Act, which contain a list of requirements for drug products to be exempt from certain current good manufacturing practice requirements, adequate directions for use in drug labeling, and drug approval for new drug applications or abbreviated new drug applications. In addition, both sections require the Secretary of Health and Human Services identify a combined drug product has “demonstrable difficulties for compounding.” Drug products in the list of drugs that have demonstrable difficulties for compounding (DDC Lists) “cannot qualify for the statutory exemptions under the applicable section,” FDA said.

The effort to create a list of difficult to compound drugs stretches back nearly a quarter century to July 2000, when the Pharmacy Compounding Advisory Committee (PCAC) advised FDA on creating such a list, which was then challenged in court based on the constitutionality of “provisions of section 503A of the FD&C Act concerning restrictions on the advertising or promotion of the compounding of any particular drug, class of drug, or type of drug and the solicitation of prescriptions for compounded drugs.”

After losing the court decision, “FDA suspended its efforts to develop the difficult-to-compound list,” the agency said.

When the Drug Quality and Security Act passed in 2013, the unconstitutional provisions were removed, and a new section 503B was added to the FD&C Act, the agency explained. After consulting with the Pharmacy Compounding Advisory Committee (PCAC) and the public, they determined the categories of drug products that would appear on the DDC Lists that are present in the current proposed rule.

Under the proposed rule, there would be one list for section 503A and one for 503B, with each list having three categories of drug products and criteria for inclusion. These include oral solid modified-release drug products that use a coated system, liposome drug products, and drug products produced with hot melt extrusion.

“Before finalizing this rulemaking, FDA intends to consider whether any changes to the proposed criteria would alter FDA’s analysis of whether the categories of drug products addressed in this notice of proposed rulemaking present demonstrable difficulties for compounding within the meaning of sections 503A or 503B of the FD&C Act,” they said.

The criteria for inclusion proposed by FDA include the complexity of the formulation, complexity of the drug delivery mechanism, complexity of the dosage form, complexity of assessing or achieving bioavailability, complexity of the compounding process, and complexity of the physicochemical or analytical testing of the drug product or drug product category.

Risks and benefits to patients who use a compounded drug product or category of drug products being considered for the lists will be weighed by the agency, and they said they “may use available information such as reports submitted to FDA about adverse drug experiences and FDA’s scientific and medical expertise to inform its analysis, as well as information about FDA-approved drug products.” Cost and convenience, they noted, would not be relevant factors for a risk-benefit analysis.

“FDA may consider actual or potential risks and benefits to patients posed by a drug product or category of drug products,” they wrote. “In particular, FDA intends to consider actual or potential risks to patients in connection with the six criteria described in this proposed rule.”

FDA is soliciting public comments on the proposed rule and may decide to use “some or all of the categories of drug products proposed here for inclusion on the DDC Lists, depending on the comments received,” they noted.

“We expect that this proposed rule may create benefits for compounders by reducing regulatory uncertainty. At this time, we are not aware of any compounding and marketing of the three proposed categories of drug products for human use,” FDA said. “Therefore, we expect that the proposed rule would only create administrative costs to read and understand the rule.”

Federal Register notice

FDA proposes rule for difficult-to-compound drugs, drug categories

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