Reed Smith Client Alerts

On April 6, 2023, the Food and Drug Administration (FDA) notified the public that it will formally exclude 10 bulk drug substances from the 503B Bulks List and include one bulk drug substance for oral use only.

For exclusion: (1) hydroxyzine HCl, (2) mannitol, (3) methacholine chloride, (4) metoclopramide HCl, (5) nalbuphine HCl, (6) potassium acetate, (7) procainamide HCl, (8) sodium bicarbonate, (9) sodium nitroprusside, and (10) verapamil HCl.

For inclusion (but limited to oral use): quinacrine hydrochloride (quinacrine).

All of these bulk drug substances previously underwent notice and comment, making this the FDA’s final decision.

By way of brief background, Section 503B of the Food, Drug, and Cosmetic Act (FDCA) provides outsourcing facilities with exemptions to section 505 (21 U.S.C. 355) (concerning the approval of drugs under new drug applications (NDAs) or abbreviated new drug applications (ANDAs)), section 502(f)(1) (21 U.S.C. 352(f)(1)) (concerning the labeling of drugs with adequate directions for use), and section 582 of the FDCA (21 U.S.C. 360eee–1) (concerning drug supply chain security requirements) when certain requirements are met. In order to qualify for Section 503B’s exemptions, in addition to other requirements, outsourcing facilities cannot use a bulk drug substance to compound unless (1) the bulk drug substance appears on a list established by the Secretary of Health and Human Services (the Secretary) identifying bulk drug substances for which there is a clinical need (the 503B Bulks List), or (2) the drug compounded from the bulk drug substance appears on the drug shortage list in effect under section 506E of the FDCA (21 U.S.C. 356e) at the time of compounding, distribution, and dispensing.

In accordance with the instructions set forth in Section 503B, after FDA evaluates bulk drug substances, it publishes a notice in the Federal Register proposing bulk drug substances to be included or excluded from the 503B Bulks List, including the rationale for such a proposal. Interested parties are provided not less than 60 calendar days to comment on FDA’s notice. After considering the comments, FDA completes its evaluation and then publishes a notice in the Federal Register designating bulk drug substances for inclusion on or exclusion from the list. (21 U.S.C. 353b(a)(2)(A)(i)(I)-(III)).

FDA began its evaluation process by publishing a December 2013 notice in the Federal Register inviting the industry to nominate bulk drug substances for FDA to consider for inclusion on the 503B Bulks List. (78 FR 72838). The nomination process was reopened in July 2014, after FDA provided additional direction regarding the information it required to evaluate nominated bulk drug substances. (79 FR 37747). FDA then evaluated the bulk drug substance to determine whether a “clinical need” existed to support the bulk drug substance’s use in compounding. FDA has interpreted “clinical need” to mean (1) there is a clinical need for an outsourcing facility to compound the drug product, and (2) the drug product must be compounded using the bulk drug substance.