The 503B outsourcing facilities are able to compound drug products in certain circumstances using bulk ingredients but “[O]ne of the conditions that must be met for a drug product compounded by an outsourcing facility to qualify for the exemptions under section 503B of the FD&C Act is that the outsourcing facility may not compound a drug using a bulk drug substance 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 FD&C Act (21 U.S.C. 356e) at the time of compounding, distribution, and dispensing.” However, the FDA does not include backorders of drugs to be determinant of a clinical need or drug shortage. Each evaluation is performed on a case-by-case basis.
There is a process for nominating bulk drugs substances for inclusion on the List. Once nominated the evaluation of the FDA review of those nominated substances are published periodically in the Federal Register (FR). On today’s FR pre-publication page (here), the Agency outlines its findings on 11 nominated bulk substances. The score card for this round of evaluations (and there are a significant backlog of nominations) is 1 inclusion and 10 refusals. The FR notice indicates that FDA considered and is including bulk quinacrine hydrochloride (HCl) to compound drug products for oral use only. The 10 products FDA considered and is not recommending at this time include hydroxyzine HCl, mannitol, methacholine chloride, metoclopramide HCl, nalbuphine HCl, potassium acetate, procainamide HCl, sodium bicarbonate, sodium nitroprusside, and verapamil HCl.
The FR notice is very instructive and provides explanation of the method and process FDA goes through for its evaluation of each bulk substance. For example, FDA will evaluate whether existing FDA approved products can be used for compounding an alternate version of a drug without having to rely on use of a bulk drug substance as a substrate. The notice also discusses the process and describes how FDA decides a bulk substance should be included on the list. The majority of this FR notice describes how the FDA reached the one positive decision to include quinacrine on the list and the reasons it decided not to include the other 10 nominated products. The reading is quite interesting, and the FR notice is very instructive about the process. Reviewing these decisions and how they are made may help others make more informed decisions when it comes to the appropriateness of submitting future nominations. You can find out more about the bulk substances list one the FDA web site here.
