Dive Brief:
- The FDA released a draft version of guidance covering compounding, called "Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act," directed primarily at outsourcing facilities, addressing the use and qualification of bulk substances in compounding.
- The proposed rules are an extension of The Drug Quality and Security Act (DQSA), passed in November 2013, which identified outsourcing facilities as its own category, separate from traditional compounders.
- Active pharmaceutical ingredients (APIs) must be accompanied by a monograph from an appropriate governing party (if a monograph exists), must be made in a facility that has prior approval, and must come with a certificate of analysis (to prove they been characterized).
Dive Insight:
The FDA has promised to reinvigorate rules surrounding compounding and last Friday, issued policies specifying that compounding facilities must qualify its bulk substances from outsourcing facilities prior to using them for compounding. It also said facilities should not use any bulk substances unless they are either identified as being in clinical need, or in short supply as listed by section 506E of the FD&C Act.
Although compounding is sometimes painted in a bad light — especially after the scandal in 2012 that allowed the spread of meningitis and was associated with more than 60 deaths — the practice can help patients who cannot physically ingest the FDA-approved formulations of certain drugs. Tablets can be converted to syrups, and special dosages can be administered to patients who would not otherwise be able to take the medications in the dosages that manufacturers make available.
While the final formulations of drugs prepared through compounding pharmacies are not governed by the FDA, the regulatory agency is now mandating which APIs can be used in preparations at outsourcing facilities. The agency has said it is more stringent with these types of facilities than it is with traditional compounding pharmacies.
Compounding pharmacies are generally supposed to make compounded items by request and in response to a valid prescription. Outsourcing facilities, on the other hand, are altering the dosage of an FDA medication for research purposes, and sometimes this alteration involves producing a drug from bulk substance to make it appropriate for patient use.
Compounding is governed by state-level laws. Compounding is legal if it is performed by a licensed pharmacist or physician for an identified patient with a valid prescription; if a substance made through compounding uses safe and approved ingredients and good manufacturing practices; and if the resulting drug is not a copy of a commercially available medication.
Outsourcing facilities, on the other hand, can make bulk supplies in advance, but FDA requires the facilities to follow good manufacturing procedures and register the facilities with the agency.
Recognizing that compounding from APIs can be more complex and involved than compounding from approved drugs, FDA's new proposed rules seek to limit how outsourcing facilities make compounded items, with the hope that this will also limit any safety issues that can be introduced when something is added to a formulation or made from scratch with bulk chemicals.
The agency proposes two specific ways to tell if a compounded drug at an outsourcing facility is safe: whether attributes of the approved drug may make it unsuitable to treat certain patients for particular conditions (including whether the compounded drug is intended to address that attribute), and second, if certain factors for each substance being proposed for use in a compounded drug product – specifically, "its physical and chemical characterization, possible or known safety issues, evidence or lack of thereof of effectiveness, and historical use" — would preclude its use by a third-party facility.
The initiative is part of the 2018 Compounding Policy Priorities Plan, launched in January. The agency says the plan will "clarify and appropriately tailor the policies for traditional compounding pharmacies and the outsourcing facilities that may supply a broader market."
A crackdown on compounding at third-party facilities may be in the offing. The announcement comes after the agency issued a cease and desist order to drug wholesaler AmerisourceBergen Corp., which acquired PharMEDium, a sterile drug compounder, in 2015. Among the PharMEDium facility's identified issues was a citation for not testing "components for compounded products prior to compounding."
PharMEDium said in an emailed statement to BioPharma Dive that its products are only compounded from sterile finished dosage form drugs rather than from bulk drug substance — a process it claims helps ensure safety.
The guidance may curb manipulation of a bulk substance in place of the use of an FDA-approved alternative because of economic incentives.
"For example, use of bulk drug substances to compound a formulation of a needed concentration, route of administration or dosage form rather than simply diluting or otherwise manipulating the approved drug reduces the incentive for sponsors to invest in and seek FDA-approval of such drugs."
Editor's note: This article was updated to include comment from PharMEDium.