The Alliance for Pharmacy Compounding (APC) is floating its first-ever best-practices guidelines for compounding pharmacies, and is anticipating the introduction of a bill in the coming weeks that would grant 503b outsourcing facilities an additional 180 days to continue compounding a drug after it is removed from FDA’s drug shortage list. The organization is aiming to set standards for compounders amid controversy over compounding of GLP-1 drugs, which are experiencing enormous demand.
Manufacturers of GLP-1s oppose mass compounding of their drugs, a practice which expected to continue even after the drugs fall off FDA’s shortage list. Eli Lilly told IHP that FDA and state regulators need to intervene to stop compounders from mass producing unapproved replicates of its weight-loss drugs, Mounjaro and Zepbound.
The prospective bill on compounding would also expand the sources of information FDA can use to evaluate drug shortages, as the agency currently relies solely on data from drug manufacturers. On GLP-1s, telehealth companies that prescribe the compounded versions disagree with brand-name manufacturers over which medications should be granted a compounding exemption.
APC CEO Scott Brunner told Inside Health Policy that compounded drugs should only be prescribed when an FDA-approved drug is in shortage or when the prescriber determines the dosage form or strength of the FDA-approved drug is not suitable for a specific patient.
FDA recently sent an alert to patients and health care providers about dosing issues with compounded versions of the type-2 diabetes and obesity drugs Ozempic and Wegovy, following reports of adverse events including acute pancreatitis, gallstones, abdominal pain and fainting.
In the alert, FDA said compounded semaglutide drugs present greater risks to patients compared to FDA-approved medications because compounded versions do not undergo the FDA’s premarket review for safety and efficacy.
Compounding facilities are regulated under two sections in the Federal Food, Drug, and Cosmetic Act: 503a and 503b. 503a compounding facilities are overseen by state boards of pharmacy and follow FDA guidelines, while 503b compounding facilities are regulated directly by FDA. APC’s guidelines address both types of facility.
Review FDA’s drug shortage list
The APC notes in its guidelines issued Thursday (Aug. 15) that FDA’s drug shortage list can be confusing. It sometimes lists specific dosage forms or strengths of a drug as “available,” while still indicating that the drug is “currently in shortage.” In these cases, compounders are allowed to continue producing the drug because the overall status indicates it is still in shortage.
Tenille Davis, pharmacist and chief advocacy offer at APC, told IHP, “Drugs with the status ‘currently in shortage’ are able to be compounded, despite what strengths may or may not be listed as ‘available.’"
The precise language of the guidance document allowing shortage drug compounding is “currently in shortage.” Any FDA-approved drug listed with that precise status may be compounded in a 503a facility pursuant to a prescription.
Pharmacies must review FDA’s drug shortage list before preparing a compounded version of an approved drug and keep records to prove that the drug was in shortage at the time of compounding. If the decision to compound is due to the drug being on the shortage list, the prescription should include a note indicating that the drug was listed and the date the list was checked, APC says.
For 503b outsourcing facilities, FDA guidance allows them to continue compounding an essential drug for up to 60 days after it has been removed from the FDA’s shortage list.
During a call with reporters on Thursday (Aug. 15), Brunner mentioned that legislation is anticipated to be introduced that would extend this period to 180 days, allowing 503b outsourcing facilities a longer period to compound drugs recently removed from the shortage list. He also said the legislation would make it “more economically feasible” for 503b facilities to prepare drugs in shortage.
“We hope that it will be introduced in the coming weeks,” Brunner told IHP.
The proposed bill will also expand the sources of information FDA can use to assess drug shortages, according to Brunner. Currently, FDA can only consider data from drug manufacturers.
“But the agency should be able to pull information from hospitals, and yes, from pharmacies . . . because in variably, pharmacists are the first to see interruptions in availability of a drug, which may be a sign of a more widespread shortage,” Brunner told IHP.
However, the 60-day grace period has not been formally extended to 503a pharmacies, and its legality remains untested. APC says 503a pharmacies should follow best practices by discontinuing the preparation and dispensing of compounded copies as soon as the drug is removed from the shortage list.
Additionally, when compounding a version of an FDA-approved drug, it is best practice to match the formulation, concentration, and preservatives exactly to those of the FDA-approved product to avoid any confusion in prescribing or administration, according to APC.
Sourcing and testing APIs
Pharmacies can only obtain active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers. APC recommends ensuring that the wholesaler confirms the manufacturer’s FDA registration, and that the API complies with section 503a requirements, with both parties holding the necessary permits or licenses in their respective states and the state to which the API is shipped.
If sourcing API from a new or unfamiliar wholesaler or manufacturer, pharmacies should submit a sample for independent third-party testing to verify the API’s potency and purity before using it for preparation and dispensing, APC says.
Pharmacies should expect vendors to have robust quality assurance processes, including identity testing to confirm that the chemical matches its label, evaluate the vendor's overall quality control procedures and ask detailed questions, the guidelines say. APC says relying solely on the manufacturer’s Certificate of Analysis is insufficient and it is important to consider requesting the wholesaler’s batch release testing, which should include at least an identity test and may also encompass purity and water content testing.
APC recommends adhering to U.S. Pharmacopeia requirements for testing sterility, endotoxin levels, stability, particulate matter, antimicrobial effectiveness and container closure integrity.
Dispensing
When dispensing compounded drugs, the guidelines say providers need to counsel the patient or their caregiver and written information should be given to help them understand how to use the compounded medication correctly.
APC recommends the instructions be clear and easily understandable for non-experts, especially when including dosage titrations and conversions between units.
Multi-dose sterile vials should be labeled with an expiration date of 28 days after the first puncture.
For medications that are shipped or delivered, compounders should conduct temperature verification studies to ensure the medication remains at the correct temperature throughout the delivery process, APC says.
Collaborating with prescribers
When collaborating with prescribers, APC says it's crucial to ensure they understand that for a compounded drug to be dispensed, it must be prescribed specifically as a compounded API, even if it is a replica of an FDA-approved drug. The decision to dispense a compounded drug is made by the prescriber, not the pharmacist.
Additionally, prescribers should be aware that the cost of a compounded drug does not legally justify its use over an FDA-approved alternative, APC says.
Marketing
Pharmacies must avoid claiming or implying that any compounded drug is “FDA-approved” or uses “FDA-approved ingredients.” FDA regulates but does not approve APIs; it only approves finished drug products.
Compounded preparations should not be referred to as “generic” or use the brand name or image of the FDA-approved drug, even if they are copies of those products, APC says.
Direct comparisons between compounded medications and generic or brand-name manufactured products are also discouraged, APC says. Pharmacies can state that their compounded drug contains the same active pharmaceutical ingredient as the FDA-approved version but should avoid further comparisons.
Claims regarding the safety or efficacy of compounded products are not permitted, as “safe” and “effective” have specific legal definitions under the Food, Drug, and Cosmetic Act and cannot be applied to compounded drugs, APC says.
Marketing materials should not feature images of FDA-approved, brand-name products, as these images are the intellectual property of the drug manufacturers and using them could result in legal issues. Instead, pharmacies should focus on showcasing their accreditations, professional affiliations, testing protocols, and patient-reported outcomes, according to APC.
Advertising claims that compounded medications will save patients money compared to manufactured products are also prohibited, APC notes. -- Maaisha Osman (mosman@iwpnews.com)