Difficulties faced by California veterinarians in obtaining compounded drugs for their patients aren’t likely to be resolved any time soon, judging by the outcome of a recent meeting of the California State Board of Pharmacy Enforcement and Compounding Committee.
A request by veterinary compounding business Roadrunner Pharmacy for exemptions from and clarifications on new state regulations resulted in an hour-long discussion in which many questions were raised and none settled. Instead, the parties decided to continue talks another day.
The confusion centers around the application of new state rules to compounding for veterinary patients. Effective as of Jan. 1, the regulations are aimed at protecting human and veterinary patients alike, and designed to bring state code in line with federal guidance regarding the testing required for compounded preparations.
The more rigorous oversight was prompted by a scandal in 2012 involving contaminated injectable steroids that were compounded by a Massachusetts pharmacy. The tainted preparations caused an outbreak of fungal infections that killed 64 people and sickened 689 more. Historically, compounded preparations have not been subject to the same type or intensity of regulation as commercial drugs.
Compounded preparations are drugs customized for a patient’s individual needs. Drug compounding ranges from adding a flavoring to or altering the concentration of an existing drug to creating a formulation not available on the commercial market. The use of compounds is important in veterinary medicine, where patients range from finch to elephant, and where administering medication can be far more complex than saying, “Here, swallow this capsule.”
“Veterinary medicine is different [from human medicine] in many ways,” Rob Eaton, founder and COE of Arizona-based Roadrunner, told the pharmacy board compounding committee during its April 18 meeting. “Compounds are one of the mainstays of veterinary clinics.”
What about in-house compounding?
Dr. Grant Miller, director of regulatory affairs at the California Veterinary Medical Association, said veterinarians in the state are reporting difficulty acquiring commonly used compounded drugs, with large compounding pharmacies reluctant to ship to California as a result of the new state rules. He said delays and increases in expense are leading to clients being unable or reluctant to treat their pets.
Two aspects of the new regulations in particular are causing friction. The first is a limit on “office stock” of compounded preparations.
Because having a drug compounded and shipped to a client can take several days, veterinarians frequently keep stock on hand to dispense to clients to cover the gap until the prescription can be filled. They also keep office stock to treat hospitalized patients.
The new regulations limit office stock to a five-day supply that must be labeled for a specific patient.
Roadrunner senior pharmacist Bruce Dell suggested the rule is inflexible to the point of potentially causing harm to patients. “There is no way for a veterinarian to know in advance the species, weight and dose [of a potential patient],” Dell said. “Absence of clinic stock delays treatment.”
Eaton concurred, complaining about what he called the “interrogative nature” of the questions Roadrunner now feels compelled to ask prescribing veterinarians. “We are asking veterinarians to read the crystal ball and know every pet that will need office stock,” he said.
The other thorny issue is the beyond-use date (BUD) of compounds that are suspended in an aqueous, or water-based, solution. Such drugs include eye drops and liquid oral medications.
Because compounded preparations are not made to the exact same formulation as commercial drugs, ingredient breakdown and likelihood of contamination over time are not known to the same degree as with commercial drugs. This uncertainty often compels a comparatively short BUD. California regulations now specify a BUD no longer than 14 days for compounds in an aqueous solution.
Many compounders and veterinarians contend that the period is unreasonably short. Miller of the CVMA said the BUD standard is so short that California veterinarians sometimes receive a shipment of compounded medications dated for expiration two days later.
The law allows the 14-day BUD to be extended, but critics say the conditions are onerous and cost-prohibitive. The rules for extending BUD call for three levels of testing:
- Proof of stability: Does the compounded preparation remain in the same form and concentration over the desired period of time without breaking down?
- Proof of sterility: Will contaminants grow in the compounded preparation during the stated time period?
- Container-closure studies: Does the compounded preparation react with its container in a way that causes it to break down or bind to the container?
Dell argued that such stability studies potentially could cost thousands of dollars — too much for medication meant to be given to a single patient. He argued that other, less expensive, methods of measuring potency of a drug would be equally valid.
Christine Acosta, pharmacy board supervising inspector, disagreed that potency testing could stand in for stability testing. Acosta said potency tests do not account for byproducts of degradation that do not provide a therapeutic benefit, yet may cause a preparation to appear potent.
Questions from the committee appeared in some instances to indicate a lack of familiarity with details of the board’s own rule. Regarding the BUD for aqueous medications, for example, one committee member asked, “Is this for oral [medications]?”
Dell from Roadrunner replied: “The standard is nebulous. It doesn’t say whether it is for oral, sterile, non-sterile, etc.”
Another member asked, “Given the vagueness of the regulation, couldn’t you determine the [type of] test [required to extend the BUD]?”
Eaton responded: “We could, but this is a contentious issue and I don’t want to feel lucky. We were hoping for more clarity.”
The U.S. Pharmacopeial Convention (USP), a nonprofit scientific organization, allows greater latitude in its BUD standard for aqueous suspensions. It establishes a 14-day BUD “in the absence of other data,” allowing for alternative dating to be used if pharmacists can show they are compounding the drug according to a published recipe with proven stability up to a different date.
Many meeting attendees expressed concern that the California rule is not consistent with USP, which, while not a government regulating body, is a respected standard-setter.
The committee tabled the discussion to an as-yet unscheduled future meeting.