Compounding is an essential part of veterinary care, and it's common for vets to prescribe compounded medications while working with a local compounding pharmacy or even handle compounding medications in-house. Nevertheless, due to recent modifications implemented by the United States Food and Drug Administration, the customary procedure for compounding will need to be adjusted.
How can you address this new challenge with minimal disruption to your practice or your patients? Let's dig in.
What is Compounding?
First, let's talk briefly about what compounding is, in case you're unsure.
When a drug is approved for use on people or animals, it has a specific range of acceptable parameters.
These parameters can stipulate things like the dosage, density of a solution, means of administration, and overall composition of the drug. This is all regulation to ensure consistency in drugs across different providers and locations; a regulated drug provided by a pharmacy in New York will be the same – within a small range of variance – as the same drug provided by a pharmacy in California.
Often, though, drugs have "side effects" that can be beneficial in some circumstances. Or, they may be better suited to treating an issue in higher doses than they're approved for or when they're more concentrated or more dilute. However, any of these alterations may be outside of the regulated and official use and composition of the drug.
The practice of compounding is any time you or your pharmacy modify a drug outside of its approved parameters. Actions such as these all compound a drug:
Combining multiple drugs into one capsule or syringe to avoid having to administer multiple pills or shots when just one will do.
Crushing pill-form tablets to mix with a liquid and create an oral suspension for administering drugs that would otherwise be slow to dissolve and take effect.
Adding a flavoring agent to a drug to make it more palatable for consumption (such as peanut butter or meat flavoring for dogs or cats.)
Changing the form of a drug, such as creating a transdermal gel out of an oral or injected drug, to increase compliance with taking it.
Essentially, any action that takes the drug outside of its approved form or dosage is a form of compounding.
"The U.S. Pharmacopeia Convention (USP) formally defines compounding as 'the preparation, mixing, assembling, altering, packaging, and labeling of a drug, drug-delivery device, or device in accordance with a licensed practitioner's prescription, medication order, or initiative based on the practitioner/patient/ pharmacist/compounder relationship in the course of professional practice.'" – American Pharmacists Association
There are a lot of concerns surrounding compounding, some of which are more pressing than others.
Is Compounding Illegal?
No. Despite regulations specifying what forms and dosages medications should take, changing those forms outside of regulations is not strictly illegal. Neither the FDA nor the government, in general, punish compounding when it's performed according to its own rules and in a licensed facility.
There are many good reasons why compounding may be necessary.
The common, approved preparation of the drug includes an ingredient like a coating or dye that the patient is allergic to.
The patient may be averse or resistant to the approved mode of delivery, like a pill or oral solution, so a different preparation is required.
The approved dosages may be too high or too low to be therapeutic to the patient.
Delivering multiple medications routinely and individually may be unnecessarily traumatic (such as multiple injections instead of one.)
The issue with compounding is that it takes a drug outside of its approved form and dosage. The resulting compounded drug may be perfectly safe and effective, but it also might not; different drugs, administered together, might have unforeseen side effects. A too-high dosage might have side effects that aren't present in lower doses, or a too-low dose might not actually be effective.
Essentially, it takes a known quantity of drugs and pulls them into the unknown. While common practice might have proven safe, until FDA approval comes through for the compounded medication, it's not FDA-approved.
While compounding itself is not illegal, the resulting medications are not approved, and misrepresenting that fact can be a problem.
"FDA has observed that some compounders have made false and misleading statements that compounded drugs are safe and effective, sometimes for the treatment of serious diseases, by incorrectly suggesting the drugs had met the standard for FDA approval." – FDA.gov
Compounding is not some underground practice; however, compounding pharmacies are generally licensed and approved.
What is a Compounding Pharmacy?
A compounding pharmacy is a pharmacy that specializes in providing compounded medications. While almost all pharmacies have some ability to do basic compounding, only a relatively small handful of pharmacies specialize in the process.
"Of the approximately 56,000 community-based pharmacies in the United States, about 7,500 pharmacies specialize in compounding services. This means the pharmacists in those facilities spend most or all of their time compounding special preparations for patients. Preparations made in these pharmacies are more likely to include both sterile and non-sterile dosage forms. Compounding also takes place in hospital pharmacies and at other health care facilities." – American Pharmacist Association.
While the drugs created via compounding are not approved, the practice of compounding is, and the pharmacies that provide the service are typically regulated by state boards.
Compounding must still be handled appropriately and consistently and within regulations, or else the pharmacy can be sanctioned or shut down. Additionally, controlled substances are still given oversight by the DEA.
Why Do Vets Need Access to a Compounding Pharmacy?
Vets, in particular, need access to compounding for several reasons.
First, vets treat a wide range of different animals across species and breeds. The medication needs of a domestic shorthair cat, a purebred Maine Coon, a Serval, and a wildcat like a leopard are all very different.
Dog breeds are even more widely varied, and that doesn't even get into other forms of veterinary medicine, such as birds, lizards, and livestock.
Secondly, the range of medications approved for use in animals is often significantly smaller than in humans. From the FDA At a Glance Fact Sheet, the organization approves over 20,000 drugs for humans, but only 1,600 for animals, across all different animal species. To no one's surprise, this means it can be much harder to find drugs to treat niche issues in animals when only a handful of medications are approved for use on those animals at all, let alone for that specific issue.
On a more practical level, veterinarians are unlikely to be handling compounding in their practices themselves. Instead, having a working relationship with a local compounding pharmacy is much more ideal.
Better facilities, better training, and greater access to medication help augment the ability of a vet to treat their patients.
New Regulations from the FDA
Why all the interest and discussion about compounding pharmacies recently? Well, recently, the FDA decided to pitch changes to how compounding pharmacies specifically for vets are handled. The proposal, known as GFI #256, was approved last year and was originally slated to go into effect in October of 2022; after many comments from vets across the country, enforcement was pushed back to April 2023. It's now in effect, and that means veterinarians and vet-focused compounding pharmacies must comply.
This is a big deal. A survey performed by Wedgewood Pharmacy found that 69% of vets are not confident in their ability to comply with the new regulations.
So, let's start by digging into that document. What are the new regulations?
An interesting answer is that it's not actually new regulation. It's a clarification of the FDA's general stance and how they may choose to enforce existing regulations in the future.
"When the FDA issues a "Guidance for Industry," it represents the agency's "current thinking." While it is neither a law nor a regulation, the FDA uses these documents as the basis for its inspection of compounding pharmacies. However, as a practical matter, it's wise for both pharmacies and veterinary practices to comply with the standards described in these documents." – VIN News.
Essentially, this new guidance is meant to do three things.
Crackdown on pharmacies and veterinary practices that compound large amounts of a given composition and offer it as if it were its own approved drug when it's not.
Require veterinarians to write "minimally viable" prescriptions; that is, prescriptions for an amount of a drug for an individual animal's case rather than a more extensive stock for use across multiple cases.
Force veterinarians to justify the use of a compounded drug over an FDA-approved drug and be able to provide that justification if asked.
Wherever an FDA-approved drug is acceptable and likely to be relevant to treatment, it should be used preferentially over a compounded drug. However, if the FDA-approved drug is not permitted for a given circumstance, the veterinarian can still prescribe a compounded drug for that case. However, veterinarians will find it more challenging to bulk-compound medications for use as necessary.
It's worth mentioning that it's still going to be possible to compound drugs from bulk materials and to keep both those drugs and the bulk materials in stock, but they need to come from specifically the "FDA's List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals." This may be a more restricted list than what you're used to using.
What Veterinarians Should Consider with Compounded Drugs
As a veterinarian, you generally don't have to be too concerned with the FDA knocking at your door.
They have said as an agency that they don't really intend to inspect every veterinary practice across the country in search of violations. The FDA intends to inspect two groups: pharmacies that compound drugs for animal use and veterinary practices that compound from bulk substances. If you're neither, you generally don't have to worry about the direct inspection and justification.
That said, you will likely see some impact from this change if you haven't already. Generally, this will come in three forms.
Drugs compounded from bulk materials and meant to mimic FDA-approved drugs as a "generic alternative" will be heavily restricted.
You will generally see a lot of pressure to prescribe FDA-approved drugs over compounded alternatives whenever possible and reasonable.
You will be expected and/or restricted on the quantities of compounded drugs you can obtain from a given prescription.
Of the three, the third one is the most likely to have a direct impact on your patients. Smaller amounts and smaller doses of a given drug are generally more expensive than larger amounts on a per-unit basis. That means when you're told to decrease the amount of a drug ordered for a patient, the cost per dose of that drug is likely to increase. Combined with the push to use more approved drugs over compounded drugs (where approved drugs are often more expensive), patient costs are likely to go up. They may not go up much, but it's worth being prepared.
Additionally, you will be expected to provide a detailed rationale for your choices of prescription with compounded drugs, which may need to be kept on file with the compounding pharmacy in case the FDA comes knocking.
The FDA has long requested that any adverse events (side effects) of medications used off-label or compounded be reported to the FDA for monitoring. GFI #256 reinforces this request and requires any adverse events to be reported.
Getting the Help You Need
Navigating the legal waters of veterinary care can be a difficult time, and when regulations change, it ripples across the entire industry. That's why it's important to have veterinary specialists in your corner, and we'd like to be those experts on your speed dial. Whether it's internal medicine, neurology, dermatology, oncology, or critical care, we're available to be reached at any time. We're even rolling out a 24/7 service and a dedicated phone number for emergency situations.
We're staffed with a range of certified expert veterinarians, and we can help answer nearly any questions you have about veterinary care. You can't be an expert in everything all the time, and with particularly complicated clients, a second opinion on diagnosis and treatment options is always helpful to have. Just contact us to get started, and we'll be ready for you whenever you need us!