Epicur Pharma’s former Advisory Council member Ann Donoghue, DVM, MS shares her personal perspective on the important relationship between veterinary oncology and compounded medications used in chemotherapy treatments. Ann has been a longstanding Epicur and Stokes Pharmacy advisor and she advocates for the education of compounding and 503B education in veterinary medicine.
From Ann:
I recently attended a Continuing Education event featuring presentations by oncologists from local specialty veterinary hospitals. Many of the presentations discussed the chemotherapies available to treat dogs. While there are approved drugs for dogs, the list is short and limited to just a few cancer types. The vast majority of dogs receiving chemotherapy are treated with a generic human drug that is compounded for use in the dog – accounting for the size, weight, and other differences important to treating animals versus humans. While the presentations offered a lot of helpful insights into veterinary oncology, none of them touched on the issues around compounded drugs or the known data on compounding errors in 503A chemotherapy medications.
A trusted 503A pharmacy partner is essential for veterinary practices to get customized individual patient prescriptions. But compounding is not easy, it requires skill, training, and consistency. The consistency aspect has been identified as a real issue in compounded medications. A compounding pharmacy, or 503A, is not required to perform potency or stability testing, it’s done at the discretion of the pharmacy. If a compounding pharmacy does not regularly run tests or analyses of the final compounded drug, there is an increased chance of quality issues and drug inconsistencies occurring from batch to batch or even prescription to prescription.
503A or 503B—Knowing When to Order from Each One
Knowing the differences between 503As and 503Bs can help you make an informed decision on which type of compounder will best meet your needs and the needs of your patients, ensuring your patients receive the highest quality of care.
Several studies have looked at compounded chemotherapy drugs and found wide variances. For example, Burton (2017) obtained chlorambucil and melphalan from four compounding pharmacies, cyclophosphamide from five pharmacies, and versions of all three drugs from manufacturers following FDA regulations. They tested all the gathered drugs on Day 0 (the first day they received them) and again 42 days later to evaluate the stability of each drug. The versions following FDA-enforced regulations manufactured under cGMP in a 503B outsourcing facility all fell within the allowed limits of +/- 10% of the label claim on both Day 0 and Day 42.
The results for the same tests run on the drugs obtained from compounding pharmacies were drastically different and quite surprising to discover:
Percent of label claims for 3 chemotherapies on Day 0 and Day 42
|
Drug
|
Day 0 low
|
Day 0 high
|
Day 42 low
|
Day 42 high
|
|---|---|---|---|---|
|
Chlorambucil
|
-30%
|
+5%
|
-48%
|
+8%
|
|
Melphalan
|
-45%
|
+24%
|
-50%
|
+9%
|
|
Cyclophosphamide
|
-11%
|
+7%
|
-21%
|
-1%
|
The results show us that stability isn’t guaranteed and the variance can be problematic for patient care. Potency dropped by as much as 50% for melphalan, and 21% for cyclophosphamide.
Additional studies are looking at other drugs such as trilostane, lomustine, fluconazole, and torsemide that had similar results.
Have you ever wondered why a patient hasn’t responded to therapy? Or questioned whether that cancer was refractory to that treatment? Your treatment plan may have been spot on, but you may have given a dose of what you trusted to be 10 mg/kg, which was actually 5.2 mg/kg due to the low potency of the compounded drug. Or, the adverse effects, which are generally always expected to occur, were more severe than expected, because the dose was actually 24% higher than you intended.
While these test results can be scary to confront, there are ways you can ensure your patients get the best – and correct – treatment.
- Make the switch to a 503B partner. You’ve probably already heard this with the new USP regulations in place, but it really is the best first step. Look first for drugs made by 503B outsourcing facilities because these facilities 100% manufacture their medications under cGMP, they are FDA regulated, and they are required to perform potency and stability testing.
- Pick partners you trust. If you can’t find what you need from a 503B outsourcing facility, it’s still okay to partner with a 503A compounding pharmacy. Advocate for your patients by asking your compounding pharmacy a few questions to make sure you can trust what you get from them. These questions include: How often do you test your products for potency? Do you do any stability evaluation? When were you last inspected by FDA? And most importantly, ask for the potency and stability data too!
- Keep learning. The options available to veterinary professionals for patient medications are increasing. Both 503A and 503B partners will be important to your practice. The best way to understand the benefits and roles of each partner is to stay educated on the differences and the risks.
