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The Impact of 503B Outsourcing Facilities and USP 800 on Veterinary Medicine: Q&A With Philip Bergman, Veterinary Oncologist

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Veterinary oncologist, Phil Bergman, current Director of Clinical Studies for VCA Animal Hospitals and Epicur Pharma Advisory Council member, spoke with our team recently. He shared his latest research findings on the quality difference offered by 503B outsourcing facilities and insights into the impact of USP 800 on veterinarians.

Great to talk with you again, Phil. When we last spoke, you cited some studies on the differences in potency for oncology medications from various 503A compounding pharmacies. Do you have new findings to share?

VCA Animal Hospitals actually undertook a study with Stokes Healthcare’s sponsorship. We used the literature published to date looking mainly at purity—purity and potency are somewhat used interchangeably, and potency is often used in literature, but purity is more accurate because it speaks to the precision of the dose delivered compared with what you requested.

We conducted this study for both chlorambucil and cyclophosphamide, and we looked at a large number of compounding pharmacies. With our first drug order (Time A), we analyzed:

– Whether there were differences between pill A and pill B within each shipment, and we did that for each pharmacy.

– How closely they hit the mark on the dose delivered.

We then asked the same questions at a later point (Time B) and repeated the study with separate orders, so we knew we’d likely be getting pills from a different batch for each compounder. We looked at:

– Differences within the shipment from each pharmacy—was pill A different from pill B in the same order?

– How different the pills were from Time A to Time B since the compounders were likely sending us pills from different batches.

And, for the second round of the study, there was now a 503B manufacturer to assess, which was Epicur. There are four 503B outsourcing facilities in veterinary medicine, but Epicur is the only one that produces cytotoxic chemotherapy medications. So, we were able to add Epicur to the Time B assessment.

What were the results of your study? And why do they matter to veterinarians?

As we hypothesized:

  1. Remarkable variety existed in the dose delivered across the different 503A compounders—sometimes we were getting 60% of what we ordered, and sometimes we were getting one and a half of what we ordered.
  2. There was sometimes a 30-40% difference between the pills in the exact same shipment, so there were significant dosing imperfections within the same batch, which is highly problematic.
  3. The 503B showed significant improvement versus the 503As in the delivered dose, and the batch issue was minimal because of all the FDA regulations 503Bs have to meet.

These issues are incredibly important in veterinary medicine in general but probably even more so for oncology because the window of dose that is appropriate is quite small. For many of these drugs, if you give 10-15% less than what you asked for, you’re significantly underdosing that patient, and the cancer cells will develop resistance. If what you give is 15-20% too high, then you’re causing remarkable toxicity or side effects.

Your study focused on chemotherapy drugs, but have you found that problems with purity exist with other compounded veterinary medications?

I presented on this topic at the American College of Veterinary Internal Medicine’s 2021 virtual forum on June 10th. I shared the literature on cytotoxic chemotherapy drugs and on products outside of oncology, including Levetiracetam, an anti-seizure medication, and an equine dewormer.

One example that was particularly memorable was that a couple of 503A compounders developed medication chews, and that study showed that none of the chews had any drug of any significance, so you’re essentially not giving your patient any drug at all. Data suggests these problems are far-ranging, which makes sense. If 503A compounding pharmacies have problems making oncology drugs, they likely have problems with drugs in all other areas as well.    

Epicur recently started packaging its chemotherapy tablets in blister packs. What are your thoughts on that change?

Veterinarians often don’t know how many different drugs they frequently use—that have nothing to do with chemotherapy—that are labeled hazardous by OSHA/NIOSH/USP 800 because they pose genetic risks. USP 800, the statute from United States Pharmacopeia (USP) on how to protect employees from hazardous drugs, will change how veterinarians think about how they deliver these drugs to their clients.

The beauty of blister packs is that they:

  • Protect employees and prevent the drug from aerosolizing.
  • Enable precise dosing without having to open a large container of the hazardous drug.
  • Allow direct delivery to the client—and you can feel better about the client giving the right drug, at the right dose, at the right time.

Do you see USP 800 impacting veterinary medicine in any other ways?

It’s likely that the government will eventually dictate beyond-use dates, which are basically expiration dates for compounded drugs. Data shows that 503B-manufactured medications will have remarkably longer expiration dates than 503A compounded drugs, and that gets incredibly important when you go to pick your supplier, especially with hospital-use medications and sending drugs home. Most of the data out there for 503A compounders suggests that stability isn’t there for extended expiration dates, and they’re not forced to do those stability tests, whereas 503Bs are.

Have you seen any changes in the veterinarians who are treating oncology patients since we last spoke?

With USP 800 being talked about a lot, more primary care veterinarians are doing less cytotoxic chemotherapy. That being said, there are new medications pointed squarely at primary care doctors including Stelfonta, an intralesional medication that’s injected into the tumor itself, and Laverdia, an oral tablet that’s taken twice a week for lymphoma. Overall, though, a lot of veterinarians want to avoid the risks and costs of conforming to USP 800, so every oncologist I know is backed up by 4-6 weeks in their appointment schedule.

The major pharmaceutical companies, like Zoetis and others, offer specific therapeutic drugs for vet cancer. Where do 503B outsourcing facilities like Epicur fit into this?

On the human side, we’ve seen that tyrosine kinase inhibitors, like Zoetis’ Palladia (toceranib), are not easy to compound. Some 503A compounding pharmacies are offering toceranib, but are you really getting the dose you need, and is it stable for as long as you think it is?

Where 503Bs like Epicur come in is if you have a patient that needs a dose of a drug that can’t be met by the name-brand drug or a generic that’s out there. For example, cyclophosphamide only comes in 25 mg and 50 mg tablets, and chlorambucil comes only as a 2 mg tablet, and invariably the dose we need for our patients is different from those. So, Epicur, or any other manufacturer, can come in and give you either a patient-specific dose or, more likely, they produce tiers of different doses, and you can select the right dose for your patients. The trick then is knowing the difference between a 503A compounding pharmacy and a 503B outsourcing facility and realizing that the dose you’re getting from a 503A is highly likely less reliable than what you’d get from a 503B like Epicur. Another consideration is that when you order from Stokes Pharmacy, Epicur’s 503A sister company, if there is a 503B equivalent being produced at Epicur, that’s what you’re going to get.

Thank you for sharing your insights, Phil!

Want more resources on 503B medications and prescribing guidance? Check out our free downloads:

You can also review the basics on 503B manufacturers and the important role they play in our video:

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