Podcast Transcript: Integrating Compounding Into Your Practice

[Dr. Jose Silva]
Jordan, you mentioned HCG and FSH. There's been notorious that some companies are not doing it. Aaron, what do you have to say about that?

[Aaron Schneider, Pharm D]
That's a big question. I don't want to bore people, but I'll give you the hopefully rough and dirty answer. I answer this question a lot. When this became a big buzz in March of 2020, I was answering this question almost every day and now that people have gotten more comfortable with what is the status of this product with compounding, it's less frequent, but it's important to explain what happened. This is information I've gathered through series of conversations with FDA consultants and ex-FDA policy manager, attorney, pharmacist, friends and family and industry members of the FDA, ex FDA officials.

What was described to me was in 2013, the Obama administration had instructed the FDA to come up with a plan to reduce the cost of insulin and not intentionally to create an impact of re-classifying HCG or any of these fertility medications. The FDA's position is not to impact the economy or the financial means of affording a medication. Their primary role is to protect the public, to make sure that facilities who are producing pharmaceuticals or even supplements are operating in a way that follows good manufacturing practices to make safe and effective products for the public, not to design a path for a way to manipulate the market to reduce the cost of a drug.

From 2013 to 2020, you had seven years and in that time span, I think we had three FDA Commissioners and so as time rolls on, you see change in control happen, and in '13 that Commissioner knew he was on the way out the door and he didn't care about that initiative and so it gets rolled over to the next person. Then rolls over to who I think at the time was either Gottlieb or whoever came before him, who finally put their stamp on the initiative that was instructed by the Obama administration. While in that process, they by way of the information I've gathered scrambled to put something together to satisfy this request and they thought of the idea of using the biologics registration that already existed for manufacturing facilities.

They just decided that they needed to reclassify insulin as a biologic. At the time insulin was insulin, it didn't really have a drug category. This was back in 2013 and insulin was insulin. You had insulin-like products and you had insulin. Those were two different categories. In order for them to create a path for insulin to be under the umbrella of biologics manufacturers that would hold a registration to do so or manufacture with a biologics registration, they reclassified insulin. They created a way to bridge insulin into that category and essentially defined it as a material that was of animal origin or human origin of a certain peptide chain based on its molecular structure.

That lose classification whether it was on purpose or an accident looped in all these other drugs with a similar qualification, and unfortunately, that included HCG, that included FSAs, so included gonadorelin, menotropins, other drug products, and they seemingly most of them fell into the fertility category. I have a hard time believing there wasn't some intent, maybe it was on purpose maybe it wasn't, but in any case, it impacted pharmacy compounding and the availability of this drug product. What's interesting about HCG is that at one time it was an over-the-counter holistic therapy.

Prior to '13, there was a few years where it actually had made it onto the shelf at retail stores as an oral holistic treatment option and then got pulled, because the FDA re-evaluated that and it became a pharmaceutical again sometime before 2013. Then all over sudden now, it's a biologic. Really the registration of a biologic is one that is to protect the individual that's producing that product, not necessarily the end user. That registration holds true to really more manufacturing purposes. Anyways, chasing a rabbit trail there, but the HCG product was reclassified as a biologic and because of that, it created some prohibitions on compounding with that material.

The reason that biologics are really prohibited or that classification prohibits certain types of compounding, is because they want to protect the people who are manipulating the product. They're not really focused on what happens to the end user, because once the end user is using it the expectation is that they're the ones that need it. This registration happens and in '19, the FDA delivers the message of this is going to happen in March of 2020. We got wind of this in '19 when everyone else did and we hopped on the phone, and we started making phone calls.

We reconnected with some FDA compliance consultants, FDA compliance attorneys to figure out what to make of this. What is the FDA's plan for enforcement? What is really their intent with this document? If you read the full memorandum that they released in '19 and then made it final in 2020, there is a process for compounding with biologics. The FDA defined that in 2018 even before that memorandum was released, which is included in the reference document of mixing, reconstitution, and diluting of biologics for the purpose of compounding. It's a reference document, you can pull down from the FDA's website.

We followed that document since we started compounding that product in 2018 and during that time we had been sourcing that product from FDA-registered manufacturers. It goes through an FDA-registered distributor. When ordering it, it goes through customs where an agent of the FDA receives that material. Whether it's contracted or carrier that is a partner with the FDA to review that documentation. It's stamped as a pharmaceutical. They know where it's going, they know it's final destination, they know who ordered it, if it's appropriately labeled. We work with these registered entities to source that product and have been since the beginning. I'm bouncing around a little bit here, but with the HCG being reclassified with the memorandum that allows for that biologics compounding, it also includes where there's a need to service the public if there's a back order. We all know that Pregnyl, and Novarel, and the current generic that's available is really not available.

In 2020 when this came to light, we recognized where we had a significant patient need, we were following all the necessary steps to continue to compound it and compounded pursuant to the FDA's recommendations. We reached out to our partners, our contacts to gather information to make sure that we were doing it in the best way fit to make sure the public is safe, that we're operating in a way that conforms to the FDA's reference documents. We have been through two FDA inspections and we have had no questions. We've produced all of that documentation. What's challenging, I think for a lot of urologists that come to us or have found us by way of knowing that we're still offering that product compounded when we can and the commercial available is not able to be dispensed, they're confused, because they've likely heard from another pharmacy that the FDA told them they couldn't or they give them some response that doesn't give context to what that memorandum said, what the FDA's reference guidance says and the proper way to source and produce a product like HCG.

I think that many pharmacies that were making it were probably making it in small volumes and they realized that product is very expensive. It's very likely the pharmacy stopped making it in some cases, because it was financially related. In some cases it was very difficult to source. There were limited sources that produced it in reference to the USP reference document for HCG as a material or an active pharmaceutical ingredient. USP is the reference document that manufacturers are supposed to produce product that is safe for let's say compounding or pharmaceutical manufacturing. Not very many manufacturers that are overseas follow that reference guidance or reference document to produce it in that way. There's a limited number of resources making it difficult to source. I think people just gave up on it and the few that I know were making it for a period, I think some of them are still, there are still others out there that are producing HCG.

The FDA visits facilities and they do a risk assessment based on what product they're producing and perhaps can they maintain the FDA's recommendations for how to produce a product or how to provide the supportive documentation for the ingredients they're using to compound with. If there's questions around whether or not the sources were capable of producing a safe and effective product or perhaps using an unregistered source for material or just not following the process that is defined in that guidance document brings a question. I can't speak for other facilities, but what I can say is we're doing everything possible to fall in line with what is safe and what is appropriate for the patient and follows the state and federal regulatory guidelines.

Sorry for the long and winded response there, but there's a lot of history there that I think people don't quite know. I think to give it at least an understanding of how that whole process started and knowing that at some point HCG was an over-the-counter, it is not an unsafe product. It's recognized as safe given it's status as a biologic, it's considered a hazardous material, which is the other area where it made it difficult for compounding pharmacies to produce. If you're going to categorize it as a hazardous material, there are some compounding regulations and requirements that require your facility to be set up to produce it in the first place. There are facilities that likely didn't want to make the investment for one product to accommodate that reclassification. You need a hazardous compounding area, which is a negative pressure room to accommodate that type of material for compounding. If you don't have that type of environment and really that environment is designed to protect the individual compounding with the material, if you don't have that type of environment, it then opens you up to state regulatory guidance.