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4 Questions to Ask About Prefilled Syringes
Here's what a compounding pharmacy consultant would want to know.
Christopher Smalley
Publish Date: June 8, 2018   |  Tags:   Financial Management
Scott LaBorwit, MD
INQUIRING MINDS What should you ask your compounding pharmacy about the prefilled syringes it produces?.

Before I would ever purchase prefilled syringes from a compounding pharmacy, I'd first ask the pharmacist a long list of questions. Aseptic filling or terminal sterilization? Have you done stability studies? Are you compliant with USP <797>? Are you a registered 503B facility?

The answers I received to these and a few other queries would determine which pharmacy got my business — and which I'd avoid like an outbreak of fungal meningitis.

Not that I'm in the market for prefilled syringes these days. You see, I was a sterile compounding pharmacist for more than 20 years in military hospitals. After retiring from the military, I worked for companies like Sanofi, Wyeth and Merck, where I saw firsthand the standards to which manufacturers are held. Now I'm a compounding pharmacy consultant, working with pharmacists to design, build and operate compliant compounding facilities. Yeah, you might say I've seen the compounding pharmacy industry from every side. But if I were in your shoes, here's what I'd ask a compounding pharmacy.

1. Aseptic filling or terminal sterilization?

You'll likely get this response: "Oh, we don't autoclave our syringes. We aseptically fill." I would be willing to pay more for terminal sterilization. The added assurance that all microbes are absent is worth a lot to me. Plus, the aseptic filling of injectable drugs is challenging.

I'd follow up with: "What kind of testing do you do to ensure that your operators have the skill to properly aseptically fill?" You'll want to hear that they test the gowning (and gloving) of their operators weekly and every several months perform a media fill with tryptic soy broth to be sure everyone's qualified. By the way, the New England Compounding Center (NECC), the compounding pharmacy that became the center of a scandal resulting from a meningitis outbreak, was aseptic vial filling the methylprednisolone for injection that was contaminated with fungi. Had NECC autoclaved their syringes, they would have destroyed the fungus.

An ordinary autoclave can't sterilize filled syringes, but a properly operated air overpressure autoclave most certainly can. The trouble with an ordinary autoclave is that when you evacuate the steam, you replace it with compressed air to keep the plunger from moving. Air over pressure is very difficult to control. For prefilled syringes, you need to know how quickly the solution is cooling and reduce the air pressure at the same rate so that the plunger is not moving in or out. Think of it this way: If the solution inside the syringe barrel is boiling, there's no place for the pressure to go unless it pushes its plunger out.

A pharmaceutical autoclave is also known as an overpressure sterilizer. Overpressure sterilization is a precisely controlled process ideal for terminal sterilization of soft packaged items, especially sealed liquids. I'd say only about 10% of compounding pharmacies have one.

2. Have you done stability studies?

In essence, you're asking how confident the pharmacy is in the expiration date of its products. A drug can't pass below 90% of its potency before its expiration date. When you do stability studies, you have to make sure nothing untoward or unexpected shows up in drugs. Some degraded drugs can be up to 90% potent, but can be toxic or harmful. The answer you're looking for: "We've done the stability study and we know what the extractable profile is and what the degradation profile is so that we can be confident in the expiration date we're putting on the product."

3. Are you compliant with USP <797>?

USP <797> helps to ensure patients receive quality preparations that are free from contaminants and are consistent in intended identity, strength and potency. It describes a number of requirements, including responsibilities of compounding personnel, training, environmental monitoring, storage and testing of finished preparations. You want to hear things like, "Yes, I have my equipment in a separate room. Instead of using laminar flow hoods, we use a barrier isolator. Our operators are well trained. We remove all cardboard packaging."

4. Are you a registered 503B facility?

503B? Was that prefilled syringe compounded at an FDA-registered outsourcing facility?

There are 2 types of compounding pharmacies: 503A and 503B. 503As are the classic practice of pharmacy where a doc writes a prescription for a patient and the pharmacist compounds to that prescription. One patient, one compound. I've worked in hospitals where if you faxed a script to a 503A compounder by 3 p.m., you'd have the drug by 5 p.m.

503Bs, on the other hand, must register with the FDA as an outsourcing facility — only 64 in the United States have done so (osmag.net/kxNX8Q). 503Bs are more like pharmaceutical manufacturers. They don't need a prescription. They'll manufacture 10,000 vials of propofol in anticipation of their surgical customers wanting to stock their shelves with a month's worth of syringes. You want a 503B pharmacy.

A quick word on price. First, expect to pay $9 to $12 or higher per syringe, depending on the drug and the quantity you buy. Second, you never want the conversation about cost to infer that you want your pharmacy to cut corners so that it can give you a better price. For example, you'll promise them the contract if they'll drop their price by 15%. Sure, that might work, but maybe the pharmacy stops terminal sterilization and simply aseptically fills.

We've come a long way

When Outpatient Surgery asked me to help you buy prefilled syringes with confidence, I was more than happy to share my expertise. I was also struck by what was acceptable a few decades ago that today would get you run out of the profession.

For example, in the 1970s and 80s at the military hospital, we'd draw up specific doses in Tubex syringes under laminar flow hoods. Tubex are no longer available and compounding under a laminar flow hood is no longer acceptable.

We'd also fill plastic disposable syringes with keflin 1g and then freeze them until they were needed for a bolus before surgery. When we got the call, we'd send a frozen syringe up to the nurses station. A nurse would microwave the syringe to thaw the antibiotic. We didn't know what we didn't know about a drug's stability profile — that freezing a drug could change its molecular structure and turn a solution into a suspension or a slurry. We didn't know that defrosting a syringe of keflin in the microwave would accelerate the release of unintended compounds from the plastic. And we thought it was OK to use disposable syringes as storage devices. If only I knew then what I know now. OSM