CLEAN ROOM Facilities that manufacture sterile injectable drugs must now adhere to the same inspections and oversight that large pharmaceutical manufacturers are subject to.

photo courtesy of Fagron Sterile Services

In the old days of prescription drug compounding, oversight for every compounder was in the hands of the state Board of Pharmacy of wherever that compounder happened to be located. Which is to say, there were 50 regulatory bodies, 50 sets of rules, and, practically speaking, there was little or no oversight.

When a compounder sought accreditation, it could expect an onsite visit that might end up lasting 4 to 6 hours. Of course, that wasn't nearly enough time to ensure compliance with the many intricacies of sterile compounding. In short, the industry as a whole didn't seem to understand that it was playing with fire.

Then came the New England Compounding Center (NECC) meningitis outbreak of 2012. As the almost inevitable culmination of what turned out to be years of reckless criminal conduct by the compounder in question, the outbreak took the lives of 64 patients, sickened hundreds more and cast a bright light on the intrinsic weaknesses of the system.

Ultimately, it also brought a new sheriff to town. In 2013, President Obama signed the Drug Quality and Security Act (DQSA). The DQSA lets compounding pharmacies voluntarily register with the FDA as 503B human drug compounding facilities. Those that do are subject to FDA inspection and current Good Manufacturing Practices (cGMP), meaning they're subject to the same inspections and oversight that large pharmaceutical manufacturers must adhere to. Believe me, it's a high bar. For example, an FDA inspection may take 8 to 10 days, not just a few hours. And all requirements are much, much stricter.

A happy ending to a tragic tale? Well, yes and no. As a result of the new approach, we're in a much safer place than we were before. But there are still some tricky areas to navigate. You can't just wave a wand and turn an entire system around overnight.

New world order
After the NECC disaster, a lot of frightened surgical facilities cut off compounders entirely. From epidural pain injections to eye dilation cocktails, the products and services compounders provide can be crucial, especially when there are drug shortages. Despite the stigma, there are safe alternatives. We're not completely out of the woods yet, and the new system isn't perfect, but the new regulations have dramatically increased safety. Knowing how the system works is the first big step toward being able to feel confident again.

SAFE SOURCES Oversight has improved dramatically, and the products and services compounders provide can be crucial, especially when there are drug shortages.

The 503B designation created by the new law is an addition to the 503A designation that all compounders had previously. The difference is that only 503B facilities can prepare sterile compounds without a patient prescription and ship via interstate commerce. 503A facilities must have individual patient prescriptions and they're limited on their ability to prepare sterile compounds for "office use" (when a physician orders specific medications for specific patients, as opposed to a pharmacist dispensing medications without instructions from a prescriber). While there are thousands of 503A compounders, there are fewer than 60 503B facilities nationwide.

But the fact that a compounder calls itself a 503B facility can be misleading. That's because after a compounder completes an application to be registered as a 503B facility, it takes time for the FDA to complete its first onsite inspection. In the meantime, that compounder can continue to make product and refer to itself as a 503B facility. But the distinction between having applied and having been inspected by the FDA is extremely important.

Once the elaborate onsite inspection is complete, the agency issues a letter outlining deficiencies. It's then up to the compounder to demonstrate that it has addressed and is correcting those concerns. How a compounder corrects deficiencies is important, and the compounder should provide a detailed plan as to how it will do so.

Fortunately, the process is transparent. The FDA website (osmag.net/rDE9Nx) includes a running list of compounders who've registered with the FDA as 503B outsourcing facilities. The list also shows whether the compounder has been inspected, whether the FDA has issued an observation letter (FDA FORM-483) or a warning letter, and, in some cases, the compounder's response.

I sometimes get calls from clients who want to know about a compounder they just met at a conference, one that's offering some really good deals. It's important to remember, though, that compounders can say they're 503B facilities because they've registered with the FDA, but that doesn't mean they've been inspected. Unless they've been inspected, I don't recommend them. The bottom line is patient safety, and I simply can't recommend a facility that hasn't been inspected.

For compounders, it's an expensive and time-consuming process to implement the technology and manufacturing systems they have to have in place. One result is that compounded drugs are going to end up costing more, but compounders are going to deliver better product, and the flaws that led to the catastrophes of the past are gradually being eliminated.

Incidentally, FDA inspections — unlike other kinds of facility accreditations you may be familiar with — are crystal clear, black and white, yes or no, correct or not correct. When it comes to safe practice in compounding, there are no gray areas.

Get to know your compounder
Why use a compounder? The government's increased emphasis on safety and quality will boost prices, but it's still a very competitive industry. And if you've decided to shun compounders altogether, you're likely paying more than you need to for certain medications. For example, a product that's packaged in single-dose containers may cost $40 for a 20 ml vial. But if you're only using 2 or 3 mls and then throwing the rest out, you're wasting money. FDA-registered outsourcers have been able to repackage products into 5 ml vials and sell them at reduced prices. If you do a thousand injections a year, and pay $15 a vial instead of $40, you save your facility $25,000 a year. I see it happening a lot as facilities continually look for ways to save money.

What about 503A compounders, the companies that aren't looking to manufacture sterile injectables? They may be fine for non-sterile compounding, limited use or "one off" sterile compounds for a specific patient or doctor. But I still recommend reaching out and having a discussion with any compounder you're thinking about using. How professional and responsive are they? How organized are they? How quickly can they answer questions?

I occasionally get calls from the sales teams of both 503A and 503B facilities. When I do, I always ask to speak to a pharmacist. If the response is vague, I get suspicious. "Oh no, I can help you," the salesperson sometimes says, refusing to transfer me to a pharmacist. When that happens, I won't recommend that facility to my clients.

The fact is, any licensed pharmacy can buy an IV hood and start to mix medications. And somebody will always be trying to get around the system. If they get caught, they'll be in trouble. But the unwary facility that does business with a pharmacy like that may end up in trouble, as well.

The information you need to be able to make smart decisions is readily available — and your consultant pharmacist should always be included in the decisions to use an outsourcing facility. Knowing how to navigate the new world of compounding regulations is what will lead you down the path that's best for patient safety. OSM