You'd think the worst pharmaceutical disaster in decades would have scared compounding pharmacies straight, but FDA investigators and state boards of pharmacy continue to see rogue pharmacies mixing supposedly sterile drug products in unsanitary conditions. During recent facility inspections, investigators have observed pharmacies sterilizing glassware in toaster ovens and in dishwashers, straining liquids with coffee filters, and mixing drugs in rooms with dirt stains on the ceiling or with a flimsy plastic drape separating the sterile lab from the construction going on in the next room. These poor practices suggest to some that another New England Compounding Center (NECC) is a matter of when, not if.

"The things that the FDA has seen are quite shocking," says Jane Axelrad, who served as the FDA's lead on enacting pharmacy compounding legislative provisions following the deadly 2012 fungal meningitis outbreak at NECC. "Since NECC, you would think that compounders would have cleaned up their acts, but in many places, that's not the case. Many rogue compounders are still out there trying to skate under the radar. Why? Because they make a lot of money doing it. Or they think they'll never get caught."

The shocking NECC story has been told many times. A mom-and-pop pharmacy in a Massachusetts strip mall shipped 17,600 mold-tainted vials of injectable methylprednisolone acetate, a steroid commonly used to treat spine and joint pain, to ambulatory surgical centers and hospitals in 23 states. You know the rest: 76 patients died of meningitis and hundreds more fell seriously ill.

Enough of a wakeup call?

The FDA and state boards of pharmacy have significantly increased their regulatory oversight of compounding facilities in the wake of NECC. In 2012, the FDA inspected 4 compounders. Since 2013, the FDA has inspected more than 400 pharmacies, says Ms. Axelrad. But it's fair to question whether NECC was enough of a wakeup call for the industry.

"Have things gotten better since NECC?" asks Ms. Axelrad. "Absolutely not."

While increased scrutiny has shuttered some rogue pharmacies — "not enough, but some," says Ms. Axelrad — who didn't want to pay to bring their facilities up to standards, it's still relatively easy for a compounder to locate in a state with lax governance and ship products produced in unsanitary conditions to unsuspecting surgical facilities all over the country, says Ms. Axelrad.

State boards of pharmacy — or in some cases state departments of health — have primary jurisdiction over 503A pharmacies. The FDA has designated 503A compounding pharmacies as those that compound according to patient-specific prescriptions and are required by state boards of pharmacy to comply with USP and other guidelines. They may not compound large batches. "Some states have gotten a lot tougher in their oversight of 503As, but a lot of states either haven't gotten tough or just don't have the resources to oversee them," says Ms. Axelrad. "Some rely on self-assessments by the compounders rather than going in and looking."

A compounding pharmacy in Irvine, Calif., received a scathing letter from the FDA in April detailing a long list of "serious deficiencies in its practices for producing sterile drug products," including producing some drugs without prescriptions for individually identified patients, using an expired sporicidal agent to disinfect its aseptic processing area and failing to demonstrate that its hoods were able to provide adequate protection of the cleanroom areas in which sterile products are processed. Investigators also noted that the underside of the aseptic processing work surface consisted of exposed plywood and fiber board that had significant discoloration and gaps around the edges of the plastic panel cleanroom walls that could allow unclassified air from the surrounding environment into the cleanroom. Testing results of the environmental samples FDA investigators collected from the facility identified microbial contamination in the aseptic processing areas, including spore-forming bacteria. The FDA said the pharmacy's products "may be produced in an environment that poses a significant contamination risk."

The federal Food, Drug and Cosmetic Act (FD&C Act) returned to oversight of a new category of high-volume sterile compounders, called 503B outsourcing facilities, to the FDA and gave state boards of pharmacy responsibility for traditional compounding pharmacies called 503As that produce patient-specific medications one prescription at a time. Since the NECC disaster, 73 high-volume compounders have registered as an outsourcing facility with the FDA under section 503B, which lets them distribute drugs without a patient-specific prescription.

"We need clear, strong, consistent federal standards that will be applied across the board to all 50 states," says FDA Commissioner Margaret Hamberg.

Among other things, 503B facilities are required to comply with current good manufacturing practice requirements, report adverse events to the FDA and label their products with certain information. The FDA notes that registration means only that the agency has received the information required to register the facility. It does not mean that the facility is making FDA-approved drugs or that it is in compliance with current good manufacturing practice requirements. However, if you buy drugs compounded at a registered outsourcing facility that has had a recent satisfactory FDA inspection, you'll have some assurance that the conditions at that facility met applicable current good manufacturing practice standards at the time of the inspection, says the agency.

"If you register as an outsourcing facility," says Ms. Axelrad, "you're publicly indicating that you're really stepping up your game and will meet higher standards. 503B provides a much better place for people to get safe compounded medications."

Compounding pharmacies operating under 503A of FD&C Act don't have to register with the FDA. The FDA would only inspect a 503A if it received a report of a problem. "There's no [federal] surveillance program," says Ms. Axelrad, who issues a couple notes of caution against 503As.

• Compounders might seek to hide out in the traditional compounding category in order to escape regulatory detection.
• There's lack of clarity over whether a state or the FDA has primary responsibility over a particular pharmacy.

The NECC catastrophe exposed a failure in drug safety, says Ms. Axelrad. Lax oversight essentially let NECC operate as manufacturer by shipping tens of thousands of vials of drugs.

"It was a wakeup call to everybody that they had to do more," says Ms. Axelrad.

Vetting your pharmacy

It should come as no surprise that Ms. Axelrad suggests you use a compounder from the FDA's list of registered outsourcing facilities. You should then review the more than 4,500 compounded products you'll find on the FDA's outsourcing product report database, a spreadsheet you can download at osmag.net/3WJYkm. Finally, she suggests you review the FDA's website, which lists inspections, recalls and warning letters. "Look for people who've been inspected, who weren't cited and are making the product you need," she says, adding you should ask to see the reports from an inspection by the FDA, the state or by an outside auditor. If a pharmacy you're considering has received a warning letter, ask to see the facility's response letter to the FDA's warning letter.

It would be good to visit the pharmacy yourself — "Call a few and ask if they'd be willing to let you inspect their facility," says Ms. Axelrad — but you could also hire an auditor who knows what to look for to examine the pharmacy for you.

Should you visit the pharmacy, Greg Rockers, RPh, who operated 2 503B compounding facilities before he cofounded the Williamson Rockers Group, a pharmacy consulting firm, says you'll get a sense of how long the leadership has been in place for and what their experience is.

"This is important because if you've been with the same company for years but its leadership has shifted, that means other aspects of the lab could've shifted, too, including its quality and its standards," says Mr. Rockers. After meeting with leadership, ask for a pharmacist to walk you through a day in the life of a batch. "Find a product they make and say, 'I'd like to see where you get the raw material, how you judge a raw material meets the standards you need, and how you make the product,'" says Mr. Rockers.

Then, ask to meet with the pharmacist responsible for checking the product for safety and have them walk you through that process. "What's their process to see if they've got an affected product?" says Mr. Rockers. Look for things like whether their air control and humidity pressure matches the needs of the product, and ask what their procedures are for drugs if the power goes out. If they don't have those protocols in place, it could indicate that they're not doing all they should be to make sure your drugs are safe.

This is also your opportunity to check for any obvious red flags firsthand. Pay close attention to whether the facility is clean, especially keeping an eye out for any dust bunnies, bugs and water damage, all of which can lead to contamination, says Mr. Rockers.

The letter included a shocking assessment of the pharmacy. "Your products may be produced in an environment that poses a significant contamination risk."

While he says most surgical facilities will stick with a pharmacy that's proven itself to be reliable, it's still a good idea to regularly check in with your compounder, says Mr. Rockers, who recommends doing so at least once a year. "A lot can change in a year," he says.

If your lab has registered with the FDA, but has yet to be inspected, take extra precautions. "I used to say that pharmacists could graduate on a Monday and work at a sterile compounding lab on a Tuesday," says Mr. Rockers. "Same thing goes with the FDA. Once you register with the FDA and pay your fee, you're registered as an outsourcing facility." But that doesn't mean that a new facility is getting inspected right away. Depending on the number of outsourcing facility registrants and other inspection priorities, the FDA expects to inspect newly registered outsourcing facilities within 2 months of initial registration.

One major one to look out for is whether your facility is sending you sterility and stability test results of the products being sent your way. "If not, that is a deal breaker," says Mr. Rockers. Before the product is shipped to you, you should always have its sterility and stability test results in your hand. If your lab isn't sending you those results? "I would walk away immediately," says Mr. Rockers.

You should also validate that your pharmacy has the proper licensure to ship to your facility, which varies by state, and check that every product it ships you has a number to contact the compounder on it. "This is an absolute requirement," says Mr. Rockers. Both of these factors could indicate to you whether your lab might be skirting the system. OSM