How new compounding, track-and-trace law may affect pharmacists; FDA issues pharmacy compounding draft guidance

Hub on Policy and Advocacy

How new compounding, track-and-trace law may affect pharmacists

President Barack Obama signed the Drug Quality and Security Act (H.R. 3204) into law on November 27. What are the practical implications for most pharmacists of the new compounding and track-and-trace legislation?

The short answer is that the compounding part of the legislation, which became effective upon enactment, may affect more pharmacists than initially anticipated (see page 56 for more information). The track-and-trace part of the legislation will affect all pharmacists to some extent, according to Michael Ghobrial, PharmD, JD, APhA Associate Director of Health Policy.

Of course, the language in the legislation is not the last word. FDA has to decide how to implement it through the regulatory process. Traditional community pharmacies are “probably” not going to be affected by the compounding part of the law “unless we get more stringent regulation from the FDA,” said Lee Rosebush, PharmD, JD, MBA, MS, Counsel at the BakerHostetler law firm in Washington, DC. “While we got by with 3204, we may not necessarily get by with the regulations proposed by FDA.” 

Compounding: Practical impact

Under the new law, traditional pharmacies are still regulated by state boards of pharmacy. Compounding pharmacies are still regulated by state boards of pharmacy, Ghobrial said. But now compounding pharmacies that voluntarily elect to be “outsourcing facilities” are regulated by both state boards of pharmacy and FDA. 

“Here’s the big question everybody’s going to be asking: If [registration with FDA] is voluntary, why would you want to have the FDA breathing down your neck? And the answer to that is brilliant,” Ghobrial said. “People will sign up because their product is less likely to be sold if they’re not an FDA-overseen outsourcing facility.” 

Traditional pharmacies that do sterile compounding based on specific, individualized prescriptions have no reason to register with FDA, emphasized Rosebush. Pharmacies that are going to supply office use medication, however, have to do the registration. “You’re going to see a business model determination,” Rosebush said. “You’re going to see entities say, ‘Well, is the $15,000 user fee and the cGMP [current Good Manufacturing Practices] compliance worth moving into this new business model?” 

Rosebush has “several clients who are large compounding pharmacies,” he said. “I do have some that are willing to register with the FDA and are currently pursuing compliance policies that use cGMPs and USP [U.S. Pharmacopeia] <797> standards. We eagerly await the publication of regulations in this area.” He added, “Some of my clients do not feel that they will have to register with the FDA and are not planning on registering with the FDA.”

Many in the industry don’t think that cGMPs (which are aimed at manufacturers) will be applied across the board to compounding pharmacies, according to Rosebush. “They can’t do it. It’s impossible,” he said. “I think you’ll see some new cGMPs put forth for compounding pharmacies, and I think those cGMPs will adopt certain aspects of <797>.”

Track and trace: Practical impact

“Track and trace affects all pharmacists, but it’s really not that difficult,” Ghobrial said. As of January 1, 2015, the manufacturers and the wholesale distributors “can’t ship anything out unless it has a transaction history” in the form of paper documentation for each individual unit of a drug; if there’s a hiccup or if, say, the paperwork gets lost somehow, pharmacies can still accept the product until July 1, 2015. Starting on that date, following the 6-month grace period, pharmacists have to reject products without an accompanying transaction history. 

When pharmacists get the product in from the distributor, they need to take the transaction history paperwork, put it in a drawer, and keep it for 6 years. 

Along the same lines, one pharmacy can transfer a drug to another pharmacy to fulfill a specific patient need without needing an accompanying transaction history—but if a pharmacy just wants to lessen their inventory because there’s too much money on their shelves, as of July 1, 2015, the drugs need to be sent back to the distributor with a transaction history. “Say they do want to lighten their inventory a year later,” Ghobrial said. “They go back into their drawer, pull out the transaction history, maybe write a line item saying it was at my pharmacy on such-and-such a date, and they can ship it. So it’s not like they have to do all this investigation and research. All the information should be in their drawer.”

As of the bill being signed, the pharmacist is required to investigate a product that he or she finds to be suspicious, quarantine it, dispose of it, and give appropriate notice to FDA. But FDA has 7 years to implement regulations for exactly what pharmacists should do in a rigorous investigation process, Ghobrial continued. “After you do all the transaction history, have all the documents where you transfer ownership, make sure that you receive the drug with the proper documentation, store the documentation away for 6 years—[the next step] is to investigate” suspicious drugs (drugs that are counterfeit, tampered, or adultered). 

“My read is that the duty begins when” pharmacists see a suspicious product, Ghobrial said. “The duty’s not to find it. The duty is to set it aside once they do find it, and contact the FDA.”

Also through FDA rulemaking, in 10 years, track and trace will be implemented electronically with technology that is not specified in the law—but which could be bar codes and/or RFID (radio-frequency identification), for example. “You have to assume that not all pharmacies have a scanner and the software and the hardware to visualize what would be in the bar code,” Ghobrial said. “In 10 years, I think that’s what they’d want to do.” 

The intent of Congress was that the track-and-trace legislation will curb counterfeit drugs entering the supply chain, Ghobrial said. The new law will not “stop all diversion,” Rosebush said. But “it’s a good step moving forward.”

FDA issues pharmacy compounding draft guidance

Hot on the heels of the Drug Quality and Security Act (H.R. 3204) being signed into law, FDA issued three draft industry guidances reflecting the agency’s current thinking on the compounding part of the new compounding and track-and-trace legislation before implementation begins. 

According to APhA’s analysis of the draft guidance of particular interest to most pharmacists, “Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act,” more pharmacists than initially anticipated may be affected if FDA’s thinking informs its future regulations.

“When we think of compounders, we think of brick-and-mortar pharmacies mixing lotions,” said Michael H Ghobrial, PharmD, JD, APhA Associate Director of Health Policy. “FDA has said their enforcement regarding traditional compounding in these settings is going to be very similar to what was in place before the passage of H.R. 3204. This guidance could have a significant effect on compounders of sterile products, especially if the guidance is translated into regulations in the future.”

The current guidance does provide some clarity to compounders, according to Jillanne Schulte, JD, APhA Director of Regulatory Affairs. “Guidance is advice,” but does not have the force of law, she emphasized. “It’s a safe harbor. If you’re complying with the guidance, it’s unlikely that you’re going to be in any enforcement danger.” Will future compounding regulations substantially mirror this guidance? “I think [FDA] thought they were offering some clarity,” said Schulte. APhA will comment on this draft guidance and may comment on the other two draft guidances that cover compounding pharmacies that voluntarily register with FDA as outsourcing facilities. Comments on the draft guidances are due February 3, 2014. 

Sterile compounding

The draft guidance suggests that compounding under section 503A of the Food, Drug, and Cosmetic Act be done in accordance with U.S. Pharmacopeia (USP) chapters <795> and <797>. Compliance with USP <795> for nonsterile compounding would not pose a significant cost or implementation burden to pharmacies. Compliance with USP <797> for sterile compounding, however, could generate implementation costs for some pharmacies, according to APhA. 

“A lot of traditional pharmacy compounding is not sterile. But if they are compounding sterile products and they cannot comply with <797>, then [if the draft guidance becomes law,] they would have to get themselves up to standard,” according to Schulte.  

Should the draft guidance become law, any potential new expenses for sterile compounders would fall into the categories of facility design; environmental testing; personnel training and competency testing; and maintaining sterility, purity, and stability of dispensed and distributed compounding sterile products. That last item, which would put the duty on the compounder to ensure that the product remains in accordance with all the <797> requirements until it gets to the patient, sets up sterile compounders for “potential liability,” Ghobrial said. 

More potential changes

Compounding pharmacies located in states that do not have a memorandum of understanding (MOU) in place between FDA and their state could not ship more than 5% of their prescription volume of compounded products outside of the state. This limitation, known as the 5% rule, would not go into effect until 90 days after FDA finalizes a new MOU through rulemaking with comments from stakeholders. FDA has not yet begun this process. An MOU can be thought of as a short contract or an agreement that compounders will comply with certain rules when they’re distributing compounded drugs, Schulte said. MOUs would vary from state to state.

One pharmacist who would feel an impact is Cheri Garvin, BSPharm, owner and CEO of Leesburg Pharmacy and the Compounding Center in Leesburg, VA—the only accredited compounding pharmacy in the Washington, DC, metro region. “One of my concerns as a practitioner is that I do not know how my state will respond to the request for the MOU. Because I am in a border town very close to Maryland and very close to DC, if this MOU were not in place, I would be limited to dispensing less than 5% of my prescriptions across state lines,” Garvin said. “That would really affect us.”

The draft guidance also indicates that FDA will regulate the bulk substances drug list but will not enforce that list until the regulations are finalized.  FDA is seeking nominations for the Pharmacy Compounding Advisory Committee, which will oversee some of the rulemaking. “Another thing we’re waiting on with this guidance is additional information regarding ‘office-use’ and also repackaging and how it’s going to be treated under the law,” said Schulte. That information is being drafted by FDA.