Pharmacy and compounding are intertwined, like strands of yarn woven into a scarf. Compounding medications from liquid suspensions to sterile injectable products is a necessary element of patient care in health systems across the country.
In the wake of the fungal meningitis outbreak caused by contaminated products from the New England Compounding Center (NECC), compounding has landed at the center of a critical situation that is shaking health care to its core, raising complex questions and concerns about regulation, safety, and drug shortages.
“This is a tragedy like no other that [we] have faced,” said Carmen Catizone, MS, BSPharm, DPh, Executive Director of National Association of Boards of Pharmacy (NABP), in a well-attended breaking news session at the American Society of Health-System Pharmacists (ASHP) 2012 Midyear Clinical Meeting in Las Vegas. This issue has totally consumed the industry, Catizone told attendees, and it has the potential to change pharmacy regulation in ways that no one has anticipated.
Catizone said he believes that there was no one single cause for this tragic event. “The regulatory system broke down, the pharmacy compounding system broke down, [and] the collaboration between FDA and the states broke down,” he explained, adding that the degree and type of responsibility will vary depending on each person’s role in the situation.
Although the future is not yet clear, change is on the way. “The pendulum is swinging and it’s going to swing away from state regulation and move [toward] federal regulation to an extent that we probably haven’t seen in the past,” said Catizone.
Progress toward a solution will include collaboration among multiple entities on state and federal levels. NABP recently announced a four-part action plan that supports state board of pharmacy efforts to enforce compounding regulations, including inspecting nonresident compounding pharmacies and developing a network of regulatory information on these pharmacies (see page 53 of January Pharmacy Today).
Along with pharmacy and compounding, drug shortages are a contributing factor woven into the fabric of the current situation. According to Catizone, the compounding controversy is one of the symptoms of how drug shortages have created significant problems in the distribution chain and for patients.
“A viable solution to the drug shortage situation was for pharmacies to compound medications,” said Catizone. He added, however, that it is only a viable solution “if you have competent pharmacists, competent regulatory system, competent oversight, [and] competent quality control.” In this situation with NECC, none of that existed, and “that is why we have a tragedy,” Catizone said.
Pharmacies compounding products as manufacturers are no longer a way to help combat drug shortages. “Drug shortages are still quite serious right now,” said Bona Benjamin, BSPharm, Director of Medication Use Quality Improvement at ASHP, in an interview with Today. There are currently more than 200 active drug shortages.
“While the rate of new shortages has decreased compared to last year during the same period, we still have leftover shortages that haven’t been resolved yet, so that’s a lot of shortages,” Benjamin said.
Medications in short supply span across multiple disease states, and many of these products are necessary for lifesaving therapies. The reasons behind shortages of particular agents vary. For example, sodium bicarbonate is a sterile injectable used in emergencies to help patients who have had a heart attack. We don’t have that drug, noted Benjamin, because there are only two manufacturers—and one isn’t producing it and the other can’t meet the demand of the whole country.
Another drug in short supply is propofol, which has been in shortage since 2010. According to Benjamin, FDA is facilitating importation of propoven, the German equivalent, “but Hurricane Sandy disrupted shipping, so now [this drug] is in very short demand, causing people to cancel elective surgeries.”
There are about 19 generic standard of care cancer drugs listed as being in short supply. The challenge is that several large generic firms have been affected by manufacturing problems at the same time, noted Benjamin. “The production lines that make the sterile generic injectable [were] compromised somewhere, and we have to figure out where it is and fix it,” she explained.
This can often be a difficult process because there are so many steps in the manufacturing pipeline. Once the problem is identified and resolved, “the manufacturer has to make the product and test it to [prove that] it is [safe],” explained Benjamin. This can be a time-consuming process, but FDA does help “firms get back up to production and facilitates regulatory paperwork, especially if it will help relieve a shortage,” she said.
The problems caused by drug shortages and the recent compounding tragedy are leaving hospital pharmacists and other health professionals feeling frustrated. This has been “brewing along, and over the years it’s been evolving, but it’s the worst it’s ever been right now and we are very sympathetic to what it must be like out in practice,” said Benjamin. “You need to acknowledge that it is a hard time not only for the patients, but the people trying to take care of them.”
For more information about current drug shortages, visit www.ashp.org/Drugshortages/Current/.
Regulatory oversight of compounding has traditionally fallen to each individual state to serve as the primary regulator of this practice. It all began in 1997 when Congress enacted the Food and Drug Administration Modernization Act to address FDA’s role in the regulation of pharmacy compounding.
In April 2002, the law was ruled invalid “because it contained unconstitutional restrictions on commercial free speech,” said Christopher J. Topoleski, Director of Federal Regulatory Affairs at the American Society of Health-System Pharmacists (ASHP), during a special breaking news session held at the organization’s 2012 Midyear Clinical Meeting in Las Vegas. FDA then issued guidance to compounders.
“The guidance states that FDA recognizes that pharmacists traditionally have compounded reasonable quantities of drugs upon receipt of a valid prescription for an individually identified patient,” said Topoleski. The guidance also states, however, that the agency may consider enforcement action when the scope and nature of a pharmacy’s activity “raise the kinds of concerns normally associated with a drug manufacturer and result in significant violations of the FD&C [Federal Food, Drug, & Cosmetic] Act,” said Topoleski.
The road ahead
FDA is currently examining regulatory gaps and looking at possible new enforcement measures such as an additional category of registration. The agency is “proposing that there be a risk-based evaluation of nontraditional compounding facilities to determine the extent to which the agency regulates these entities,” said Topoleski. “We believe this could mean frequency of inspections, or it could be a method to determine whether the entity is subject to good manufacturing practices.”
As this situation continues to evolve, one thing is certain: the process of developing and implementing regulatory changes will require system-wide communication and collaboration among entities on the state and federal levels.