Currently, while FDA approves the ingredients used in medicines, responsibility for regulating their use by compounding pharmacies largely rests with state boards of pharmacy. [© sil - Fotolia.com]
Compounding pharmacies are bracing for new regulation following the lethal fungal meningitis outbreak that authorities have attributed to contaminated steroid injections distributed by a Massachusetts manufacturer of custom medications.
As of Oct. 22, according to CDC, the outbreak resulted in 23 deaths of patients in seven states, among 285 fungal meningitis cases reported to authorities in 16 states. CDC and state health departments have estimated that about 4,000 patients may have received injections from three lots of methylprednisolone implicated in the cases, with some 97% of patients contacted for further follow-up. The deaths and illnesses have been traced to a steroid used in treating back pain, known as preservative-free methylprednisolone acetate. The steroid in question was prepared at New England Compounding Center (Framingham, MA), a large-scale compounding pharmacy that shipped more than 17,500 vials of the medicine to 23 states.
NECC has ceased operations and recalled all of its products, while criminal investigators from FDA and Massachusetts state authorities investigate the company’s actions for possible wrongdoing.
“NECC is alleged to have been operating outside of the law and we are eager to learn from the investigation exactly what occurred there. Most important, whatever results from this situation must not disrupt legitimate patient care,” David Miller, executive vp & CEO of the International Academy of Compounding Pharmacists (IACP), said in a statement to GEN. IACP represents more than 2,700 pharmacists and other professionals engaged in pharmacy compounding—the making of custom versions of approved medications produced by pharmacists specializing in the practice.
‘Ready to Work with Congress’
“If additional regulation or legislation could prevent another situation like the one we are dealing with now, then we stand ready to work with Congress and state legislators to make that happen,” Miller said.
That’s a change from a decade ago, when IACP led the way in rolling back regulations that compounding pharmacies feared would curb their industry, especially smaller pharmacies that account for most compounding acvitity. But with the death toll rising in the meningitis outbreak, nobody wants to appear on the side of the NECCs of the world.
Massachusetts has begun requiring all of the state’s compounders to sign an affidavit swearing that they follow state regulations, and that they do not mass-produce medications as NECC did. On the federal level, Reps. Rosa DeLauro (D-CT) and Edward Markey (D-MA) earlier this month promised they would introduce bills in Congress to bring drugs from compounding pharmacies under the regulatory eye of FDA. The members of Congress said their legislation aims to clear up the long-lasting legal limbo surrounding compounded drugs: While FDA approves the ingredients used in medicines, responsibility for regulating their use by compounding pharmacies largely rests with state boards of pharmacy.
All acknowledge the need to maintain a compounding practice designed to meet the needs of individual patients. They can range from children who want a sweeter flavor for the pill they don’t want to take, or need a junior-sized dosage of an adult medicine; to adults who need alternatives to a commercially-available drug to which they have an allergy, or who need a drug that manufacturers have stopped making.
But as more drugs have succumbed to manufacturing shortages, more doctors have scrambled to find alternative sources through compounders, helping add to the number of compounding pharmacies. According to IACP, more than half the nation’s roughly 56,000 community-based pharmacies provide some basic compounding services to local patients and physicians; while 7,500 U.S. pharmacies specialize in advanced compounding services, of which approximately 3,000 provide sterile compounding.
What An Elephant Likes
Another source of growth for compounded drugs has been the veterinary medicine market: “Animals come in all different sizes, so it’s very hard for a manufacturer to address every size animal often and to accommodate every flavor needs. For example, what a snake likes is going to be very different than what an elephant likes,” Joe Cabaleiro, a registered pharmacist and executive director of the Pharmacy Compounding Accreditation Board, told GEN. PCAB promotes, develops, and maintains standards for practicing pharmacy compounding, assists compounding pharmacies seeking accreditation, and aims to raise public awareness of quality pharmacy-compounding practices.
Starting in 1992 with a compliance policy guidance, FDA signaled willingness to end the legal limbo and address regulation of compounded drugs on its terms. Five years later, President Bill Clinton enacted the Food and Drug Administration Modernization Act of 1997, which required the agency to ensure compounded drugs met standards for production and labeling, and banned compounding pharmacies from advertising their products.
Industry opposed the law, however, and seven compounding pharmacies successfully persuaded the U.S. Courts for the 9th Judicial Circuit to strike down the advertising ban as infringing their First Amendment rights of commercial speech—a ruling upheld by the U.S. Supreme Court in Thompson v. Western States Medical Center (2002). The following year, the Senate Committee on Health, Education, Labor, and Pensions (HELP) held a hearing on what the federal and state roles should be in drug compounding, but no legislative solution emerged, and the issue has remained in limbo until now.
“The law is very unclear as to what constitutes a pharmacy, and where a pharmacy crosses a line into compounding. So that’s one of the things that needs to be really clarified,” PCAB’s Cabaleiro acknowledged.
Staking Out Ground
FDA sought to stake out ground for regulating compounding about a decade ago. In his Oct. 23, 2003, testimony before Senate HELP, the then-head of FDA’s Center for Drug Evaluation and Research, Steven K. Galston, M.D., outlined four areas where tighter federal regulation was appropriate:
- Removing from the market compounded drugs made from ingredients FDA deemed to be unsafe.
- Addressing the quality of bulk drug substances used in compounding.
- Investigating allegations of poor-quality compounded drugs, in conjunction with the states whenever possible.
- Determining when a pharmacy crosses the line from “appropriate” pharmacy compounding and larger-scale manufacturing warranting more regulation.
Those are good areas to start increasing FDA’s scrutiny, though the agency shouldn’t necessarily always act along with states given the patchwork of rules each state maintains. FDA should hold clear authority over the states in enforcement of compounding standards, though it could deputize states to act on its behalf in overseeing of smaller pharmacies based on volume or other measures.
“There should be some very clear national quality criteria that pharmacies have to meet. They should be standardized and national,” Cabaleiro said.
Sounds good, though PCAB envisions every state board of pharmacy switching to a singular set of rules based on the nonprofit U.S. Pharmacopeial Convention, whose standards for identity, strength, quality, and purity of medicines FDA already has power to enforce. Yet state boards have not always articulated uniform standards on other issues, and it remains to be seen whether they would respond with urgency to a single national standard envisioned by Cabaleiro, or whether the boards will go their own ways once the meningitis outbreak fades from the headlines.
“The Food and Drug Administration has more regulatory authority over a drug factory in China than over a compounding pharmacy in Massachusetts,” declares Kevin Outterson, an associate professor who teaches corporate law and health law at Boston University’s School of Law and School of Public Health, on his blog The Incidental Economist. The rising toll in meningitis deaths and sick cases should finally change that, and soon.