Lack of FDA Oversight of Compounding Pharmacies
Custom-compounding pharmacies have not been closely regulated by FDA. There have been no requirements to test for efficacy, safety, quality, purity, or potency; to provide product information about proven benefits and risks; or to give proof of batch-to-batch consistency. Dosing and purity can vary substantially from batch to batch. In 2003, FDA examined 29 compounded pharmaceuticals and found that a third failed a standard quality test and nine had fewer active ingredients than the prescription. In 2012, MORE magazine sent 12 filled prescriptions of Tri-Est with progesterone to Flora Research Laboratories in Grants Pass, Oregon, which specializes in natural products research. Compared with the prescription labels, lower quantities of estriol were present. In 10 out of 12, estrone and estradiol had different doses than prescribed (58.4%-272.5% of estrone and 95.9%-259% of estradiol), with inadequate doses of progesterone in 11 out of 12 (60%-80%), potentially increasing the risk of endometrial cancer.
Compounding pharmacies have traditionally fallen under the jurisdiction of state regulators. To date, only 188 out of 7,500 US compounding pharmacies have accreditation by the Pharmacy Compounding Accreditation Board, which requires compliance with strict regulations and periodic renewal (pcab.org lists accredited pharmacies). All drug producers are expected to follow federal Good Manufacturing Practice regulations, but compounded products are not well monitored for these standards.
In 2012, the New England Compounding Center in Framingham, Massachusetts, was shut down after contaminated intrathecal steroids were linked to more than 750 cases of fungal meningitis or related illnesses and more than 64 deaths.
In November of 2013, the Drug Quality and Security Act was passed. It clarifies the FDA's regulatory authority over drug compounding. BOutsourcing pharmacies[ are allowed to sell products in bulk to hospitals and physician practices in the absence of individual prescriptions but must register with FDA, pay a fee, adhere to good manufacturing standards, subject themselves to routine inspections, and report adverse events. As of January 10, 2014, 11 US compounding pharmacies had registered with FDA under the new legislation. Unregistered pharmacies will continue to be regulated by state boards of pharmacy and allowed to compound a product in advance of receiving a prescription but not allowed to sell without a prescription. FDA can inspect unregistered pharmacies in response to a complaint but will need a court order to access records. FDA draft guidance available to compounding pharmacies stipulates potential violations if:
The product is a "filthy, putrid, or decomposed substance, or [is] prepared, packed, or held under insanitary [sic] conditions whereby it may have been contaminated with filth or whereby it may have been rendered injurious to health."
The drug is recognized in an official compendium (U.S. Pharmacopeial Convention [USP] or similar official pharmacopeia), its "strength must not differ from, and its quality or purity must not fall below, the standards set forth in the compendium, unless the difference is plainly stated on its label," and "it must be packaged and labeled as prescribed in the compendium."
"The drug product's labeling, advertising, and promotion [is] false or misleading."
Compounding by a licensed pharmacist or licensed physician for an identified patient should be based on receipt of a valid prescription order with a notation that the compounded product is necessary for the identified patient or, in limited quantities, before the receipt of a valid prescription order for an individual patient if there have been prior valid prescription orders.