Compounding pharmacies get an F in FDA tests. (34% Failure Rate).SAN FRANCISCO -- Ten of 29 prescriptions that were obtained in a Food and Drug Administration survey of compounding pharmacies failed assays, Vaiyapuri Subramaniam, Pharm.D., reported at the annual meeting of the American College of Clinical Pharmacology.
Of the 10 failed samples, 9 were significantly subpotent and 1 contained unacceptable levels of endotoxin, he said at the meeting.
The take-home message is, "Professionals and patients beware," Dr. Subramaniam, a Food and Drug Administration compliance officer, told this newspaper. "There are risks involved."
Compounding is defined as the combining, mixing, or altering of ingredients by a licensed pharmacist to create a customized drug for a patient based on the receipt of a valid prescription.
The FDA survey included compounds for oral use, for ophthalmic use, for injection, for inhalation, and for pellet implants.
The drugs that failed potency assays were injectable betamethasone betamethasone /be·ta·meth·a·sone/ (ba?tah-meth´ah-son) a synthetic glucocorticoid, the most active of the antiinflammatory steroids; used topically as the benzoate, dipropionate, or valerate salts as an antiinflammatory, topically or , hyaluronidase Hyaluronidase
Any one of a family of enzymes, also known as hyaluronate lyases or spreading factors, produced by mammals, reptiles, insects, and bacteria, which catalyze the breakdown of hyaluronic acid. , papaverine papaverine (pəpăv`ərēn), alkaloid found in opium that acts as a muscle relaxant and vasodilator. The drug relaxes the smooth muscle of the larger blood vessels and is used to increase the blood supply to the brain or to the heart, as , and progesterone; ophthalmic ciprofloxacin, dexamethasone dexamethasone /dex·a·meth·a·sone/ (dek?sah-meth´ah-son) a synthetic glucocorticoid used primarily as an antiinflammatory in various conditions, including collagen diseases and allergic states; it is the basis of a screening test in the , and timolol maleate; and oral progesterone. A sample of injectable alprostadil contained high levels of endotoxin.
The agency recruited patients who had legitimate prescriptions.
Those prescriptions were compounded at 12 pharmacies, and the pharmacies were selected based on their prominence on the Internet.
The 29 compounds were selected based on their common use and potential heath risk if improperly compounded.
Investigators judged a compound subpotent only if the assay demonstrated levels outside the U.S. Pharmacopoeia pharmacopoeia or pharmocopeia (fär'məkəpē`ə), authoritative publication designating the properties, action, use, dosage, and standards of strength and purity of drugs. limits, which generally allow a 10%-25% variation in activity.
In recent years, there have been several highly publicized incidents of adverse events resulting from compounding, according to Dr. Subramaniam. In one instance, there were eight cases of meningitis--including three deaths--following injections of contaminated compounded betamethasone.
Another case involved the death of a child who received imipramine imipramine /imip·ra·mine/ (i-mip´rah-men) a tricyclic antidepressant of the dibenzazepine class, used as i. hydrochloride or i. pamoate. oral liquid that had been compounded at five times the prescribed strength.
And in a third case, a patient suffered unilateral blindness after using compounded indomethacin eyedrops that proved to be nonsterile.
The FDA Modernization Act of 1997 included a section (503A) regulating pharmacy compounding. Shortly after the act s passage, seven compounding pharmacies challenged Section 503A alleging, among other things, that it involved an impermissible regulation of commercial speech.
After the case made its way through lower courts, the U.S. Supreme Court rendered a decision in April 2002 that essentially left invalid the entire section.
The FDA has since issued a document aimed at providing guidance to those pharmacies that are engaged in making and distributing unapproved new drugs. But that compliance policy guide does not have the force of law.
The guide says the agency intends to defer to state authorities the job of regulating pharmacy compounding--unless a pharmacy's activities raise concerns.
One of the objectives of Dr. Subramaniam's study was to assist the FDA in developing a regulatory strategy for compounded drug products.
To access the FDA guidance go to www.fda.gov/OHRMS/DOCKETS/98fr/02D-0242_gdl0001.pdf.