Introduction
Pharmacy Compounding is an ancient practice in which pharmacists combine, mix or alter ingredients to create unique medications that meet specific needs of individual patients. Compounding is a practice that continues to attract the scrutiny of the U.S Food and Drug Administration (FDA) – mainly because of instances where compounded drugs have endangered public health.
The FDA considers virtually all compounded drugs as unapproved new drugs for which safety and efficacy have not been demonstrated with the type of data the FDA requires to approve a new drug. However, the FDA also considers "traditional compounding" to be a valuable service and does not take enforcement action against these practices. The FDA defines traditional compounding as customizing a drug for someone who is allergic to a dye or preservative in an FDA approved medicine, or compounding a liquid dosage form specifically for a younger patient, etc. Compounding does not generally include mixing or reconstituting commercial products in accordance with the manufacturer’s instructions or the product’s approved labeling.
Red Flags and Enforcement Activities by the FDA
The emergence over the past 10-15 years of firms with pharmacy licenses making and distributing unapproved new drugs in a way that is clearly outside the bounds of traditional pharmacy practice is of great concern to the FDA. FDA enforcement has been directed to those pharmacies whose activities raise the kinds of concerns normally associated with a drug manufacturer and whose compounding practices result in significant violations of the new drug, adulteration, or misbranding provisions of the federal Food, Drug, and Cosmetic Act (FDCA). In addition, unlike commercial drug manufacturers, pharmacies are not required to report adverse events associated with compounded drugs. In a May 2007 consumer newsletter, the FDA reported knowing of more than 200 adverse events involving 71 compounded products since 1990. Examples of some of these adverse events included: three deaths due to contaminated compounded intravenous solutions, and blinding of two patients as well as damaged eyesight to others from a bacterially contaminated compounded product used in cataract surgery. In a 2001 FDA survey of compounded drug products, the agency found 34% of the products tested failed standard quality tests (usually failing potency analyses) as opposed to a less than 2% failure rate for commercially produced drug samples. Examples of medications included in the testing sample included sterile injectables (e.g. dipyridamole, papaverine, phentolamine, etc.), pellet inplants (e.g. estradiol), ophthalmic solutions/ointments (e.g. ciprofloxacin, dexamethasone, timolol, etc.), inhalation (e.g. tobramycin), and oral products (e.g. progesterone, estradiol, etc.). As a consequence, the FDA has issued a number of warning letters to pharmacies that specialize in female hormone products (e.g. ‘Bioidentical hormone replacement therapies’), anti-infective inhalation products, sustained-release/delayed-release/extended-release products, and local anesthetic pain products. FDA Warning Letters have also been sent in cases where the FDA believes pharmacy communications (e.g. advertisements, website information, etc.) contain false and misleading claims about product safety, effectiveness, and superiority to FDA approved and commercially available products. When contemplating further action against compounding pharmacies the FDA considers whether the pharmacy engages in the following acts:
- Compounding drugs in anticipation of receiving prescriptions, except in very limited quantities in relation to the amounts of drugs compounded after receiving valid prescriptions.
- Compounding drugs that were withdrawn or removed from the market for safety reasons.
- Compounding finished drugs from bulk active ingredients that are not components of FDA approved drugs (e.g. estriol) without an FDA sanctioned investigational new drug application (IND).
- Receiving, storing, or using drug substances without first obtaining written assurance from the supplier that each lot of the drug substance has been made in an FDA registered facility.
- Receiving, storing, or using drug components not guaranteed or otherwise determined to meet official compendia requirements.
- Using commercial scale manufacturing or testing equipment for compounded drug products.
- Compounding drugs for third parties who resell to individual patients or offering compounded drug products at wholesale to other state licensed persons or commercial entities for resale.
- Compounding drug products that are commercially available in the marketplace or that are essentially copies of commercially available FDA-approved drug products. In certain circumstances, it may be appropriate for a pharmacist to compound a small quantity of a drug that is only slightly different than an FDA-approved drug that is commercially available. In these circumstances, FDA will consider whether there is documentation of the medical need for the particular variation of the compound for the particular patient.
- Failing to operate in compliance with applicable state law regulating the practice of pharmacy.