Compounding and Unapproved Drugs
Microbial Solutions
Lloyd V. Allen, Jr.

Compounding and Unapproved Drugs

Previous posts this month on Eureka have focused on regulation of compounding pharmacies, environmental monitoring in these facilities, and the amazing horseshoe crab that makes some of the most important safety tests possible. We now welcome guest blogger Dr. Loyd Allen, editor-in-chief of the International Journal of Pharmaceutical Compounding, to give a broader perspective on what exactly compounded drugs are and how they fit into the U.S. regulatory system.

These days you might see breaking news with headlines such as, “Compounders are selling unapproved drugs!” Although true, there is much more to the story.

Terminology is oftentimes confusing. What is the difference between an FDA approved drug, an FDA “unapprovable” drug, and an unapproved drug? Which ones are legal in the U.S.? Of these, which can I, as a pharmacist, compound?

An FDA approved drug is one for which the manufacturer or sponsor has received an approval letter from the FDA, an official communication allowing the commercial marketing of the product. If a drug product fails the review process, the FDA issues a letter deeming the drug “unapprovable.”  This may subsequently change if additional information is supplied to the FDA, changing their evaluation of the medicine.

An unapproved drug is one that has not undergone the extensive FDA review process with subsequent approval, but is nevertheless legally marketed in the U.S. These drugs were grandfathered in due to being on the market prior to the passage of the 1938 Food, Drug, and Cosmetic Act, which gave the FDA authority to oversee safety of medicines. Examples include such standards as aspirin and nitroglycerin.). In addition there are 3,000 to 4,000 unapproved veterinary products on the market today. The unapproved drug category also includes all compounded preparations or modified commercial products. The preparation of an intravenous admixture from two FDA-approved drugs results in a new, unapproved drug.

The public tends to think that unapproved drugs are “illegal” and that only FDA approved drugs are legal to use in the U.S. This is simply not true. FDA approval is required for drugs that are going to be manufactured and marketed by a manufacturing facility in the U.S. and distributed through interstate commerce.  Compounded preparations are prepared pursuant to a prescription issued by a prescriber (legally authorized to prescribe by the state) for a specific patient and compounded by a pharmacist (legally authorized by the state to practice pharmacy). The FDA is generally not involved in pharmacy compounding since it is regulated by the individual states.

FDA approved drugs can be compounded under certain conditions, though not if patented.  The same is true for unapprovable drugs. For example, if the FDA rejects an NDA for marketing of a particular drug by a manufacturer, the active pharmaceutical ingredient in that drug may still be suitable for compounding for specific patients. Under no circumstances, regardless of approval status, can pharmacists compound drugs that are on the “Drugs not to be compounded” list.

All of the above, done appropriately and within the laws and regulations of the state boards of pharmacy, is legal. Compounding may be done in hospitals, clinics, independent and chain pharmacies, specialty compounding pharmacies, nuclear pharmacies, etc. All compounded preparations are unapproved drugs; this includes intravenous admixtures, cancer cocktails, pediatric formulations, flavoring of preparations, nuclear pharmaceuticals, and all the nonsterile and sterile compounding that occurs daily. These preparations are all necessary and legal and this activity is governed primarily by the state boards of pharmacy. Again, compounded prescriptions are prepared as the result of a prescription from a prescriber and are for a specific patient, and not for manufacturing and marketing to the public.