Compounding is the creation of a drug product by mixing ingredients. For hundreds of years this was the exclusive way pharmacists practiced. However, as professional manufacturing developed, compounding decreased. Fifty years ago, about 60% of medications were compounded. Today, only about 1% of new prescriptions are compounded, but compounding may be undergoing a resurgence.
State and federal laws permit compounding because it sometimes provides value to patients. In most hospitals, intravenous antibiotic solutions, total parenteral nutrition units, and special pediatric dosages are compounded with products specially manufactured for these purposes. In community pharmacies, concentrations, dosage forms or combinations of medications that are unavailable or not readily available can be manufactured. In a pinch, compounding can be used to prepare products that are hard to acquire or are temporarily unavailable from their manufacturer. Very rarely, products that are free of dyes or preservatives are required. Community pharmacy compounding requires a written prescription specifying that the product be compounded for the specific patient. It is assumed that the formula will be written on the prescription so that other pharmacists can provide refills using the same recipe.
Most compounding is done honestly at physician request. When I practiced pharmacy, most requests came from dermatologists who wanted ointments or creams made to their specifications. However, the profit motive is luring pharmacists to bend the rules in situations where bulk ingredients are available for preparing products that cost less than brand-name drugs. In some cases, savings are passed along to the patients; but in other cases, they are not.
Increasingly, the idea to compound a product comes from the pharmacist’s request—whether a comparable generic product is available or not. In some instances, existing products are remanufactured to “tailor the product to the patient.” This involves, for example, the preparation of 5 mg capsules from the comparatively less expensive 20 mg tablets of Vasotec (an antihypertensive drug). The FDA requires manufacturers to meet stringent quality control measures for the contents of each tablet and to document how quickly the drug dissolves in the stomach. Compounded capsules may vary significantly in dosage and absorption characteristics, with no independent check of quality or variation. Strictly speaking, many compounded products could be viewed as an unapproved new drug items.
In addition, compounding enables pharmacists to create what amounts to their own line of generic nonprescription products. Manufacturers of generic drugs are required to show quality control analyses, while pharmacists are not. Some pharmacists are even promoting compounded products whose ingredients are based on interpretations of preliminary research. This practice lacks the safeguards associated with legitimate experimental trials.
Laser printers enable pharmacists to make professional-looking labels that do not state where a product is manufactured, making it difficult or impossible for the patient or physician to tell whether a product has been compounded. In many cases, the quality, purity, and potency of bulk ingredients cannot be assured. Dr. John Perrin at the University of Florida has noted the powder used to make Caverject (a patented, injectable product used for diagnosing and treating certain types of erectile dysfunction) is imported illegally from Czechoslovakia, enabling the pharmacist to make, in effect, an unapproved generic for a patented product. The pharmacist has no way to determine whether the powder used for such a product has degraded before compounding or is contaminated with bacteria.
I am quite concerned about the safety of compounded products. A segment of the May 12, 1998 “ABC News” dealt with of improper compounding and pharmacy fraud. Done in cooperation with the Florida Board of Health (and Pharmacy), the report checked albuterol (an inhalation agent used for asthma or emphysema) compounded by several pharmacies and noted the lack of regulatory oversight for these products. Samples sent to an independent lab tested superpotent - enough to produce dangerous side effects such as heart rhythm disturbances. The possibility of bacterial contamination was also raised.
Sustained-release products (such as theophylline, a medication commonly used for asthma) are notoriously difficult to manufacture. I do not believe that local pharmacists can produce reliable sustained-release products based on information from third parties. For example, theophylline products now commercially available reliably release their contents into the body over a 12- to 24-hour period. A defective sustained-release agent might instead dump the active agent into the system over a very short period of time (or not at all), leading to palpitations, anxiety, and erratic control of the asthma.
Product stability may also be an issue. Reflavoring antibiotic suspensions “to enhance compliance” does not take into account the stability of the suspension needed to maintain potency. The stability of other ingredients in water or in containers is not even considered when the “house brand” is manufactured. Sterility is yet another issue that most pharmacies are not adequately prepared to deal with.
Some local pharmacists tell customers that compounded products are “just as good” as the generic or brand-name products, although the quality control of a local pharmacy is negligible or nonexistent.
In 2002, FDA researchers sampled 29 products from 12 pharmacies that market through the Internet. Nine products were not potent enough; one was contaminated; and three others failed an initial test but were not counted as failures because an inadequate amount was left for retesting. By comparison, 1% to 2% of drugs from manufacturers fail to meet standard assays .
Since compounding is rarely if ever discussed during medical training, most physicians know very little about its associated problems. It can be very difficult to tell from the label of an empty bottle that the product had been manufactured by the pharmacy. The physician may not realize the product has been compounded for a patient. Physicians have come to expect products to be free from contamination and of uniform quality. They often do not appreciate risks created or enhanced by these agents.
Professional Compounding Centers of America (PCCA), of Houston, Texas, offers courses to refresh the pharmacists’ compounding skills learned as an undergraduate and strongly encourages compounding. PCCA has a membership of about 2,400 worldwide. A number of other companies offer bulk chemicals and varying degrees of support
The International Academy of Compounding Pharmacists (IACP), of Sugar Land, Texas, has about 1,000 members and publishes a monthly newsletter and a quarterly case-report journal. The IACP provides political support for compounding and helps provide organization for member pharmacists.
Curiously, the PCCA and IACP web sites link to the American College for Advancement in Medicine (ACAM), a medical group that promotes chelation therapy and other questionable treatments. I suspect that ACAM’s members favor compounding because it enables them to obtain products that cannot be legally marketed as drugs because their effectiveness has not been substantiated. Though the PCCA appears to be careful in what it recommends for compounding, pharmacists have a wide latitude in deciding which products to make.
Storey Marketing, of Meadville, Pennsylvania, which offers “solutions for the compounding pharmacist,” markets brochures, weekly newspaper columns, “Problem Solver” patient handouts, telephone tapes, and “The Mortar and Pestle,” a 2-page monthly pharmacist-to-prescriber newsletter—each of which can be personalized so that the pharmacist appears to be the author. Many of these items promote ingredients that have not been scientifically substantiated. The newsletter section called “Rx Solutions” contains anecdotes illustrating “how compounding has helped a particular patient.” The November 1999 issue encourages pharmacists to compound a thyroid preparation for treating “Wilson’s Syndrome” but did not mention that, in E. Denis Wilson, MD, who concocted this “fad” diagnosis, was severely disciplined by the Florida Board of Medicine in 1992 and no longer practices medicine.
Greater Regulation Is Needed
Some community pharmacies may reasonably emphasize compounding certain prescription items (rectal or vaginal suppositories and cream/ointment combinations for example), as a service to patients. However, pharmacies compounding products that already exist in commercially available forms are likely to be harming consumers and violating the law. State boards of pharmacy are responsible for these activities, and some are very concerned about this problem. Major manufacturers have not attacked this problem for fear that they will be perceived as bullies. In 2003, the U.S. General Accounting Office concluded:
While drug compounding is important and useful for patient care, problems that have occurred raise legitimate concerns about the quality and safety of compounded drugs and the oversight of pharmacies that compound them. However, the extent of problems related to compounding is unknown. FDA maintains that drug compounding activities are generally subject to FDA oversight under its authority to oversee the safety and quality of new drugs, but the agency generally relies on states to provide the necessary oversight. At the state level, our review provides some indication that at least some states are taking steps to strengthen state oversight, and national pharmacy organizations are developing standards that might help strengthen oversight if the states adopted and enforced them. However, the effectiveness of these measures is unknown, and factors such as the availability of resources may also affect the extent of state oversight .
A 1997 FDA Modernization Act states that compounding pharmacies are not manufacturers and are therefore exempt from standard FDA regulation on that basis. The act prohibited pharmacists from advertising or promoting compounded drugs, but in April 2002, the U.S. Supreme Court ruled that the FDA could not restrict pharmacists from advertising or promoting products solely because they were compounded . This ruling places consumers at risk because the FDA does not have adequate resources to police what compounders do.
Advice for Consumers
Compounding is frequently employed by dermatologists for topical agents. It may also be advisable when a certain agent is in short supply, is not readily available, or in certain emergencies. However you should:
- Avoid sustained-release compounded products.
- Avoid antibiotic reflavoring.
- Avoid compounded agents when sterility is important (e.g., injectable or inhalation agents).
- Avoid a compounded product when a generic or brand-name agent is readily available.
- Ask for the charge for both compounded and brand name drugs. Call a non-compounding pharmacy for a comparison price. Ask also if any other similar agents are available that could take the place of a compounded product.
For Additional Information
- Pharmacy Compounding Facts
- The Special Risks of Pharmacy Compounding
- Compounding Pharmacists Sued for Death from Intravenous Hydrogen Peroxide
- FDA Warning Letters to Compounding Pharmacies
- Subramaniam V and others. Survey of drug products compounded by a group of community pharmacies: Findings from a Food and Drug Administration study. Presented Sept 21, 2002.
- Heinrich J. Prescription drugs: State and federal oversight of drug compounding by pharmacies. GAO-04-195T, Oct 23, 2003.
- Thompson et al. v. Western States Medical Center et al., U.S. Supreme Court Case No. 01-344, decided April 29, 2002. [Text] [PDF]
Dr. Bouts practices internal medicine with the Blanchard Valley Medical Associates in Findlay, Ohio, and is Adjunct Professor of Clinical Pharmacy at Ohio Northern University.
This article was revised on June 10, 2012.