Comments of Larry D. Sasich, Pharm.D., M.P.H, FASHP, Public Citizen’s Health Research Group
Before FDA’s Pharmacy Compounding Advisory Committee on the FDA Concept Paper: Drug Products That Present Demonstrable Difficulties for Compounding Because of Reasons of Safety or Effectiveness
Public Citizen is opposed to the pharmacy compounding provisions of the Food and Drug Administration Modernization Act (FDAMA). These anti-scientific provisions of the law permit compounding pharmacists to conduct an “end run” around the FDA’s drug approval process. They have opened the door for unethical pharmacists to abuse a professional privilege granted to them by the public and to perpetrate the quackery that now goes on, for all practical purposes, unrestrained.
Given the few options available to this committee within the pharmacy compounding provisions of FDAMA, we do support the science-based approach taken by the FDA in its concept paper on developing a list of drugs that cannot be compounded by pharmacists. Clearly, Congress was concerned about the safety and effectiveness of drug products compounded by pharmacists when it said in FDAMA that the FDA has the responsibility to identify and place on a list of drugs that cannot be compounded any product that “presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product.”
The FDA’s approach in developing the list has been to include certain categories of drugs that are sophisticated final finished dosage forms and whose production is technologically complex or requires highly specialized facilities and trained personnel. This is scientifically sound, intuitive, and within the common and legal definition of a drug.
Science-based drug regulation has evolved over the past century with the purpose of preventing avoidable harm to patients. History and science have taught us that waiting for a tragedy to materialize before taking regulatory action needlessly harms patients. Primary prevention, in the form of enforceable regulations, has always been the best approach to protecting the public health from avoidable drug-induced injury and death.
Any suggestion that the safety of pharmacy-compounded products is proven because there have been few reports of serious adverse events is clearly absurd. The FDA’s postmarketing adverse event reporting system does not, and cannot, identify all instances of harm to patients from prescription drugs, let alone those from compounded ones. And this system does not have the sensitivity to detect a negative impact on patient survival from the drugs they receive. Compounding pharmacists are well aware that they are under no regulatory requirement to report adverse events that are associated with the use of their products. Their financial self-interest makes it even more likely that they will not report these adverse events.
Public Citizen agrees that transdermal delivery systems, metered dose and dry powder inhaler products must be placed on the list of drugs that are demonstrably difficult to compound. We also agree that it should not only be appropriate, but mandatory, to include all sterile products that are not compounded in accordance with Chapter 1206 of the United States Pharmacopeia, (USP ) “Sterile Drug Products for Home Use” on the list, with one exception.
We do not agree that the procedures described in Chapter 1206 for compounding sterile products from non-sterile bulk drug substances, even if they could be enforced, would ensure the safety or effectiveness of these products. We believe that it is essential that all sterile drug products that are compounded from non-sterile bulk drug substances be on the list.
We have particular concerns about the preparation of sterile products. Our objection is due in part to a study cited in the FDA’s concept paper that evaluated the sterility and concentration of 100 samples of 1% pilocarpine eye drops used to treat glaucoma. Of the 100 samples, 66 were prepared by local pharmacies and 34 were prepared by FDA-regulated manufacturers. Of the 66 solutions prepared by local pharmacies, 52 (79%) were contaminated with bacteria or fungi or both, whereas one of 34 (3%) samples prepared by regulated manufacturers was contaminated. This result is chilling and will be repeated more often as a result of the irresponsible action of Congress in passing the pharmacy compounding provisions of FDAMA.
Chapter 1206 of the USP provides two examples of high-risk sterile products intended for intravenous injection that can be produced from non-sterile bulk drug substances: morphine and total parenteral nutrition (TPN) solutions. Because these products are already available in a variety of formulations, we can conceive of no medical reason why they should be compounded from non-sterile bulk drug substances. Morphine injection is available from numerous FDA-regulated manufacturers in concentrations ranging from 0.5 milligrams/milliliter (mg/ml) to 50 mg/ml. Preservative-free morphine injection is also available in 0.5 mg/ml and 25 mg/ml concentrations. Total parenteral nutrition (TPN) solutions, including dextrose (sugar) solutions, vitamins, and trace elements that may be needed to meet the individual requirements of a patient, are available as sterile products for injection from a number of FDA-regulated manufacturers.
Public Citizen is unable to conceive of a legitimate medical scenario in which the benefits to a patient from compounding an injectable product from a non-sterile bulk drug substance would outweigh the risks. This is particularly true if the compounded product is intended to be used in a setting other than an organized, professionally staffed health care facility.
In addition to the products just mentioned, we urge the FDA to include in the list of drug products that present demonstrable difficulties in compounding the following categories of drugs: all sustained- or time-release dosage forms; re-flavored antibiotics that according to their FDA approved labeling require reconstitution by a pharmacist at the time of dispensing; and enteric-coated products. All products intended for sublingual (under-the-tongue) use should also be considered for listing.
An article appearing in the September-October 1998 issue of the International Journal of Pharmaceutical Compounding concerning the compounding of TPN solutions from non-sterile bulk substances plainly reveals that the motive for compounding these solutions is not the health and welfare of patients. It is instead, in substantial part, financial:
In an effort to eliminate the threat of product shortfalls and remain competitive with home infusion companies that were divisions of amino acid solutions manufacturers, HHCA [Home Health Care of America, Inc. Santa Ana, CA] refined and developed this compounding method. The company determined that compounding TPN solutions using bulk drug substances would be the first step toward full vertical integration and decreased costs.
 Chamallas S. TPN bulk compounding from bulk drug substances. International Journal of Pharmaceutical Compounding 1998;2 Sept/Oct:347.
This author’s affiliation is listed as NMC Homecare, Two Ledgemont Center, 95 Hayden Avenue, Lexington, MA 02173.