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Comments on Drugs that Present Difficulties for Compounding

Public Citizen’s Health Research Group
Submission to Docket Number [00N-1357]
on the FDA Concept Paper: Drug Products That Present Demonstrable Difficulties for Compounding Because of Reasons of Safety or Effectiveness

In 1997 Congress passed the ill advised Food and Drug Administration Modernization Act (FDAMA) to, in part, exempt pharmacists who produce drug products, under certain defined conditions, from three central provisions of the Food Drug and Cosmetic Act (FDCA): (1) the adulteration provision concerning current Good Manufacturing Practice requirements; (2) the misbranding provision; and (3) the requirement to prove that a drug product is both safe and effective before it is sold. Pharmacy compounded drugs are not FDA-approved drugs.

In passing FDAMA Congress rolled back scientifically based regulations that evolved during the last century and were intended to protect patients from the preventable harm that can result from using untested drug products produced in unregulated facilities. This change in the law has given compounding pharmacists an “end run” around the FDA approval process and has opened the door for unethical pharmacists to copy commercially available FDA-approved drugs and to perpetrate the dangerous quackery that is now rampant within the practice of pharmacy compounding.

This FDA concept paper describes the agency’s current thinking on one of the conditions that compounding pharmacists must satisfy in order for the drugs they produce to qualify for exemption under FDAMA. Specifically, a drug product may only be compounded if it has not been identified by FDA regulation as a product that “presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product.”

Public Citizen commends the FDA for adhering to the principles of science-based consumer protections as articulated in this concept paper. We strongly support this approach: it identifies categories of drugs, or dosage forms, that are technologically too complex to be produced by pharmacists, or require sophisticated facilities to ensure their quality, safety and effectiveness.

The FDA has identified four dosage forms for placement in the list of drug products that pharmacists cannot compound. These are: (1) sterile products that are compounded under procedures other than those described in Chapter 1206, “Sterile Drug Products for Home Use” of the United States Pharmacopeia (USP). These products include those intended for intravenous use, oral inhalation solutions often used by asthmatics and patients with cystic fibrosis, eye drops, and topical products intended to treat burns and wounds; (2) transdermal delivery systems (TDSs), or skin patches; (3) metered dose inhaler products that are frequently used by asthmatics to treat their condition; and (4) dry powder inhaler products also used by asthmatics.

The Pharmacy Compounding Advisory Committee voted unanimously at its July 13 and 14, 2000 meeting to support the FDA’s approach and place the four dosage forms identified by the agency in the list of drugs that are demonstrably difficult to compound. We concur. We do have additional suggestions regarding future proposed regulations addressing sterile products.

First, a clear distinction should be made in any proposed regulations between the manipulation of FDA-approved sterile products, according to the approved labeling for these products, by a pharmacist, using sterile technique, and the production of a sterile product by a pharmacist from non-sterile bulk drug substances. We suggest that the first activity be referred to as “pharmacy admixing” and the second as “pharmacy compounding.” We agree that standards must be set for pharmacy admixing. We suggest that standards be proposed after the FDA has the opportunity to review both Chapter 1206 of the USP and the American Society of Health-Systems Pharmacists’ Guidelines on Quality Assurance for Pharmacy-Prepared Sterile Products.

Second, Public Citizen strongly urges the FDA to place all pharmacy compounded sterile products (those prepared from non-sterile bulk drug substances) on the list of drugs that are demonstrably difficult to compound. Such action would eliminate the highly profitable and dangerous copying of FDA-approved sterile products, particularly oral inhalation solutions used to treat asthma and the injectable painkiller morphine, and stem the quackery that now permeates so much of the business of compounding pharmacists.

The FDA has requested suggestions for other dosage forms to be considered for placement in the list of drugs that are demonstrably difficult to compound. Public Citizen suggests the following categories of drugs compounded by pharmacists be evaluated as soon as possible for placement on the list:

  1. All sustained or timed release dosage forms. Because there is no requirement to test these products it is not known if 90 percent of the active ingredient is released within the first 30 minutes after a dose is taken, or if 90 percent of the active ingredient remains in the dosage form after a dose is taken.
  2. Reflavored antibiotics that according to their FDA-approved labeling require reconstitution by a pharmacist at the time of dispensing. This practice may alter and inactivate the antibiotic and result in children with infections not being adequately treated.
  3. All sublingual dosage forms of bulk drug substances, These are intended for administration under the tongue.
  4. Enteric-coated preparations intended for drugs that are either destroyed by gastric acidity or that cause gastric irritation. Enteric-coated preparations may, if not properly formulated, resist dissolution in the intestine, and very little if any of the active drug may be absorbed into the blood stream.

Thank you this opportunity to comment on this important public health issue.


Larry D. Sasich, Pharm.D., M.P.H., FASHP
Public Citizen’s Health Research Group