This language outlining the pharmacy exemption reflects the continuing debate over FDA's authority to regulate large-scale
compounders as drug manufacturers. Compounding pharmacists, who are regulated by state law, traditionally produce liquid versions
of solid oral-dosage forms for children and patients who cannot swallow pills. They also formulate custom medicines for patients
who are allergic to certain excipients and dyes found in commercial products. To avoid being considered drug manufacturers,
pharmacists perform such compounding in response to legal prescriptions for specific patients. Some drug formulation may be
done in anticipation of receiving a certain number of prescriptions, but not in large volumes for sale through third parties
or via Internet Web sites.
FDA, pharmacists, Congress, and the courts have struggled for years over just where to draw the line between legitimate compounding
and large-scale operations that qualify as drug manufacturing. FDA wants large compounders to register and comply with GMPs
and other requirements to ensure product quality. Growing concerns about drug safety and counterfeiting have generated support
for tighter controls, particularly for sterile products to treat serious health conditions. An emerging fear is that compounders
open the door for counterfeit active pharmaceutical ingredients (APIs) to enter the US market.
The scope of compounding is unclear. An FDA study in 2001 estimated that some 650 pharmacies fill more than 13 million prescriptions
for compounded products each year. But this may be a minimum: FDA officials frequently cite estimates of 30 million compounded
prescriptions. Another measure of compounding might be the number of specific problems linked to compounded products. Between
1990 and 2003, FDA says it identified more than 55 product-quality problems associated with compounded drugs, many resulting
In the past, FDA has challenged compounding in various product categories, including hormonal products, veterinary drugs,
steroids, and injectibles. Last year, FDA sent a warning letter to a veterinary compounding facility in Nebraska for large-scale
compounding of drugs for resale by third parties. Manufacturers and patient groups have petitioned FDA to take action against
compounders. Last year, Wyeth filed a citizens' petition seeking restrictions on the compounding of hormonal therapies identical
to its "Premarin."
The latest skirmish involves home health agencies' distribution of large volumes of compounded sterile liquids used in nebulizers
by patients with asthma and other respiratory diseases. FDA sent a warning letter in August 2006 instructing CCS Medical (Clearwater,
http://www.ccsmed.com/) to halt large-scale production of albuterol and other respiratory medications. A similar letter cites Rotech Healthcare
http://www.rotech.com/) for failing to comply with GMPs in producing budesonide and albuterol inhalation products. Another letter to Lincare's Reliant
Pharmacy Services (Clearwater, FL,
http://www.lincare.com/) reiterated concerns raised in a warning letter issued in December 2004.
In announcing this compliance action, Steven Galson, director of the Center for Drug Evaluation and Research (CDER), noted
that using unapproved inhalation drugs that are not produced according to GMPs and "typically are not sterile" may "expose
patients to unnecessary risk." Rotech said that even though it disagreed with FDA's findings, it would stop accepting prescriptions
for inhalation products and begin the process of shifting some 30,000 patients to commercially available treatments.
Charges that home healthcare companies are substituting compounded products for prescription nebulizer medications prompted
Senate Finance Committee Chairman Charles Grassley (R-IA) to launch a probe of these activities last March. The investigators
found the use of unregistered below-grade bulk chemicals, and Astra Zeneca and other pharmaceutical manufacturers provided
Grassley's staffers with independent tests of compounded drug samples indicating different concentrations, failed sterility
tests, and bacterial contamination that could cause infections in people with weakened immune systems. In response to Grassley's
report, the Centers for Medicare and Medicaid Services (CMS) said it would revise its coding system to reduce Medicare payments
for inhalant drugs produced by compounders, as opposed to products from registered manufacturers.