By: Alex Kanarek (akanarekbptccom) and Howard L. Levine (hlevinebptccom)
Why did it take the death of several patients from systemic fungal infections to publicize the fact that there are so-called “Compounding Pharmacies” which are actually operating as un-approved drug manufacturers throughout the US? Due to loopholes and vague legislation, FDA has been restricted from applying the rules of GMP to these organizations by the fact that they are not required to be registered under the Food & Drug Act and, even more importantly, they are not required to report adverse reactions to their products. There is a long-established practice and legitimate need for pharmacies to be allowed to compound drugs for a specific patient on a doctor’s prescription. This enables the doctor to avoid potentially allergenic constituents of the standard product or adjust the dose, or the means of administration. The problem arises when organizations like the New England Compounding Center (NECC) go beyond providing a custom formulation for the individual patient to distribute low-cost versions of frequently-used drugs to many doctors and hospitals and do not comply with the standards for purity and efficacy laid down by the FD&C Act. A recall notice for all products was issued by NECC on October 6, finally prompting inspection by FDA who issued a Form 483 on October 26 listing shocking examples of contaminated products, environmental contamination and poor sanitary practices in areas dedicated to the manufacture of sterile products.
In May 2007, FDA published a commentary for consumers on its website noting that it was aware of 200 cases of adverse effects, involving over 70 different compounded products, since 1990. A Compliance Policy Guide specifically addressing this problem was issued in 2002, identifying those factors which would initiate enforcement action. These factors include pharmacies using drugs which have been withdrawn from the market, making exact copies of approved drug products, failing to ensure that active pharmaceutical ingredients have been made in approved facilities and compounding drugs in advance of receiving a specific prescription. The article specifically advises patients receiving a compounded drug to ask the pharmacist if it was prepared according to their doctor’s prescription. The Agency has issued Warning Letters and enforced recalls under this Policy. For example, in August 2006 it warned three firms to stop manufacturing and distributing thousands of doses of compounded, unapproved inhalation drugs across the USA. But no change in the regulations was made. Sadly, as the NECC scandal unwinds, it is becoming apparent that this is not an isolated incident at this facility, but the latest in a long line of borderline practices that jeopardized patient health and safety.
A solution to the problem has been proposed by Representative Edward J. Markey, (D) of Massachusetts, who introduced a bill on November 8, requiring that compounding pharmacies that produce on a large scale be regulated as drug manufacturers by FDA and that compounded drugs be labeled as such. Is this too little, too late? We hope not. As Steve Silverman, Assistant Director of CDER’s Office of Compliance, noted in 2007, the poor practices on the part of drug compounders can result in contamination or in products that don’t possess the required strength, quality, or and purity, putting patients who use these drugs at special risks. While this topic is a bit afield from our normal postings on bioprocessing issues, we feel it important to speak out on this issue. As professionals involved in the manufacture of products intended to treat human disease, it is our duty to do everything we can to ensure that we are not putting patients at risk. Regulatory authorities such as FDA cannot be ubiquitous and all-seeing. It remains for individuals involved in production of these products to be vigilant in observance of good manufacturing practices, whether required by regulation or not, and to realize that the responsibility for the safety of the recipients of our products rests with us, not the regulatory agencies. This, apparently, was something that did not reach the minds of those running the NECC, and patients died unnecessarily.