Like many of you, I receive emails regularly from FDA informing me of drug shortages. The list is comprehensive, including products, suppliers and a brief description of the issue causing the shortage. In recent articles and editorials on this subject, authors put the blame for these shortages squarely on FDA and its regulatory oversight practices.
In the absence of information it is easy to blame the regulator. After all, if the quality of products were poor enough to warrant stopping their sale, surely we would have seen or heard evidence of this before shortages became chronic.
So, why would the Agency prevent the distribution and sale of products, causing major shortages and depriving the nation of much needed medications? We who live in a society founded on the principles of justice and the rule of law, with open access to information, should exercise our right to judge the reasons for these shortages, based on evidence.
According to various reports, 246 drugs were in short supply this year. Earlier, FDA had acted to approve products quickly enough to prevent drug shortages. So how is it that one day FDA is the champion for preventing shortages, and another day, the cause of these shortages? Is there bias in the way it oversees regulations?
In recent research, the American Societies of Health System Pharmacists, Anesthesiologists and Clinical Oncology, and the Institute for Safe Medication Practices, traced several shortages (for example, of concentrated morphine sulfate solution and levothyroxine injection) to actual or anticipated action by FDA, as part of the Unapproved Drug Initiative.
According to this research, the cost and complexity of completing a New Drug Application for unapproved drugs has become a disincentive for companies to enter or maintain a market presence. They cited other barriers including the time required for FDA review of ANDAs and supplemental applications, which are required for changes to FDA-approved drug products—for example, a change in source for API. Manufacturers described the approval process as lengthy and unpredictable, which limits their ability to develop reliable production schedules.
The other reason for the shortages that the research points out is "inability to comply fully with current good manufacturing practices.” Some of the products on the market had not been reviewed and approved by FDA, but the facilities making the products have been regulated under GMPs. The report also states that "FDA's zero tolerance regime is forcing manufacturers to abide by rules that are rigid."
Maybe we should be fair and convey the complete message. FDA has always demanded that firms do as they say and say as they do. If the intention was never there to adhere to zero tolerance policies, why even have an agreement, such as an NDA or ANDA, with FDA?
Let us look at those GMPs, which some firms are struggling to comply with. The GMPs specific to drugs span under 40 pages, most of them date from the 1970s, with some amendments in 2008. They are the minimum acceptable practices.
Years ago, I recall Dr. Ajaz Hussain, when he worked as deputy director of CDER's Office of Pharmaceutical Science, urging the industry to be honest, and not to claim adherence to zero tolerances when they did not or could not achieve it. No one listened. Even the USP states that single determinations cannot be used for batch release.
As an ex-regulator, I agree that some aspects of FDA regulation may be burdensome. But, if you approach FDA with good science, appropriate engineering, relevant process control and transparency, timely success will be assured.
As a former pharma industry employee, working in operations, I know that cGMP's are not even the silver standard. They are, as per the CFR, minimally acceptable practices.
As a consumer, I must demand that, if and when a manufacturer cannot meet the minimum standards, then its license to operate should be revoked.
If a firm is not willing to submit an application for review, then it must not produce for the market either. After all, the same regulations apply to everyone.
Shortages or no shortages, should we accept anything less?
