There have been questions raised in the last few weeks as to what it means when the U.S. FDA says a particular drug is adulterated. Although the U.S. FDA has clear criteria by which the agency determines if a particular drug is adulterated, for most patients, the key question is whether – and how – a lay person who does not work in a regulatory agency can identify an adulterated drug. Quality-related defects are not very obvious to detect, yet they have a significant impact on overall public health.
How can we tell if a drug is adulterated?
Identifying and getting to the root cause of risks posed by poor product quality is addressed by the industry in two different ways. Product Quality Complaints are a category of “data” collected from the consumer (“the patient”) by the pharmaceutical manufacturers where the defect is obvious. For example, if the glue on a pain relief patch doesn’t stick to the skin for the prescribed period of time to allow the medicine to be topically administered, it is an obvious quality defect that a consumer can see. Consumers typically report such defects to the manufacturer, which is required to conduct an investigation into each such report and take corrective action.
More challenging are those drugs that act in a manner inconsistent with the data that was reviewed by the U.S. FDA in granting approval for market access. If the drug is metabolized faster or slower than it ought to be, thereby increasing or decreasing its concentration in the bloodstream, its affect may be much more severe. An example of such a case is Budeprion XL1 (generic Wellburtin), which was eventually recalled from the market. Such undesirable side effects, which are called adverse events, are much harder to detect. This is the second mechanism by which the problems with the quality of a drug are identified.
Regulatory agencies like the U.S. FDA have clearly articulated guidelines for pharmaceutical manufacturers to collect and report all such reports of Adverse Events. Over a reasonable period of time, one can effectively evaluate the frequency and the trends of unlisted (those that haven’t been seen earlier) adverse events and correlate them to the quality of its manufacture.
Is there a better process for identifying adulterated drugs?
Historically, product quality complaints have been effective in identifying package deficiencies (broken tablet strips, malfunctioning injector pens, etc.) and problems with storage conditions that impact the stability of the product (discoloration of the product, degradation, “bad smells” emanating from the drug product, etc.). Most patients do not take the drug when such defects are apparent.
Adverse events, on the other hand can give us a lot more information about the way an adulterated drug behaves. If, on a consistent basis, one begins to notice these side effects that are not listed on the label of the drug, there is a reason to suspect something untoward is happening with its usage. Let’s consider the example mentioned earlier in a little more detail.
Budeprion1 (generic Wellbutrin) is a good example to consider. The first indication of something being wrong with this formulation came from the unexpected adverse events in patients taking this narrow therapeutic index medication. As often is the case, patients who were dispensed the generic form of this medication began to notice that the generic formulation, Budeprion XL, made them woozy, sick to their stomach or even suicidal. This is a well-documented case that was pursued by concerned citizens and helped result in U.S. FDA action. There are many anecdotal cases that haven’t yet been subjected to the same scientific rigor to link product quality to safety. One such example is generic Sumatriptan (Imitrex), a migraine drug for which there is anecdotal evidence that the generic causes “rebound headaches” that are often more prolonged than the original migraine.
It is critical for patients and providers to report if a drug does not behave as it should, as unexpected adverse events are an important red flag that can indicate safety problems. The recently released report on Countering Falsified and Substandard Drugs from the Institute of Medicine2 makes this point. It says “When pharmacovigilance systems indicate lack of medicines efficacy, these signals should be followed. In-depth investigations can eventually produce data on the specific consequences of falsified and substandard medicines.”
Poor quality manifests itself as either “lack of effect” or “serious adverse events,” which are easily identifiable. In both case, regulators rely on patients and providers to raise specific concerns, which get rolled up into aggregate safety reports. This reporting apparatus is an important and effective way of ensuring drug safety. However, as with all communication technology, regulators should consistently strive to ensure that reporting is as easy and intuitive as possible for patients and providers.
Why does the U.S. FDA tell us to continue taking adulterated drugs?
A question emerges regarding what to do when the U.S. FDA tells us to continue taking drugs that are “adulterated.” We have seen this happen with Ranbaxy drugs over the last several years. The U.S. FDA is a science-based organization, and it first needs to establish a causal relationship between adverse events and the drug quality before asking us to stop taking these medications. Unfortunately, this is easier said than done.
Reporting of adverse events for multi-sourced products (generics) needs attention. Historical data shows that adverse events are reported less frequency for generics than brand name drugs. This needs to significantly improve. Given the differences between generic formulations and their brand name counterparts (which I addressed in a previous blog post), it becomes so much more important to collect as much data on adverse events as possible for generic drugs. As consumers, we all need to be more proactive in reporting any adverse events for our medications to the U.S. FDA.
The U.S. FDA has a robust system and a process for collecting and analyzing adverse event data. A higher reporting rate of individual case reports and a deeper analysis of trends over longer periods of the aggregate case report data will allow the U.S. FDA to identify any potential safety signals that could be directly linked to product quality.