If there was ever a time for an informed discussion about the purpose and use of Risk Evaluation and Mitigation Strategies (REMS), it is now. Rather than impeding the arrival of more effective treatments to the market, Congress gave the Food and Drug Administration (FDA) authority to require REMS as a way to approve needed medicines that are also known to carry severe risks.
As a result, patients now have access to new treatments for asthma, chronic obstructive pulmonary disease, blood disorders, multiple myeloma, thyroid cancer, irregular heartbeat, hypertension, multiple sclerosis, seizures, schizophrenia, bipolar disorder, Crohn’s disease and specific bowel disorders, and a number of rare disorders. Without REMS, it is unlikely most of these new treatments would ever have reached patients.
Contrary to the assertions in the Health Affairs Blog post by Ameet Sarpatwari and Aaron Kesselheim, “Ensuring Timely Approval of Generic Drugs,” REMS is an integral component of ensuring safety regulations, covers a small number of drugs known to carry very high risks, and has not impeded the development of generics. At the same time, our analysis of the Fair Access for Safe and Timely Generics (FAST) Act identifies a number of provisions that, far from being reasonable solutions, would dilute the safety systems now in place under REMS to protect patient safety.
High Risk Drugs Require Oversight
While examining the important role of generic drugs in increasing access to medicines, the authors start by underplaying the need for REMS while overstating just how widely the program is actually used. Due to FDA actions in 2011 to streamline the REMS program, 71 medications now have authorized unique REMS programs in place and six more products exist in shared REMS systems.
Of these medicines, only 30 drugs known to carry the highest risks of adverse events—including death, organ failure, and severe birth defects—are subject to the more restrictive “Elements to Assure Safe Use” (ETASU) and require restricted distribution systems to ensure they are not taken by the wrong person or taken incorrectly.
Among these 30 high risk drugs is thalidomide. From 1956 to 1962, as many as 10,000 babies outside the U.S. were born with severe birth defects because their mothers had taken the drug during early pregnancy. As a result, thalidomide was banned for decades until drug safety protections, such as rigorously restricted distribution systems, were implemented in the U.S. and other countries.
REMS Don’t Impede Development Of Generics
Key facts posted on the FDA’s own website also refute the authors’ arguments that REMS Elements to Assure Safe Use (ETASU) requirements are frequently used to impede the development of generic medicines. In fact, a dozen medicines subject to REMS have gone generic, including nine with strict ETASU provisions.
Moreover, a number of abbreviated new drug applications for new generic medicines subject to REMS have been filed with FDA resulting from generic manufacturers accessing drug samples and conducting bioequivalence testing. This was possible thanks to protections written into the Food and Drug Administration Amendments Act of 2007 (FDAAA) (21 U.S.C. § 355-1(f)(8)), which FDA permits brand-name drug makers to sell samples of a REMS drug for clinical (bioequivalence) testing by those developing generic alternatives. Just as crucial has been the agency’s 2014 draft guidance informing brand manufacturers of the circumstances under which sharing samples will not violate their REMS.
Unintended Consequences
Beyond these facts, the FAST Generics Act, while well intended, could have the unintended consequence of a substantial decrease in safety assurances for patients. While requiring that REMS drugs go to generic marketers for bioequivalence testing, the ACT does not contain sufficient safeguards to prevent harmful exposure to these medicines.
One serious flaw is how the Act defines those eligible to buy drug samples through a forced sale. Currently, the Act broadly and ambiguously defines an “eligible product developer” as “a person that seeks to develop a [generic drug application].” With this definition, any person or business would qualify as an eligible product developer without any system in place to verify the individual or company is, in fact, a legitimate generic drug manufacturer.
Today, medicines requiring restricted distribution systems are typically administered by certified distributors, pharmacies, and physicians to ensure the medication only passes through the hands of individuals trained to prevent harmful exposure and adverse events. For example, a drug known to cause birth defects, such as ambrisentan, requires restricted distribution and pregnancy tests as part of its REMS. If bad actors took advantage the FAST Act’s vague definitions to acquire the drug under false pretenses, the medication could end up in the hands of a physician without training who might unwittingly administer it to a woman who is pregnant.
Compounding the problem, another provision of the FAST Generics Act would allow wholesalers and distributors to obtain and sell drug samples in large quantities essentially to anyone in the stream of commerce who claims to be an eligible product developer. Without a rigorous verification system, this laissez-faire approach opens the door to drug diversion, increasing the likelihood patients will be put at added risk.
Patenting of REMS Is Not Particularly Problematic
Contrary to the assertions made by Sarpatwari and Kesselheim, patenting REMS plans will not artificially extend market exclusivity for brand manufacturers. Although the FDAAA requires a single, shared REMS plan for brand drugs subject to REMS with ETASU, the FDA may waive this requirement and permit the generic manufacturer to use a different, comparable ETASU plan if the burden of creating a single, shared system outweighs the benefits of a single system, taking into account the impact on health care providers, patients, the generic manufacturer, and the brand manufacturer. This waiver authority protects generic manufacturers from being delayed by patented aspects of the REMS plan.
It is time for policymakers to ask questions before accepting that the Fair Access for Safe and Timely Generics (FAST) Act is “common-sense” legislation that will help the public. While FAST supporters are keen to highlight the benefits of expedited approval of generic drugs, including saving patients money, this should not supersede patient safety. Instead, ensuring patients’ safe use of medications with known dangerous risks is a goal that must come first.
No comments:
Post a Comment