REMS Policy Issues
At a time when medicines are becoming more targeted and complex, ensuring patients’ safe use of medications with known dangerous risks is critical for public health and safety. This is why Congress authorized the REMS program under the Food and Drug Administration Amendments Act of 2007 (FDAAA) and reaffirmed the need for rigorous REMS controls through passage of the FDA Safety Improvement Act of 2012 (FDASIA).
However, the sense of urgency that led Congress to establish the REMS program has been replaced by calls to change this system in order to bring more generic drugs to the market. The claim – which some Congressional members accept as true – is that REMS safeguards, and especially restricted distribution systems, are used to block generic manufacturers from getting the samples needed to create cheaper alternatives, resulting in billions of dollars in avoidable costs.
Additionally, REMS has become a convenient target for legislators reacting to the tactics of certain bad actors, such as Turing Pharmaceuticals, to maximize profits by limiting the distribution of needed medications. Unfortunately, what some lawmakers may not understand is that the reprehensible actions of some bad actors are completely separate from the FDA-mandated restricted distribution systems under REMS that carefully control the use of high-risk medicines. These systems may include physician qualification and registration, pharmacist distribution limitations, patients enrolling in a registry, and patients undergoing routine testing, such as women having a monthly pregnancy test.
Currently, only 74 REMS programs are in place for currently marketed medications, including 46 that require “Elements to Assure Safe Use” (ETASU), the most restrictive type of REMS. Of these REMS with ETASU, 10 are shared systems involving both generic and branded drugs (as of July 2018). Yet, allegations persist that REMS are overused or may not be necessary and some members of Congress are responding with legislative proposals that could put patients at risk of significant harm and open the door to drug diversion.
Of special concern are bills that would force the sale of high-risk medicines requiring REMS controls to generic drug developers but without sufficient safeguards to prevent harmful exposure. Although generic drugs provide significant value to patients and physicians, it is important for policymakers to balance cost savings with necessary drug safety precautions for medicines known to cause serious or fatal risks.
Below is a summary of the legislative proposals now before Congress along with the positions raised by members of the Patients Alliance for Drug Safety Protections.
Fair Access to Safe and Timely (FAST) Generics Act of 2017 (HR 2051)
Introduced by Reps. David McKinley (R-WV) and Peter Welch (D-VT) on April 6, 2017, the Fair Access to Safe and Timely (FAST) Generics Act of 2017 is the current version of a 2015 bill (H.R. 2841) to require branded manufacturers to sell samples of drugs subject to REMS requirements to generic drug developers for clinical (bioequivalence) testing. Under the bill’s provisions, generic developers would first seek authorization from FDA to obtain samples of drugs requiring ETASU REMS and to submit a testing protocol to the agency. After receiving FDA authorization, generic developers will be entitled to purchase samples from a drug wholesaler or other entity designated by the branded manufacturer at a “commercially reasonable, market-based) price and receive the samples within 30 days of making the request. The FAST Generics Act would also require brand manufacturers to sell sufficient quantities of non-REMS products to generic developers at market prices within 30 days of receiving a request.
Compared to the 2015 version of the bill, which presented significant safety risks, the 2017 bill removes some of the most worrisome provisions. However, serious problems remain and should not be ignored. Specifically, the bill contains language that:
- Defines an eligible developer as “a person that seeks to develop a [generic drug application].” By this definition, any individual or business could claim to be an eligible product developer, as long as the business or individual intends to file a generic drug application with the FDA.
- Limits FDA’s authority to require that generic drug developers follow the same rigorous REMS controls (ETASU) when conducting clinical testing. This is because the bill allows generic developers to obtain samples of ETASU REMS drugs based on submitting testing protocols that are not equivalent. Instead, the bill calls for “comparable” protections as determined by the drug developer.
- Allows generic and biosimilar manufacturers to bring a civil action in federal court if the innovator company fails to provide samples of a drug or biological product within 31 days of a request or if there is no agreement on the development of a single, shared REMS system, even if both companies are actively negotiating the terms of the sample distribution and safety protocols.
Absolves generic companies from liability should testing of a generic version of a drug lead to serious injury, birth defects, or death.
In light of these issues, members of the Patients Alliance for Drug Safety Protections have submitted comment letters to the relevant House and Senate Committees urging policymakers to keep patient safety in mind when considering REMS modifications. Stressing that REMS protocols, such as Elements to Assure Safe Use, are essential drug safety mechanisms, these letters call on members of Congress to preserve the integrity of ETASU in the name of public health.
Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act (S 974; HR 2212)
On April 27, 2017, Senator Patrick Leahy (D-VT) re-introduced the Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act, which is co-sponsored by members of the Senate Judiciary Committee’s Subcommittee on Antitrust, Competition Policy and Consumer Rights. A companion bill sponsored by Rep. Tom Marino (R-PA) was introduced in the House of Representatives on April 28.
Addressing both the availability of drugs and biologics to generic developers for clinical testing and shared REMS negotiations (which involves how multiple manufacturers develop a single REMS to distribute both branded and generic drug products safely), the stated purpose of the CREATES Act is to accelerate generic drug development – a desired goal. However, due to the focus on medicines that are known to carry very high risks, this legislation could have the unintended consequence of weakening the REMS system and substantially decreasing the safety assurances for patients and researchers involved in clinical testing.
From a patient safety perspective, there are a number of concerns about the CREATES Act, including the same provisions in the FAST Generics Act allowing generic drug developers to sue within 31 days if brand-name manufacturers do not supply their drug samples for testing and absolving generic companies from liability for harm caused during clinical testing. Additionally, provisions of CREATES will weaken necessary safety protections for patients and increase the potential drug diversion by:
Eliminating established procedures whereby FDA ensures both innovator and generic manufacturers are held to the same safety requirements when testing potentially dangerous drugs. CREATES only requires that a generic developer show FDA that its protocols provide safety protections that are “comparable to those” of the original REMS drug instead of demonstrating its protections are “equivalent” to the safeguards employed by the brand manufacturer.
Curtailing the methods FDA now uses to verify a generic developer has the safety track record and capability to follow a rigorous risk management system.
Changing the existing requirement that branded and generic developers of drugs with ETASU REMS use a single, shared REMS protocol and follow the same safety procedures, use the same materials and documentation, and share the same database and infrastructure. Instead, CREATES would allow generic manufacturers to establish their own ETASU REMS using “a different, comparable aspect of the elements to assure safe use” unless FDA determines no different ETASU REMS exists.
The Lower Drug Cost Through Competition Act of 2017 (HR 749)
Introduced on January 30, 2017 by Reps. Gus Bilirakis (R-FL) and Kurt Schrader (D-OR), the Lower Drug Costs Through Competition Act would require the FDA to review applications for generic versions of drugs for which there is little or no competition with 180 days. Additionally, the bill recognizes the need for accurate and up-to-date information on the REMS program and calls for a General Accounting Office (GAO) study on REMS with a report to Congress on its findings.
In support of the GAO study, on May 5, 2017 members of the Patients Alliance for Drug Safety Protections sent a joint letter to Reps. Bilirakis and Schrader and members of the House Energy & Commerce Health Subcommittee stating that this review can provide new data on the use of FDA-mandated “Elements to Assure Safe Use” (ETASU), the most stringent REMS. The joint letter from Alliance members also calls for the GAO study to provide data to help decide whether some existing REMS are still needed and to develop an evidence-based pathway for those that are no longer necessary.