On Wednesday, the U.S. Senate overwhelmingly passed the 21st Century Cures Act (the “Act”) by a vote of 94 to 5.  Spearheaded by Michigan Representative Frank Upton, the bill now heads to President Obama who has promised to sign it. The Act is ambitious, and will impact a wide swath of the U.S. health care system. The Act provides, among other things:

• $4.8 billion over 10 years to support NIH research on precision medicine, neuroscience, cancer and regenerative medicine.

• $1 billion in state grants to increase opioid abuse prevention and treatment services, including prescription drug monitoring programs, training programs and treatment programs.

• Substantial changes to FDA regulations to accelerate the pace of bringing pharmaceuticals and medical devices to market.

• New obligations on the part of both FDA and industry stakeholders to implement the research initiatives and regulatory changes mentioned above.

• Other health care initiatives addressing health information technology, vaccines, national security and health care delivery.

At 996 pages, the Act cannot be summarized in one post. Instead, we plan to analyze the various aspects of the Act in multiple posts over the coming weeks. The remainder of this post will highlight provisions that support one of the Act’s primary objectives: the acceleration of drugs and devices to market.

Easing and Accelerating the Pathway to Market

A review of the Act uncovers a number of provisions whose purpose is to accelerate the process of bringing drugs and devices to market. We have summarized these provisions below and have provided context when applicable.

Pharmaceuticals and Biologics:

• Qualification of Drug Development Tools. In 2012, FDA created the Drug Development Tools (DDTs) Qualification Program that it used to validate biomarkers, clinical outcomes assessments, and animal models. Biomarkers, for example, can be used to show whether a certain biological response has occurred in a patient receiving a pharmaceutical treatment. The Act establishes a formal review pathway at FDA for biomarkers and other drug development tools that can be used to help shorten drug development time and reduce the failure rate in drug development.

• Targeted Drugs for Rare Diseases. The Act clarifies FDA’s authority with respect to genetically targeted drugs for rare diseases. Sponsors of genetically targeted or variant protein targeted drugs will be permitted to rely on data for the same or similar technology from previously approved applications by the same sponsor.

• Reauthorization of Pediatric Rare Disease Priority Review. The Act reauthorizes the pediatric rare disease priority review voucher program until 2020. The program offers vouchers to companies for gaining approval of new rare pediatric treatments affecting fewer than 200,000 patients under the age of 18. These vouchers enable companies to have any one of their drugs reviewed under FDA’s priority review system.

• Novel Clinical Trial Designs. FDA will be required to hold public meeting and issue guidance documents that would assist sponsors in incorporating adaptive designs and novel statistical modeling into new drug applications. “Adaptive designs” refer to changes in the design or analyses of a trial based on an examination of the accumulated data at an interim point in the trial. For example, adaptive designs can be used to make studies more efficient (e.g. by reducing the duration of the study) or more informative (e.g., by providing broader dose-response information.) The FDA provided guidance on adaptive designs in 2012.

• Real World Evidence for New Indications of Previously Approved Drugs. FDA will be required to evaluate the use of real world evidence to help support the approval of a new indication of a previously approved drug and to help support or satisfy post-approval study recommendations.

• Data Summaries to Support Approval for New Indications. FDA will be allowed to rely upon qualified data summaries to support the approval of an application for a new indication of an already approved drug. Sponsors will still be required to submit all of the traditional information to the FDA.

• Expanded Access Policy. The Act requires pharmaceutical companies to have publicly accessible compassionate use policies for drugs treating serious or life-threatening conditions. Compassionate use (also known as expanded access) allows physicians to request FDA approval of the use of an investigational drug outside of a clinical trial when a patient is terminally ill or has no other treatment options. However, this process cannot begin without cooperation by the pharmaceutical company producing the drug, hence the provision.

• Accelerated Approval for Regenerative Therapeutic Products. FDA will be allowed to grant accelerated approval for regenerative therapeutic products. FDA is directed to consider the unique characteristics of regenerative therapeutic products and provide a rationale with a determination of whether or not to grant accelerated approval. The Act does not change the standards of evidence or limit any other of the FDA’s authorities. Regenerative therapeutic products include stem cell therapies that are derived from a patient’s own cells. The magazine Wired recently published an in-depth article on the current state of regenerative therapeutic products.

Medical Devices

• Creation of Breakthrough Device Pathway for Medical Devices. The Act establishes a breakthrough device pathway, which builds on the existing priority review device pathway.

• Increase in Humanitarian Device Exemption Cap. The FDA will now have the authority to apply the humanitarian device exemption to devices that treat diseases and conditions that affect up to 8,000 individuals in the U.S. The current cap is 4,000.

• Updates to Class I and II Devices. FDA is requires to update lists regarding the appropriate regulation of Class I and Class II devices.

• Institutional Review Board Flexibility. The Act strikes the requirement that a sponsor of a medical device trial always use a local institutional review board. This change will allow the use of centralized IRB models, which FDA has published guidance on in the past.

• Least Burdensome Device Review. The Act clarifies that FDA reviewers shall consider the least burdensome appropriate means necessary for demonstrating a reasonable assurance of safety and effectiveness when requesting additional information from manufacturers during the pre-market approval (PMA) process. The Act also requires an audit by the FDA ombudsman and an assessment of the measurements used to track the implementation of the least burdensome requirements.

• Clarifying Medical Software Regulation. The Act identifies 5 specific categories of medical software that, given certain conditions, will not be regulated as a medical device by the FDA based on their low level of risk to patients. It also provides FDA with the authority to regulate software in these categories if there is found to be safety concerns.

Combination Products

• Classification of Devices Used with Regenerative Advanced Therapies. The Act establishes that devices used with a regenerative therapeutic product will be considered moderate risk devices, unless the Secretary determines that the device or intended use requires a higher risk classification.

• Dispute Resolution for Combination Products. The Act clarifies how dispute resolution works when the different centers of the FDA do not agree on how to treat a combination product. Combination products are products that contain both a drug and device.

Commentary

Will the Act in fact accelerate the process of bringing drugs and devices to market? The answer depends on numerous factors including the stance of the new administration as well as how FDA approaches the regulations needed to implement the Act.  Further complicating the Act’s implementation is the fact that the FDA is either opposed to, or at least conflicted about, some of the provisions. For example, the FDA has previously objected to the Pediatric Rare Disease Priority Review program which essentially allows companies to jump the review line.  And there is always the issue of money. The FDA has been allocated $500 million over 10 years to implement these changes. Whether that will cover these ambitious reforms is certainly an open question.

Future posts will dive deeper into a number of these and other provisions, including those related to:

• Medical software

• Real world evidence

• Intercenter Institutes at FDA

• Human Subject Protections