United States: 21st Century Cures: Food And Drug Administration (FDA) Drug Provisions

Summary

The 21st Century Cures Act, substantial legislation intended to accelerate "discovery, development and delivery" of medical therapies by encouraging biomedical research investment and facilitating innovation review and approval processes, among other things, was signed into law by President Obama on December 13. The legislation includes portions of five previously introduced bills relating to FDA regulation of drugs, biologics, and combination products. 

This On the Subject summarizes the FDA drug-related provisions in title III of the new legislation. Our continuing coverage of the 21st Century Cures Act addresses additional titles and provisions.

In Depth

On December 7, 2016, the US Congress approved the 21st Century Cures Act, substantial legislation intended to accelerate "discovery, development and delivery" of medical therapies by encouraging biomedical research investment and facilitating innovative review and approval processes, among other things. The massive bill, however, also served as a vehicle for a variety of other health-related measures, including portions of:

  • Advancing Targeted Therapies for Rare Diseases Act of 2016,
  • Patient-Focused Impact Assessment Act of 2016,
  • Promise for Antibiotics and Therapeutics for Health (PATH) Act,
  • Combination Products Regulatory Fairness Act of 2016, and
  • FDA and NIH Workforce Authorities Modernization Act.

These bills were introduced, but not advanced by the Senate.

On December 13, 2016, President Obama signed the bill into law. This On the Subject summarizes the Food and Drug Administration (FDA) provisions in title III that pertain to drugs.

Overview of the Drug Provisions in the Cures Act

The drug provisions of the Cures Act are generally friendly to sponsors and manufacturers, and largely impose additional requirements on FDA. In general, the Cures Act provisions seek to:

  • Expedite the review process for certain drugs,
  • Facilitate the recognition of drug outcome measures,
  • Encourage the consideration of data beyond that produced in randomized clinical trials to support approval,
  • Create a new priority review voucher (PRV) for material threat medical countermeasures,
  • Extend the current rare pediatric disease PRV program,
  • Clarify the scope of permissible dissemination of health care economic information (HCEI) by manufacturers, and
  • Require manufacturer publication of expanded access policies.

Why These Provisions Matter

Changes to the Review and Approval Process Generally

The Cures Act does not modify the statutory standard for the approval of a new drug or biologic. As outlined below, however, the Cures Act included several provisions that may impact the types of evidence FDA will consider when deciding whether individual products meet the statutory standard.

The codification of FDA's current guidance-based qualification process for Drug Development Tools (DDT)—e.g., biomarkers, clinical outcome assessments, and other methods, materials or measures—may benefit drug developers and biomedical research consortia, promote drug innovation and expedite review of regulatory applications. The Cures Act requires FDA to create a process by which a sponsor, consortia or other requestor can seek to qualify a DDT for its proposed context of use. A DDT is qualified if FDA determines its proposed context of use can be relied upon to have a specific interpretation and application in drug development and regulatory review. Qualified DDTs may be used to support or obtain approval or licensure of a drug or biologic, or to support an investigational use. Companies developing drugs for conditions that lack well-established outcome measures, or for which existing measures fail to assess critical performance parameters, may benefit from an established process for the qualification of DDTs. FDA has also stated that companies can pool resources and data to develop a DDT, which may reduce the cost associated with development and recognition of such measures. 

Notwithstanding objections from certain consumer advocacy groups, the statute also requires FDA to establish a program to evaluate the potential use of "real world evidence"—i.e., data regarding the usage or potential benefits or risks of a drug that is derived from sources other than randomized clinical trials—in support of applications for new indications for FDA-approved drugs and/or to support or satisfy post-approval marketing requirements. FDA must, in consultation with industry, advocacy groups and others, draft a framework for the program's implementation, and then implement the program within two years of the law's enactment. 

Drug and biologics developers may also benefit from a provision that allows FDA to rely on a "qualified data summary"—a summary of clinical data that demonstrates the safety and effectiveness of a drug with respect to a qualified indication—to support the approval of applications for new uses of previously approved products. A qualified indication is an indication for a drug that FDA determines is appropriate for summary level review; the Cures Act does not, however, provide guidance on how FDA should assess whether an indication is "appropriate" for such review. A supplemental application is eligible for summary level review if (1) there is existing data available and acceptable to FDA that demonstrates the safety of the drug; and (2) data used to develop the qualified data summaries are submitted to FDA as part of the supplemental application.

Changes to the Review and Approval Process for Certain Drugs

Sponsors of drugs that FDA designates as regenerative advanced therapies (RAT)—e.g., cell therapies, therapeutic tissue engineering products, human cell and tissue products—may benefit from a provision authorizing priority review and accelerated approval. For a sponsor's drug to be designated a RAT by FDA, the drug must be intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and preliminary clinical evidence must indicate that the drug has the potential to address unmet medical needs for such disease or condition. A new drug application (NDA) or biologics license application (BLA) for a RAT may be eligible for accelerated approval through reliance on surrogate or intermediate endpoints reasonably likely to predict long term clinical benefit or data from a meaningful number of sites.

Similarly, sponsors of antibacterial and antifungal drugs intended to treat serious or life-threatening infections in a limited population of patients with unmet needs may benefit from the creation of a new "limited population" approval pathway. The new pathway is designed to expedite approval of these drugs without requiring large-scale clinical trials or testing in specific populations. The labeling and advertisements for such drugs must contain a statement that the drug's safety and effectiveness has only been demonstrated with respect to a "limited population," and the promotional materials for such drugs must be submitted to FDA prior to dissemination. FDA Commissioner Robert Califf explained that the drugs are to be "used narrowly ... while additional evidence is generated to assess safety and effectiveness for broader use."

Sponsors of genetically targeted or variant protein targeted drugs—drugs for the treatment of rare diseases or serious or life-threatening conditions which, respectively, may modulate the function of a gene or modulate the function of a product of a mutated gene—may benefit from a provision that enables FDA to permit a sponsor to rely on data previously developed and submitted by the sponsor (or another sponsor, with the appropriate right of reference) as part of an approved NDA or BLA. The law is intended to address the challenge of conducting clinical trials in small populations of patients, especially subgroups of patients with the same disease or condition but different genetic mutations. To be eligible under this provision, drugs must incorporate or use the same or similar technology as the drug in the previously approved application.

Priority Review Voucher Programs 

Sponsors of material threat medical countermeasures may benefit from the law's creation of a new Priority Review Voucher (PRV) program, which entitles the holder of a PRV to expedited FDA review of a subsequent drug product application within six months, which is four months faster than the standard review process. A sponsor would receive a PRV upon approval of an application for a material threat medical countermeasure application that (1) prevents or treats harm from biological, chemical, radiological or nuclear agents that present a material threat against the US population sufficient to affect national security or (2) mitigates, prevents or treats harm from a condition that may result in adverse health consequences or death, and may be caused by administering a drug or biologic against an agent that presents a national security threat. Like other PRV programs, holders must notify FDA before using the PRV, and the program sunsets on a date certain (October 1, 2023). PRVs issued under this program are also transferable, which, given the robust market for PRVs issued under other authorities, may make the program a significant incentive toward the development of "material threat" medicines.

Sponsors of drugs for rare pediatric diseases may benefit from the extension of the corresponding PRV program through September 30, 2020.

Dissemination of Health Care Economic Information

Manufacturers and others who disseminate "health care economic information" (HCEI) related to drugs and devices may benefit from the clarification and expansion of permissible communications. HCEI will not be considered false or misleading labeling if it (1) is disseminated to persons to whom such information may be communicated; (2) relates to approved indications and is based on competent and reliable scientific evidence; and (3) includes a "conspicuous and prominent statement describing any material differences" between HCEI and FDA-approved labeling. As compared with previous interpretations of labeling, advertising and misbranding provisions in the Federal Food Drug and Cosmetic Act (FFDCA) which restricted the content and contexts in which HCEI could be disseminated, the Cures Act provides greater flexibility. The Cures Act expands the audience to whom HCEI may be communicated (to include payors and similar entities with expertise in health care economic analysis that select drugs for coverage or reimbursement), expands the types of analysis that may be shared (to include clinical data, inputs, clinical or other assumptions, methods, results, and other components underlying or comprising the analysis, as well as separate or aggregated consequences from the represented health outcomes), and liberalizes the previous requirement that HCEI "directly relate" to approved indications (now HCEI must only "relate" to such indications). The provision does not apply, however, to any analysis that relates only to unapproved indications.

Susceptibility Test Interpretive Criteria

Holders of existing NDAs and BLAs must remove susceptibility test interpretive criteria, which characterize the susceptibility of bacteria or other microorganisms to the antimicrobial drug tested and categorize a drug's susceptibility (i.e., susceptible, intermediate, resistant), from approved drug labeling and replace the information with a reference to the newly-mandated FDA interpretive criteria website. Similarly, antimicrobial drugs approved after the website is created must reference the website in their labeling in lieu of susceptibility test interpretive criteria. The statute requires FDA to include certain disclaimers about the limits of safety and efficacy of such drugs, the clinical significance of susceptibility information and approved product labeling, on the website. Antimicrobial drug manufacturers and others may benefit from a provision permitting FDA to consider information provided by "interested third parties" when evaluating new or updated susceptibility test interpretive criteria standards.

Combination Products

In response to complaints that FDA improperly regulated certain combination products as drugs or biologics based on an overly restrictive application of the "primary mode of action" test, the Cures Act prohibits FDA from determining that a combination product's primary mode of action is that of a drug or biologic solely because the combination product has any chemical action within or on the human body. Chemical action in the body is a statutory concept that distinguishes a drug or biologic from a medical device. The Cures Act requires FDA to determine how a combination product will be regulated based on a new statutory definition of "primary mode of action," which focuses on the single mode of action expected to make the greatest contribution to the overall intended therapeutic effects of the combination product.

What Is Required by These Cures Act Provisions

Stakeholder-Related Requirements

Manufacturers or distributors of investigational drugs for serious diseases or conditions must make publicly available their expanded access policies on requests for such drugs within 60 days of the law's enactment or the initiation of a phase 2 or phase 3 study of an investigational drug, whichever date is later.

Requirements Imposed on FDA

FDA must issue guidance on:

  • The collection and use of patient experience data— data intended to provide information about patients' experiences with a disease or condition—in drug development (draft guidance due 18 months after enactment);
  • The process for qualification of DDTs (draft guidance due three years after enactment);
  • The circumstances under which drug sponsors and FDA may rely on real world evidence (draft guidance due five years after enactment);
  • Pre-submission interactions with sponsors developing combination products and submissions of information with meeting requests (final guidance due four years after enactment); and
  • The criteria, processes and considerations for demonstrating safety and effectiveness of limited population antibacterial and antifungal drugs (draft guidance due 18 months after enactment).

The agency may also issue updated guidance and regulations within one year of developing standards to support the development, evaluation and review of regenerative medicine therapies and RATs.

FDA must issue the following reports assessing:

  • The use of patient experience data in regulatory decision-making (by June 1 of 2021, 2025 and 2031);
  • The qualification process for DDTs (five years after enactment);
  • Approval of RATs, as well as the number of applications for which FDA granted accelerated approval or priority review (by March 1 of each year);
  • Approvals of antibacterial or antifungal drugs under the limited population pathway (every two years); and
  • The implementation of the new statute on the susceptibility test interpretive criteria (two years after enactment).

The Cures Act also requires FDA to take other actions:

  • Issue a draft framework for implementation of a program to evaluate real world evidence;
  • Post information on the review of supplemental applications that rely on qualified data summaries;
  • Develop standards and consensus definitions related to the development, evaluation and review of regenerative medicine therapies and RATs;
  • Provide advice to sponsors of limited population drugs on data needed for approval;
  • Identify, list and update susceptibility test interpretive criteria and susceptibility test interpretive criteria standards on the new FDA interpretive criteria website; and
  • Post guidelines of best practices for drug safety surveillance using the FDA Adverse Event Reporting System and criteria for public posting of adverse event signals.

Action Steps for Drug Manufacturers and Other Stakeholders

Manufacturers should re-evaluate the extent to which they hold promising data but set aside certain FDA submissions due to an inability to run the randomized controlled trials that would likely have been required. Insofar as one or more of the additional sources of evidence recognized in the Cures Act could support an application, sponsors should consider citing the Cures Act in negotiations with the agency regarding the amount and type of evidence required to support a successful application.

Manufacturers should also evaluate the extent to which new drugs or new indications for old drugs may be candidates for an expedited review pathway or a PRV, and evaluate the extent to which they have the data to support such applications or can generate the required information. Sponsors of genetically targeted drugs and variant protein targeted drugs should consider what previously submitted data may be used in support of subsequent NDAs and BLAs.

With regard to marketing and labeling, manufacturers should re-evaluate whether the relaxed restrictions on HCEI might make it more feasible to proactively address payor and other reimbursement issues that they previously declined to discuss due to regulatory concerns.

Finally, insofar as many of the above provisions require FDA to take steps to implement the changes envisioned by Congress, stakeholders such as manufacturers, clinical trial sponsors, academic institutions, clinicians, industry organizations and standard setting organizations should consider participating in public meetings or other outreach efforts by FDA to develop or revise applicable standards, guidance documents and regulations.

21st Century Cures: Food And Drug Administration (FDA) Drug Provisions

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Authors
Similar Articles
Relevancy Powered by MondaqAI
Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
 
In association with
Related Topics
 
Similar Articles
Relevancy Powered by MondaqAI
Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
Related Articles
 
Related Video
Up-coming Events Search
Tools
Print
Font Size:
Translation
Channels
Mondaq on Twitter
 
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
 
Email Address
Company Name
Password
Confirm Password
Position
Mondaq Topics -- Select your Interests
 Accounting
 Anti-trust
 Commercial
 Compliance
 Consumer
 Criminal
 Employment
 Energy
 Environment
 Family
 Finance
 Government
 Healthcare
 Immigration
 Insolvency
 Insurance
 International
 IP
 Law Performance
 Law Practice
 Litigation
 Media & IT
 Privacy
 Real Estate
 Strategy
 Tax
 Technology
 Transport
 Wealth Mgt
Regions
Africa
Asia
Asia Pacific
Australasia
Canada
Caribbean
Europe
European Union
Latin America
Middle East
U.K.
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.

Disclaimer

The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.

General

Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions