Aug 07 2012

FDASIA, Part 3: Generating Antibiotic Incentives Now (GAIN) and Drug Approval and Patient Access Changes

On 09 July 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA, otherwise known as PDUFA V) was signed into law.  In a 4-part weekly series, we are covering the major changes in FDASIA as follows:

Part 1: The “UFAs”: PDUFA, MDUFA, GDUFA, and BsUFA

Part 2: Pediatric Drugs and Devices and Medical Device Regulatory Improvements

Part 3: Generating Antibiotic Incentives Now (GAIN), and Drug Approval and Patient Access Changes (including updates to accelerated approvals and the new “Breakthrough Therapies” program)

Part 4: Drug supply chain changes, Drug Shortages, and Other Provisions (including provisions for nanotechnology and citizen petitions)


FDASIA created Section 505E for Qualified Infectious Disease Products (QIDPs).  A QIDP is defined as “an antibacterial or antifungal drug for human use intended to treat serious or life threatening infections” including those caused by antibiotic or antifungal resistant pathogens, novel or emerging infectious pathogens, or “qualifying pathogens”.  A qualifying pathogen is defined as “a pathogen identified and listed by the Secretary…that has the potential to pose a serious threat to public health.”  The FDA is required to establish and maintain a list of qualifying pathogens and to adopt final regulations for QIDPs by 09 Jul 2014.  There will be a 60 day comment period on the proposed rules, and the rules must be published 30 days before the effective date. 


  • Exclusivity:
    • NCE Exclusivity: 10 years (ANDAs for QDIPs that are NCEs cannot be submitted until 9 years after approval)
    • Clinical Investigation Exclusivity: 8 years
    • Orphan Drug Exclusivity: 12 years
    • Pediatric Exclusivity: Extends exclusivity by 6 months
  • Regulatory Pathway:
    • Sponsor can request QDIP designation any time before NDA submission, and the FDA will confirm or deny QIDP designation within 60 days of the request submission
    • Sponsors can request that the FDA provide written recommendations for “non-clinical and clinical investigations” for QIDP drug approval
    • QIDP designated drugs qualify for priority review IF the NDA is submitted after 09 Jul 2012
    • Sponsors can also request fast-track status
  • Guidances: The FDA must review and revise at least 3 guidance documents per year, including the following:
    • Reviewing guidances relating to the conduct of clinical trials for antibacterial and antifungal drugs
    • Revising guidances to ensure clarity regarding the procedures and requirements for approval of antibacterial and antifungal drugs
    • Address appropriate “animal models of infection, in vitro techniques, valid microbiological surrogate markers, the use of noninferiority versus superiority trials, trial enrollment, data requirements, and appropriate delta values for noninferiority trials”
    • Draft guidance that specifies how preclinical and clinical data can inform a streamlined pathogen-focused antibacterial drug development program and provides advice on approaches for the development of antibacterial drugs that target a more limited spectrum of pathogens

QIDP status does not apply to supplements to NDAs for which an extension is in effect or has expired; subsequent applications for a change in indication, route of administration, dosing schedule, dosing form, delivery system, delivery device, or strength for an approved drug; or a product that does not meet the definition of a QIDP.


FDASIA creates several new provisions to speed the development of drugs for life-threatening or rare diseases, including enhancing the fast-track system, developing a pathway for “breakthrough therapies”, and implementing a priority review voucher system for sponsors of treatments for pediatric rare diseases.

  • Enhancement of Accelerated Patient Access to New Medical Treatments
    • Designed to enhance the authority of the FDA to expedite development and access to novel treatments for patients with serious or life-threatening diseases or conditions
    • Expands the definition of accelerated approval to “ a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.”
    • Expands the types of evidence that can be used as a surrogate endpoint to epidemiological, pathophysiological, therapeutic, pharmacologic, or other evidence developed using biomarkers or other scientific methods or tools.
    • Postapproval studies must “verify and describe the predicted effect on irreversible morbidity or mortality or other clinical benefit”
    • Allows the FDA can withdraw approval if the sponsor fails to show due diligence in conducting postapproval studies, if postapproval studies fail to show benefit, or if there is evidence that the product is not safe or efficacious
    • Requires the FDA to conduct studies to develop new surrogate endpoitns and biomarkers
    • Requires the FDA to issue a draft guidance within 1 year about fast-track and accelerated approvals, including for drugs for rare diseases or conditions
  • Breakthrough Therapies
    • Drugs that are intended to treat a serious or life-threatening illness with preliminary clinical evidence that the drug has a substantial improvement over existing therapies on one or more clinically significant endpoints
    • Can request breakthrough therapy designation concurrently with or after the submission of an IND (the FDA has 60 days to respond)
    • Actions to expedite the review of a breakthrough therapy can include sponsor and review team meetings; FDA advice regarding drug development; cross-disciplinary review; taking steps to ensure the efficiency of clinical trials
    • Requires the FDA to issue a draft guidance within 18 months about the process of breakthrough therapy designation and the actions the FDA will take to accelerate the review of breakthrough therapies
  • Priority Review to Encourage Treatments for Rare Pediatric Diseases
    • Provides “priority review” (review and action within 6 months of receipt by the FDA) for applications of new treatments for rare pediatric diseases
    • The request for designation of a product for a rare pediatric disease must occur at the same time as orphan disease status or fast-track designation requests, and the FDA will make a determination within 60 days.
    • Directs the FDA to issue a priority review voucher to the sponsor of a rare pediatric disease product application.  The voucher is transferable and entitles the holder to priority review of a NDA or BLA.
      • The FDA must be notified of intended use of the voucher for an application no later than 90 days prior to application submission.  The priority review user fee is due at this time.
      • The voucher can be revoked if the pediatric drug for which the voucher was awarded is not marketed within 365 days of approval
    • Within 5 years of approval of the rare pediatric disease product, the sponsor must submit a report to the FDA including the estimated population in the US suffering from the disease, the estimated demand for the product, and the actual amount of the product distributed in the US.
  • Grants and Contracts for the Development of Orphan Drugs
    • Appropriates $30 million per year from 2013 to 2017 for grants and contracts for Orphan Products
  • Reporting of Demographic Subgroups in Clinical Trials
    • Requires the FDA to publish a report, within 1 year, addressing the extent to which clinical trial participation and the inclusion of safety and efficacy data by demographic subgroups is included in applications submitted to the FDA
    • Requires the FDA to publish an action plan, within 1 year, with recommendations to improve the analyses of data on demographic subgroups in product safety and efficacy summaries and in labeling
  • Accessibility of Information on Prescription Drug Container Labels by Visually Impaired and Blind Consumers
    • Directs the FDA to convene a working group to develop, within 1 year,  “best practices on access to information of prescription drug container labels for individuals who are blind or visually impaired”
    • The working group will consider the use of Braille, auditory means, enhanced visual means, and other relevant alternatives
  • Consultation with External Experts
    • Requires the FDA to establish a list of external experts with scientific or medical training on one or more rare diseases.  These experts will serve as consultants to the FDA to improve the efficiency of review of drugs for rare diseases and drugs and biological products that are genetically targeted
  • Risk-Benefit Framework
    • Requires the FDA to implement a structured risk-benefit assessment framework in the new drug approval process, which will not alter the criteria for an application for premarket approval of a drug.