Jul 27 2012

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

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 mandates that within 18 month of enactment of FDASIA, at least one public meeting must be held to “discuss ways to encourage and accelerate the development of new therapies for pediatric rare diseases.”  Within 180 days of that meeting, the FDA must issue a report including a strategic plan for the development of these therapeutics.

Additionally, FDASIA makes both the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) permanent.  BPCA was enacted in 1997 as part of the Food and Drug Administration Modernization Act (FDAMA) and provides 6 months of marketing exclusivity for studies of drugs and biologics performed in the pediatric population.  BPCA has been renewed every 5 years, with some changes, since 1997.  PREA became law in 2003 and requires sponsors to conduct pediatric studies for NDAs, BLAs, and supplements to such application.

FDASIA provisions in PREA include the following:

  • Details on the pediatric study plan:
  • Must contain an outline of the pediatric studies and any request for a waiver or deferral .
  • To be submitted within 60 days after an end-of-phase 2 meeting, unless an alternate date is agreed upon by the applicant and the FDA.
  • FDA will either meet with the applicant to discuss the plan or provide written comments within 90 days of receipt of study plan.
  • Within 90 days of the above meeting or written comments, the applicant must document agreement on the study plan.
  • The FDA will confirm the agreement within 30 days.
  • In certain cases, the ability to extend of PREA deferral deadlines. (Deferrals and waivers are detailed here).  Sponsors must submit an extension request within 90 days before the current deadline expires and the FDA will respond within 45 days.
  • The issuance of a “non-compliance letter” upon the failure to submit a required pediatric assessment, keep a deferral current, or submit a request for pediatric formulation approval.  These letters require a response within 45 days, and the letters as well as the responses will be made public.
  • The Pediatric Review Committee is required to consult on the review of the pediatric study plan and significant amendments.

FDASIA provisions in BPCA include the following:

  • To qualify for 6 months of pediatric exclusivity, the applicant must receive a Written Request from the FDA for pediatric studies.  FDASIA requires that if the Written Request does not require neonatal studies, the rationale for not requiring the studies must be described.
  • Within 3 years of FDASIA implementation, the FDA must make public the medical, statistical, and pharmacology reviews from studies submitted between 04 Jan 2002 and 27 Sept 2007 that resulted in market exclusivity or a labeling change.
  • The Pediatric Review Committee must issue internal standard operating procedures for the review of “significant modifications” to pediatric study plans or Written Requests.  These SOPs must be in place by July 2013.
  • Studies performed under PREA can be used for BPCA exclusivity if the studies are described in the Written Request


  • Investigational Device Exemptions: Adds language that the FDA shall not disapprove an IDE application solely because the study may be unlikely to support a  510(k) or PMA.
  • Clarification of Least Burdensome Standard: Defines that the “necessary” clinical data to support device clearance or approval as “the minimum required information that would support a determination by the Secretary that an application provides reasonable assurance of the effectiveness of the device.”
  • Agency Documentation and Review of Significant Decisions: Requires that the FDA provide, upon request, a summary of the scientific and rationale for any “significant decision” regarding a submission or review of a report of IDEs, 510ks, and PMAs.  The applicant has 30 days to request an appeal.  The FDA must decide the appeal within 45 days of the request, or within 30 days after a meeting discussing the appeal (if one was held).
  • Device Modifications Requiring Premarket Notification Prior to Marketing: Requires the FDA to withdraw the Guidance “510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device” and to provide Congress (within 18 months) with a report regarding when a new 510(k) is needed for a change to a legally marketed device.  The 1997 Guidance is still in effect.
  • Program to Improve the Device Recall System: Requires the FDA to establish a program to assess information relative to device recalls and to use that information to identify strategies to mitigate health risks; to clarify procedures for device audit checks; to develop criteria for assessing if an effective CAPA plan was instituted for the recall; and to document the basis of termination by the FDA for the recall.
  • Clinical Holds on IDEs: Allows the FDA to place a clinical hold on IDEs if there is an “unreasonable risk to the safety of the persons who are subjects of the clinical investigation” or for other reasons that the FDA may establish.  If a sponsor requests a removal of a clinical hold, the FDA will respond within 30 days.
  • Modification of de Novo Application Process: Allows a sponsor to directly request a classification of a device if there is no predicate device available.  If the FDA agrees that the device is of “low-moderate risk” and that there is, indeed, no predicate device, the FDA will issue the classification within 120 days.
  • Reclassification Procedures: Allows the FDA to change the classification of a device by administrative order after a publication of the proposed reclassification, a meeting of the device reclassification panel, and consideration of public comments to the proposal.
  • Harmonization of Device Premarket Review, Inspection, and Labeling Symbols: Allows the FDA to “enter into arrangements” for international device regulation harmonization.
  • Participation in International Forums: Allows the FDA to participate in international forums to discuss harmonization of regulatory requirements, to seek public input on harmonization and, likewise, inform the public of the FDA’s activities.
  • Reauthorization of ThirdParty Review and Inspection: Extends third-party review and inspection until 01 Oct 2017, deems that third-party accreditation is valid for 3 years, and gives the FDA 60 days after receipt of a request to approve or deny reaccreditation.
  • Humanitarian Device Exemptions: Allows manufacturers to profit from HDE devices in both pediatric and nonpediatric populations, and it removes the limit to profit on only up to 4,000 of each device per year.  Manufacturers of HUDs approved before 09 Jul 2012 can petition the FDA to allow future profits.
  • Unique Device Identifier (UDI): Directs the FDA to issue a proposed UDI rule by 31 Dec 2012 and to finalize that rule no later than 6 months after the close of the comment period.  The regulations will be implemented no later than 2 years after they are finalized.
  • Sentinel: Directs the FDA to use “private sector health-related electronic data” for postmarket risk analysis and identification.  The FDA must collect stakeholder input on the program.
  • Postmarket Surveillance: Allows the FDA to order postmarket surveillance at any time, and the manufacturer must commence surveillance within 15 months of the FDA order.
  • Custom Devices: Revises the definition of custom devices so that a custom device is “designed to treat a unique pathology or physiological condition that no other device is domestically available to treat” and be “assembled from components or manufactured and finished on a case-by-case basis” but “may have common, standardized design characteristics, chemical and material compositions, and manufacturing processes as commercially distributed devices.”  Additionally, the device must be for treating a rare condition, no more than 5 units per year can be produced, and the manufacturer must notify the FDA every year it produces a custom device.  The FDA must issue final guidance on custom devices within 2 years.
  • Health Information Technology: Requires the FDA to issue a report (within 18 months) on the proposed strategy and recommendations on a risk-based regulatory framework for health information technology, including mobile medical applications.
  • Good Guidance Practices Relating to Devices: Deems that “a notice to industry guidance letter, a notice to industry advisory letter, or any similar notice sets forth initial interpretations of a regulation or policy” shall be treated as a guidance document.
  • Pediatric Device Consortia: Authorizes $5.25 million to nonprofit consortia for pediatric device development.