Aug 15 2012

FDASIA, Part 4: Drug Supply Chain, Drug Shortages, and Other Provisions

FDASIA Part 4On 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)


Title VII of FDASIA, Drug Supply Chain, creates new systems and makes other changes to ensure the safety of drugs through domestic and foreign establishment registrations, inspections, and new penalties.  Here is a summary of the major provisions in the Drug Supply Chain.

  • Establishments must be registered annually between 01 October and 31 December.
  • Directs the FDA to create a Unique Facility Identifier (UFI) system to electronically store registration and listing information for establishment registration
    • Excipient manufacturers and commercial importers also are also required to have a UFI.
    • If a drug or device is from a unregistered facility, it will be misbranded.
    • Requires foreign establishments to register with the name, UFI, email address, US agent, and names of importers or those who offer to import drugs.
    • Device establishments will be inspected biennially.
    • Drug establishments will be inspected on a “risk-based schedule” based on compliance history, recall history, risk of manufactured drug(s), inspection frequency and history, whether a foreign inspection has occurred, and “any other criteria deemed necessary and appropriate”.
    • Allows the FDA to request records or other information in advance or in lieu of an inspection.
    • Drugs will be misbranded if manufactured at any establishment that “delays, denies or limits and inspection, or refuses to permit entry or inspection”.  A guidance with further definitions will be released within 1 year of FDASIA passage.
    • cGMPs are to include “managing the risk and establishing the safety of raw materials, materials used in the manufacturing of drugs, and finished drug products.”
    • Foreign government inspections of foreign registered establishments will be recognized if the FDA deems the government  has the capability to conduct inspections.
    • The FDA has the ability to both protect confidential information from foreign governments and to exchange information with foreign governments upon a written agreement.
    • By 01 Feb 2014, the FDA will issue a report on their website of the number or domestic and foreign establishments registered in the previous year; the number and type of establishments that were inspected in the previous year that produce active ingredients, excipients, or finished drug products , and the percentage of the budge the FDA used to complete inspections in the previous year.
    • A new standard of admission, including a risk-based approach to screening, for imported drug products will be implemented, and regulations will be promulgated within 18 months.
    • Requires a “regulated person” to notify the FDA if they know that a drug may result in injury or death, that a drug has been stolen and is intended for use in the US, or if a drug has been counterfeited.
    • Establishes drug adulteration penalties of imprisonment for not more than 20 years or fines not more than $1 million.


FDASIA implements several new policies to prevent, identify, and correct shortages in the supply of prescription drugs, including the following:

  • The requirement that the manufacturer of a drug that is life-supporting, life-sustaining, or “intended for use in the prevention or treatment of a debilitating disease or condition” submit a notice to the FDA of a discontinuation or interruption of the manufacture of the drug that could lead to a “meaningful disruption” to the supply of the drug.  The notice must be submitted at least 6 months prior to the discontinuation or interruption or “as soon as practicable.”
  • The requirement that the FDA submit an annual report to Congress detailing the manufacturers reporting potential drug shortages and the communications concerning the FDAs actions to prevent drug shortages.
  • The establishment of a drug shortage list.
  • The establishment of a task force to “develop and implement a strategic plan” to enhance the FDA’s ability to prevent and mitigate drug shortages.
  • The requirement to conduct a study that examines the cause of drug shortages and formulates recommendations on the prevention and alleviation of such shortages.


  • Requires the FDA to optimize global clinical trials and to accept data from foreign clinical investigations if the applicant demonstrates that such data are adequate.
  • Reauthorizes of enantiomer marketing exclusivity and critical path public-private partnerships.
  • Creates of new standards to established designated medical gases, certify medical gases, define approved uses for medical gases, and, when used alone or in combination with another medical gas will not be assessed drug fees.
  • Adds synthetic drugs, including “cannabimimetic agents” to Schedule I of the Controlled Substances Act.
  • Requires the FDA to “intensify and expand activities” to enhance scientific knowledge of nanomaterials included in products regulated by the FDA.
  • Reduces the time for the FDA to respond to a Citizen’s Petition for a request a stay on pending generic AND biosimilar applications from 180 days to 150 days.
  • Requires the issuance a guidance within 2 years describing its policy on product promotion using the internet .
  • Requires the FDA to issue a report with findings and recommendations on preventing prescription drug abuse
  • Requires the FDA to “develop and implement strategies to solicit the views of patients” during development and regulatory processes.
  • Modifies the REMS system to allow review and modification to approved REMS strategies.  The FDA will review and act on a proposed modification within 180 days unless it’s a minor modification or a modification due to safety label changes, in which case the FDA will review and act within 60 days.
  • Requires a public meeting, with stakeholder input, to discuss hydrocodone scheduling.
  • Requires the establishment of a strategy and implementation plan to advance regulatory science for medical products to “promote public health and advance innovation”.
  • Requires the submission of a report to Congress within 1 year about a “comprehensive information technology strategic plan” for the FDA.
  • Requires submission of a report to Congress within 1 year about “any problems posed pharmacy Internet Web sites”.
  • Requires submission of a report to Congress within 1 year about FDA resources for small businesses and the number of applications by small businesses under the Orphan Drug Act
  • Extends the date for compliance with the Labeling and Effectiveness Testing run for over-the-counter sunscreens.
  • Requires submission of a “strategic integrated management plan” for CDER, CBER, and CDRH to identify common strategic goals and mechanisms, to describe the recruitment, training and retention of employees, and to identify results-oriented methods to measure progress.
  • Gives ANDA applicants with a Paragraph IV patent certification 40 months (if filed between 09 July 2012 and 30 September 2015) or 36 months (if filed between 1 October 2015 and 30 September 2016) to obtain tentative approval and still maintain 180-day exclusivity.  Additionally, if the ANDA with  Paragraph IV patent certification is amended between 10 July 2012 and 30 September 2017, then the date of filing the amendment will be the beginning of the 30 month period.
  • Establishes a 270 day deadline for the FDA to respond to citizen petitions for withdrawal of reference listed drugs.
  • Requires the FDA to develop a communication plan to ensure adequate information regarding pharmaceuticals for all populations, especially underrepresented subpopulations including racial subgroups.
  • Requires electronic submissions of NDAs, INDs, ANDAs, reference product and biosimilar BLAs no earlier than 24 months after the issuance of a guidance on electronic formatting of submissions.  Additionally, it requires the submission of an electronic copy of submissions for devices after the issuance of a final guidance.
  • Requires the FDA to conduct a study on electronic drug labeling and to submit a report to Congress on the results of the study within 1 year.
  • Allows the FDA to facilitate the exchange of prescription drug information across state lines and to submit a report to Congress within 1 year on enhancing the interoperability of state prescription drug monitoring programs.
  • Updates the conflicts of interest regulations for potential members of advisory committees
  • Requires the FDA to notify Congress at least 60 days before the issuance of a guidance about the regulation of laboratory-developed tests.