introduction to u.s. drug shortages

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Introduction to U.S. Drug Shortages. CDR Emily Thakur, R.Ph. LCDR Helen Saccone, Pharm.D. U.S.Public Health Service Center for Drug Evaluation & Research U.S. Food & Drug Administration. Overview. U.S. Drug Shortage Trends Reasons for Drug Shortages FDAs Role View of the Future. - PowerPoint PPT Presentation


  • Introduction to U.S. Drug Shortages

    CDR Emily Thakur, R.Ph.LCDR Helen Saccone, Pharm.D.U.S.Public Health ServiceCenter for Drug Evaluation & ResearchU.S. Food & Drug Administration

  • Overview

    U.S. Drug Shortage Trends Reasons for Drug ShortagesFDAs Role View of the Future

  • Drug Shortage Program HistoryCenter for Drug Evaluation & Research Drug Shortage Program (DSP) began in 1999Today have 11 full time staff Many others in involvedMission: address potential and actual drug shortages Facilitate prevention and resolution of shortages by collaborating with FDA experts, industry, and external stakeholders Inform the public Outreach to healthcare professional organizations, patient groups and other stakeholdersWho works on this?

    Office of New DrugsOffice of ChemistryOffice of Generic DrugsOffice of ComplianceOffice of Regulatory AffairsField InspectorsMANY OTHERS!

  • Growing problem and FDA responseFDA website updated dailyStaffing and management coordinationPublic reports encouraged industry reports of problems even more soPublic workshop September 26, 2011Collaboration on system fixesAmerican Society of Healthcare Pharmacists (ASHP) Industry (GPHA, PhRMA, BIO)Prevent and mitigate individual shortages

  • Chart1








    All Dosage Forms Shortages

    Sterile Injectable Shortges

    U.S. Drug Shortages

















    All Dosage Forms Shortages

    Sterile Injectable Shortges

    U.S. Drug Shortages



  • 2011 Shortage Data

    There were 251 shortages reported in 2011High percentage are sterile injectable productsTreatments for cancer, anesthesia, serious illnessHighly specialized manufacturing High risk to patient if not meticulous

    When there are quality or production problemfor a sterile injectable drug, a shortage is almost always results

  • Sterile Injectables:> 75% lapsed product quality & production

  • Reasons for Shortages: Sterile InjectablesReport by Assistant Secretary for Planning & Evaluation 2011

    State of the industrySeven (7) manufacturers make up most of marketContract manufacturers firms contract out manufacturing as well as acting as contract manufacturersLack of redundancy Multiple products made on existing manufacturing lines 24/7 production with no cushionComplex manufacturing processNo simple fixesProblems typically affect multiple productsInvestment economics question e.g., propofol 20ml sells for $0.48/vial

  • Quality and Manufacturing ExamplesLack of sterility Particulates of foreign matterCrystallization of the active ingredientPrecipitatesNew/unintended impurities or degradantsEquipment breakdownNatural disasters

  • What doesnt cause shortagesIncreased stringency of CGMPs & standards Increased inspections/enforcement actionsForeign manufacturingUnapproved drugs initiativesDrug approval delays

  • How does FDA fit?Patient care is our #1 concernWe get involved when we are informedSeek ways to prevent & mitigate shortagesSecondary response to industry problemFind root cause and get manufacturer on trackSome shortages can be prevented, but not allUnforseen breakdown in manufacturing systemLongstanding quality manufacturing problemsSome can be addressed quickly, others notRisks to the patient always considered

  • FDAs RoleFDA is responsible for protecting the public health by assuring the safety and efficacy of drugsFDA facilitates responses to prevent or mitigate a drug shortage when we are aware of itThis is a secondary response to mitigate a problem that has already happened

  • Medical NecessityA medically necessary drug product is a product that is used to treat or prevent a serious disease or medical condition for which there is no other alternative drug, available in adequate supply, that is judged by medical staff to be an adequate substitute

    CDER Manual of Policies and Procedures on Drug Shortage Management 6003.1

  • Regulatory discretion: allow manufacture of medically necessary product(s) to continueMinor, low risk issues usually best suited for this toolIn some cases require additional safety controlsRequest other firms to ramp up manufacturing.Expedite any review of company proposals In rare cases, controlled temporary importation from unapproved sourcesFDA Tool Box

  • What cant FDA doMandate firms to continue to manufacture products at certain quantities Require DEA to increase quotas of controlled substances Publish the exact cause of manufacturing/ quality issues Be consultants to manufacturers to fix quality problemsBuild robust quality management systems (QMS) and build in quality at manufacturing firms

  • What Can Prevent ShortagesCommitment to quality from senior management down to line workers Proactively identify & promptly correct issuesDesign/qualify robust operationsReinvestment into equipment, facilities and personnel Investigate problems to identify and fix root cause

    Anticipate supply problemsPlan ahead by adding redundancy to manufacturing & raw material suppliesArrange for additional manufacturing capacityDevelop alternate supplies of components

    It is important to consider the root cause of a shortageIf the root cause that leads to a shortage can be prevented, one can get to primary prevention

  • CommunicationGood agency-industry communication can facilitate resolution of a drug shortage. FDA is committed to working with industry to quickly resolve any quality or manufacturing problems that arise to ensure continued patient access to vital safe and effective medicinesCAPT Valerie JensenFDA Drug Shortage Program

  • CommunicationProblem of drug shortages is complex and multifaceted-requires continued collaborations Communication and collaboration with groups has become increasingly important- DSP has taken a proactive approachDSP routinely communicates with manufacturers, health care professionals, stakeholders, organizations, patient advocate groups, and others

  • CommunicationNotify FDA Drug Shortage Program (DSP) of potential and actual supply problemContact FDA DSP with creative strategies to mitigate shortagesContingency plans to increase capacityInterested in coming into the market to alleviate shortagesPresidents Executive Order issued 10/31/11 encouraged more voluntary reporting by manufacturers6 fold increase in notifications of potential shortagesnormally received 10/month on average in 2010 and now receiving over 60 notifications per month

  • 2011 Data Higher Executive Order Presidents Executive Order issued 10/31/11 encouraged more voluntary reporting by manufacturers

    6 fold increase in notifications of potential shortagesnormally received 10/month on average in 2010 and now receiving over 60 notifications per month)Total of 195 shortages prevented in 201142 shortages prevented as of April 28, 2012

  • DISCONTINUANCE OF A LIFE SAVING PRODUCTSEC. 506C. [ 21 U.S.C. 356c] DISCONTINUANCE OF A LIFE SAVING PRODUCT. (a) IN GENERAL.A manufacturer that is the sole manufacturer of a drug (1) that is (A) life-supporting; (B) life-sustaining; or (C) intended for use in the prevention of a debilitating disease or condition; (2) for which an application has been approved under section 505(b) or 505(j); and (3) that is not a product that was originally derived from human tissue and was replaced by a recombinant product, shall notify the Secretary of a discontinuance of the manufacture of the drug at least 6 months prior to the date of the discontinuance.

    See also 21CFR 314.81(b)(3)(iii)

  • 38 Shortages Prevented in 2010All due to firms notifying FDA of problems early16 through regulatory discretion Risk of quality/manufacturing issue able to be mitigated and was outweighed by benefit of the drug13 through expedited review New manufacturing sites, suppliers, etc.8 through encouraging other firms to ramp up1 through communication with DEA regarding firms need for controlled substance quota increase

  • 195 Shortages Prevented in 2011Most due to firms notifying the FDA of early problemsThe main FDA action taken to prevent drug shortage was Expedited ReviewOther actions taken include:Regulatory discretionRamping up productionAssistance with releaseExtension of expiry of available productsAdditional testing

  • Recent Public Outreach FDA Drug Shortage Website Public Meeting FDA Report Review of FDAs Approach to Medical Product ShortagesLetter to IndustryGuidance for Industry Notification to FDA of Issues that May Result in a Prescription Drug or Biological Product ShortageInterim Final Rule Revision of Postmarketing Reporting Requirements Discontinuance Meetings with stakeholders PhRMA, ASHP, GPhA, BIO, Eli Lilly, Amgen, and others

  • Shortages cant always be preventedUnanticipated problems, such as a manufacturing line breakdown or natural disasterManufacturer(s) may not be able to make up production shortfallRisks are significant and would cause patient harm (e.g. sterility problems) FDA will work with company to encourage smart distributionNo easy answers on how to do this well

  • The FutureFDA Drug Shortage work will continueMultidisciplinary: clinicians, pharmacists, chemists, biotechnology, regulatory and manufacturingWe can only prevent shortages if problems are reportedPublic communication of existin


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