Department of Health and Human Services DHHS Food and Drug Administration FDA Center for Drug Evalua

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Department of Health and Human Services
(DHHS)Food and Drug Administration (FDA)Center
for Drug Evaluation and Research (CDER)

• CDER Drug Shortage Program

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Drug Shortage Presentation

• Overview of Drug Shortage Program (DSP)
• Drug Shortage Management Process
• Ongoing Issues Related to Shortages
• Who to Contact

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CDER Drug Shortage Staff

• Drug Shortage Program Staff
• Coordinator (Dr. Mark Goldberger)
• Drug Shortage Project Managers (CDR Valerie
  Jensen and LCDR Jouhayna Saliba Christine Moser
  LT Yon Yu)
• Network of FDA liaisons
• -Office of Compliance (Recall Manager/Shortage
  Coordinator)
• -Office of Generic Drugs (CAPT Harvey Greenberg)
• -CDER Review Division Contacts
• -CDER Drug Information (LCDR Larry Lim)
• -ONDQA Chemistry Consultant (Dr. Eric Duffy)

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Liaison Roles

• DSP works closely with the following entities to
  manage shortages
• - Other Government Entities
• - Regulated Industry
• - Professional Associations
• - International Organizations
• - Public

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Reasons for Shortages

• Bulk drug/API shortage
• Corporate decisions
• Manufacturing difficulties/Compliance Issues
• Market Concentration/Limited Capacity
• Changes in Clinical Practice
• Hospital/Pharmacy based issues
• Emergency Situations (natural disasters/CT
  related)

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REASONS FOR SHORTAGES
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Reporting a Shortage

• Shortages may be reported to CDER Drug Shortage
  Program from the following sources
• Pharmaceutical companies
• Professional organizations healthcare providers
  patients (through our public e-mail account/phone
  number)
• Other FDA offices

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Shortage Management Process

• Verify that a national shortage exists
• Communications with pharmaceutical companies
  wholesaler/distributors
• Market share data
• Maintain contact with professional organizations
  to know what is actually happening at the
  hospital/pharmacy level

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Shortage Management

• Obtain determination of Medical Necessity (MN)
  from appropriate Review Division(s)
• CDER Review Division(s) with clinical expertise
  in that area makes decision regarding Medical
  Necessity
• Off label uses as well as labeled uses are
  considered
• Investigational drugs can also be medically
  necessary

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Determination of Medical Necessity

• Seriousness of the disease
• Availability of alternatives
• Role of the firm
• Consequences of this determination
• -How proactive we need to be
• -The potential role of enforcement discretion

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Definition of a Medically Necessary Product

• A product is considered to be medically
  necessary if it is used to treat or prevent a
  serious disease or medical condition and there
  is no other adequately available source of that
  product or alternative product that is judged by
  medical staff to be an acceptable substitute.
  Inconvenience alone is an insufficient basis to
  classify a product as a medical necessity.

NOTE drug shortages focuses on Medically
Necessary products since they have the greatest
impact on the public health
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Medical Necessity Determination

• 2005 data
• Products evaluated as NMN 32
• Products evaluated as MN 68

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Albuterol Inhalers

• Background CFCs vs. HFAs
• Federal Register notice
• One firm exited the CFC market earlier than
  anticipated (30 of mkt)
• FDA had no advance notice
• FDA met with all firms to work on short term and
  long term management plan
• FDA receives weekly inventory updates from all
  firms

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Albuterol Inhalers (cont.)

• Working with firms and professional
  organizations such as ASHP to make the
  transition from CFC to HFA inhalers as smooth as
  possible
• HFA inhalers anticipated to increase
  significantly in relation to the CFCs over the
  next year
• Total albuterol inhalers expected to meet demand
  (no shortage is anticipated)
• During the transition some patients will need to
  be switched to HFA products
• FDA Considers CFC and HFA inhalers to be
  clinically interchangeable
• Post December 31st 2008 only albuterol HFA
  inhalers will be available on the market

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Methotrexate Injection

• cGMP issues at manufacturing site
• Site shut down to upgrade facility
• 2 firms used the same manufacturing site (both
  hold a significant of overall market)
• Other suppliers ramped up to cover shortfall
• One firm supplies the same product for ROW and
  Division expedited approval of NDA and used
  regulatory discretion to allow product with ex-US
  label to be used until US label approved

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5-Fluorouracil

• cGMP issue with product (involved glass particles
  in vials)
• Firm initiated recall of affected lots and
  quarantined all current inventory
• Oncology Division Drug Shortage and Compliance
  worked with the firm to resolve issues so
  inventory could be released due to drug shortage
• Product was released with corrective action (use
  of filter needle with product) due to medical
  need (benefit outweighs the risk)
• Firm completed long term resolution of problem

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Shortage Management

• Facilitate formulation of short term/long term
  plan for shortage management (e.g. Division(s)
  Compliance Company)
• Manage communications post information on Drug
  Shortage website share information with
  pertinent healthcare professional organizations
  patient groups

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Actions that can be taken in the Event of a
Shortage

• Protocol for limited distribution
• Expedite
• -Pharm-tox or CMC reviews
• -Plant inspections
• -New marketing application (NDA/ANDA)
• Identify alternate supply sources
• Request company to continue manufacturing a
  product which they plan to discontinue
• Encourage other manufacturers to ramp-up
  production
• Utilize Regulatory Discretion (when benefit
  outweighs any risks involved)
• Allow temporary imports (RARE)

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Ongoing Issues Related To Shortages

• FDA cannot force a manufacturer to produce a
  product
• Manufacturers are not required to report plans to
  discontinue producing a product unless it is a
  sole source product for a life-supporting/life-sus
  taining condition. (Section 506C of the Food
  Drug and Cosmetic Act)
• Communication/interaction with firms improving

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Discontinuance Regulation

• Section 506C of the Food Drug and Cosmetic
  Act
• A manufacturer that is the sole manufacturer of a
  drug that is life-supporting life-sustaining or
  intended for use in the prevention of a
  debilitating disease or condition for which an
  application has been approved under section
  505(b) or 505(j) and that is not a product that
  was originally derived from human tissue and was
  replaced by recombinant product shall notify the
  Secretary of a discontinuance of the manufacture
  of the drug at least six (6) months prior to the
  date of the the discontinuance
• Proposed Rule published in Federal Register
  November 7 2000

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Ongoing Issues

• Critical to have advance notice of any potential
  shortage situation (plant closures cGMP issues
  import problems)
• Early determination of impact of shortage (market
  share data alternate sources)
• Increasing number of shortages and greater
  public interest
• Enhance public access to shortage information
  (website e-mail account partnership with
  American Society of Health-System Pharmacists and
  other professional organizations)

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Proactive approaches to preventing shortages

• FDA
• -Enhanced product monitoring (Critical Product
  database)
• -Contacts established and maintained with all
  manufacturers and distributors
• -Earlier information on potential problems
• -Interface with trade organizations such as
  GPhA PDA
• Industry/Trade organizations
• -Alternate manufacturing sites
• -Alternate sources of material
• -Increased inventories of selected products
• -Better understanding of available capacity

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Contacts

• CDER Drug Shortages
• CDR Valerie Jensen LCDR Jouhayna
  Saliba Christine Moser and LT Yon Yu
• Phone [phone]
• Email drugshortages_at_cder.fda.gov Web
  address http//www.fda.gov/cder/drug/shortages/d
  efault.htm

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