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

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

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

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

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

5. 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)

6. REASONSFOR SHORTAGES

7. 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

8. 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

9. 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

10. 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

11. 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

12. Medical Necessity Determination 2005 data: Products evaluated as NMN 32% Products evaluated as MN 68%

13. 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

14. 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

15. 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

16. 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)

17. 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-sustaining condition. (Section 506C of the Food, Drug , and Cosmetic Act) Communication/interaction with firms improving Ongoing Issues Related To Shortages

18. 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 Discontinuance Regulation

19. 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)

20. 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

21. Contacts • CDER Drug Shortages Val Jensen or Jouhayna Saliba Phone: (301) 796-1300 Email: drugshortages@cder.fda.gov Web: www.fda.gov/cder/drug/shortages