Introduction to U.S. Drug Shortages

Transcription

1 Introduction to U.S. Drug Shortages CAPT Valerie Jensen, R.Ph. Associate Director Drug Shortage Program Center for Drug Evaluation & Research U.S. Food & Drug Administration 1 Overview U.S. Drug Shortage Trends Reasons for Drug Shortages FDA s Role View of the Future 2 1

2 Drug Shortage Program History Center for Drug Evaluation & Research Drug Shortage Program (DSP) began in 1999 Today have 11 full time staff Many others in involved Mission: 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 stakeholders Who works on this? Office of New Drugs Office of Chemistry Office of Generic Drugs Office of Compliance Field Inspectors MANY OTHERS! 3 Growing problem and FDA response FDA website updated daily Staffing and management coordination Public reports encouraged industry reports of problems even more so Public workshop September 26, 2011 Collaboration on system fixes American Society of Healthcare Pharmacists (ASHP) Industry (GPHA, PhRMA, BIO) Prevent and mitigate individual shortages 4 2

3 FDA Authorities are very limited What we can require Notification by sole source manufacturers* For discontinuance of product 6 months in advance No penalty for not reporting Notification of manufacturing changes What we can t require A company to make a drug or make more Notification of most production delays, etc. How much and to whom drug is sold or distributed FDA Drug Shortages Program is largely depends on voluntary notification by manufacturers and the public. 5 DISCONTINUANCE OF A LIFE SAVING PRODUCT SEC. 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 (b)(3)(iii) 6 3

4 Number As presented at the NCCS Cancer Policy Roundtable U.S. Shortages All Sterile Injectables Year 7 Sterile Injectibles: > 75% lapsed product quality & production Product Quality 54% Delays, capacity and loss of manufacturing site 25% Discontinuations 11% Raw Materials 5% New demand 4% Other 2% 8 4

5 2011 Shortage Data Over 250 shortages reported in 2011 High percentage are sterile injectable products Treatments for cancer, anesthesia, serious illness Highly specialized manufacturing High risk to patient if not meticulous When there are quality or production problem for a sterile injectable drug, a shortage is almost always results 9 Reasons for Shortages: Sterile Injectibles Report by Assistant Secretary for Planning & Evaluation 2011 State of the industry Seven (7) manufacturers make up most of market Contract manufacturers firms contract out manufacturing as well as acting as contract manufacturers Lack of redundancy Multiple products made on existing manufacturing lines 24/7 production with no cushion Complex manufacturing process No simple fixes Problems typically affect multiple products Investment economics question e.g., leucovorin injection < $5.00/vial 10 5

6 How does FDA fit? Patient care is our #1 concern We get involved when we are informed Seek ways to prevent & mitigate shortages Secondary response to industry problem Find root cause and get manufacturer on track Some shortages can be prevented, but not all Unforseen breakdown in manufacturing system Longstanding quality manufacturing problems Some can be addressed quickly, others not Risks to the patient always considered 11 Quality and Manufacturing Examples Sterility - bacterial and mold contamination Particles of foreign matter glass, metal and fibers in vials Crystallization of the active ingredient Precipitate formation due to reaction with raw materials or container/stopper with the drug New impurities or degradants Equipment breakdown Natural disasters 12 6

7 FDA s Approach to Prevention/Mitigation Consider medical necessity Risk/Benefit of the drug always considered Do everything possible within our authority to continue availability while minimizing risk to patients. Work with firm to address We can advise, assist and expedite, but only the manufacturer can fix the problem Be flexible and creative and fast 13 Medical Necessity A 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 cedures/ucm pdf 14 7

8 FDA Tool Box Regulatory discretion: allow manufacture of medically necessary product(s) to continue Minor, low risk issues usually best suited for this tool In some cases require additional safety controls Filters packaged with product; extra testing at plant; 3 rd party oversight of production; special instructions for safe use Request other firms to ramp up manufacturing. Expedite any review of company proposals New manufacture site, increased expiry, new raw material source, changes in specifications, etc. In rare cases, temporary importation from unapproved sources 2010 temporary importation of propofol 2011 temporary importation of foscarnet, ethiodol, thiotepa, norepinephrine, Xeloda, levoleucovorin, leucovorin 2012 temporary importation of Lipodox, methotrexate preservative free vials Shortages Prevented in 2010 All due to firms notifying FDA of problems early 16 through regulatory discretion Risk of quality/manufacturing issue able to be mitigated and was outweighed by benefit of the drug 13 through expedited review New manufacturing sites, suppliers, etc. 8 through encouraging other firms to ramp up 1 through communication with DEA regarding firm s need for controlled substance quota increase 16 8

9 2011 Data Higher Executive Order President s Executive Order issued 10/31/11 encouraged more voluntary reporting by manufacturers 6 fold increase in notifications of potential shortages normally received 10/month on average in 2010 and now receiving over 60 notifications per month) Total of 195 shortages prevented in 2011 In 2012, 18 shortages prevented as of February 9, Shortages can t always be prevented Unanticipated problems, such as a manufacturing line breakdown or natural disaster Manufacturer(s) may not be able to make up production shortfall Risks are significant and would cause patient harm (e.g. sterility problems) FDA will work with company to encourage smart distribution No easy answers on how to do this well 18 9

10 The Future FDA Drug Shortage work will continue Multidisciplinary: clinicians, pharmacists, chemists, biotechnology, regulatory and manufacturing We can only prevent shortages if problems are reported Public communication of existing shortages Congress discussing new legislation Would REQUIRE broader reporting by industry to FDA Public expects and deserves high quality drugs Must have industry commitment to culture of quality manufacturing Many firms are building new plants today Need better methods and redundancy Promptly report and correct even small problems 19 Thank You FDA drug shortage website is: To report shortages our account is FDA Webinar on Prescription Drug Shortages Sept. 30, 2011, ucm htm 20 10