Presentation on theme: "Drug Shortages: Experiences in the U.S. and Abroad Kasey K. Thompson, Pharm.D., M.S. Vice President, Office of Policy, Planning and Communications American."— Presentation transcript:
Drug Shortages: Experiences in the U.S. and Abroad Kasey K. Thompson, Pharm.D., M.S. Vice President, Office of Policy, Planning and Communications American Society of Health-System Pharmacists Bethesda, Maryland, U.S.A. International Summit on Medicines Shortages Toronto, Canada June 20-21, 2013
Objectives Define causes and current trends in drug shortages Discuss implications of drug shortages Describe lessons learned from efforts in the United States to address drug shortages.
Drug Shortages in the United States: A Historical Perspective Not a new issue ASHP and others have been addressing drug shortages for almost 14 years ASHP web resource center—Updated Daily (www.ashp.org/drugshortages) Current challenge is the extent, duration, and type of drug shortages Has a major impact on patient safety and pharmacy practice
Drug Shortage Definition A drug supply issue requiring a change Impacts patient care Requires use of an alternative agent American Society of Health-System Pharmacists. ASHP Guidelines on Managing Drug Product Shortages in Hospitals and Health Systems. AJHP. 2009;66:1399-1406.
U.S. Food and Drug Administration (FDA) Policy is to “prevent or alleviate shortages of medically necessary products” Shortages of “medically necessary” drugs are listed on FDA’s website Jensen V, Kimzey LM, Goldberger MJ. AJHP. 2002;59:1423-1425.
FDA - Medical Necessity Product treats or prevents a serious or life- threatening illness (off-label or labeled) No reasonable alternatives exist (single-source).
Quality Problems Drug shortages Raw Materials Few Plants Limited Lines GMP Violations Unknown
Supply Chain Issues Manufacturers and wholesalers typically have a 15 to 40 day inventory on hand Pharmacies - 10 to 16 annual inventory turns The Pink Sheet. May 6, 2002:17-18 ASHP Guidelines on Managing Drug Product Shortages in Hospitals and Health Systems. AJHP. 2009;66:1399-1406.
Manufacturing Problems Sources Sole source raw materials Time to establish new source Capacity Few manufacturers of sterile injections Same production lines for multiple items Limited lyophilization capacity Provisional observations on drug product shortages: effects, causes, and potential solutions. AJHP. 2002;59:2173-2182
Complex Manufacturing Over 23 steps to manufacture meropenem Starting materials (Italy, Japan) Crude meropenem (Japan) Purified meropenem (Italy, Japan) Bulk Meropenem (Italy, Japan) Vial Filling (Switzerland, US) Packaged in boxes (US) Biologic products Take longer to produce Any problems take longer to resolve
Multifactorial Reasons Multiple reasons can play a role in any particular shortage A product may be recalled due to concern for microbial contamination or particulate matter in the vials (propofol) 3 manufacturers of propofol, 2 had recalls, and the 3 rd could not keep up with demand—U.S. imported product from Europe. A product may be recalled and the manufacturer may have difficulty accessing raw materials (lipid emulsion)
Business Decisions Profitability Manufacturing fixes Capacity – most factories running 24/7
22 Fragile Supply Chain Sterile Injectables Few suppliers –Majority of the market supplied by 7 manufacturers –Contract manufacturers – the company that supplies the product didn’t always manufacture Lack of redundancy –Multiple products made on existing manufacturing lines –Limited resiliency in manufacturing process Complex manufacturing process –No simple fixes for quality problems –Problems typically affect multiple products http://aspe.hhs.gov/sp/reports/2011/DrugShortages/ib.shtml
Raw Material Issues Raw material availability 20 years ago – 90% from US and Europe Currently, 75 – 80% from China and India Some materials are no longer accessible or only available as single source products Schweitzer SO. N Engl J Med. 2008;358:1773-1777 Provisional observations on drug product shortages: effects, causes, and potential solutions. AJHP. 2002;59:2173-2182 Fox ER, Tyler LS. AJHP. 2009;66:798-800
Example – Fragile Supply Chain Manufacturing plant closes April 2010. Impacts 49 drugs – 18 are chemotherapy. Problems occurred at the same time at other facilities. Manufacturing resumed spring of 2011, but still not up to prior capacity for some agents.
FDA’s Strategy Prioritize medically necessary agents (determined on a case by case basis) Evaluate risks and benefits for patients Offer assistance and advice, but up to the manufacturer to fix Success hinges on early notification Jensen V, Kimzey L M, and Goldberger MJ. FDA’s role in responding to drug shortages. AJHP. 2002; 59:1423-5
How Does FDA Prevent Shortages? Regulatory discretion Require filters (products with particulates, glass fragments) Ask clinicians to double check volume (overfill) Ask others to increase production Expedite reviews (new product, longer expiration, new raw material, new manufacturing sites A Review of FDA’s Approach to Medical Product Shortages. October, 2011. http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm275051.htm http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/ucm275051.htm
Imports 12 different agents 2010-2013 propofol, foscarnet, ethiodol, thiotepa, norepinephrine, capecitabine, leucovorin, levoleucovorin, methotrexate, doxorubicin liposomal, phentolamine, sodium bicarbonate Limited by quantity available to share with US market Importation is not a viable long-term solution for U.S. market
Shortages Prevented by FDA 2010 - 2012 Source: CDER Drug Shortages
FDA Can Only Do So Much… FDA CAN require *notification of supply disruptions (FDASIA) FDA CANNOT require *continued production *increased production *disclosure of distribution
International Perspective on Drug Shortages Drug shortages is a global issue! Globalization of the pharmaceutical supply chain: 1 40 percent of finished drug products are manufactured abroad 80 percent of drug components (e.g., active pharmaceutical ingredients) are from foreign countries Quality issues in the global supply chain contribute to drug shortages 1. www.prescriptionproject.org/assets/pdfs/Pew_Heparin_Round4b_SinglePgs_b.pdf
European Association of Hospital Pharmacists—Drug Shortages Surveys Surveyed 346 hospital pharmacists in 31 countries Focus on the prevalence of drug shortages Surveyed 266 hospital pharmacists in 29 countries Focused on causes and impact on patients
EAHP Survey Results 98.8% of respondents had experienced a shortages in the past 12 months 63.1% reported that problems associated with shortages occur at least weekly; 27% reported monthly problems.
EAHP Survey Results Medicines in Short Supply Oncology70.6% Emergency43.8% Cardiovascular35.1% Hematology22.2% Respiratory18.9% Pediatric18.9% Other31.4%
EAHP Survey Results Originator Versus Generic Shortages Originator/Brand42.9% Generic57.1%
EAHP Survey Results Root Causes of Shortages Single or Limited Suppliers52.4% Raw Chemical Shortage43.7% Manufacturing Quality Problem43.7% *Small Country with Limited Market41.7%
Practice Impact of Drug Shortages No advance warning Limited or no information Significant increase in resources used to manage shortages Personnel: pharmacists, pharmacy technicians, nurses, physicians Financial: increased cost of alternative products/off-contract purchasing; gray market Diverts health care providers from direct patient care activities The resulting impact on patient safety and outcomes may be substantial but is difficult to quantify University of Michigan/ASHP Survey. AJHP. 2011;68:1811-9.
Time Spent by Health Care Practitioners AJHP. 2011;68:1811-9.
Patient Care Impact Patient care issues Delayed or unavailable care Safety implications Adverse impact on patient outcomes
Percent of Hospitals Reporting the Impact on Patient Care as a Result of a Drug Shortage Source: AHA analysis of survey data from 820 non-federal, short-term acute care hospitals. Survey completed in June 2011
Cause for Concern: Errors that May Be Caused by Drug Shortages Clinicians may be less familiar with dosing, administration, or monitoring of the alternative therapy Use of different package sizes can lead to over or under dosing Compounding of unavailable therapies can lead to errors or sterility issues
ASHP Guidelines on Managing Drug Shortages www.ashp.org/DocLibrary/BestPractices/ProcureGdlShortages.aspx
Drug Shortages Summit Bethesda, Maryland; November 2010 Goals Define the scope, causes, and potential patient harm from drug shortages Discuss potential changes in public policy and stakeholder practices Partner Organizations ASHP American Society of Anesthesiologists American Society of Clinical Oncology Institute for Safe Medication Practices American Hospital Association (joined post summit) 21 recommendations to improve communication and remove barriers faced by the FDA and drug manufacturers www.ashp.org/drugshortages/summitreport
Addressing Drug Shortages in the U.S.: ASHP Advocacy Early notification to FDA by manufacturers for all drugs regulated by FDA Civil monetary penalties Inter-agency coordination Contingency plans Generic user fee program
Why Early Notification? Prevented shortages 201038 2011195 201242
Impact of New L aw A good first step – not a total solution Increases scrutiny on shortages Strengthens FDA’s Drug Shortages Program Expedites approval of additional industry capacity and applications Does not directly address capacity and economic factors
Conclusions Drug Shortages Remain a Major International Problem There is No Single Cause of Shortages The Reasons for Shortages May Differ From Country- to-Country, But there are also Likely Similarities Communication is key between stakeholders (providers, government, manufacturers, and patients)