Pharmaceutical Shortages: Impact on Patients, Professionals and the Public

Bernadette Belgado, Pharm.D. UF Health at Jacksonville West Paul, M.D., Ph.D. Wake Med Health

Drug Shortages: causes & solutions

Bernadette Belgado, Pharm.D. Director, Drug Information Center Manager, Department of Pharmacy Shands Jacksonville Department of Pharmacy Clinical Assistant Professor UF College of Pharmacy

Objectives
Explain the reasons for medication shortages Discuss drug shortage legislation

No disclosures

New Drug Shortages by Year

Keuhn BM. JAMA. 2013;309(6):532-533

Reported reasons for sterile injectable drug shortages in 2011

Woodcock J, Wosinska M. Clin Pharmacol Ther 2013;92:170-6.

Drug Supply Chain

Raw materials

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm277626.htm

Raw Materials
2008 heparin recall Over 200 patients died as a result of contaminated heparin with over-sulfated chondroitin Raw materials plant in China was never inspected by the FDA Foreign markets supply 80% of raw materials Increased quality awareness and regular inspection of foreign raw materials plants mandated by FDA

This family-owned workshop in Xinwangzhuang, a village in Juangsu Province, China, processes pig intestines for heparin

http://www.nytimes.com/2008/03/30/weekinreview/30bogdan

Drug Supply Chain

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm277626.htm

Drug Manufacturers
Generic injectable drugs (73%) Lack of redundancy in manufacturing processes
71% of market controlled by 3 manufacturers

Routine facility maintenance

Business decisions to discontinue drug

Unable to support demand

Woodcock J, Wosinska M. Clin Pharmacol Ther 2013;92:170-6.

Drug Manufacturers
Lack of sterility

Particulates of foreign matter

Crystallization of the active ingredient Precipitates New/unintended impurities or degradation Equipment breakdown

Woodcock J, Wosinska M. Clin Pharmacol Ther 2013;92:170-6

Drug Supply Chain

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm277626.htm

Regulatory Issues
New FDA Commissioner in 2009 Enforcement and regulatory activities spiked from 20092011 Warning letters to pharmaceutical manufacturers regarding quality increased 42% in 2009 and up 156% in 2010. Simultaneously shutting down 4 major generic manufacturers of generic medications
30% of decrease in manufacturing capacity

112th Congress 2012. http://oversight.house.gov/report/fdas-contribution-to-the-drug-shortage-crisis.

FDA Warning letters 2004-2011

Number of letters

FDA Fiscal Year 2011 Enforcement Statistics

Regulatory Issues
FDA increased enforcement of Unapproved Drugs Drug Evaluation & Safety Initiative (DESI)
Drugs approved or deemed identical, related, or similar (IRS) between 1938 1962

Pre-1938 drugs grandfathered

No change to the formulation, dosage form, potency, route of administration, indication, or intended patient population

FDA requests NDA for any unapproved drug

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070290.pdf http://www.ashp.org/DrugShortages/NotAvailable/Bulletin.aspx?id=602

Regulatory Issues - MMA

Medicare Modernization Act (MMA) 2003
Changed pricing formula for reimbursement in outpatient setting
Originally average wholesale price (AWP)

Generic availability erodes selling prices by ~ 85-90% after a year Average selling price (ASP) + 6% MMA limits - Manufacturers only allowed to increase prices by 6% biannually
Cabner BA. N Engl J Med 2011 365:2147-49

340B Pricing Program

Provides nominal pricing for outpatient medications One-third of all hospitals are eligible for 340B prices Unintended consequence of MMA and 340B
New manufacturers are not entering the marketplace to produce generic medications Only 7 generic companies make sterile injectables

Drug Supply Chain

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm277626.htm

Group Purchasing Organizations

GPOs 98% of hospitals
Negotiate price and volume contracts with drug manufacturers

Six GPOs control about 90% of drugs purchased

Contract awarded on multiple factors

lowest cost, returns, rebates, stipulations for failure to supply

Speculation that fewer generic manufacturers are a direct result of the GPO structure

Nelson R. Medscape. http://www.medscape.com/viewarticle/778146

Drug Supply Chain

http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm277626.htm

Health Systems

Just in time inventory practices

Pharmacy inventory turns short 30 days

Hoarding and stockpiling

Medicare Modernization Act

Heparin recall

Unapproved drugs initiative

New FDA Commissioner

Keuhn BM. JAMA. 2013;309(6):532-533

FDA Solutions
Allow temporary importation of foreign equivalent
Propoven from UK for propofol shortage Phenylephrine from UK Sodium Bicarbonate from Australia

Allow affected drug with conditions safety considered

Potassium Phosphate double filtration required Mannitol heat medication to dissolve crystals Alteplase rubber stopper particles filtering required

FDA Safety & Innovation Act (FDASIA)

Executive presidential order October 2011 FDASIA July 2012 Requires at least 6 month notification to FDA and other manufacturers of potential shortages or ASAP
No civil or monetary penalties for industry noncompliance

FDA required to keep updated list of drugs and reasons

Expedited review of new generics

Presidential Executive order Medicare Modernization Act Heparin recall

Unapproved drugs initiative FDASIA

New FDA Commissioner

Keuhn BM. JAMA. 2013;309(6):532-533

Keuhn BM. JAMA. 2013;309(6):532-533