Pharmaceutical Shortages Belgado

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Pharmaceut ical Shortages:Impact on Pat ien ts,

Profess ionals and the Publ ic

Bernadette Belgado, Pharm.D.

UF Health at Jacksonville

West Paul, M.D., Ph.D.

Wake Med Health


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Drug Shortages: causes &

solutionsBernadette Belgado, Pharm.D.

Director, Drug Information CenterManager, Department of Pharmacy

Shands Jacksonville Department of PharmacyClinical Assistant ProfessorUF College of Pharmacy


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Objectives

Explain the reasons for medication shortages

Discuss drug shortage legislation

No disclosures


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

New Drug Shortages by Year


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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 theFDA

Foreign markets supply 80% of raw materials

Increased quality awareness and regular inspection of

foreign raw materials plants mandated by FDA


9/29http://www.nytimes.com/2008/03/30/weekinreview/30bogdan

This family-owned workshop in Xinwangzhuang, a village in Juangsu

Province, China, processes pig intestines for heparin


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Drug Supply Chain

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


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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.


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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


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Regulatory Issues

New FDA Commissioner in 2009

Enforcement and regulatory activities spiked from 2009-

2011

Warning letters to pharmaceutical manufacturersregarding 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.


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FDA Warning letters 2004-2011

FDA Fiscal Year 2011 Enforcement Statistics

Numberofletters


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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


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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 Med2011 365:2147-49


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340B Pricing Program

Provides nominal pricing for outpatientmedications

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


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Drug Supply Chain


G P h i


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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


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Drug Supply Chain



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Health Systems

Just in time inventory practices

Pharmacy inventory turns short 30 days

Hoarding and stockpiling


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

New FDA

Commissioner

Heparin recallMedicare

Modernization Act

Unapproved

drugs initiative


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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


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FDA Safety & Innovation

Act (FDASIA)

Executive presidential order October 2011

FDASIA July 2012

Requires at least 6 month notification to FDA and othermanufacturers 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


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

New FDA

Commissioner

Heparin recallMedicare

Modernization Act

Presidential

Executive order

FDASIA

Unapproved

drugs initiative


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


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Documents

Pharmaceutical Shortages Belgado