heparin litigation

8/12/2019 Heparin Litigation

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HEPARIN LITIGATION

Melanie S. Bailey

Burg Simpson Eldredge Hersh &Jardine, P.C.

Cincinnati, Ohio


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What is heparin?

Heparin is one of a class of medicationscalled anticoagulants that are commonlyreferred to as blood thinners.

Heparin makes an anti-clotting protein inyour body work better, thus decreasing theclotting ability of the blood.

Heparin is made from pig intestines.

Has been marketed in the United Statessince the 1930s.


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General uses of heparin

Prophylaxis purposes to prevent bloodclots.

Coronary artery bypass surgery.

Kidney dialysis to prevent clotting indialysis lines and prevent blood clots when

blood returned to body.

Medically coated stents, catheters, etc.


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Heparin Administration

Heparin is a liquid solution.

Intravenous injections; i.e. bolusdose.

Injection subcutaneously under theskin; usually abdomen.

Intravenous drip; usually mixed withanother solution such as dextrosesodium.


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Baxter Heparin

Baxter Heparin Single Dose and Multi-Dose vials


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Dennis Quaid case

Overdose of heparin, led to extensivebleeding in infant twins.

Received 10,000 u/mL of heparin insteadof 10 u/mL of heparin lock flush.

Inadequate labeling of heparin vialssimilar labeling with blue background.


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Dennis Quaid Case


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Dennis Quaid Testimony

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Dennis Quaid Case

Three premature infants at an IndianaHospital died as a result of an accidentaloverdose of heparin.

In December 2007, Baxter changed thelabeling for its heparin products. Thelabel features an increase of 20 percent

font size, a unique color combination, anda large red cautionary tear-off label.

Baxter press release, Dec. 3, 2007


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Heparin Manufacturing

Pig farmers / slaughter houses use pigintestines to obtain the crude heparin.

Crude heparin is processed to removeimpurities and results in the activepharmaceutical ingredient (API).

API is then used in the final production ofheparin sodium drug.


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Chinese Heparin

Workshop/Slaughterhouse.

NY Times photo


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Chinese Heparin

Consolidators

NY Times photo


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Heparin Contamination Crisis

Scientific Protein Laboratorieslocated inWisconsinmanufactured & distributedheparin API.

In 1999, SPL entered into joint venturewith Changzhou SPL in China to operate aheparin API manufacturing facility in China

Why China?

Pigs are abundant and labor is cheap


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Heparin Contamination

Heparin API from Changzhou SPL in Chinais shipped back to SPL in Wisconsin.

SPL distributes heparin API to variousmanufacturers of heparin sodium,including Baxter.

Baxter uses heparin API in their finishedheparin sodium vials and sells to endusers.


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February 6, 2004, Baxter submitted NDAPrior Approval Supplement to haveChangzhou SPL approved as its supplier of

API for its heparin.

June 8, 2004, Baxter received letter fromFDA that Changzhou SPL is approved as

alternate supplier.


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Heparin Supply Chain


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In 2007, Baxter was one of the largestproducers of heparin in the United Statesand owned 50% of the marketplace.

In 2007, Baxter sold an estimated 35million units of Heparin per year, withannual sales of ~ $30 million.


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In November 2007, pediatric dialysisfacility in Missouri identified allergic typereactions during dialysis.

Late December 2007, Baxter received firstadverse event reports associated with useof heparin multi-dose vial products.

January 7, 2008, CDC was notified ofallergic type reactions by Missouri Deptof Health.


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January 2008, CDC investigated allergictype reactions occurring at dialysis centersand concludes that it may be a result of

heparin. January 9, 2008, CDC notified FDA of

association between allergic type reactionsand heparin.

January 9, 2008, Baxter placed a hold ontheir heparin inventory.


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January 17, 2008, Baxter issued a recall ofnine lots of its multi-dose heparin vials.

February 2008, Baxter continued receivingreports of adverse reactions to its heparinproducts.

February 29, 2008, Baxter recalled all ofits heparin single dose, multi-dose andheparin flush products.


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March 19, 2008, FDA identified the heparincontaminate as oversulfated chondroitin sulfate(OSCS).

OSCS: a heparin-like product derived from animalcartilage

FDA determined that OSCS originated from thesource product that came from China.

Levels of OSCS contaminate in Baxter and SPLsheparin ranged from 3% - 30%.


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In January 2008, FDA learned that it hadmistakenly approved the use of theChangzhou China plant for the

manufacturing of heparin API. FDA never inspected the Changzhou plant.

FDA staff entering information in adatabase confused the name of theChangzhou plant with another plant thathad previously been inspected.


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Baxter heparin distributed in marketplace fromSept 19, 2008Feb. 29, 2008 (recall).

Recall was not immediate.

Several weeks for Baxter to send out recallnotices to all customers; i.e., hospital, doctors,dialysis clinics, pharmacies, etc.

Concern about shortage of heparin supply.


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CDC epidemiology study published in NEJM Dec.2008.

Looked at adverse events from 21 dialysis

facilities in 11 different states Conclusion: strongest association with the

adverse reactions was Baxter heparin

Conclusion: no safe level of OSCS contaminate


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Adverse Reactions Hypotension

Facial edema

Loss of consciousness Sensation of burning, warmth, or flushing

Numbness or tingling

Difficulty swallowing

Shortness of breath, audible wheezing, chesttightness

Tachycardia

Nausea, vomiting, diarrhea


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McMahon, Pharmacoepidemiology and Drug Safety (2010)


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Heparin CNN Video

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Heparin Litigation

February 14, 2008first lawsuit was filedin N.D. Ohio

May 29, 2008argument at MDL Panel

June 6, 2008cases consolidated andsent to Judge Carr in N.D. Ohio.


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Heparin Litigation

First bellwether case was scheduled to goto trial in March 2011; postponed.

Daubert hearing April 19 & 20, 2011

Daubert opinion issued by Court July 21,2011.

Cases limited to those with symptomsoccurring within 60 minutes of administrationof contaminated heparin; HIT; excessivebleeding/clotting cases


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Heparin Litigation

Problems: Pre-existing medical condition of Plaintiffs

No previous science on OSCS

Product identification Hospitals dont keep track of manufacturer of

heparin or lot numbers of heparin given to patients

Subpoenas to hospitals.

Best evidenceplaintiff was in hospital thatreceived Baxter heparin during contaminationperiod and suffered injuries consistent withcontamination.


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Baxter has never been approved by theFDA to sell heparin since thecontamination.

FDA has never been able to identify whowas responsible for the contamination orwhether it was intentional.

FDA has implemented new testingstandards for heparin to specifically testfor OSCS.


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As of June 2011, the U.S. House Energy andCommerce Committee is still investigating thecontamination incident.

July 2011FDA published Pathway to GlobalProduct Safety and Quality. FDA does not nor will ithave the resources to

adequately keep pace with the pressures ofglobalization.

FDA is developing international plans and operatingmodels in order to provide safety and qualityassurance.


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Sept 14, 2011 Senate hearingsDeborahAutor, Deputy Commissioner for GlobalRegulatory Operations and Policy at FDA

40% of drugs Americans take are madeelsewhere.

80% of API used in drugs manufactured in UScome from outside the U.S. - from more than

150 countries; many with less sophisticatedmanufacturing and regulatory systems thatU.S.


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60 minutes video

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