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 medications called
  anticoagulants that are commonly referred to as
  blood thinners. 
• Heparin makes an anti-clotting protein in your
  body work better, thus decreasing the clotting
  ability of the blood.
• Heparin is made from pig intestines.
• Has been marketed in the United States since the
  1930s.

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General uses of heparin

• Prophylaxis purposes to prevent blood clots.
• Coronary artery bypass surgery.
• Kidney dialysis to prevent clotting in dialysis
  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. bolus dose.
• Injection subcutaneously under the skin usually
  abdomen.
• Intravenous drip usually mixed with another
  solution such as dextrose sodium.

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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 extensive bleeding in
  infant twins.
• Received 10,000 u/mL of heparin instead of 10
  u/mL of heparin lock flush.
• Inadequate labeling of heparin vials similar
  labeling with blue background.

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Dennis Quaid Case
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Dennis Quaid Testimony

• ..\My Documents\HEPARIN\Video clips\Quaid takes
  on drug company.avi

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Dennis Quaid Case

• Three premature infants at an Indiana Hospital
  died as a result of an accidental overdose of
  heparin.
• In December 2007, Baxter changed the labeling for
  its heparin products. The label features an
  increase of 20 percent font size, a unique color
  combination, and a large red cautionary tear-off
  label.
• Baxter press release, Dec. 3, 2007

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Heparin Manufacturing

• Pig farmers / slaughter houses use pig intestines
  to obtain the crude heparin.
• Crude heparin is processed to remove impurities
  and results in the active pharmaceutical
  ingredient (API).
• API is then used in the final production of
  heparin 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 Laboratories located in
  Wisconsin manufactured distributed heparin
  API.
• In 1999, SPL entered into joint venture with
  Changzhou SPL in China to operate a heparin 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 China is
  shipped back to SPL in Wisconsin.
• SPL distributes heparin API to various
  manufacturers of heparin sodium, including
  Baxter.
• Baxter uses heparin API in their finished heparin
  sodium vials and sells to end users.

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Heparin Contamination

• February 6, 2004, Baxter submitted NDA Prior
  Approval Supplement to have Changzhou SPL
  approved as its supplier of API for its heparin.
• June 8, 2004, Baxter received letter from FDA
  that Changzhou SPL is approved as alternate
  supplier.

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Heparin Supply Chain
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Heparin Contamination Crisis

• In 2007, Baxter was one of the largest producers
  of heparin in the United States and owned 50 of
  the marketplace.
• In 2007, Baxter sold an estimated 35 million
  units of Heparin per year, with annual sales of
  30 million.

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Heparin Contamination Crisis

• In November 2007, pediatric dialysis facility in
  Missouri identified allergic type reactions
  during dialysis.
• Late December 2007, Baxter received first adverse
  event reports associated with use of heparin
  multi-dose vial products.
• January 7, 2008, CDC was notified of allergic
  type reactions by Missouri Dept of Health.

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Heparin Contamination Crisis

• January 2008, CDC investigated allergic type
  reactions occurring at dialysis centers and
  concludes that it may be a result of heparin.
• January 9, 2008, CDC notified FDA of association
  between allergic type reactions and heparin.
• January 9, 2008, Baxter placed a hold on their
  heparin inventory.

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Heparin Contamination Crisis

• January 17, 2008, Baxter issued a recall of nine
  lots of its multi-dose heparin vials.
• February 2008, Baxter continued receiving reports
  of adverse reactions to its heparin products.
• February 29, 2008, Baxter recalled all of its
  heparin single dose, multi-dose and heparin flush
  products.

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Heparin Contamination Crisis

• March 19, 2008, FDA identified the heparin
  contaminate as oversulfated chondroitin sulfate
  (OSCS).
• OSCS a heparin-like product derived from animal
  cartilage
• FDA determined that OSCS originated from the
  source product that came from China.
• Levels of OSCS contaminate in Baxter and SPLs
  heparin ranged from 3 - 30.

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Heparin Contamination Crisis

• In January 2008, FDA learned that it had
  mistakenly approved the use of the Changzhou
  China plant for the manufacturing of heparin API.
  
• FDA never inspected the Changzhou plant.
• FDA staff entering information in a database
  confused the name of the Changzhou plant with
  another plant that had previously been inspected.

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Heparin Contamination Crisis

• Baxter heparin distributed in marketplace from
  Sept 19, 2008 Feb. 29, 2008 (recall).
• Recall was not immediate.
• Several weeks for Baxter to send out recall
  notices to all customers i.e., hospital,
  doctors, dialysis clinics, pharmacies, etc.
• Concern about shortage of heparin supply.

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Heparin Contamination Crisis

• 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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Heparin Contamination Crisis

• Adverse Reactions
• Hypotension
• Facial edema
• Loss of consciousness
• Sensation of burning, warmth, or flushing
• Numbness or tingling
• Difficulty swallowing
• Shortness of breath, audible wheezing, chest
  tightness
• Tachycardia
• Nausea, vomiting, diarrhea

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Heparin Contamination Crisis
McMahon, Pharmacoepidemiology and Drug Safety
(2010)
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Heparin CNN Video

• ..\My Documents\HEPARIN\Video clips\How safe are
  your drugs.avi

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Heparin Litigation

• February 14, 2008 first lawsuit was filed in
  N.D. Ohio
• May 29, 2008 argument at MDL Panel
• June 6, 2008 cases consolidated and sent to
  Judge Carr in N.D. Ohio.

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Heparin Litigation

• First bellwether case was scheduled to go to
  trial in March 2011 postponed.
• Daubert hearing April 19 20, 2011
• Daubert opinion issued by Court July 21, 2011.
• Cases limited to those with symptoms occurring
  within 60 minutes of administration of
  contaminated heparin HIT excessive
  bleeding/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 evidence plaintiff was in hospital that
  received Baxter heparin during contamination
  period and suffered injuries consistent with
  contamination.

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Heparin Contamination

• Baxter has never been approved by the FDA to sell
  heparin since the contamination.
• FDA has never been able to identify who was
  responsible for the contamination or whether it
  was intentional.
• FDA has implemented new testing standards for
  heparin to specifically test for OSCS.

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Heparin Contamination

• As of June 2011, the U.S. House Energy and
  Commerce Committee is still investigating the
  contamination incident.
• July 2011 FDA published Pathway to Global
  Product Safety and Quality.
• FDA does not nor will it have the resources
  to adequately keep pace with the pressures of
  globalization.
• FDA is developing international plans and
  operating models in order to provide safety and
  quality assurance.

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Heparin Contamination

• Sept 14, 2011 Senate hearings Deborah Autor,
  Deputy Commissioner for Global Regulatory
  Operations and Policy at FDA
• 40 of drugs Americans take are made elsewhere.
• 80 of API used in drugs manufactured in US come
  from outside the U.S. - from more than 150
  countries many with less sophisticated
  manufacturing and regulatory systems that U.S.

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60 minutes video

• ..\My Documents\HEPARIN\Video clips\60
  Minutes-Counterfeit drugs.avi