In re Heparin Prods. Liab. Litig.

• Decision Date: 21 July 2011
• Docket Number: Case No. 1:08HC60000.MDL No. 1953.
• Citation: 85 Fed. R. Evid. Serv. 1158,803 F.Supp.2d 712
• Parties: In re HEPARIN PRODUCTS LIABILITY LITIGATION.
• Court: U.S. District Court — Northern District of Ohio

803 F.Supp.2d 712

85 Fed. R. Evid. Serv. 1158

In re HEPARIN PRODUCTS LIABILITY LITIGATION.

Case No. 1:08HC60000.MDL No. 1953.

United States District Court,N.D. Ohio,Western Division.

July 21, 2011.

MEMORANDUM OF OPINION AND ORDER

JAMES G. CARR, Senior District Judge.

This multi-district products liability litigation arises out of the manufacture and sale by defendants of contaminated heparin. The plaintiffs allege that the use of contaminated heparin caused a myriad of adverse reactions leading to serious injuries and, in some cases, death.

Pending is defendants' motion for summary judgment on the following categories of claims:

• Claims lacking evidence of any symptoms within sixty minutes of heparin administration;

• Claims alleging heparin-induced thrombocytopenia (HIT);

• Claims alleging sepsis or sepsis-like conditions;

• Claims alleging bleeding or clotting;

• Claims alleging injury due to administration of non-bolus doses of contaminated heparin;

• Claims alleging exposure to contaminated heparin containing less than 15% of the contaminant Oversulfated Chondroitin Sulfate (OSCS); and

• Claims falling outside the CDC case definition.

[Doc. 527].

Also pending are several Daubert challenges ancillary to the summary judgment motion. Defendants have filed a motion for exclusion of general causation testimony by plaintiffs' experts Drs. Hoppensteadt, Jeske, Kiss, Buncher, Luke and Ohr [Doc. 528]. Plaintiffs have filed motions for exclusion of the testimony of Dr. Howard William Ory [Doc. 438] and Dr. Ronald M. Burch [Doc. 442]. I also take notice of plaintiffs' motion, which became decisional as this order was being completed, for an order to show cause relating to the licensing and board certification of Dr. Burch. [Doc. 583].

For the reasons that follow, I grant in part and deny in part the parties' Daubert motions. I grant in part and deny in part defendants' motion for summary judgment.

Background

A. Heparin Contamination

Heparin, one of the oldest clinical drugs still in wide-spread use, has been marketed in the United States for nearly seventy years. Over one million multi-dose vials of heparin are sold per month in the United States. Baxter Healthcare Corporation (Baxter) supplies about half the heparin sold in the United States.

An anticoagulant, heparin decreases the clotting ability of blood, thereby preventing formation of clots and stopping the growth of already existing clots. Heparin is used as a prophylaxis against blood clots among bed-ridden hospital patients, as an anticoagulant during surgeries and in catheters and pumps during procedures such as kidney dialysis, and as a treatment of such conditions as pulmonary embolism and deep-vein thrombosis.

Many patients who receive heparin have serious pre-existing medical conditions. Patients with end-stage renal disease and patients undergoing coronary artery bypass surgery make up a significant number of those receiving vial heparin.

To survive, patients with end-stage renal disease must undergo dialysis or receive a kidney transplant. There are two forms of dialysis: hemodialysis, in which a machine filters wastes, salts and fluid from the blood, and peritoneal dialysis, in which dialysate is washed in and out of the peritoneal cavity. Heparin is incorporated into both therapies.

Even when receiving dialysis, end-stage renal disease patients suffer a significant background mortality rate. Dialysis patients also commonly experience side effects such as drop in blood pressure, shortness of breath, abdominal cramps, nausea and vomiting.

A coronary artery bypass graft is an open-heart procedure that involves grafting a new artery or vein around diseased or blocked sections of the arteries in order to increase blood flow to the heart muscle tissue. A bolus dose of heparin is often administered at the outset of the procedure. Coronary artery bypass graft patients may experience side effects including drops in blood pressure and platelet counts. Complications include heart failure, heart attacks, serious arrhythmia, stroke and respiratory, renal and multiple organ failure.

Heparin is generally well-tolerated. Although laboratory monitoring is necessary to ensure its therapeutic effect and safety, it has predictable pharmacokinetics.

The most common adverse event related to heparin administration is bleeding, which is variable in severity. Serious bleeding occurs with a reported frequency of 1–3%. Heparin-induced thrombocytopenia (HIT) is another serious complication of heparin therapy. HIT is the development of thrombocytopenia (a low platelet count) associated with the administration of heparin.

When a person suffers from HIT, the immune system forms antibodies against heparin. These antibodies are bound to a protein called platelet factor 4 (PF4) and usually develop between four and fourteen days after initial exposure to heparin. HIT predisposes a patient to thrombosis, the abnormal formation of blood clots in a blood vessel. Immune-mediated HIT is a potentially life-threatening complication occurring in 1–2% of patients receiving unfractionated heparin. Hypersensitivity and allergic-type reactions are rare.

In late December, 2007, the U.S. Food and Drug Administration (FDA) and Baxter received over 350 adverse event reports associated with the use of heparin. The FDA characterized this as a marked increase from the usual number of reports associated with heparin use. This led to investigations by the U.S. Centers for Disease Control and Prevention (CDC) beginning in January, 2008.

The CDC identified a cluster of symptoms based upon initial reports of allergic-type reactions among pediatric hemodialysis patients. After the CDC solicited further reports of similar reactions among hemodialysis patients, the agency identified Baxter heparin as a common feature among the reported cases. On January 17, 2008, Baxter recalled nine multi-dose lots, and on February 29, 2008, Baxter recalled all its heparin single and multi-dose vials and HEP–LOCK flush products.

Intense efforts to determine the nature and source of the contaminant followed. On March 19, 2008, the FDA announced that the active pharmaceutical ingredient (API) in Baxter's heparin had been intentionally contaminated with Oversulfated Chondroitin Sulfate (OSCS). OSCS is a synthetic compound with anticoagulant properties mimicking those of heparin. Baxter obtained this contaminated API from its Chinese supplier, defendant Scientific Protein Laboratories (SPL), and incorporated it into some of its heparin products.

B. Retrospective Studies

In December, 2008, researchers with the CDC's Epidemic Intelligence Service and others published a retrospective study of reported adverse event data using a facility-based case-control methodology (the Blossom Study). ¹ This study resulted from the CDC's January, 2008, investigation of the severe adverse reactions associated with heparin reported between November, 2007, and January, 2008.

Preliminary findings suggested that heparin was a possible cause of the reactions. Seeking to identify the source of the outbreak of adverse events, the CDC investigation began collecting information about adverse events and identifying control facilities (those facilities reporting no reactions).

For this investigation, the CDC defined a definite case of adverse reaction as the sudden onset of angioedema (i.e., facial swelling) or urticaria (hives) in a patient within one hour of heparin administration. It defined a probable case as the development, also within one hour of heparin administration, of hypotension, loss of consciousness, or signs and symptoms from at least two of the following categories: sensation of burning, warmth, or flushing; numbness or tingling; difficulty swallowing; shortness of breath, audible wheezing, or chest tightness; tachycardia; and nausea, vomiting, or diarrhea.

The researchers found that the adverse reactions were most often characterized by hypotension, nausea, and shortness of breath occurring within thirty minutes of administration, with a mean time to reaction of 5.1 minutes during dialysis and 15.9 minutes during cardiac treatments. The researchers observed that similar adverse reactions had been documented in the past among hemodialysis patients. Those reactions had been attributed to a variety of different causes, including dialyzer membranes, water impurities, residual disinfectants and medications. Heparin alone, however, rarely causes the symptoms observed.

The Blossom study concluded that “[h]eparin contaminated with OSCS was epidemiologically linked to adverse reactions in [the] nationwide outbreak,” and “[t]he reported clinical features of many of the cases further support the conclusion that [OSCS contaminated heparin] was the cause of the outbreak.” Use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions.

The Blossom study researchers made no determination of a causal relationship between deaths reported to the CDC and heparin administration. They noted that many deaths occurred among patients suffering from life-threatening diseases. The researchers also cautioned that the cases described likely did not encompass all cases of adverse reactions to contaminated heparin.

The Blossom study included analytic and in vitro testing of contaminated heparin vials received from surveyed facilities. These tests confirmed the findings of an earlier animal study that OSCS activates the kinin-kallikrein biological pathway in human plasma.

The kinin-kallikrein system plays a role in inflammation, blood pressure control, coagulation and pain. Activation of the kinin-kallikrein pathways in human plasma generates bradykinin, a potent vasoactive mediator that causes blood vessels to dilate, thereby lowering blood pressure. Activation of these systems can potentially result in adverse reactions.²

Researchers at the FDA's Office of Surveillance and Epidemiology published a second...