East Hills, NY (February 8, 2005) - - Assessing the risk of potential exposure to variant Creutzfeldt-Jakob Disease (vCJD), the human form of ?mad cow disease,? from blood transfusion was the focus of the Food & Drug Administration (FDA) Transmissible Spongiform Encephalopathies (TSEs) Advisory Committee in Silver Spring, Maryland today. In response to the Committee's encouragement that new technologies should be considered that might lead to greater reduction of risk while not deferring many donors unnecessarily, Pall Corporation (NYSE: PLL) presented the latest scientific data on its new prion reduction technology. The Leukotrap® Affinity Prion Reduction Filter, expected to be launched commercially in Europe this spring, removes infectious prions from red cells, the most widely transfused blood component. Prions are associated with causing vCJD and other fatal neurodegenerative diseases, known as TSEs.
Sam Coker PhD, Principal Scientist and Technical Director of Pall Medical, acknowledged the public health community's heightened concern about the possibility of a second wave of mad cow disease in humans of unknown magnitude globally, including North America. Japan is the latest nation to confirm a human case of mad cow disease.
The unknown time interval between exposure to the infected prion and onset of symptoms exacerbates the challenge of determining the size of a second wave or epidemic. This asymptomatic characteristic poses the key question: How many dormant carriers of vCJD are out there who are at risk of developing clinical disease and who also may be blood donors'
There is currently a ban on blood donations from people who lived in countries with bovine spongiform encephalopathy (BSE) infected cattle, which can have an impact on availability and result in shortages of lifesaving blood components. A loss of one percent of donors involves approximately 75,000 to 85,000 individuals in the first year, not to mention their future potential donations. Leukocyte (white blood cell) reduction, which has been adopted by several nations to help decrease the risk of vCJD transfusion-transmission, removes only about 42 percent of TSE infectivity of blood.
The Pall Leukotrap Affinity Prion Reduction Filter was developed in response to these problems as part of the Company's mission to help ensure safety of the blood supply. It can remove leukocytes and all types of prions -- both cell and non cell-associated -- from blood prior to transfusion in a single step. Dr. Coker presented an overview of the key study results that show that the novel technology concurrently reduces leukocytes and prions with a 99 percent reduction of the infectious agent. He concluded that the new filter could be used to remove different strains of infectious prions, including those that cause vCJD.
He reviewed a study where it was found that the new filter reduces the human form of vCJD prions from red cells below the limit of detection of the Western blot assay, the gold standard of prion detection. He also discussed a study with the infectious scrapie prion that causes disease in sheep, which showed that the new filter removed all the infectious prions below the limit of detection of the Western blot assay.
Dr. Coker described in detail an animal infectivity study comparing filtered and unfiltered blood infected with scrapie prion. After the 300-day study, three of the 18 control hamsters that received the unfiltered blood developed scrapie. Only two of these animals had displayed clinical signs of the disease. None of the hamsters receiving filtered blood developed scrapie.
Dr. Coker also described the results of studies demonstrating that the filter does not damage red cells thereby not impacting their efficacy, purity and therapeutic value.
Pall Corporation expects to introduce the Leukotrap Affinity Prion Reduction Filter commercially in Europe this spring followed by submission to regulatory agencies in both Canada and the United States. The Company is also working on applying the basic technology to a diagnostic device to aid in the detection of (BSE) in cattle before entering the food supply.
About Pall Corporation Pall Corporation is the global leader in the rapidly growing field of filtration, separations and purification. Pall's business is organized around two broad markets: Life Sciences and Industrial. The Company provides leading-edge products to meet the demanding needs of customers in biotechnology, pharmaceutical, transfusion medicine, semiconductors, water purification, aerospace and broad industrial markets. Total revenues are $1.8 billion. The Company headquarters are in East Hills, New York with extensive operations throughout the world. Visit Pall at www.pall.com.
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Dr. Coker's FDA TSE Advisory Committee presentation along with photos and additional information on prions and The Leukotrap Affinity Prion Reduction Filter can be found at www.pall.com/corporate_35354.asp
Interviews with Pall scientists and executives are available upon request.
Removal of Infectious Prions from Red Cell Concentrates Samuel Coker, PhD Principal Scientist and Technical Director, Pall Medical Transmissible Spongiform Encephalopathies Advisory Committee Meeting February 8, 2005
Although neither the appearance of BSE in North America or the apparent transfusion transmission of vCJD are entirely unexpected, these events provide impetus for further consideration of means to safeguard the blood supply from the risk of transmission of infectious prions. While many feel that existing measures to deal with this risk are sufficient, there is still a serious need to balance their potential efficacy against the safety and availability of life saving blood components.
Animal studies have demonstrated that the agent that causes the human form of Mad Cow disease can be transmitted through blood transfusion. With the recent news from the United Kingdom confirming that a patient who received donor blood during an operation in 1997 developed variant CJD and died six years later, transfusion medicine professionals and the general public now perceive the risk of developing vCJD from a blood transfusion may be a growing, NOT a declining, threat to patient safety.The existence of asymptomatic prion carriers raises real concerns of a second-wave of transmission Because Mad Cow disease has spread to other countries?and given the unknown time interval between exposure and symptoms?public health officials are faced with the complexity of estimating the true size of the vCJD epidemic.
Are there thousands of dormant carriers of vCJD at risk of developing clinical disease? This question needs to be addressed with priority and urgency because it raises deep concerns that many more cases of undetected prion protein infection may underlie the overt epidemic--with major implications for future estimates and the surveillance of vCJD
Pall?s approach to improving the safety of the global blood supply grows out of our core competency in material science engineering and a legacy of leadership in blood filtration technology. It is only natural that our solution involves a novel, proprietary surface modification technology that removes all types of prions including: aggregated, denatured and normal. Because only a low titer of prion infectivity is believed to exist in a unit of blood--the use of affinity filtration would be an efficient and effective method of reduction while eliminating the higher costs and additional steps associated with an antemortem detection assay or pathogen inactivation process.
Over the past twelve (12) months we have been conducting tests to validate the removal of infectious prions from red cell concentrates using our new prion removal filter. In these validation studies, which I will discuss in a moment, we used all of the methods that are currently available for validating the removal of prions. At the same time, we have completed an extensive battery of in vitro and in vivo studies demonstrating the safety and efficacy of the filter for use with packed red blood cells for transfusion.
Endogenously Infected Red Cell Concentrate: In this study, we initially injected hamsters with an agent that induces scrapie in hamsters. This particular strain is called the 263K. About 150-200 hamsters were injected intracerebrally with the scrapie agent. After 70 days the animals developed scrapie and blood samples were collected into CPD anticoagulant. About 500mL of blood were collected and then processed into red cell concentrate using standard blood bank procedure. The red cell concentrate was then filtered with the new prion reduction filter in a manner that was similar to what I showed you earlier.
Note that the level of infectious prion in the red cell concentrate before filtration is very low and the sample had to be concentrated in order for us to detect it on the Western blot assay. After filtration with our new prion and leukocyte reduction filter, all the infectious prions were removed well below the limit of detection of the assay.
The result in this slide shows that the new filter is effective in reducing the level of leukocytes from red cell concentrates in additive solution (SAGM) to less than 1 x 106 which is below the current standard regulatory guideline for leukocyte reduced blood products.
The level of free haemoglobin in the filtered units of red cell concentrates in SAGM additive solution is well below the most stringent guideline of 0.8% at the end of 42 storage.
Similar results were obtained with red cell concentrates in CPD anticoagulant (Next slide)
In addition red cell to haemolysis, we also measured the the biophysical properties of the cells that are responsible for their normal in vivo survival and performance of physiologic functions. Results obtained to date show that the cells maintained properties that are similar to normal unfiltered red blood cells.
The results obtained to date show that the qualities of the red blood cells are not adversely affected by filtration with the new filter as demonstrated by maintenance of normal biophysical properties, and level of free haemoglobin during extended storage.
Initial bio-assay (prototype filters) in hamsters confirmed removal of about 4 logs of infectious prion. Additional bioassays using CE Mark filters are planned to confirm log removal. After 300 days, 0/20 hamsters injected with filtered red cell concentrate developed scrapie. In contrast, 2/18 control hamsters that received unfiltered red cells developed clinical signs of scrapie while the third animal showed the presence of infectious prion in it?s brain at autopsy.
Summary: Our preliminary results using scrapie animal models show that prototypes (non CE Marked versions) of the Pall prion removal filter are effective in removing infectious prions from red cell concentrate.
Market Introduction: Pall Medical is completing the safety and efficacy testing required to declare CE Mark compliance on the Leukotrap® Affinity Prion Reduction Filter (for sale in Europe in the Spring 2005). The new filter is also expected to enter the regulatory process in the US and Canada later in the calendar year. This product represents the first of a new generation of proprietary SMART filters that will concurrently reduce leukocytes and the risk of transmission of variant CJD through blood transfusion.