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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Variant Creutzfeldt-Jakob Disease (vCJD) and Factor VIII (pdFVIII) Questions and Answers

What is vCJD and how is it spread?

Variant Creutzfeldt-Jakob disease, or vCJD, is a very rare, fatal disease that can infect a person for many years before making them sick by destroying brain cells. Eating beef and beef products contaminated with the infectious agent of bovine spongiform encephalopathy (BSE) is the main cause of vCJD.

Most cases of vCJD have occurred in the United Kingdom (UK). Individuals in the UK are at a greater risk for this rare disease than are individuals elsewhere because of the previous higher risk of potential exposure to contaminated beef in the UK diet. As of April 2007 there have been 202 individuals with vCJD reported worldwide, 165 of them in the UK. In the United States (US), there have been three reported cases of vCJD. Two of these individuals had lived in the UK during 1980-1996, a key exposure period to the BSE agent. The third US individual with vCJD probably acquired the disease in Saudi Arabia.

The reported incidence of vCJD in the UK based on disease onset peaked in 1999 and declined thereafter. In the UK, where most cases of vCJD have occurred, the current risk of acquiring vCJD from eating beef and beef products appears to be negligible.

Only three cases of BSE have been found in US cattle, and safeguards are in place to help prevent infected beef products from entering our food supply. These safeguards include restricting importation of cattle and beef products from almost all countries with BSE, a surveillance program to detect BSE in the US, prohibiting the use of high-risk animal-derived proteins in cattle feed, prohibiting meat from sick cattle to be used for human consumption, and requiring the removal of high-risk materials from carcasses of cattle over a certain age.

While vCJD is primarily due to eating infected beef and beef products, four people in the UK became infected with the vCJD agent after receiving red blood cells from three donors who later developed vCJD. Three of the red blood cell recipients developed typical vCJD and died from the disease. A fourth died of an unrelated illness but had evidence of infection. To date, there have been no reports of vCJD transmission by close personal contact (such as being in the same room with someone who has vCJD, hugging, kissing, or having sexual relations).

How does vCJD differ from Creutzfeldt-Jakob disease (CJD)?

Both variant Creutzfeldt-Jakob disease (vCJD) and CJD cause progressive degeneration of the brain leading to death. However, the variant form—never seen before 1994—usually affects persons much younger than other forms of CJD. Unlike CJD, vCJD has been acquired by food exposure and transmitted by blood transfusion. vCJD also has somewhat different clinical symptoms, a longer survival after onset of illness (the majority of illnesses lasting more than one year), and produces a characteristic abnormality in brain tissue called "florid plaques" rarely if ever seen in the other forms.

How many people in the US use pdFVIII products?

Approximately 2,500 people with hemophilia A and 250 people with severe von Willebrand disease use pdFVIII products in the US. PdFVIII is manufactured from the plasma of thousands of blood donors and is used to prevent or treat bleeding episodes.

Is it known that pdFVIII can transmit vCJD?

No. However, pdFVIII is made from plasma. Plasma is the liquid part of blood remaining after the cells are removed. Animal studies show that if blood carries the vCJD agent, so can the unprocessed plasma.

Manufacturing steps used in making pdFVIII products have been shown to help remove infectious agents, including agents similar to that causing vCJD. The manufacturing steps may reduce or eliminate most risk even if a vCJD-infected donor contributed plasma.

What is the likelihood that a patient who receives pdFVIII could become infected with vCJD because of the potential risk for vCJD from the product?

The US Public Health Service (PHS) including the FDA, CDC, and NIH, believes that the risk of developing vCJD infection from pdFVIII made from US plasma is most likely to be extremely small. This is based on the results of a risk assessment. It is also based on the lack of any reported cases of vCJD following decades of use by patients who received plasma-derived blood products, including in the UK, where the risk is considered greatest. While the risk is most likely to be extremely small, there are many major uncertainties in the computer model that FDA used to assess this risk, and a precise estimate of the risk is not currently possible. Right now, there is no test available to detect vCJD in blood donors or recipients. There is no way of knowing whether a person is infected if they do not show symptoms of the disease.

At this time FDA, CDC, and NIH are not aware of any cases of vCJD having been reported worldwide in patients receiving plasma-derived clotting factors, including pdFVIII. This includes patients who have received, over a long period of time, large amounts of clotting factor products manufactured from plasma donations from the UK , where the risk of vCJD is highest.

Why does FDA recommend deferral of some blood donors?

FDA developed recommendations for donor deferral based upon consideration of risk in the donor and product. Donor deferral criteria are intended to minimize the possible risk of vCJD transmission from blood and blood products while still maintaining their availability. Donors are deferred if they visited or resided in, for a certain period of time, countries where BSE exposure is higher (e.g. UK, France, rest of Europe, some European military bases); used UK-sourced bovine insulin; or received transfusions in the UK or France since 1980. Products made from plasma of a donor with vCJD are to be withdrawn. FDA encourages reporting of donors with possible vCJD.

See “Guidance for Industry, Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products” and “Amendment (Donor Deferral for Transfusion in France Since 1980) to "Guidance for Industry: Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products").

Why does FDA recommend different deferral criteria for Source Plasma donors, whose plasma is used exclusively for further manufacturing, compared with blood donors whose blood is intended for transfusion?

In consideration of the relatively greater risk of vCJD in persons with exposure to beef products from the UK, FDA recommends that Source Plasma and recovered plasma not be collected from donors with a history of travel or residence for a period of time in the UK, US military bases in Europe, and in France. However, FDA does not recommend deferral of Source Plasma donors who have lived or traveled elsewhere in Europe, in contrast to deferral of donors of Whole Blood and blood components intended for transfusion, Source Leukocytes, and recovered plasma. This difference in deferral criteria between Source Plasma donors and others takes into account that, in contrast to Whole Blood and other components used for transfusion, plasma derivatives made from Source Plasma are highly processed materials. Also FDA has taken into consideration the estimated low prevalence of vCJD infections in Europe compared to the UK, the likely ability of plasma fractionation processes to reduce TSE infectivity, and the uncertain effect of a deferral upon the supply of plasma derivatives.

Why did FDA do a vCJD risk assessment for pdFVIII?

We conducted a risk assessment for pdFVIII because the plasma fraction from which it is made is likely to contain more of the vCJD infectious agent, if present, than plasma fractions from which other plasma-derived products are made, such as Factor IX, (used to treat hemophilia B), albumin, and immune globulins. The FVIII containing fraction is further processed using a variety of methods that are likely to reduce or potentially eliminate vCJD from the final pdFVIII product. Methods likely to reduce or potentially eliminate vCJD are also used in the manufacture of other plasma-derived products, including plasma-derived Factor IX.

What is the risk of vCJD to patients in the US who receive blood components like red blood cells and plasma?

A. The PHS, including the FDA, CDC, and NIH, believes that the risk of vCJD to patients who receive blood components like red blood cells and plasma is extremely small in the US. In addition, in the US , FDA has taken a number of steps to further reduce the potential vCJD risk from blood components. These steps include donor deferral recommendations, and quarantine and withdrawal of products at increased vCJD risk. Donor deferral guidance, first issued in August 1999 and subsequently updated, includes, among other things, deferral of donors who visited or resided in countries where BSE prevalence is high compared to the US. Also, blood components and plasma derivatives are to be withdrawn if a donor is later diagnosed with vCJD. The potential spread of vCJD through red blood cell or plasma transfusion is limited by these deferral and quarantine measures that are in place.

Why is FDA informing patients, healthcare providers, and the public about vCJD and pdFVIII now?

The FDA has recently completed its risk assessment. While the risk is most likely to be extremely small, we do not know the risk with certainty. We therefore think it is important that a von Willebrand disease or hemophilia A patient who receives pdFVIII be aware of the results of the risk assessment and have an opportunity to discuss any questions he or she may have with a suitable health care provider, such as a hemophilia or von Willebrand disease specialist. The first case of probable vCJD infection transmitted by transfusion in the UK was reported in December 2003, and the second case in July 2004. Both cases resulted from transfusion of red blood cells from donors who later developed vCJD. These events prompted UK authorities to communicate the potential risk of vCJD to recipients of clotting factors and some other plasma derived products in 2004. FDA initiated its risk assessment analysis for FVIII in 2004, presented a discussion of the model input parameters to the Transmissible Spongiform Encephalopathies Advisory Committee (TSEAC) in October 2005, and published a summary of this meeting on its website). Since then FDA, with scientific advice from the TSEAC and other experts, has made further refinements to the risk assessment model. Results of this extensive analysis are now available.

FDA, CDC, NIH, and Office of Public Health and Science (OPHS), of the US Department of Health and Human Services, with advice from patient advocates and communication experts, have now developed key message points and related communication materials to accurately convey the possible risk to patients, health care providers, and others who may have an interest.

Should hemophilia A or von Willebrand Disease patients inform their primary health care providers about a possible vCJD exposure from US licensed pdFVIII?

Advising your primary health care provider (e.g. a family physician, internist, hemophilia specialist, etc.) about your history of having received pdFVIII might be beneficial in that your provider can tell you about any new information as it becomes available, interpret its significance, and advise you about further appropriate actions in the future. However, sharing your personal health information is your choice.

Do patients who receive pdFVIII need to do anything special when seeking dental or surgical care?

At this time, the US Public Health Service (US PHS) does not believe that pdFVIII recipients need to inform their surgeons or dentists about the recipient’s potential exposure to vCJD. Also, the US PHS does not recommend that surgeons and dentists take any special precautions with patients who have such potential exposures. This belief is based on the results of the FDA risk assessment, as well as on the lack of known cases of vCJD transmitted by plasma-derived clotting factor products in the UK or anywhere else in the world.

In the UK, public health authorities notified recipients of plasma-derived products such as pdFVIII, that they may have an increased risk of vCJD in addition to the risk from eating potentially contaminated UK beef products. The UK health authorities asked patients to inform their surgeons and dentists about their potential exposure, as a public health precaution intended to prevent possible secondary spread of the disease from dental and surgical instruments. The US PHS, including the FDA, CDC, and NIH, does not believe that such notifications are necessary in the US. This is based on the extremely small risk in the US suggested by the FDA risk assessment, and on the lack of known cases of vCJD transmitted by plasma-derived clotting factor products in the UK or anywhere else in the world. Given this information, the PHS believes that there is no need to alter the standard current practices.

PHS agencies will continue to monitor and reevaluate the situation as new information becomes available.

What can recipients of pdFVIII do with this information?

While no new actions are recommended now, you can stay informed by keeping in contact with a hemophilia or von Willebrand Disease specialist at a Hemophilia Treatment Center to find out about new scientific advances in this field such as testing and diagnosis, and also to monitor your general health. In addition, FDA is encouraging physicians and patients to consider this information about pdFVIII and vCJD in the larger context of the known benefits of product use and the known and potential risks for pdFVIII and alternative therapies when making treatment decisions.

What are Hemophilia Treatment Centers, and where can I find out about them?

Hemophilia Treatment Centers (HTC) are a network of federally funded, comprehensive care clinics that promote the management, treatment, and prevention of complications experienced by persons with hemophilia and other hereditary bleeding disorders.

You can find information about HTC’s on the CDC website:

  1. CDC informational posting, containing information about the kinds of services provided by federally funded HTC’s
  2. Regional HTC websites are also a good place for information

Where can I find more information about vCJD and pdFVIII?

You can find additional information at:

FDA

  • FDA informational posting, containing current pdFVIII risk assessment, fact sheet, and briefing materials
  • Blood Products Advisory Committee meeting - summary of recent TSEAC meeting and statement about FXI from the UK, on October 21, 2006
  • TSEAC meeting with discussion of first FXI draft risk assessment, on February 8, 2005, and discussion of UK risk communication for plasma derivatives
  • TSEAC Meeting with further discussion of the FDA risk assessment model, October 31, 2005
  • TSEAC Meeting with update on FXI risk assessment, September 18, 2006

CDC

  • Information on vCJD: Centers for Disease Control and Prevention
  • Regional HTC websites

USDA

  • Information on Bovine Spongiform Encephalopathy ("Mad Cow Disease"): US Department of Agriculture

Patient Organizations:

  • Committee of Ten Thousand
  • Hemophilia Federation of America
  • National Hemophilia Foundation and/or HANDI
  • World Federation of Hemophilia
 

Contact FDA

(800) 835-4709
(240) 402-8010
Consumer Affairs Branch (CBER)

Division of Communication and Consumer Affairs

Office of Communication, Outreach and Development

Food and Drug Administration

10903 New Hampshire Avenue

Building 71 Room 3103

Silver Spring, MD 20993-0002