Bovine Spongiform Encephalopathy (BSE)

Questions and Answers on Bovine Spongiform Encephalopathy

Questions and Answers on Bovine Spongiform Encephalopathy:

  • What is BSE?
  • What causes BSE?
  • Where is the BSE agent found in infected cattle?
  • Which countries have reported BSE?
  • How was BSE spread?
  • What has the British government done in response to the BSE epidemic?
  • Does BSE occur in the US?
  • What measures has the US government taken to ensure that people are not exposed to the BSE agent in foods?
  • How is the BSE agent detected?
  • Does BSE or a similar disease occur in humans?

Questions and Answers on Variant CJD (vCJD):

  • What is the new variant form of CJD that the experts in the United Kingdom believe might be related to the BSE outbreak in cattle?
  • Exactly how does this newly recognized variant of CJD differ from classical CJD?
  • How did people get this new variant of CJD?
  • What is the evidence directly linking this newly recognized variant of CJD to BSE exposure?
  • How many cases of variant CJD have occurred?
  • Could anyone in Europe diagnosed with the newly recognized variant of CJD (vCJD) have acquired this from vaccines?

Questions and Answers on Bovine Derived Materials Used in Vaccine Manufacturing:

  • Why are animal products used in the manufacture of vaccines?
  • Which bovine derived materials are used in vaccine manufacture?
  • Do all bovine materials have the same risk of transmitting the BSE agent?
  • What measures have the FDA taken to ensure that people are not exposed to the BSE agent in vaccines?
  • Are bovine derived materials from North America used in the manufacture of vaccines?

Questions and Answers Related to FDA Guidance on Sourcing of Bovine Materials:

  • How did the FDA discover that some manufacturers are not universally following letters, Points to Consider (PTC) and guidance documents?
  • What is FDA doing now to assure that companies follow guidance, letters, and PTC documents?

Questions and Answers Related to Vaccines and vCJD:

  • Why did the FDA ask the Transmissible Spongiform Encephalopathy Advisory Committee (TSEAC) and the Vaccines and Related Biological Products Advisory Committee (VRBPAC) to meet on July 27th, 2000?
  • What is the chance/risk that a vaccine on the market in the US contains the BSE agent?
  • What is the risk of getting vCJD if a vaccine contained the BSE agent?
  • How did FDA derive its risk estimates and decide the risk of vCJD from vaccines was remote and theoretical?
  • Why did FDA leave on the market vaccines that did not follow its own recommendations regarding sourcing of bovine derived materials?
  • If vaccines are safe, why did the UK recall the polio vaccine?
  • What was the concern in the Republic of Ireland about polio vaccine and vCJD?
  • Have there been vaccines produced using cow materials from countries where there is a significant risk of BSE?
  • Is there a possibility that some vaccines might be contaminated with the BSE agent?
  • My child was just immunized. Should I be worried?
  • Why are you continuing to vaccinate children with a vaccine that may be contaminated with BSE causing materials?
  • What is being done to ensure the United States' vaccine supply is safe?
  • When will vaccine manufacturers finish replacing cow-derived materials in vaccines with materials obtained from countries free of BSE?
  • Shouldn't all potentially contaminated vaccines be destroyed?

What is BSE?

BSE (bovine spongiform encephalopathy) is a progressive neurological disorder of cattle; its symptoms are similar to a disease of sheep, called scrapie. BSE has been called "mad cow disease." BSE and scrapie both result from infection with a very unusual infectious agent. As of January 2004, more than 180,000 cases of BSE were confirmed in Great Britain in more than 35,000 herds of cattle. The epidemic peaked in January 1993 at almost 1,000 new cases per week. Although the origin of the disease is uncertain it may have resulted from the feeding of scrapie containing meat and bone meal (MBM) to cattle or from feeding cattle MBM derived from a cow or other animal that developed the disease due to a spontaneous mutation (http://www.bseinquiry.gov.uk/). There is strong evidence and general agreement that the outbreak was amplified by feeding meat-and-bone meal prepared from cattle to young calves.

What causes BSE?

The nature of the infectious agent that causes BSE and scrapie is unknown. Currently, the most accepted theory is that the agent is a modified form of a normal cell protein known as a prion. A prion is not a bacterium, parasite, or virus, and thus treatments usually used for treating or preventing bacterial infections (e.g. antibiotics) or viral infections are not effective against prions.

Where is the BSE agent found in cattle?

In cattle naturally infected with BSE, the BSE agent has been found in brain tissue, in the spinal cord, and in the retina of the eye. Additional experimental studies suggest that the BSE agent may also be present in the small intestine, tonsil, bone marrow, and dorsal root ganglia (lying along the vertebral column).

Which countries have reported BSE?

The vast majority of cases of BSE (more than 97% as of 2003) have been reported from the United Kingdom during an epidemic. However, endemic cases have also been reported in other European countries including: the Republic of Ireland, Switzerland, France, Liechtenstein, Luxembourg, Netherlands, Portugal and Denmark. The numbers of reported cases by country are available on the web site of the Office International des Epizooties (www.oie.int/). These numbers should be interpreted with caution, however, because the intensity and methods of surveillance probably vary over time and by country. In 2003 one case was reported in Canada and one in the United States (in a cow born in Canada).

How was BSE spread?

It is thought that BSE was spread via meat-and-bone meal fed to cattle. The practice of using this material as a source of protein in cattle feed has been common for several decades. In the late 1970s there was a change in the production (rendering) process used to make this meat and bone meal. One hypothesis has been that this change permitted the infectious agent of scrapie (a transmissible spongiform encephalopathy, or TSE, of sheep) to survive the rendering process, and get transmitted to other animals, such as cows, that are fed meat-and-bone meal nutritional supplements. An inquiry by the British government has however, concluded that scrapie infected MBM was not the source of BSE nor was the change in the rendering practices responsible for survival of the BSE agent. Rather, this inquiry has stated that BSE may have originated spontaneously as a result of a genetic mutation and was amplified by the feeding of contaminated MBM to cattle ( http://www.bseinquiry.gov.uk/).

What has the British government done in response to the BSE epidemic?

In response to the BSE epidemic, the British Government instituted a series of measures to minimize the risk of disease transmission among both animals and humans. These included a ban on feeding ruminant protein (ruminants are animals, such as cows, sheep and goats) to ruminants (1988), removal of some "high risk" materials (such as brain, spinal cord and intestines) from cattle at slaughter (1989 and 1995), and a ban on cattle over 30 months of age from being used for food (1996). Following institution of these measures, Great Britain has seen a decrease in the number of cattle with BSE from a peak incidence of 36,682 confirmed cases in 1992 to 1044 confirmed in 2002 (www.oie.int; information on the BSE epidemic in Great Britain is available at: http://www.defra.gov.uk/).

Does BSE occur in the US?

According to the Animal Health and Plant Inspection Service (APHIS) of the United States Department of Agriculture, BSE has been detected in one cow in the United States. Following complications of pregnancy this cow was slaughtered December 9, 2003. As part of the APHIS ongoing surveillance of downer animals a brain sample was taken to test for the BSE agent. On December 25, 2003 it was confirmed that this animal tested positive for the BSE agent (on December 23, 2003 this was a "presumptive" case). Following this discovery the USDA and FDA announced additional measures to enhance the US protections against BSE (see: What measures has the US government taken to ensure that people are not exposed to the BSE agent in foods?).

What measures has the US government taken to ensure that people are not exposed to the BSE agent in foods?

The USDA is responsible for the health of US livestock. To prevent BSE from entering the country, the USDA Animal and Plant Health Inspection Service (APHIS) has, since 1989, prohibited the importation of live ruminants from countries where BSE is known to exist in native cattle. On December 12, 1997, APHIS stopped the importation of live ruminants and most ruminant products, including meat, meat-and-bone meal, offals, glands, etc. from all of Europe. FDA is responsible for animal feeds in the US. In August 1997, FDA prohibited the use of most mammalian protein in the manufacture of animal feeds given to ruminants. Following the discovery of one cow with BSE in the US, the USDA and FDA have announced additional measures to enhance protections against the spread of BSE in US cattle and to minimize human exposure to bovine materials that may contain the BSE agent. USDA has issued an interim final rule (Federal Register January 12, 2004 Vol. 69, Number 7) removing downer animals and specified risk materials and tissues from the human food chain; requiring additional process controls for establishments using advanced meat recovery (AMR); holding meat from cattle that have been targeted for BSE surveillance testing until the test has confirmed negative; and prohibiting the air injection stunning of cattle (http://www.aphis.usda.gov/lpa/issues/bse/bse.html). In January 2004, FDA proposed additional safeguards including: excluding brain, spinal cord, gut and eyes of older animals from human food and from rendered material in animal feeds, eliminating poultry litter, cow blood and processed plate waste as feed ingredients for cattle, labeling requirements for pet food, and additional control measures to prevent cross contamination of feed and feed ingredients at feed mills. In addition, since 1990, the USDA has led an interagency surveillance program for evidence of BSE in the US. USDA has tested 20,000 animals annually for each of the last 2 years, and approximately 75 percent of these were downers at slaughter (http://www.aphis.usda.gov/lpa/issues/bse/bse-surveillance.html). A BSE risk assessment performed by Harvard University's Center for Risk Analysis at the School of Public Health concluded that even if BSE were to occur in the US the measures already taken would largely prevent its spread to animals or humans, and the disease would gradually disappear over a number of years (2001, www.aphis.usda.gov/lpa/issues/bse/bse-riskassmt.html).

How is the BSE agent detected?

The presence of the BSE agent in tissues is generally determined by injecting animals, usually mice, with samples, then observing the mice to see if they die and have characteristic brain tissue changes. Mouse inoculation studies take a long time (up to 700 days) to detect the agent, and a negative result (that is, lack of brain tissue changes in the injected mice) may only mean that there was too little of the infectious agent to cause symptoms, not that the material was completely free of the infectious agent. It is also possible to detect the presence of the abnormal prion protein in tissues (such as brain) using special staining procedures although these methods do not allow an accurate assessment of infectivity of the infected material.

Does BSE or a similar disease occur in humans?

BSE belongs to a group of progressive degenerative neurological diseases known as transmissible spongiform encephalopathies (TSEs). TSE diseases are always fatal. The TSE diseases include scrapie, which affects sheep and goats; transmissible mink encephalopathy; feline (cat) spongiform encephalopathy; and chronic wasting disease of deer and elk. There are six TSE diseases that affect people: kuru, classical Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and sporadic fatal insomnia. The human diseases are very rare; for example, classical CJD has been well studied and occurs sporadically worldwide at a rate of about one case per one million people each year.


Questions and Answers on Variant CJD (vCJD)

What is the new variant form of CJD that the experts in the United Kingdom believe might be related to the BSE outbreak in cattle?

In contrast to the classic form of CJD, the new variant or variant form (vCJD) in the United Kingdom and France affects younger persons (average age at onset: 26 years), and has different clinical features from CJD. People with vCJD begin with serious psychiatric problems or problems with their senses (ears, eyes or smell). This first set of symptoms is followed weeks or months later by poor muscle coordination, muscle spasms, and mental confusion. The illness lasts for at least 6 months, and on average people with vCJD die approximately 13 months after their symptoms begin. When patients' brains are examined by autopsy, there are clear changes in brain tissue structure, including many "spongiform," or open spongy-looking areas, abnormal clumps of prion protein called plaques, and other areas with less prominent accumulations of abnormal prion protein.

Exactly how does this newly recognized variant of CJD differ from classical CJD?

In 1996 the Spongiform Encephalopathy Advisory Committee (SEAC) of the UK announced the identification of 10 cases of variant CJD (vCJD, Lancet, 1996, 347: 921-25). Since then over 100 people have died of vCJD in the UK. The following features describe how vCJD cases differ from the sporadic or classical form of CJD (Lancet, 1996, 347: 921-25, Rev.Med.Virol. 2002;12: 143-50):

  • The affected individuals were much younger than the classical CJD patient. Typically, CJD patients are over 63 years old. The average patient with vCJD is 26 years old; patients ranged from 12-74 years old.
  • The course of vCJD averaged 13 months (range 6-40 months). Classical CJD cases average a 4 month duration.
  • In the vCJD cases, electroencephalographic (EEG) electrical activity in the brain, while abnormal (slowed), was not typical of classical CJD, which often has periodic bursts of increased electrical activity.
  • Although changes in brain tissue structure of patients with vCJD were recognizable as CJD, the pattern was different from classical CJD, with large aggregates of prion protein plaques often surrounded by vacuoles.

How did people get this new variant of CJD?

On March 20, 1996 a statement from the Spongiform Encephalopathy Advisory Committee (SEAC) of the United Kingdom indicated concern that before November 1989, when inclusion of certain cow and sheep by-products in human food was banned, the BSE agent may have been transmitted to people through contaminated food products. The SEAC said that food might account for the 10 vCJD cases described in 1996 (Lancet 1996; 347:921-5). The specific foods, if any that may be associated with the transmission of this agent from cattle to humans are unknown. However, the SEAC has indicated that milk and milk products are unlikely to pose any risk for human exposure to the BSE agent.

What is the evidence directly linking this newly recognized variant of CJD to BSE exposure?

There is strong epidemiologic and laboratory evidence suggesting that new variant CJD (vCJD) and BSE are caused by the same infectious agent. For instance, all cases of confirmed vCJD have occurred in people who have lived in geographic areas which have had BSE cases. The majority of cases of vCJD have occurred in the UK, which has had the largest number of cases of BSE in cattle. In addition, the time interval or "incubation period" between the most likely period for the initial exposure of the population to potentially BSE-contaminated food (1984-1986) and onset of initial vCJD cases (1994-1996), about 10 years, is similar to the known time intervals between exposure to the classical CJD agent and the development of CJD. An experimental study reported in June 1996, showed that three cynomolgus macaque monkeys that were injected with brain tissue from cattle with BSE later developed symptoms and changes in brain tissue that were strikingly similar to vCJD (Nature 1996;381:743-4). Another study published in 1996 showed that prion proteins obtained from 10 vCJD patients and BSE-infected animals had molecular characteristics that were similar to each other but distinct from prion proteins obtained from patients with classical CJD (Nature 1996;383:685-90). Furthermore, results of an ongoing experimental study involving injection of a panel of various strains of mice with the agent that causes BSE and vCJD suggested that these agents cause a similar disease in mice (Nature 1997;389:498-501). Histological analysis of mouse brains from this study showed no significant differences in the neuropathological changes observed in the BSE and vCJD-infected mice (Neuropathology and Applied Neurobiology 2003; 29:262-272). A study using transgenic mice (PNAS 1999; 96:15137-15242) also supports the hypothesis that the BSE agent from cattle causes vCJD.

How many cases of variant CJD have occurred?

Cases of variant CJD are very rare, and most have occurred in the United Kingdom. Information provided by the UK Creutzfeldt-Jakob Disease Surveillance Unit (February, 2004, www.cjd.ed.ac.uk/figures.htm) indicates that there have been 146 cases of definite and probable vCJD in the United Kingdom. These cases have all been diagnosed since 1995. France has reported six cases. The Republic of Ireland, Italy, Canada and the US have each reported one case. The cases in Ireland, Canada and the US each occurred in individuals who had spent several years in the UK.

Could anyone in Europe diagnosed with the newly recognized variant of CJD (vCJD) have acquired this from vaccines?

In the UK the majority of cases of vCJD were born before 1980, and it is very unlikely that they received vaccines contaminated with the BSE agent (Vaccine 2000; 19:409-410). Surveillance of vCJD in the UK has identified three "risk factors," or characteristics common to most if not all of the people who had vCJD: i) residence in the UK; ii) a particular genetic susceptibility (met/met homozygosity at codon 129 of the PrP gene); and iii) age. Epidemiological evidence to date suggests that these cases of vCJD acquired the disease from eating beef products containing the BSE agent after 1980. To date (February 2004) there have been 156 reported cases of vCJD. Of these, 146 have occurred in the UK. Six cases of vCJD have been diagnosed in France, and one each in Canada, Ireland, Italy and the US. The cases in Canada, Ireland and the US each occurred in individuals who had spent several years in the UK.


Questions and Answers on Bovine Derived Materials Used in Vaccine Manufacturing:

Why are animal products used in the manufacture of vaccines?

Vaccines contain either killed or weakened forms of disease-causing bacteria or viruses, or components of these that stimulate a response by the body's immune system, which then protects against the development of disease. In the late 19th century, microbiologists began to grow bacteria in the laboratory. The early bacteriologists tried to mimic as closely as possible the environment in an infected person's tissues by using solutions containing sugars, salts, and various meat extracts to make "growth media." These kinds of conditions were quite successful in growing bacteria and then viruses in the lab, because these media supplied the many necessary nutrients. Although synthetic media have been developed for growth of many medically important microorganisms, some still require additional nutrients which are easily provided by animal-derived products such as serum and blood. Viral vaccines are produced in living cells, which, similarly, require the addition of complex growth media components, such as fetal calf serum.

Which bovine derived materials are used in vaccine manufacture?

Microorganisms for vaccine manufacture are grown under controlled conditions in media which provide the nutrients necessary for growth. Cow components are often used simply because cows are very large animals, commonly used for food, and thus much material is available. Animal-derived products used in vaccine manufacture can include amino acids, glycerol, detergents, gelatin, enzymes and blood. Cow milk is a source of amino acids, and sugars such as galactose. Cow tallow derivatives used in vaccine manufacture include glycerol. Gelatin and some amino acids come from cow bones. Cow skeletal muscle is used to prepare broths used in certain complex media. Many difficult to grow microorganisms and the cells that are used to propagate viruses require the addition of serum from blood to the growth media.

Do all bovine materials have the same risk of transmitting the BSE agent?

Scientists have found that different bovine tissues contain different amounts of the BSE agent. It is generally believed that the highest amounts of infectivity are found in the brain and spinal cord from animals in the final stages of clinical disease. Some tissues, such as skeletal muscle and milk, have never been shown to have any infectivity. However, the slaughtering and butchering methods used to obtain tissues and prepare materials can affect the amount of infectivity that may be present. Also the production processes used to prepare bovine-derived materials (such as heat sterilization and chemical treatment) may reduce or remove infectivity.

What measures have the FDA taken to ensure that people are not exposed to the BSE agent in vaccines?

It is believed that variant CJD was acquired from eating food products containing the BSE agent. However, FDA wants to minimize any chance that the BSE agent could be introduced into biologic products during manufacture. The Center for Biologics Evaluation and Research (CBER) is responsible for regulation of biologic products, including vaccines. In a 1991 letter to manufacturers CBER expressed concern about bovine sourced material. In December 1993 and May 1996 FDA issued letters advising that bovine derived materials from animals born in or residing in countries where BSE had occurred should not be used to manufacture FDA-regulated products intended for administration to humans. A 1993 Points to Consider document ("Points to Consider in the Characterization of Cell Lines Used for the Production of Biologics") stressed the importance of control of sourcing of bovine materials. On April 19, 2000, CBER issued a letter reminding manufacturers that the USDA list of BSE-countries had been expanded to include not only those countries where BSE was known to exist but also those where BSE may exist (FR, January 6, 1998). CBER strongly recommended "that manufacturers take whatever steps are necessary to assure that materials derived from all species of ruminant animals born, raised or slaughtered in countries where BSE is known to exist, or countries where the USDA has been unable to assure FDA that BSE does not exist, are not used in the manufacture of FDA-regulated products intended for administration to humans." Although Canada and the US have each reported one case of BSE and the USDA has placed Canada on the list of countries with BSE, FDA has not recommended that manufacturers find a new source for bovine derived materials obtained from these countries for use in manufacture of drugs or biological products. The FDA believes that the control measures in place assure the safety of bovine derived materials sourced from these countries and used in manufacture of vaccines.

Are bovine derived materials from North America used in the manufacture of vaccines?

Yes, bovine derived materials from North America, specifically the US and Canada, are used in vaccine manufacture. Since there has been extensive movement of live cows and cow-derived materials between Canada and the US it is difficult to establish that an animal has not been born, raised or slaughtered in Canada. Moreover, control measures, such as the ruminant-to-ruminant feed ban have been similar in the two countries. Therefore, FDA has not recommended that manufacturers using bovine derived material from Canada replace those materials with materials from countries not on the USDA list of countries that have BSE or are at risk of BSE.


Questions and Answers Related to FDA Guidance on Sourcing of Bovine Materials:

How did the FDA discover that some manufacturers are not universally following letters, Points to Consider (PTC) and guidance documents?

During review of new license applications manufacturers are asked to provide detailed descriptions of the manufacturing process and documentation of source country for all materials of animal origin. In 2000, during review of a license application it was determined that some of the material used during manufacture had been obtained from countries which are on the USDA list of countries which either have or may have BSE. This finding prompted an inquiry of all licensed vaccines.

What is FDA doing now to assure that companies follow guidance, letters, and PTC documents?

The Center for Biologics Evaluation and Research (CBER) has asked licensed vaccine manufacturers to evaluate all bovine sourced material used at any stage of manufacture. Manufacturers have been requested to identify all material of animal origin. For materials of bovine origin CBER has asked manufacturers to identify the source country from which the animals originated, the date the material was obtained and the date the material was used in manufacture of vaccine lots. When it is determined that any bovine-derived component used to make the working seeds or during routine production was obtained from a country on the current USDA list of countries (with the exception of Canada) which either have or may have BSE or from an unknown country, the manufacturer has been asked to change the source of such material. CBER inspects vaccine manufacturers on a routine basis to determine whether sourcing and documentation are consistent with current recommendations contained in letters and guidance documents.


Questions and Answers Related to Vaccines and vCJD:

Why did the FDA ask the Transmissible Spongiform Encephalopathy Advisory Committee (TSEAC)and the Vaccines and Related Biological Products Advisory Committee(VRBPAC) to meet on July 27th, 2000?

The Center for Biologics Evaluation and Research (CBER), FDA regulates biological products including vaccines. For several years CBER has recommended that bovine derived components from countries which have or may have BSE (bovine spongiform encephalopathy, the so called "mad cow disease") not be used for the manufacture of US-licensed biological products including vaccines. The consumption of food contaminated with the BSE agent has been linked to a fatal disease in people called new variant or variant CJD (vCJD). There is no evidence that any case of vCJD has resulted from use of a vaccine, and there is no evidence that any vaccines harbor the BSE agent. In 2000, CBER determined that some vaccines were manufactured using bovine components from countries which the USDA has determined have or may have BSE. CBER believed that the chance of getting vCJD through vaccines is remote and theoretical. However, CBER has responsibility to ensure that vaccines used in the US are safe and asked for this special joint meeting to ask vaccine and TSE experts to formally discuss the risk of transmitting vCJD from vaccines.

What is the chance/risk that a vaccine on the market in the US contains the BSE agent?

Studies of the BSE agent have shown that infectivity depends on nature of material used, how much is used and the route of administration. Other factors, such as the country of origin of the cattle used to supply the manufacturing material, also have to be factored into any risk estimate. Both the European Community and the US Pharmaceutical industry have presented risk assessment calculations which attempt to account for all these factors. In 1999, the Council on Scientific Affairs (CSA) of the American Medical Association considered the risk of BSE to public health and determined that the current risk of transmission of BSE in the US is minimal, concluding that adequate guidelines exist to prevent high risk bovine materials from contaminating products intended for human use. The report from the CSA did not address the possibility that regulated industry might not follow all of the recommendations made by the FDA. However, both FDA and the joint advisory committees (TSEAC and VRBPAC) have considered the risks posed by bovine material in vaccines and concluded that any risk is remote and theoretical See Section I, Section II and Section VI and MMWR Recommendations and Reports.

What is the risk of getting vCJD if a vaccine contained the BSE agent?

There is no evidence to date that vaccines have contributed to the cases of vCJD seen in Europe. Nor is there evidence that any vaccines harbor the BSE agent. Vaccines are given a very limited number of times via the intramuscular, subcutaneous or oral route. Even in experimental studies, these routes of administration are less effective at spreading the agent than the intracerebral route usually used to assess infectivity in animal studies. The amount of infectivity present and the efficiency with which the BSE agent passes from cow material to humans will also affect the likelihood of infection.

How did FDA derive its risk estimates and decide the risk of vCJD from vaccines was remote and theoretical?

Scientists, regulatory authorities in Europe and the pharmaceutical industry of the US have considered the risks of BSE in pharmaceutical products. In estimating these risks it is necessary to consider the country of origin of any bovine material, the type of bovine tissue used, the steps used to process the bovine tissue, the amount of bovine derived material used and the stage of vaccine manufacture at which the bovine material is used. Using previously published methods for calculating theoretical risk of cases of vCJD from pharmaceutial products, FDA has calculated a conservative estimation of the risk of a vaccine causing a case of vCJD. These estimates were presented in public session at the joint advisory committee on July 27th 2000. FDA believes these estimations are a realistic worst case scenario and that the real risk any US licensed vaccine could cause vCJD is even lower than the estimates presented. See Section VI and Section II.

Why did FDA leave on the market vaccines that did not follow FDA recommendations regarding sourcing of bovine derived materials?

One of FDA's main concerns is the safety of vaccines and other drugs given to consumers. In its efforts to monitor the safety of products FDA continually reviews the potential risk of products in relation to new entities, including the BSE agent. The FDA has looked at the benefit of vaccines and the risk of contamination of vaccines with the BSE agent. The Public Health Service, FDA, and FDA's advisory committees on Transmissible Spongiform Encephalopathy (TSEAC) and Vaccines and Related Biological Products (VRBPAC) believe the risk that anyone will get vCJD from a vaccine to be remote and theoretical. Vaccines have a proven benefit in reducing the incidence of serious, often life-threatening diseases. The absence of high levels of routine vaccination leads to an increased incidence of vaccine preventable diseases. Therefore, removal of licensed vaccines from the market for a remote, theoretical risk can have serious medical and public health consequences. In considering the balance of risks and benefits, the use of all vaccines, even those which were manufactured with bovine derived materials from unapproved sources, should continue.

If vaccines are safe why did the UK recall their polio vaccine?

The UK recalled the Evans/Medeva Oral Polio Vaccine in October, 2000. This vaccine has never been licensed for use in the US. The Medicines Control Agency (MCA) had requested and received assurances from drug companies that they were implementing guidance not to use UK-sourced bovine materials in the manufacture of injectable medicinal products. The recall was prompted by evidence that the Evans/Medeva vaccine was manufactured using fetal calf serum from the UK at a time when there was a risk of BSE in that country. This is in contravention of European Union guidelines. According to a statement from the Chief Medical Officer at the UK Dept. of Health (10.20.00) the company had assured the MCA of the UK that UK-sourced bovine materials were not used in the manufacture of the vaccine. However, these assurances were inaccurate, thus the vaccine was withdrawn. (www.dh.gov.uk/Home/fs/en)

What was the concern in the Republic of Ireland about polio vaccine and vCJD?

In December, 2000 the Irish Government issued a statement indicating that an oral polio vaccine distributed in 1998 and 1999 in Ireland had been manufactured using human serum albumin from a pool of donors, one of whom had since been diagnosed with vCJD. Evans/Medeva manufactured this oral polio vaccine. This vaccine is not licensed for use in the US.

Have there been vaccines produced using cow materials from countries where there is a significant risk of BSE?

During review of a license application, FDA learned that one manufacturer had used bovine-derived material from a country in which the USDA had determined that BSE might exist. CBER requested all vaccine manufacturers review the source of any bovine derived material used in the manufacture of their vaccines. Additional vaccines manufactured using bovine derived products from European countries were identified. These vaccines are identified in the "Recommendations for the Use of Vaccines Manufactured with Bovine Derived Materials" section of this web site. (See Section I)

Is there a possibility that some vaccines might be contaminated with the BSE agent? (See above "What is the chance/risk that a vaccine on the market in the US contains the BSE agent")

My child was just immunized. Should I be worried?

No. FDA and other Public Health Service agencies believe that the risk of contamination of any US licensed vaccine with the BSE agent is remote and theoretical. FDA asked a special joint meeting of the Transmissible Spongiform Encephalopathy and the Vaccines and Related Biological Products Advisory Committees to review the available vaccine risk and benefit information. This joint committee concluded that the substantial risk of disease due to not vaccinating children far outweighs the theoretical risk posed by vaccines that have a remote chance of containing the BSE agent (see PHS statement in MMWR and "Recommendations for the Use of Vaccines Manufactured with Bovine Derived Materials" section of this web site for details)

Why are you continuing to vaccinate children with a vaccine that may be contaminated with BSE causing materials?

Also see above "Why is FDA leaving vaccines on the market that did not follow its own recommendations regarding sourcing of bovine derived materials?" FDA and other Public Health Service agencies believe that the risk of contamination of any US licensed vaccine with the BSE agent is remote and theoretical. FDA asked a special joint meeting of the Transmissible Spongiform Encephalopathy and the Vaccines and Related Biological Products Advisory Committees to review the available vaccine risk and benefit information. This joint committee concluded that the substantial risk of disease due to not vaccinating children far outweigh the theoretical risk posed by vaccines that have a remote chance of containing the BSE agent (see PHS statement in MMWR and "Recommendations for the Use of Vaccines Manufactured with Bovine Derived Materials" section of this web site for details)

What is being done to ensure the United States' vaccine supply is safe?

Also see above "What is FDA doing now to assure that companies follow guidance, letters and PTC documents?" FDA and the other PHS agencies believe that vaccines licensed for use in the US are safe and effective. However, because even the perception of risk could have negative consequences for the use of vaccines and because it is possible to decrease the risk of an already safe product even further, manufacturers of affected vaccines have agreed to change the source of the bovine derived material used during production of the working seeds and cell banks and for routine production (see "Recommendations for the Use of Vaccines Manufactured with Bovine Derived Materials" section of this web site for details).

When will vaccine manufacturers finish replacing cow-derived materials in vaccines with materials obtained from countries free of BSE?

The time to make a vaccine and bring it to market can take several months to a year. Most vaccine made using bovine derived material from non-BSE risk countries was available at the end of 2001.

Shouldn't all potentially contaminated vaccine be destroyed?

Also see above "Why is FDA leaving on the market vaccines which may be contaminated with the BSE agent?" FDA and other PHS agencies believe that the vaccines currently licensed for use in the US are safe. A special joint meeting of the TSE and Vaccines and Related Biological Products Advisory Committees concluded that the real risk of disease due to not vaccinating far outweighs the theoretical risk posed by exposure to vaccines that have a remote chance of containing the BSE agent.

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Updated: September 20, 2004