- Questions about Animal Products and Vaccine Manufacturing
- Questions about Risk Estimates and Vaccine Safety
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.
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.
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.
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.
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")
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")
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").
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.