Barbara Loe Fisher
National Vaccine Information Center
April 7, 2010
On March 22, 2010, Food and Drug Administration (FDA) officials adhering to the precautionary principle advised American doctors to suspend use of Rotarix 1 vaccine until the agency finds out why DNA from a swine virus (porcine circovirus 1 or PCV1) was found in the live rotavirus vaccine. The FDA said there is “no evidence at this time” that the vaccine manufactured by GlaxoSmithKline and given to babies at 2,4 and 6 months of age to prevent diarrhea poses any safety risk. 2
Independent Lab Using New Technology Found Contamination
The discovery that viral DNA is contaminating Rotarix vaccine was made by a team of scientists at an independent research lab in San Fransisco, California, where they used new technology to detect fragments of viral genetic material in vaccines using genetic sequencing. 3
More testing confirmed that many copies of DNA from the pig virus were present in all Rotarix vaccine lots released since the vaccine was licensed in 2008 because the pig virus DNA also contaminated the working cell bank and the original viral “seed” stock, from which Rotarix vaccine was first produced. 4
Two Other Live Virus Vaccines Contaminated
The surprising discovery reportedly was made after the independent lab used new technology to evaluate the purity of eight live virus vaccines for polio, rubella, measles, yellow fever, human herpes 3 (varicella or chicken pox), rotavirus (Rotarix and RotaTeq) and MMR. In addition to pig viral DNA found in Rotarix vaccine, low levels of DNA fragments from avian (bird) leukosis virus (a retrovirus) was found in measles vaccine and DNA fragments of a virus similar to simian (monkey) retrovirus was found in RotaTeq vaccine. 5
FDA Looking For Answers
After the team double checked their findings, researchers notified GlaxoSmithKline (GSK) on February 9, 2010 and GSK notified the FDA on March 15, 2010, which prompted the FDA’s action on March 22, 2010 to suspend use of Rotarix. The FDA says it “does not know how DNA from PCV1 came to be present in Rotarix” or whether “this means that intact virus is present. Additional studies are being conducted.” 6
Rotavirus Vaccines Use Monkey, Cow, Pig Materials for Production
Rotarix is a genetically engineered vaccine that GSK created by isolating human rotavirus strain infecting a child in Cincinnati and using African Green monkey kidney cells to produce the original viral seed stock from which all Rotarix vaccine has been made. 7 In the FDA licensing process, Rotarix had to meet certain FDA standards, that included demonstrating the vaccine was not contaminated with, for example TSE (Transmissable Spongiform Encephalopathy or “mad cow” disease, a brain wasting disease) 8 or with cow viruses because bovine (cow) serum was used to prepare the original viral seed stock. Porcine trypsin, an enzyme in the pancreatic juice of a pig, was also used to make the viral seed stock. 9
RotaTeq is a genetically engineered vaccine containing five human-cow reassortment strains of rotavirus that were created at the Children’s Hospital of Pennsylvania (CHOP), where strains of rotavirus that give cows diarrhea were combined with strains of rotavirus that cause diarrhea in humans. The reassortment viruses were transported to Merck, where master seeds were produced using African Green Monkey kidney cell cultures. Fetal bovine (cow) serum and porcine trypsin was used to make the “seed” stock. 10 There are small amounts of bovine serum and cell culture media (monkey viral DNA) that remain in RotaTeq vaccine. 11 12
FDA Suggests Drug Companies Test for Vaccine “Purity”
In a February 2010 FDA document, Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications, the FDA lists “non-binding recommendations” for drug companies making vaccines using animal and human cell substrates. 13 Under the heading “Testing for Adventitious Agents,” the FDA states “assurance that products are free of adventitious agents is a critical component of meeting the [FDA regulations] requirement for purity.” Under the heading “Testing for Residual Cellular DNA,” the FDA states, “Residual DNA might be a risk to your final product because of oncogenic (cancer causing) and/or infectivity potential.”
Déjà Vu: Monkey Viruses Contaminated Polio Vaccines
Contamination of vaccines with animal viruses is not new. In the 20th century, polio vaccines given to tens of millions of people worldwide were contaminated with simian virus 40 (SV40), which was found to cause cancer in animals and is associated with human brain, bone and lung cancers but the government denies SV40 is causing those cancers in humans. 14 15 16 17
There has been controversy about the link between experimental polio vaccines tested in Africa in the 1950’s and 1960’s that were contaminated with a monkey virus, simian immunodeficiency virus (SIV). Soon after the polio vaccine trials in Africa, the human immunodeficiency virus (HIV) emerged. 18 Many questions about the failure of researchers and technology to screen for monkey viruses in those vaccines remain to this day.
Using Cancer Cells to Produce Vaccines?
Vaccine manufacturers have long used cell material that comes from the bodies of mammals, including humans, monkeys, cows, pigs, dogs and rodents, as well as birds or insects to make vaccines now in use or to make experimental vaccines. There is an inherent risk of contamination with viruses and other microbes (or DNA from those microbes) that can escape detection during the vaccine development, testing, licensing, manufacturing and oversight process. 19 There has even been discussion among vaccine manufacturers and the FDA in the last decade about using neoplastic (cancer) cell substrates to make vaccines but the risk of contamination with cancer cell DNA is a big risk. 20
New Influenza Vaccines: Is Contamination Possible?
In searching for ways to make seasonal influenza vaccines in a faster, easier and less expensive way than relying on chicken eggs for production, drug companies have experimented with using dog kidney cells and human fetal retinal cells. However, these cell lines have been documented to cause tumors in animals, especially dog kidney cells (MDCK). 21
At a November 19, 2009 meeting of the FDA Vaccines & Related Biological Products Advisory Committee, a vaccine manufacturer asked for permission to use insect (caterpillar) cells to make pandemic influenza shots. But insect cells can be contaminated with insect viruses that are hard to detect. The FDA Committee, on that day, voted “no.” 22
Unanswered Questions about Rotarix Contamination
There are lots of questions about how the manufacturer of Rotarix vaccine and the FDA both missed the pig virus DNA contaminating the original seed stock and all doses of Rotarix vaccine given to more than one million American children in the past few years. 23
Is there state-of-the-art technology that is being used by private laboratories but not by drug companies and the FDA?
Why did the independent team of scientists, who found the contamination, notify the vaccine manufacturer first rather than also immediately reporting their finding directly to the FDA?
What about the significance of finding bird viral DNA in measles vaccine and the monkey viral DNA in RotaTeq vaccine?
Wake Up Call for Industry & Government
- A d v e r t i s e m e n t
The contamination of Rotarix vaccine is only the latest in a long history of vaccine contamination issues that require a re-examination of the way vaccines are made and tested. It is a wake-up call for industry and government
The big question people are asking is: why do drug companies making vaccines continue to use cells from animals, birds and insects that can be contaminated with viruses and other adventitious agents that are hard to detect?
The FDA was right to suspend use of Rotarix vaccine until they know more. Hopefully, this serious vaccine production and testing issue will be addressed immediately by vaccine manufacturers. If not, the next pandemic or serious health problem affecting large populations may be one that comes out of a vaccine lab.
1 National Vaccine Information Center (NVIC). Rotarix and Rotarix Vaccine.
2 FDA. News Release: Components of Extraneous Virus Detected in Rotarix Vaccine: No Known Safety Risk, FDA Recommends Clinicians Temporarily Suspend Use of Vaccine As Agency Learns More. March 22, 2010. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm205625.htm
3 Racaniello V. Deep sequencing reveals viral vaccine contaminants. www.virology.ws. March 29, 2010. http://www.virology.ws/2010/03/29/DEEP-SEQUENCING-REVEALS-VIRAL-VACCINE-CONTAMINANTS/?
4 FDA. Detection of DNA from PCV1 in Rotarix. March 22, 2010. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm205545.htm
5 See Reference #3 above.
6 FDA. See Reference #4 above.
7 FDA. Memorandum: Review of Vero Cell Banks used for Vaccine Production and Adventitious Agent Testing of Virus Seeds and Vaccine Human Rotavirus Vaccine (HRV) – Rotarix. April 1, 2008. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm134138.htm
8 FDA. Summary Basis for FDA Regulatory Action – Rotarix. June 4, 2007. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm133543.htm
9 European Medicines Control Agency. Evaluation of Medicines for Human Use: Rotarix Vaccine (Control of Materials (Reagants) page 4). 2006. http://www.ema.europa.eu/humandocs/PDFs/EPAR/rotarix/063906en6.pdf
10 European Medicines Control Agency. Evaluation of Medicines for Human Use: RotaTeq Vaccine (Active Substance (Manufacture). Pages 3-10. http://www.ema.europa.eu/humandocs/PDFs/EPAR/Rotateq/066906en6.pdf
11 FDA. Memorandum: Clinical Review of New Biologics License Application – RotaTeq (Description of the Product). Page 12. April 6, 2005. http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM142304.pdf
12 European Medicines Control Agency. See Reference #10 above. Page 6.
13 FDA. Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications. February 2010. http://www.fda.gov/downloads/BiologicsBloodVaccines/
14 Bookchin D, Schumacher J. The Virus and the Vaccine: The True Story of a Cancer-Causing Monkey Virus, Contaminated Polio Vaccine, and the Millions of Americans Exposed. St. Martin’s Press: New York. 2004. http://www.nvic.org/resource-center/books.aspx
15 Fisher BL. Congressional Testimony: The SV-40 Virus: Has Tainted Polio Vaccine Caused an Increase in Cancer? U.S. House Government Reform Committee. September 10, 2003. http://www.nvic.org/vaccines-and-diseases/Polio-SV40/BLFTestimonySV40.aspx
16 U.S. Congress. Congressional Hearing: Preventing Another SV40 Tragedy: Are Today’s Vaccine Safety Protocols Effective? U.S. House Government Reform Committee. November 13, 2003. http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=108_house_hearings&docid=f:92772.wais
17 Carlsen W. Rogue Virus in the Vaccine: Early Polio Vaccine Harbored Virus Now Feared to Cause Cancer in Humans. San Francisco Chronicle. July 15, 2001. http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2001/07/15/MN193825.DTL
18 Carlsen W. Quest for the Origin of AIDS: Controversial Book Spurs Search for How the Worldwide Scourge of HIV Began. San Francisco Chronicle. January 14, 2001. http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2001/01/14/MN140641.DTL
19 See Reference # 13 above.
20 FDA. Designer Cells as Substrates for the Manufacture of Viral Vaccines. 2001. http://www.fda.gov/OHRMS/DOCKETS/AC/01/briefing/3750b1_01.pdf
21 WHO. Initiative for Vaccine Research: Use of Cell Lines for the Production of Influenza Virus Vaccines: the Appraisal of Technical, Manufacturing and Regulatory Considerations. April 10, 2007.
22 FDA. Vaccines & Related Biological Products Advisory Committee. Safety & Effectiveness of Purified Recombinant Influenza Hemagglutinin Vaccine for the Prevention of Influenza (FluBlok). November 19, 2009. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/
23 FDA. Background on Rotavirus Vaccines: How Many Doses of Rotarix Have Been Sold? March 22, 2010. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm205543.htm