1. 1 Vaccines and Related Biological Products Advisory Committee (VRBPAC) Meeting Detection of Porcine circovirus (PCV) and PCV DNA Sequences in U.S. Licensed Rotavirus Vaccines and the Use of Emerging Analytical Technologies for the Detection of Adventitious Agents in Vaccines Norman W. Baylor, PhD Director, Office of Vaccines Research and Review Center for Biologics Evaluation and Research Food and Drug Administration May 7, 2010

2. 2 Background In February 2010, GlaxoSmithKline (GSK) Biologicals was informed by a UCSF investigator that DNA sequences originating from porcine circovirus (PCV-1) were detected in two batches of Rotarix ® (live attenuated rotavirus vaccine) –GSK initiated experiments to confirm results, and conduct further investigations –Tests confirmed the presence of PCV-1 DNA in Rotarix, intermediates in the production process the working cell bank the viral seed from which the vaccine was derived final container GSK informed FDA of the detection of PCV-1 DNA fragments in Rotarix ®

3. 3 Background (cont’d) FDA began its own internal examination and confirmed the presence of DNA from PCV-1 in Rotarix ® vaccine. On March 22, 2010, FDA recommended that clinicians temporarily suspend the use of Rotarix vaccine while the agency gathers additional information as a precautionary measure. Although testing by Victoria et al. did not find PCV1 DNA sequences in Merck’s rotavirus vaccine (RotaTeq), FDA embarked on testing RotaTeq and recommended Merck to do the same. FDA recently received information from Merck that preliminary studies identified fragments of DNA from porcine circovirus type 1 and type 2 (PCV1 and PCV2) in RotaTeq vaccine.

4. 4 Porcine Circovirus Porcine circoviruses (PCV) are small viruses composed of a single strand of circular DNA. PCV is common among pigs, but is not known to cause disease in humans. There is no evidence at this time that porcine circovirus or PCV DNA in US licensed rotavirus vaccines poses a safety risk. To date, no serious or unexpected safety concerns have been identified in post-market surveillance of Rotarix or RotaTeq. GSK, Merck and FDA continue to investigate these findings of porcine circovirus and/or PCV DNA in these vaccines.

5. 5 Outline of Today’s Presentations Topic 1: PCV and Rotavirus Vaccines FDA safety update for rotavirus vaccines CDC update on rotavirus disease and the impact of rotavirus vaccines on rotavirus disease burden in the US and globally GSK current assessment of PCV 1 in Rotarix® Dr. Gordon Allan (Queen’s University Belfast) overview of Porcine Circovirus FDA current laboratory assessment of PCV in rotavirus vaccines

6. 6 Outline of Today’s Presentations (cont’d) Topic 2: Advanced Analytical Methods in the Characterization of Cell Substrates –Characterization of Cell Substrates Used in the Production of Viral Vaccines for Human Use and Summary of New Technologies

7. 7 DISCUSSION POINTS 1.Based on the information presented today on the detection of porcine circovirus (PCV) or PCV DNA in US licensed rotavirus vaccines: a)Please discuss the available scientific evidence and identify factors to be considered in assessing the potential risk of the use of US licensed rotavirus vaccines. b)Please discuss any additional scientific studies and information that you would recommend FDA consider in its deliberations.

8. 8 DISCUSSION POINTS 2. Given the available data about porcine circoviruses, including the lack of known infectivity and pathogenic effects in humans, and that porcine circoviruses or PCV DNA may be present in both US licensed rotavirus vaccines, please discuss factors to be considered in determining whether, or in what circumstances, the benefits of using rotavirus vaccines outweigh the theoretical risk from PCV.

9. 9 DISCUSSION POINTS 3.Please discuss the application of emerging technologies, and the implications for their use in the detection of known and unknown adventitious agents in vaccines currently licensed, as well as those under development.