(System Info - 107580 SHONE DEANNA 10/13/2009 17:31:25 SHONEDE)
RECORD OF TELEPHONE CONVERSATION
Submission Type: BLA Submission ID: 125259/0 Office: OVRR
Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant
Telecon Date/Time: 21-Aug-2007 12:00 AM Initiated by FDA? Yes
1. Information Request
Author: MANETTE NIU
Pharmacovigilance Request: Comments on Safety Outcomes
Trans-BLA Group : No
Related STNS :
Related PMCs :
To: Mr. Matthew Whitman
File: STN 125259/0 CERVARIX
RE: Safety Outcomes
Date: August 21, 2007
Please respond to the following comments in regard to safety outcomes:
1. Please comment whether the demographics of the National Health Service (General Practitioner database) in Scotland reflect those of the U.S. population. We request that you add a study which will assess the general safety of Cervarix ®, including new onset autoimmune disease, in the United States.
2. In regard to timelines for protocol submission and pharmacovigilance activities, we have the following comments:
a. We request that you provide deadlines for completion of pharmacovigilance protocols after licensure.
b. We request that you provide deadlines for finalizing the studies and for reporting and submission of results.
3. In regard to Routine Pharmacovigilance, we have the following comments:
a. For the first three years following vaccine licensure, we request that you provide FDA with monthly batches of all adverse event reports not included among the serious and unexpected (15-day) reports received by GSK. Also, we recommend that you include all available follow-up information obtained from (“obtained for” instead of “obtained from”?) previous adverse event reports in these monthly batches.
b. We recommend that you provide FDA with monthly electronic submissions of vaccine lot distribution data during the first three years after licensure.
c. Please consider including plans for analysis of safety signals identified after licensure through the Vaccine Adverse Events Reporting System (VAERS) among the outcomes to be studied.
d. Regarding the pregnancy registry, please consider addressing elements in the Guidance for Industry: Establishing Pregnancy Exposure Registries -9/20/2002
4. In regard to the AID Post-Licensure Observational study, we have the following comments:
a. We request that you add the following outcomes to the AID study: rheumatoid arthritis, transverse myelitis.
b. We request that you monitor the following specific outcomes in your study: thrombotic events (deep venous thrombosis, pulmonary emboli), thrombocytopenia, seizure, syncope, proteinuria, arthritis, arthralgia, arthropathy.
c. We recommend that you add a controlled (e.g. cohort or case control) observational sub-study of abnormal pregnancy outcomes including congenital anomalies, congenital heart disease (e.g., VSD) and spontaneous abortion, for pregnancy exposures.
5. In regard to the Finnish cancer registry studies, we have the following comments:
a. We recommend using stratification by age at vaccination for the study of cervical disease (including all stages of cervical cancer) caused by vaccine and non-vaccine HPV types.
b. We recommend that you indicate if data on HPV seroprevalence by age group is available from the populations from which study participants are being recruited.
c. Please discuss how the long term follow-up aspect of the study will be used to assess whether the removal of HPV16 and HPV18 from the ecological niche in the cervix will result in replacement with other HPV types.
d. Please consider providing information regarding what specimens will be HPV typed, what assays will be used, if there will be any central reading of the biopsy results, and what minimum information (e.g. date of vaccination) will be recorded for each subject.
6. In regard to pregnancy outcomes, please consider continuing the follow up of pregnancy outcomes (including congenital anomalies and spontaneous abortions) for women who became pregnant while they were enrolled in the Phase 3 trials but whose pregnancy outcomes were not known.
* International Conference on Harmonization (ICH). Guidance for industry. E2E Pharmacovigilance planning. : http://www.fda.gov/cber/gdlns/ichpvp.htm