From: Valenti, Elizabeth
Sent: Thursday, January 29, 2009 9:50 AM
Cc: Valenti, Elizabeth; Fiore, Cara
Subject: 125300 PVP Comments
We have the following pharmacovigilance plan comments for BLA 125300:
- Given the concern regarding Guillain Barre Syndrome (GBS) reports following Menactra, please propose specific plans for evaluating GBS after Menveo.
- Please present as soon as possible your plans for conducting a large post-marketing safety study. We recommend that you conduct an open label, descriptive, epidemiological, safety surveillance study that enrolls 50,000 Menveo recipients or enrolls for 1 year, whichever results in the larger enrollment, to be reported in accordance with 21 CFR 601.70. Please propose deadlines (e.g., relative to a potential approval date) for: protocol submission to CBER, study initiation, study completion, and final study report submission to CBER. Please note that if a previously undetected safety concern is identified during the ongoing review of your BLA, the above recommended sample size and/or study design may require revision.
- We recommend that, if your BLA is approved, the following adverse events should be reported in addition to 21 CFR 600.80 requirements. This expanded adverse experience reporting should be provided to the Vaccine Adverse Event Reporting System for one year following product licensure as follows:
- 15 day reports: All serious adverse events whether expected/labeled or unexpected/unlabeled, including but not limited to vaccine failure, seizures, shock, respiratory distress or difficulty breathing, angioedema, inspiratory stridor, and bilateral wheezing.
- 30 day (monthly) reports if not already submitted as 15 day reports: all allergic events, including anaphylaxis; neurological events including Bell's palsy, Guillain-Barré Syndrome, encephalitis, encephalopathy, brachial neuritis, optic neuritis, other neuropathy, myelitis including transverse myelitis, ptosis, ataxia, multiple sclerosis, acute disseminated encephalomyelitis, cerebrovascular accidents, and transient ischemic attacks; idiopathic thrombocytopenic purpura; Kawasaki disease; myasthenia gravis; other new onset autoimmune disease; and all cases of non-intentional injury.
- We note that you are planning to establish a pregnancy registry to prospectively collect safety data on spontaneously-reported exposures to Menveo during pregnancy and lactation, including courses and outcomes of such pregnancies. Please submit a protocol for a U.S. pregnancy registry that addresses elements found in FDA's Guidance for Industry on Establishing Pregnancy Exposure Registries (http://www.fda.gov/cber/gdlns/pregexp.htm). Please notify CBER of significant deviations from this guidance and/or specify the deviations in the protocol. Patient accrual/data collection should begin at the time of CBER's approval of the protocol and end no sooner than five years later. Please submit annual reports and a summary report of the U.S. pregnancy registry's findings five years after initiation of patient accrual/data collection. The five-year summary report should be submitted to CBER no later than five years and six months after initiation of patient accrual/data collection. After CBER's review of the five-year data, please discuss with CBER the possible need to continue further data collection in the U.S. pregnancy registry.
Thank you, Betsy