Merck/Centers for Disease Control and Prevention Varicella Vaccine Pregnancy Registry: 19-Year Summary of Data From Inception Through Closure, 1995-2013.

BACKGROUND: The VARIVAX® Pregnancy Registry was established in 1995 to monitor pregnancy outcomes of women who received varicella vaccine (ie, VARIVAX) inadvertently while pregnant. METHODS: Health care providers and consumers sent voluntary reports about women who received VARIVAX 3 months before or during pregnancy. Follow-up occurred to evaluate pregnancy outcomes for birth defects. Outcomes from prospectively reported pregnancy exposures (ie, reports received before the outcome of the pregnancy was known) among varicella-zoster virus (VZV)-seronegative women were used to calculate rates and 95% confidence intervals (CIs). RESULTS: From 17 March 1995 through 16 October 2013, 1601 women were enrolled-966 prospectively-among whom there were 819 live births. Among 164 infants born to women who were VZV seronegative at the time of vaccination, no cases of congenital varicella syndrome (CVS) were identified (rate, 0 per 100, 95% CI, 0.0-2.2) and the birth prevalence of major birth defects was 4.3 per 100 liveborn infants (95% CI 1.7-8.6) with no pattern suggestive of CVS. No defects consistent with CVS were identified in any registry reports. CONCLUSIONS: Data collected through the VARIVAX pregnancy registry do not support a relationship between the occurrence of CVS or major birth defects and varicella vaccine exposure during pregnancy, although the small numbers of exposures cannot rule out a low risk. VARIVAX remains contraindicated during pregnancy.

Closure of varicella-zoster virus-containing vaccines pregnancy registry - United States, 2013.

Vaccines that contain live attenuated varicella-zoster virus (VZV) (Varivax, ProQuad, and Zostavax [all products of Merck & Co., Inc.]) are contraindicated during pregnancy. To monitor the pregnancy outcomes of women inadvertently vaccinated with VZV-containing vaccines immediately before or during pregnancy, Merck and CDC established the Merck/CDC Pregnancy Registry for VZV-Containing Vaccines in 1995. This report updates previously published summaries of registry data, provides the rationale for the closure of the registry, and describes plans for continued monitoring of the safety of these vaccines when inadvertently administered to pregnant women or immediately before pregnancy. From inception of the registry in 1995 through March 2012, no cases of congenital varicella syndrome and no increased prevalence of other birth defects have been detected among women vaccinated within 3 months before or during pregnancy. Although a small risk for congenital varicella syndrome cannot be ruled out, the number of exposures being registered each year (approximately two varicella-susceptible women exposed during the high-risk period for congenital varicella syndrome) is now too low to improve on the current estimate of the risk.

Varicella Virus Vaccine Live: A 22-Year Review of Postmarketing Safety Data.

BACKGROUND: Varicella, a contagious infectious disease caused by varicella zoster virus (VZV), can result in hospitalization and, occasionally, death. Varicella virus vaccine live (VVVL [VARIVAX]) was introduced in the United States in 1995. METHODS: This comprehensive review of the VVVL safety profile is based on 22 years of postmarketing adverse event (AE) data received through spontaneous and noninterventional study reports submitted by health care providers and on a review of the published literature (cumulatively from March 17, 1995, through March 16, 2017, during which period >212 million doses were distributed globally). RESULTS: The VVVL safety profile was consistent with previous publications, with common AEs including varicella, rash, and pyrexia. AE reports have decreased over time, from ~500 per million doses in 1995 to ~40 per million doses in 2016; serious AEs comprise 0.8 reports per million doses. Secondary transmission was rare (8 confirmed cases); polymerase chain reaction analysis indicated that 38 of the 66 reported potential secondary transmission cases of varicella were attributable to wild-type VZV. The prevalence of major birth defects in the Pregnancy Registry was similar to that in the general US population. In total, 86 cases of death were reported after vaccination with VVVL; immunocompromised individuals appeared to be most at risk for a fatal varicella- or herpes zoster-related outcome. CONCLUSIONS: This comprehensive 22-year review confirms the overall safety profile for VVVL, with no new safety concerns identified. Since VVVL's introduction in 1995, notable declines in varicella cases and in varicella-related deaths have occurred compared with the prevaccination period.

Turning up the heat: Effect of new vaccine for children's (VFC) program recommendations for use of temperature monitors upon incorrect product storage adverse event reporting.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) coordinates the Vaccines For Children (VFC) program, which provides free vaccines to qualified children in the US. In 2009, the CDC issued Vaccine Storage Requirements, which were later replaced (2012) with an interim guidance and toolkit for vaccine storage and handling. The guidance called for use of Digital Data Loggers (DDL) to monitor vaccine storage temperatures. We describe a change in frequency of Incorrect Product Storage Reports (IPSRs) following issuance of the 2009 CDC guidance. METHODS: Merck & Co., Inc., Kenilworth, NJ, USA, systematically evaluates vaccine safety concerns for all products. The safety database was queried (01-Jan-2004 through 31-December-2016) to identify all IPSRs associated with 10 vaccines. We compared IPSRs received prior to and following the 2009 CDC guidance, comparing reports received from the US with those received from international sources during the same period. RESULTS: Following the release of the DDL guidance, a progressive increase in IPSRs was identified in the US (1 report received in 2004, 12,993 reports in 2016). In contrast, non-US IPSRs - have not had a similar increase: no reports received in 2004, 216 reports received in 2016. US reports of IPSRs 2004 through 2016 account for 96% of reports worldwide. There were no serious reports found in the database in conjunction with IPSRs, nor were there any additional safety findings in any of the reports with additional events reported. CONCLUSION: VFC DDL guidance was followed by an increase in IPSRs. No similar trend was seen outside the US (where no broad change in DDL guidance occurred). Despite the increase in IPSRs, there have been few associated adverse events (AEs) reported; no new safety concerns were identified. These findings suggest that the increase in IPSRs was associated with the introduction of use of DDLs, and suggests the need for further impact assessment.