Investigations into an outbreak of suppurative lymphadenitis with BCG vaccine SSI(®) in Singapore.

INTRODUCTION: From 2011 to 2012, we received an unexpectedly high number of reports of suppurative lymphadenitis following administration of a BCG vaccine used in our childhood vaccination programme in Singapore. We sought to determine the local incidence rates of BCG-associated suppurative lymphadenitis across the 2009 to 2012 vaccinated cohorts, and to analyse the potential factors contributing to this outbreak. METHODS: Reports of lymphadenitis following BCG vaccination from an AEFI active surveillance system at the KK Women's and Children's Hospital (KKH) and passive surveillance data from other healthcare institutions were reviewed. All valid reports received from January 2009 to December 2013 involving neonates vaccinated with the BCG vaccine in 2009 to 2012 that met case definitions were included in our analysis. Details of the demographics and vaccination history of the child, and statistics from the local vaccination programme were also obtained. Potential contributory factors were selected for further investigation based on a literature review of similar outbreaks overseas. RESULTS: We identified 283 cases of lymphadenitis, of which 76% were suppurative. A spike in suppurative lymphadenitis cases was seen in the 2011 vaccinated cohort, with an incidence rate of 3.16 per 1000 vaccinees, as compared to 0.71 to 0.85 per 1000 in the 2009, 2010 and 2012 cohorts. Our investigations identified the likely cause of the outbreak to be batch-related, arising from manufacturing issues encountered by the manufacturer, after ruling out vaccine administration-related and host-related factors. CONCLUSIONS: The three-fold spike in BCG-associated suppurative lymphadenitis cases observed in the 2011 vaccinated cohort, possibly due to batch-to-batch variation of the vaccine, highlights that manufacturing controls can continue to be a challenge. Development of a more sensitive assay to test the reactogenicity of the BCG vaccine may help reduce the occurrence of such outbreaks and improve public confidence in the nation's vaccination programme.

Registration of similar biological products--Singapore's approach.

The expiration of patents on many biological medicinal products has prompted the development of these products as similar biological (biosimilar) products. The standard approach of demonstration of bioequivalence for chemical generic products is scientifically not applicable for biosimilar products. The biosimilar product approach, based on comparability (demonstration of similarity), should be adopted. In view of the impending submissions and to facilitate access of such products at a more affordable price in Singapore, the Health Sciences Authority (HSA) formalised the procedures and requirements for registration of biosimilar products in 2009. HSA has published the "Guideline on Registration of Similar Biological Products in Singapore" which describes the basic principles, submission procedure, and requirements pertaining to documentation, pharmacovigilance, and post-approval batch release for the registration of biosimilar products. This article provides a brief overview as well as key points on the registration of medicinal products and biosimilar products in Singapore.