A local reaction at or near injection site: case definition and guidelines for collection, analysis, and presentation of immunization safety data.

The need for developing a case definition and guidelines for a local reaction at or near the injection site, methods for the development of the case definition and guidelines as an adverse event following immunization as well as the rationale for selected decisions about the case definition for a local reaction at or near the injection site are explained in the Preamble section. The case definition is structured in 2 levels of diagnostic certainty: level 1 includes any description of morphological or physiological change at or near the injection site that is described or identified by a healthcare provider. Level 2 is any description of morphological or physiological change at or near injection site that is described by any other person. In Guidelines section, the working group recommends to enable meaningful and standardized data collection, analysis, and presentation of information about a local reaction at or near the injection site. However, implementation of all guidelines might not be possible in all settings. The availability of information may vary depending upon resources, geographic region, and whether the source of information is a prospectively designed clinical trial, a post-marketing surveillance or epidemiologic study, or an individual report of a local reaction at injection site.

Safety of MF59 adjuvant.

The need to enhance the immunogenicity of purified subunit antigens has prompted the development of new adjuvants. The adjuvant emulsion MF59 has been tested in animals in combination with different antigens and finally evaluated in humans. It was licensed after the successful outcome of preclinical and clinical testing. This paper summarizes the main characteristics of the MF59 adjuvant, including animal testing, clinical experience with various vaccines, and information from current postmarketing surveillance data. This review supports the hypothesis that MF59 is a safe adjuvant for human use.

Protection against tick-borne encephalitis with a new vaccine formulation free of protein-derived stabilizers.

BACKGROUND: Vaccination against tick-borne encephalitis (TBE) has been successfully employed for many years in TBE-endemic countries. Post-marketing experience gained from widespread use, however, prompted the development of improved TBE vaccines, the most modern versions of which do not contain the commonly used protein-derived stabilizers (human albumin or polygeline) of former vaccines. METHOD: This article summarizes both the medical need for and clinical experience with a new TBE vaccine formulation (pediatric and adult versions). To this end, data from clinical trials and post-marketing experience are presented. The clinical database comprises immunogenicity and/or safety data of approximately 7,500 subjects ages 1 to 77 years who participated in eight clinical trials. The clinical trials were conducted at 69 centers in five European countries. Post-marketing experience includes safety data from passive pharmacovigilance systems in 18 countries where these vaccines have been licensed since 2001. RESULTS: All subjects analyzed for immunogenicity achieved postimmunization levels of TBE antibodies that meet the definition of seroconversion or represent a fourfold increase. The pooled data of clinical trials revealed the expected rate of solicited local and systemic reactions. The majority of these transient postimmunization reactions were mild. Pharmacovigilance data confirm the high level of safety of these new TBE vaccines: only a common range of the side effects already noted for licensed TBE vaccines was reported. After the distribution of more than five million vaccine doses, no potential safety risk was noted. CONCLUSION: Post-marketing experience supports results from clinical trials showing that these new TBE vaccines may safely be used for the vaccination of children, adolescents, and adults.

Post-marketing surveillance of immediate allergic reactions: polygeline-based versus polygeline-free pediatric TBE vaccine.

Scattered cases of immediate allergic reactions occurred in the nineties after widespread use of the original (polygeline-based) pediatric tick-borne encephalitis (TBE) vaccine and were reported to Pharmacovigilance, Chiron Vaccines. Although, still indicating a very rare frequency of about two cases per 100,000 doses sold, the benefit/risk assessment resulted in its withdrawal from the market in early 1998. An intensive evaluation revealed that polygeline used as a vaccine stabilizer was the most probable cause of the reported allergic reactions. Consequently, an improved pediatric TBE vaccine, free of polygeline and other protein-derived vaccine stabilizers, was developed. A post-marketing surveillance analysis covering the first two vaccination seasons after the introduction of this new pediatric TBE vaccine in early 2002 reveals a very low reporting rate of immediate allergic reactions post immunization (within the range as noted for other widely used vaccines for childhood immunization), i.e., 0.08-0.24 cases per 100,000 doses sold depending on case definition and medical assessment. In conclusion, this analysis provides post-marketing surveillance evidence that the change in the vaccine formulation, with regards to the potential risk of immediate allergic reactions, has led to an intended improvement in the vaccine's safety profile.

Biologics safety preclinical, clinical and regulatory.

Biologicals offer particular challenges for all concerned, whether they be scientific researchers, profit-oriented companies (including not yet profit-producing start-ups), public health-focused regulators, physicians, or, most importantly, patients. One of the most important of these challenges is safety. Hence, this conference was organised by Vision in Business (the trading name of Analysis and Networking Ltd) to provide practical solutions and advice for comprehensive, effective safety testing. It provided a wide spectrum of presentations, ranging from the usefulness of animal models for biologicals safety predictions, to an FDA perspective on implications of its recent restructuring, to a real-life case study on erythropoietin and pure red cell anaemia. For anyone seriously interested in the safety of biologicals, this was a very good opportunity to gain an overview of all major aspects of biologicals safety, broaden existing expertise and to network with those concerned with these issues.

Electronic Reporting for Clinical Drug Safety and Pharmacovigilance. 29 - 30 October 2002, Amsterdam, The Netherlands.

The 31 January 2003 deadline for electronic reporting to the European Agency for the Evaluation of Medicinal Products has helped to focus industry and regulator attention alike. This conference provided a wide perspective on background and scope, recent successes, and possible future developments by specialists from regulators, pharmaceutical industries, software vendors and more. Organised by IIR Conferences Ltd, attendees had the opportunity to gain an overview of all major aspects of electronic reporting of individual case safety reports, to broaden their knowledge, and to network with individuals concerned by these issues.

Immediate allergic reactions after vaccinations--a post-marketing surveillance review.

UNLABELLED: Immediate systemic allergic reactions after vaccination with commonly used vaccines are very rare. Consequently, the risk of these reactions cannot be verified before widespread use. A data analysis of spontaneously reported suspected adverse drug reactions following the administration of 15 marketed vaccines, from 1994 to 1998, shows an average reporting rate for "allergic" reactions of one case report per 450,000 vaccine doses sold. Of these, potentially life-threatening events are extremely rare. In 31% of our case reports the reaction was reported after the first vaccination. In these cases a pre-sensitisation or a pseudo-allergic reaction can be assumed. There was no evidence for an increased risk of "allergic" reactions for patients with atopy. CONCLUSION: our data support a high level of safety for the vaccines included in the analysis. They also emphasise the importance of a careful vaccination management after occurrence of "allergic" reactions and the necessity of a post-marketing surveillance system for recording adverse drug reactions.