Effective Pharmacovigilance System Development: EFPIA-IPVG Consensus Recommendations.

Pharmaceutical legislation provides a legal framework to ensure the safe and effective use of medicines. This framework requires national regulatory authorities (NRAs) to establish and maintain a pharmacovigilance system (PV system) stating and enforcing the regulatory commitments that key stakeholders, including marketing authorisation holders (MAHs), are required to fulfil. In recent years, national legislative bodies and NRAs across the world have issued a significant amount of legislation and guidance enforcing the obligation to perform pharmacovigilance activities. In countries where the NRA is a member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), safety management requirements are generally consistent with ICH guidelines. In a number of countries beyond this scope, requirements may deviate from internationally agreed standards, adding a substantial complexity and increasing burden on the stakeholders involved, whilst the benefit for patients' safety may not be evident. Committed to fulfilling safety-regulatory obligations in any country where a product licence is held, global pharmaceutical companies have accumulated a broad and deep experience acquired whilst meeting the expectations of a large array of diverse PV systems across the world. These range from sub-optimal frameworks, according to the World Health Organization (WHO) Global Benchmarking Tool, to highly effective resource-optimised PV systems. In order to support countries creating or further developing their PV systems, especially where infrastructure and resources are limited, the European Federation of Pharmaceutical Industries and Associations (EFPIA) International Pharmacovigilance Group (IPVG) has developed consensus recommendations consistent with harmonised standards for the development and step-wise implementation of key PV system components. These recommendations endorsed by the EFPIA membership constitute the focus of this review article.

An observational study of sucrose-formulated recombinant factor VIII for Japanese patients with haemophilia A.

The safety and efficacy of sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate FS) under usual clinical practice were evaluated for 12 months in an observational, postmarketing surveillance study conducted at 214 treatment centres throughout Japan. The study included 631 patients with haemophilia A, 80% of whom had severe or moderately-severe disease (< or = 2% FVIII:C). Most patients (n = 477; 75.6%) had >100 prior exposure days (EDs), but the study also included 62 (9.8%) patients with <20 EDs who were at high risk for inhibitor development. A total of 71,240 infusions were administered during the observation (mean, 113 +/- 108 per patient). Physicians rated efficacy and tolerability of rFVIII-FS as "very good" or "good" in >99% of patients. FVIII inhibitors were observed in seven patients (5 de novo; 1 persistent/fluctuating; 1 recurrent). The overall de novo inhibitor incidence was 0.8% (5/631; or 5/599 among the subgroup of patients with negative baseline titre and no known inhibitor history). De novo cases represented 3.2% (2/62) of patients with <20 EDs at enrollment (2/57 in the no inhibitor subgroup) and 0.2% (1/477) of patients pretreated with >100 EDs (1/452 in the no inhibitor subgroup) at enrollment. The results of this large observational study demonstrate that rFVIII-FS is both safe and efficacious as used in the usual clinical setting for the treatment of Japanese patients with mild to severe haemophilia A. This study supports the efficacy of rFVIII-FS with an incidence of inhibitor formation no greater than in a comparable European study or previous phase III clinical studies.