As we look to the future, the recent proposals from the European Commission to strengthen and rationalise European Union (EU) pharmacovigilance are a positive step forward, and should serve to simplify and clarify the roles of all stakeholders involved in pharmacovigilance, which will not only benefit Market Authorisation Holders and regulators but also the public. Importantly, the establishment of the concept of Good Vigilance Practice in European legislation will standardise the conduct of pharmacovigilance across Europe.
Since the voluntary programme of pharmacovigilance inspections commenced in October 2002, followed by the statutory programme in July 2003 onwards, the pharmacovigilance inspectors within the MHRA have acquired a wealth of experience about different pharmacovigilance systems in operation, including examples of both good and poor practice.
Similarly the Pharmacovigilance Group within the Vigilance and Risk Management of Medicines Division has accumulated extensive experience of assessment issues and pharmacovigilance standards. It is hoped that the benefit of this knowledge and practical advice can be shared with professionals involved in pharmacovigilance.
While this UK guide does not replace existing documents on the subject, it does offer valuable practical guidance on good vigilance practice and will also serve to complement the new EU legislation and guidance that comes out of the Commission’s review.
The MHRA has identified the need for creating and publishing a guide to good pharmacovigilance practice (GPvP). Similar guidance documents exist for other areas of GxP (The Guide to UK GLP Regulations, Rules and Guidance for Pharmaceutical Manufacturers and Distributors). Publication of Volume 9A in January 2007, and the subsequent update in April 2007, saw a number of changes to pharmacovigilance practice and the MHRA felt it was pertinent to produce a guide to address practical issues in response to this.
The guide relates to pharmacovigilance of medicinal products for human use. It is intended that this guide will complement currently available EU legislation and guidance and provide practical advice to key stakeholders, in particular Marketing Authorisation Holders, about achieving an appropriate system of pharmacovigilance. The guide is aimed at any organisation involved in pharmacovigilance activities (e.g. Marketing Authorisation Holders), as well as consultants, contractors and service providers, but it does not include guidance on the pharmacovigilance activities performed by Regulatory Authorities.
This guide applies to herbal medicines; however, there are certain practical issues specific to such medicines arising from the implementation of Directive 2004/24/EC on traditional herbal medicinal products. Supplementary information about the application of the guide to herbal medicines within the UK is available on the MHRA website.
Pharmacovigilance is not confined to one department within an organisation, and so the guide aims to take a holistic approach, considering the specific requirements defined in legislation and also other activities that impact on pharmacovigilance in a more subtle way.
The programme of statutory pharmacovigilance inspections in the EU is relatively recent in comparison to the inspection programmes of other GxPs. For many organisations, the expectations placed upon them by regulators are not fully apparent and it is hoped that this guide will help to address this issue.
The two key pieces of legislation that underpin pharmacovigilance expectations in the EU are Regulation 726/2004 and Directive 2001/83/EC (as amended). Additional legislation and guidance documents are detailed in Annex 2. It is important to note that the guide is not intended to replace the existing legislation and guidance and it does not act as a single reference document for all requirements. Also, the guide does not address vigilance issues for medical devices nor pharmacovigilance of veterinary products.
It is recognised that there are differences in terms of structure, organisation, resources and philosophy between large and small pharmaceutical companies, innovative and generic companies, conventional pharmaceuticals and herbal products. In general, the legislation does not differentiate between types of company and as such it is not possible to have different sets of expectations for different types of organisation.
However, the way in which companies achieve an appropriate system of pharmacovigilance varies immensely; what is appropriate for one company may be hugely unrealistic or unnecessary for another. It is not possible to address all scenarios within the guide or to provide information that will satisfy the requirements of all individual organisations. Where possible, we have tried to provide advice on how different types of organisation may achieve compliance with the requirements.
This guide is the result of collaboration between different groups within the MHRA, including the GPvP Inspectorate, the Pharmacovigilance Group and the Clinical Trials Unit. With a combined experience of over 200 inspections of UK Marketing Authorisation Holders, the MHRA GPvP Inspectorate team has encountered many models for conducting pharmacovigilance and also many examples of both good and poor practice. It is hoped that by highlighting the areas of common inspection findings and providing specific examples of good or poor practice, the guide can assist organisations in developing effective pharmacovigilance systems.
With the ever-changing regulatory environment, it is inevitable that aspects of this guide will not remain current, although the general principles of GPvP will always be relevant. The MHRA intends to revise and update the guide at appropriate time points and, in particular, after updates to EU pharmacovigilance legislation are adopted.
The MHRA’s mission is to enhance and safeguard the health of the public by ensuring that medicines and medical devices work and are acceptably safe. We aim to protect, promote and improve public health, and it is hoped that the information provided within this guide will contribute to these aims by assisting organisations in developing and maintaining appropriate and effective pharmacovigilance systems.
Good Pharmacovigilance Practice Guide