Pharmacovigilance and Drug Safety

Archive for the ‘Safety’ Category

The role of this site is to provide information on how drugs are developed and the role of pharmacovigilance in ensuring drug safety throughout the lifecycle of pharmaceutical products. We cover several different topics and, should you wish to investigate further, maintain links to some of the top experts and specialists in the field of pharmacovigilance. Our expert panel includes individuals with both industry and regulatory experience. We have access to people who have helped to define and shape the science of drug safety into what it is  today and are working on what pharmacovigilance will become in the future.

Many people believe the pharmaceutical industry to be a shady cartel developing poisonous concoctions with no control from governments or the scientific community. The Pharmacovigilance Information Service is here to share information about drug safety and to explain some of the steps that pharmaceutical companies are required to take in order to get their products to market and to keep them there. It also explains the safety roles that the regulatory bodies expect the pharmaceutical companies to fulfill.

DEVELOPMENT OF MEDICINES AND PHARMACOVIGILANCE IN THE EUROPEAN UNION: a guide for the perplexed

This review is intended as a brief introduction to understanding the complex environment in which medicines are developed and their safety monitored. Much of it is applicable generally, but the focus is on the situation in the UK and the European Union.

Issues in pharmacovigilance outsourcing and consulting

Companies may seek to outsource some or most of their drug safety surveillance activities or to obtain the services of consultants for a variety of reasons:

• To save on recurring personnel and infrastructure costs

• To provide for flexibility to cover times of high work throughput

• To cover temporary gaps in workforce

• To obtain specific expertise and support not available in house

The nature of the work and functions outsourced can include any or all of the following, both for clinical trial and post-marketing spontaneous adverse event reporting:

• Safety data receipt, triage, database entry, coding narrative and medical review

• Expedited reporting to regulatory authorities, including electronic reporting

• Preparation of periodic safety update reports, US periodic reports, annual safety reports

• Signal detection and evaluation

• Literature screening for safety issues and case reports

• Qualified Person for Pharmacovigilance for Europe and local Qualified Person

• Evaluation of benefit and risk for a product

• Preparation of development risk management plan, RMP, RiskMAP and REMS

• Preparation of Detailed Description of Pharmacovigilance System

• Preparation or review of safety data exchange agreements with third parties / business partners

• Pharmacovigilance training, inspection readiness training

• Organisation set up or organisational change

• Preparation of SOPs and other controlled quality documents

• System evaluation, database evaluation, database validation

• Pharmacovigilance audit, development of corrective action plan, implementation of CAPA

• Labelling evaluation and variations; preparation of Company Core Safety Information and Development Core Safety Information

• Responses to regulatory authority enquiries about safety

• Dossier preparation for product registration

• Crisis management

• Support for medicolegal activities and litigation defense

• Evaluation of options for pharmacoepidemiology studies

• Assessment of published reports

Clearly there are different levels of skills, experience and knowledge required for the various activities. This is reflected in the types of organisation that are available for outsourcing of pharmacovigilance work. Individual consultants or contractors may act as an interim resource, sitting in the client company for a period of days, weeks or months, working as if a member of the client pharmacovigilance team. There are also agencies (e.g. Harten Group) that specialise in this type of arrangement and have numerous pharmacovigilance freelance consultants on their books.

At the other extreme of the spectrum, the client may wish to outsource most of the pharmacovigilance activities, routine and non-routine, to a contract organisation (a “PV service provider”). These companies may be very large Contract Research Organisations (CROs) such as Quintiles or Parexel, that concentrate on clinical research, but carry out pharmacovigilance activities as well. There are also specialist PV service providers, such as PrimeVigilance Ltd, PharSafer and Vigilex, that carry out all pharmacovigilance activities but do not perform clinical trials. In the case of PrimeVigilance, there is an interesting model in that routine pharmacovigilance activities are carried out in Eastern and Southern Europe, where overheads are lower than in Western Europe and N.America, but where there is a strong emphasis on quality management. This is combined with a specialist consulting arm and a specialist phase 4 CRO to provide the possibility of a comprehensive range of services from one organisation.

Other clients may need a more limited range of routine activities, such as individual case processing, expedited reporting and PSUR preparation, but not involving other elements. Again, the large CROs may do this work, although the cost can sometimes be prohibitive. The specialist PV providers may be able to provide a competitive approach in terms of cost-effectiveness without sacrificing quality. In addition, there are a number of companies operating in India that carry out this basic work: whilst cost may be reduced there could be concerns about the ability to keep control of events and of quality this far removed geographically.

Specialist pharmacovigilance consultancies do not generally include a provision for safety database and expedited reporting, although some have made arrangements with third parties to perform this function. Again there is a range of expertise available among consultancies, some such as Elliot Brown Consulting, based in the UK, having medically trained staff as well as involving former senior regulators and an international network of pharmacovigilance associates. A similar model is provided by Pietrek Associates. Such companies are able to offer high end consulting on serious safety issues affecting a client’s products, as well as more mundane activities such as auditing, PSUR writing and review etc. While cost can sometimes seem high for these consultants, experience and knowledge may result in less time being taken to complete a project than might be the case with less experienced contractors.

There is a dilemma for companies wishing to outsource pharmacovigilance activities. On the one hand, many companies still consider pharmacovigilance merely to consist of a routine activity necessary for compliance with regulations, but basically a drain on resources and a cost with no benefit. On the other hand, there may be a recognition that safety issues, unless identified early and managed properly, can ruin a company financially. However, more enlightened companies realise that high quality safety data and effective pharmacovigilance are in effect a form of life insurance, protecting patients and products and ultimately the company itself.

Regardless of the type of pharmacovigilance service provider, contractor or consultant used, there is an important concept that the company that is holder of the marketing authorisation (manufacturer in the US) can delegate some or most pharmacovigilance activities, but must retain overall responsibility for the safety of its products. Thus, there needs to be clear accountability, a transparent management hierarchy and a robust decision-making process within the client company. In addition, it is essential that there is comprehensive and detailed contractual documentation specifying which party carries out each of the various pharmacovigilance activities. Only in this way can the legal obligations of the client company be satisfied and the patients’ interests protected.