Pharmacovigilance and Drug Safety

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.

What specific Pharmacovigilance tasks can be out-sourced?

• Pharmacovigilance for a specific trial or series of studies including clinical trial site set-up
• EU Qualified Person Responsible for Pharmacovigilance (QPPV) and Deputy QPPV
• Post-Marketing Pharmacovigilance; the entire process from initial receipt of an AE through to expedited reporting
• Generation of Clinical Trial Annual Safety Reports and Periodic Safety Reports
• Adverse Event Management including holding and maintaining the Safety Database and Case Entry of AEs, coding, narrative writing, QC, expedited reporting of AEs.
• Development of Safety Specifications and Risk Management Plans
• Signal detection and evaluation
• Safety issue investigation and generation of ad-hoc reports for submission to Regulatory Authorities
• Literature Screening
• Process design and SOP development
• Pharmacovigilance audits, mock inspections and due diligence
• Pharmacovigilance training
• Generation of Safety Agreements for licensing or distribution partners or third parties involved with pharmacovigilance activities

What are the benefits and risks of outsourcing specific tasks?

Out-sourcing clinical trials can be useful when a company lacks experience in a new therapeutic area or a specific type of study. It can be especially useful for companies who may have limited experience in clinical trials as the out-sourcing company can provide expertise in study protocol, study start-up and selection of investigators. The company must determine if it will also outsource the process of handling of AEs throughout the study, entry into a safety database and expedited reporting to investigators and Regulatory Authorities. It is important to choose a partner with sufficient experience and capacity if the trials are particularly large and located in multiple sites across the globe.

Out-sourcing the QPPV can be of obvious benefit to smaller organisations. The QPPV needs to be available 24/7 and is a highly skilled individual with expertise in Pharmacovigilance. There is risk involved in out-sourcing this function if the QPPV lacks sufficient experience or company infrastructure to take on the role or has conflicting interests which may impact on their availability.

Outsourcing the Pharmacovigilance database results in reduced cost for database infrastructure and reduced license costs for software programmes.

Outsourcing the entire Post-Marketing function can be especially beneficial to new and emerging companies who may historically only have experience with products in development and have limited experience of handling Pharmacovigilance when a product comes to market. This will allow the company to buy-in expertise while developing a Pharmacovigilance department of their own and will reduce costs in terms of investment in a safety database and validation of systems and processes. Similarly this can be useful for companies with relatively small volumes of AEs reported annually as the IT costs of systems and updating these systems and re-validation when regulations change are minimised. While small and medium companies may out-source pharmacovigilance as it is not economical to have an in-house department, larger companies may out-source for efficiency. Risks involved are ensuring that the outsourcing partner has a robust, validated system capable of meeting complex requirements worldwide and sufficient processes and procedures and appropriately qualified staff in place with sufficient knowledge of the Pharmacovigilance requirements to handle the entire process.

Outsourcing allows flexibility as a company will be able to manage peaks and troughs that can occur with workload. For example with products that are taken seasonally such as products for colds and flu or hayfever – adverse events tend to peak at certain times of the year and are directly related to sales; specific adverse event reporting increases following media attention; adverse event reporting tends to be high following the launch of a new product and can increase following identification of a potential safety issue. This variation in workload requires companies to try to plan staff to meet peak demands resulting in some resources being under utilised during slack periods. For a company with older products with established safety profiles no new knowledge is likely to be gained from generating PSURs and single case processing, even though the processes must occur to maintain regulatory compliance. The benefits of out-sourcing include freeing up valuable resource time within the company allowing the company to focus attention where needed. These resources can be re-directed to strategic business objectives and not routine data discovery and data entry.

Conversely a company with a single proprietary product which accounts for a significant proportion of the company’s annual revenue may decide only to out-source specific Pharmacovigilance tasks or may decide to maintain Pharmacovigilance in-house.

Out-sourcing literature screening can be beneficial for generic companies where the frequency of searching required to meet the Pharmacovigilance requirements leads to the generation of hundreds of articles which require review to determine if the cases qualify for expedited reporting.

Out-sourcing of generation of safety agreements with third parties is especially useful for those companies operating as virtual companies. There are often complex arrangements for Pharmacoviguilance provision between multiple parties. In a pharmacovigilance inspection any partner could be interviewed by the Competent Authorities and is an area where there are often inspection findings. It is important that all responsibilities in terms of Pharmacovigilance between all parties are specified in detailed documents. Safety agreements need to be drawn up by individuals with expertise in this area and this may be lacking in virtual companies.

Out-sourcing Pharmacovigilance provides a cost effective solution especially for small and medium sized companies. Complying with Pharmacovigilance regulations requires highly trained staff to accurately code and clinically assess cases, enter the cases into a safety database and determine whether particular cases qualify for expedited reporting. This Pharmacovigilance team needs to be familiar with regulatory requirements at regional, national and international levels. An outsourcing partner can provide this capability. There are a variety of out-sourcing options available ranging from individual contractors and Pharmacovigilance consultants, specialist Pharmacovigilance consultancies, and CROs or Pharmacovigilance Service Providers. These individuals may operate from a single site or may have offices spread across several countries which could be beneficial if a presence is required in a specific territory to meet the local Pharmacovigilance requirements.

Consequently, it remains important to choose your partner wisely so check out their credibility – qualifications and experience including any previous client recommendations. Has the partner an understanding of the Pharmaceutical industry and ability to demonstrate compliance with the regulations? Are they experienced in dealing with queries from Regulatory Authorities?  Finally, ensure that there is a detailed contractual arrangement in place which clearly describes the roles and responsibilities of each party for all aspects of Pharmacovigilance to be outsourced.