Pharmacovigilance and Drug Safety

Archive for the ‘risk management’ Category

A safety database is both a core element of any pharmacovigilance system and a legal pre-requisite for pharmaceutical companies wishing to place a medicine or medicinal product onto any EU/EEA market ^[1]. To enter those markets, each product must first be granted a Marketing Authorisation (MA) by the regulatory authorities ^[1]. The safety database must already be in place and described within the Detailed Description of Pharmacovigilance System (DDPS) accompanying the MA application ^[1]. This article explains key functions of safety databases, to create a better understanding of their overall purpose.

Why have a Safety Database?

Safety databases should allow pharmaceutical companies to rapidly gather relevant information about the medicine or medicinal products in question. There will be information which needs to be supplied to regulatory authorities via statutory electronic reporting and the database must support this. The database must therefore be validated and acceptable to those regulatory authorities. In essence, the database must be entirely suitable to the task, in compliance with Part III of the relevant legislation, Volume 9A of The Rules Governing Medicinal Products in the European Union – Guidelines on Pharmacovigilance for Medicinal Products for Human Use ^[1]. Details of the database are assessed during the application stage for each MA, as they will form part of the DDPS ^[2]. To paint perhaps a more rapidly accessible picture here, the safety database is the tool used to help staff collate and analyse key drug safety data. One example could be any Adverse or Suspected Adverse Event Reports for one particular product. The database will be electronic but not ‘autonomous’: it will not perform tasks without key interaction by highly skilled staff, no matter which process is underway.

Signal Detection

A compliant, suitable Safety Database is able to process data related to signal detection. Signal detection essentially uses data to detect any new patterns or findings. These can be identified by analysing data tables according to principles of statistical disproportion. Upon detection the subsequent course will be variable but can involve action by the regulatory authorities.

Periodic Safety Update Reports Production (PSURs)

Any medicine or medicinal product granted an (EU) MA is legally required to become the subject of post-marketing Periodic Safety Update Reporting. PSURs are always more than an in-house assessment. Presented directly to regulatory authorities, as you might expect whenever drug safety is concerned, they will of course be subjected to an extremely thorough inspection of their contents. A comprehensive database will be able to process the required data in a manner which facilitates the production of PSURs in the appropriate format as far as those authorities are concerned. For example, modern databases integrate regionally-tailored support on regulations.

Statutory Electronic Reporting

Certain safety databases are able to incorporate functionality to file expedited and aggregate reports to regional regulatory authorities. Again, this would always take place with core staff input, rather than becoming any type of scenario where a computer simply somehow ‘spits out’ a report. Electronic reporting will be required within strict time deadlines and differing formats by differing authorities throughout the world. In the EU for example, expedited reporting is obligatory within 15 days of a spontaneous adverse drug reaction case report.

These are just some of the core functions of a suitable safety database, which make it easy to see why it’s one of the pillars of good quality drug safety monitoring. It may be web-based, but whatever the platform it will be electronic. It is not however necessary for pharmaceutical companies to purchase and install a dedicated ‘in-house’ safety database. Instead it is common to find them using commercially available fully compliant products introduced by external pharmacovigilance services firms, who simply provide them with the necessary ongoing support.

References:

1. EMEA. Volume 9A of The Rules Governing Medicinal Products in the European Union – Guidelines on Pharmacovigilance for Medicinal Products for Human Use. 2011. [ONLINE] Available at: http://ec.europa.eu/health/files/eudralex/vol-9/pdf/vol9a_09-2008_en.pdf. [Accessed 22 January 2011].

1. EMEA. Volume 9A of The Rules Governing Medicinal Products in the European Union – Guidelines on Pharmacovigilance for Medicinal Products for Human Use. 2011. Article 2.2.3 d [ONLINE] Available at: http://ec.europa.eu/health/files/eudralex/vol-9/pdf/vol9a_09-2008_en.pdf. [Accessed 22 January 2011].

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.

A major change in the approach to drug safety surveillance after marketing has been introduced in the last 5 years in the EU in the form of risk management planning. This has been incorporated into EU law and is extensively covered by guidelines in Volume 9A. There has been a similar initiative by the US FDA.

For the EU, it is mandatory for companies to submit a Risk Management Plan in accordance with a detailed template and guideline at the time of application for a Marketing Authorisation for most products. Plans also have to be submitted if new safety concerns are identified for a marketed product and all plans must be updated as circumstances change.

Thus companies are required to specify at the time of first marketing areas of safety about which they are currently uncertain and how they will resolve this uncertainty. They must also indicate what measures they will take to reduce known risks and how they will test whether these measures work.

The EU Risk Management Plan (EU-RMP) has 3 main elements. First, a detailed consideration of what is known about the safety of the product, based on pre-clinical and clinical studies. This “safety specification” considers identified risks and potential risks – the latter being areas of uncertainty regarding safety. It also specifies what the limitations of the clinical research program are and what important information about safety is currently missing. In the second component, the “pharmacovigilance plan”, the company must indicate how it proposes to resolve the uncertainties – what extra studies it will carry out after marketing to fill the important gaps in knowledge. The third component is the “risk minimization plan”. This states how the company proposes to reduce the severity or frequency of known adverse reactions. This may involve special communication programs, or educational exercises, or perhaps registration programs for patients, doctors or pharmacists, or other measures. The pharmacovigilance plan and risk minimization plan must include timelines for setting up the programs and milestones for their evaluation.