Signal Detection and Benefit-Risk
Signal detection begins by ensuring that individual case assessments are accurately processed, are properly coded and contain as much information as possible from performing detailed and specific follow-up to ensure that the company has enough information to assess the causality of the reported events.
Safety Studies; Marketing Studies; Investigator led Studies; Patient Support Programmes (PSPs); PTU/ATU Schemes
There are many occasions on which companies will need to conduct safety studies and they may arise as part of the condition of obtaining a license in Europe.
This can also be once a potential safety issue has been identified and requires further detailed investigation.
Marketing Studies, such as Observational studies or Research Outcome Studies, where safety data may be inadvertently captured, as well as Investigator led Studies, also require the Company to have processes in place to capture and assess any safety information produced from the studies.
This will require the Company to produce safety plans/protocols to ensure the safety data is properly captured and reported. PharSafer® has multi-national experience in making sure such plans and protocols can be successfully implemented and followed to ensure Regulatory compliance.
- Safety Studies; Marketing Studies; Investigator led Studies; Patient Support Programmes (PSPs); PTU/ATU Schemes
- Compassionate Use/Named Patient Studies
- Safety Review and Signal Detection
- Risk Management Plans (RMPs) & Risk Evaluation Mitigation Strategy (REMS)
- Management Plans / Risk Evaluation and Mitigation Strategies
Compassionate Use/Named Patient Studies
PharSafer® has worked in many situations involving compassionate use programmes, either as extensions to clinical trial studies or for use during the products post-marketing phase in countries where licenses have yet to be obtained.
There is a need for such programmes to follow the varied legislation in terms of safety monitoring and reporting and PharSafer® has multi-national experience of conducting very large compassionate use programmes including using such data as supportive data in further license submissions.
Safety Review and Signal Detection
PharSafer® works with its clients to produce a customised template to cover the items that will be routinely discussed in all safety reviews. PharSafer® has its own template which it adapts to fit client requirements to ensure that no safety data is omitted in any assessments. The information generated from the safety reviews is subject to quality management assessment, as well as containing detailed information concerning action points and recommendations concerning individual products.
An essential part of safety management involves safety review, whether this is for generic products, over the counter, herbal products or new chemical entities.
Part of the regular and routine safety assessments performed in the safety review, are the cumulative safety data reviews by product, to ensure that there are no new safety signals requiring analysis, quantification, amendments to labelling, benefit-risk revisions or the implementation or revision of Risk Management Plans.
PharSafer® has many years of experience in signal detection and safety review for many different types of products, both clinical and post-marketing.
PharSafer® uses a number of techniques to enhance and determine new safety signals and changes in Benefit-Risk (B/R) for client products in order to maintain patient safety and ensure Regulatory compliance.
PharSafer® has detailed templates for the safety review process, robust SOPs and working practices, explaining the processes, and proactive scheduling by product for safety review to ensure that all products are routinely and thoroughly assessed.
Records of all safety reviews are approved, signed by PharSafer® and the client and maintained for possible Regulatory Inspector review.
Risk Management Plans (RMPs) & Risk Evaluation Mitigation Strategy (REMS)
All products, whether generic or innovator, submitted for license approval in the European Union (EU) will require a Risk Management Plan. This document, which also fits into the Company approach to Pharmacovigilance, is mentioned in the PSMF and forms part of the CTD in section 1.8.2.
PharSafer® has and does provide RMPs for clients for a range of products including generic products, biologics, new chemical entities, new product combinations and new formulations of established products. We also design the plans and follow their execution, submission, approval and monitoring as part of license approval.
PharSafer® has submitted and reviewed over 100 RMPs of these for various Companies both in Europe and beyond and have either had the RMPs approved or successfully argued that no additional activities, other than routine surveillance, was required for marketing to commence.
Additionally, PharSafer® has worked with the production and use of REMS, the FDA equivalent of RMPs in Europe, and although they are similar, there are some subtle differences. By co-ordinating the activities of both RMPs and REMS, the client Company can achieve the safety goals and satisfy Regulatory requirements for individual products more efficiently.
Management Plans / Risk Evaluation and Mitigation Strategies
Risk Management Plans (RMPs)
Following on from ICH E2E and Module V of the EU Regulations, the requirements for a Risk Management Plan to accompany license submissions is now fully mandated in Europe, whether the product is generic or an innovator product. PharSafer® has written and continues to write both RMPs for generic products as well as for innovator products.
Additionally, on behalf of clients, PharSafer® has helped maintain the RMPs for both generic and innovator products and has also registered and maintained the RMP on Annexe 1.
PharSafer® has written RMPs for generic products, innovator which has included drug-device combinations, products with more than one active (fixed combination products), RMPs with minimisation activities, RMPs with associated registries, Biologic products and across many therapeutic areas including respiratory, oncology, gastrointestinal, neurological, anti-infective and anti-inflammatory.
Some of the RMPs produced also link to the REMs (see below) we have implemented for our US clients, where a joint launch of the product in the USA and Europe has resulted in similar approaches regarding Risk assessment and monitoring.
All RMPs produced to date and submitted to the Agencies by PharSafer® to the Agencies have been approved. This includes both submissions to the EU and Japan. PharSafer® has also written supportive educational material for Healthcare professionals and developed FAQs for Medical Information Departments associated with the Risk activities, to provide a seamless solution to Risk monitoring for the client product. PharSafer® has been involved in RMPs since 2008.
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Risk Mitigation and Evaluation Strategies (REMs)
The FDA interpretation of the ICH E2E Pharmacovigilance planning resulted in the production of the PDUFA III documents, which included the use of REMs to reduce the risk elements associated with the Company product. These types of activities ranged from educational material, to more interventional methods of product restriction, routine patient testing, as well as monitoring the progress of the various schemes themselves to ensure maximum efficiency in having robust systems in place.
PharSafer® has engaged in the assessment and amendment of such REMs to improve the current levels of success in reducing patient risks. We have been involved in such schemes since 2010.