A practical guide to achieving and maintaining global oversight and ensuring end-to-end pharmacovigilance

Transcription

1 FOR PHARMA & LIFE SCIENCES WHITE PAPER A practical guide to achieving and maintaining global oversight and ensuring end-to-end pharmacovigilance The increasing complexity of today s pharmaceutical industry operating environment makes getting and maintaining global oversight and ensuring end-to-end pharmacovigilance challenging and, at the same time, necessary. The aims are clear: protecting patient safety, mitigating risk, and ensuring compliance all while working more efficiently and effectively. As the scope and complexity of activities required of the pharmacovigilance function continue to grow, budgets and available resources have not kept pace. Pharmacovigilance leaders must therefore be both strategic and practical in their approach to achieving more with less, making wise use of existing resources. This whitepaper outlines a series of practical steps that leaders can take with regard to getting and maintaining global oversight and ensuring end-to-end pharmacovigilance. Additionally, within the context of ensuring end-to-end pharmacovigilance, there is a sidebar discussion of the role that technology can play, not only in terms of driving efficiencies but also in terms of monitoring and measuring performance, identifying operational risks, and improving signal detection. As a case in point, we focus on the area of literature monitoring and outline how a workflow-specific decision tool can support key uses cases, as well as integrated cross-domain workflows.

2 Practical steps toward achieving and maintaining global oversight The regulatory requirement to ensure global oversight for activities related to a company s product, regardless of the commercial status of the product, is well-established. Here are three practical steps that can be taken to guide your efforts to achieve and maintain global oversight: ACTION STEP 1: Understand the scope and risks within your pharmacovigilance system. ACTION STEP 2: Educate. ACTION STEP 3: Proactive monitoring, maintenance, and updating. Action Step 1: Understand the scope and risks within your pharmacovigilance system. The pharmacovigilance department leadership and the QPPV need to work together to understand the pharmacovigilance system across the organisation. For example: Product authorisations: In Europe, for instance, you may hold centralised, MRP, DCP, or single national licenses. It might be that a conditional approval exists or perhaps the product is used as a special or through a named patient or compassionate use programme. Understand whether the product is under additional monitoring, or if there are other special conditions attached to the license. If so, know who in the company is responsible for tracking and managing adherence to these. Clinical trials and organised data collections: Interventional trials have specific requirements under GCP, including for safety, and all of these activities are seen as sources of safety data. It is important that a global list of these trials is maintained, and that these activities are effectively managed. Consider training for those managing these programmes, including appropriate provisions in contracts with any third parties performing this work, and ensure that regular reconciliation is performed. Commercial partners: What types of partnerships exist, such as co-development, co-promotion, in/out-licensing, distribution, and so on? Be sure to look at the scope of agreements the products, territories and, most importantly, the balance of responsibilities. Existing procedures (including local/affiliate procedures): Do you have procedures for all parts of the PV system? This will include procedures across the company, and may well include some outside of GxP control. Examine your company-wide approach to quality systems and documentation. Organisational charts (including position of QPPV and resourcing counts): The regulators are keen to see that companies are providing adequate resources for the products that are licensed (regardless of commercial status). These counts should include any third party support used. The PV System Master File (PSMF) is a very useful tool for this purpose. Understanding the scope of your systems and where there are deficiencies is vital so that you can create a list of priorities and prepare for further actions. Addressing and fixing problems in these systems is of the utmost importance, as it will help eliminate risks that could expose the company to audits, fines, lawsuits, and other costly actions. 2

3 Action Step 2: Educate. The right level of support is essential to ensuring that the QPPV can effectively perform their job, that products maintain a positive benefit-risk profile, and that patient safety is upheld. This message needs to be heard loud and clear across the organisation, through strong communication and leadership. Other functions within the organisation need to be educated as to what they need to do, how, and by when. The role of senior management support in this should not be underplayed. For many departments there are competing priorities, so it is critical that these departments understand and buy into what is required of them and why. Ultimately, if senior management and other colleagues do not buy into the need to perform these responsibilities, Pharmacovigilance departments will need to find a way to perform these responsibilities. This may be questioned by auditors and inspectors. Regulators see these responsibilities as company responsibilities, and are looking for the most appropriate and most qualified persons to perform the tasks. Action Step 3: Proactive monitoring, maintenance, and updating. This is an ongoing process; the QPPV needs continuous global oversight, and the upto-date PSMF can be requested by any authority, at which point it must be provided by the organisation within 7 calendar days. The approach here should consider: The systems that are in place for ensuring that information is provided on an ongoing basis. Designate the QPPV office or responsible person to gather this information. Performance of periodic test PSMF requests and periodic PSMF reviews, including Pharmacovigilance department management and the QPPV. If there are deficiencies in the information being received, this should be addressed through ongoing quality management processes, and escalated where no improvements are seen. 3

4 Practical steps toward ensuring end-to-end pharmacovigilance Pharmacovigilance activities should cover the whole lifecycle management of medicinal products for human use in relation to safety. Processes must be linked to create a systematic approach across the product lifecycle. Inherent in this is a requirement that different parts of the organisation (pharmacovigilance, clinical, medical affairs, and local affiliates) communicate to make certain that there is a complete dataset for pharmacovigilance activities. In this context, these three steps are offered to guide your approach to ensuring end-to-end pharmacovigilance: ACTION STEP 1: Understand the main hand-offs within the current PV systems. ACTION STEP 2: Look for areas where efficiencies can be improved and agree on what the system should look like. ACTION STEP 3: Implement the new systems educate and communicate. Action Step 1: Understand the main hand-offs within the current PV systems. With recent changes, there is a much bigger focus on wider collaboration across the company, as opposed to the traditional model of the pharmacovigilance group receiving case data for processing and outputting regulatory reports for submission to the authorities. Maintaining a top level understanding of the inputs, processes, and outputs in the pharmacovigilance system, company-wide, as well as the responsible parties (be aware that it may not be the pharmacovigilance department), makes it easy to spot duplicate efforts. From here, consider where efficiencies can be found through reducing the number of hand-offs within a process or eliminating duplicate processes. Look into the possibility that a process could be centralised, with output being made available to relevant personnel, rather than having people working in siloes. 4

5 Action Step 2: Look for areas where efficiencies can be improved and agree on what the system should look like. Now that all processes are mapped out, look for areas where efficiencies can be improved: Process duplication: For example, note if there are multiple groups performing literature searches. Too many hand-offs: In case processing, for instance, if information is being passed back and forth through multiple assessment and review steps unnecessarily, this could be an opportunity for streamlining. Appropriate activity assignments for departments. For example, for periodic reporting, benefit assessments might be better under the responsibility of medical affairs rather than pharmacovigilance. Also consider if the process is truly covering everything that is required; does it start and end at the correct points? For example, management of changes to reference safety information should cover from when the change occurs (e.g., via signal management), through management and submission of relevant variations to the authorities, right up to confirmation of implementation of the change being implemented in product packs. For a process such as this, going across several departments, ensure that: someone is held accountable that the correct information is being tracked that there is global pharmacovigilance (including QPPV) oversight of this Action Step 3: Implement the new systems educate and communicate. Now that places where process improvements can be made have been identified, it is important to work with other stakeholders to find a way to implement these changes. As above, where activities have traditionally sat within departments outside of pharmacovigilance, educating and communicating why something needs to be done is crucial to ensure the necessary change occurs. Many of these processes and documents are not owned by pharmacovigilance. For example, with reference information management, documents such as CCDS and national labelling documents (e.g., US-PI, J-PI, SmPC/PIL) are traditionally owned by regulatory, as is dossier information, including variation submissions. Likewise, artwork information is traditionally owned by regulatory or QA. It is crucial, therefore, that you make sure your colleagues understand what is required and buy into this, as there needs to be a seamless set of cross-functional processes. 5

6 The Role of Technology in Pharmacovigilance Technology-based solutions already play a role in the pharmacovigilance workflow, as is the case with the following examples: Periodic report submissions Regulatory information management (xevmpd) Access to regulatory authority or large scale public safety databases (FDA AERS, WHO Vigibase) Registries and systems to support risk management activities Literature monitoring Digital and social media, mobile apps Cloud computing Expanded use of technology-based solutions is inevitable. Demand for web-based information will only grow in light of increasing globalisation and big data is also playing a more significant role, given the potential to focus on real life use of drugs by patients. Future applications for storing, processing and accessing information include: HL7 standards (E2B(R3)/ICH M5)) Direct company access to EudraVigilance database IDMP Electronic health records Aside from storing, processing, and accessing information in the workflow, technology solutions offer ways to assess and manage an organization s operations. This can and should include monitoring and measuring performance, identifying operational risks, and improving signal detection all in the interest of achieving greater patient safety and compliance. Case in point: Elsevier s literature monitoring and review capabilities Elsevier provides literature monitoring and review capabilities that enable pharmacovigilance and drug safety groups to be more efficient and cost-effective, while staying compliant and mitigating risk. These capabilities include: Workflow-specific decision tools that support key uses cases and research outcomes Tools that work together to support integrated, cross-domain workflows Services that address custom use cases, transforming the way companies capture and manage safety/adr data. Here is an outline of Elsevier s four-pronged approach to literature monitoring and review for regulatory compliance: Case Input: To help ensure that companies do not miss critical information, Elsevier provides comprehensive journal coverage and indexing, including information such as conference abstracts that are not available in other tools. The custom development of complex search strategies increases the likelihood of early signal detection. With automatic deduplication of files from multiple literature sources, companies save time reviewing and reduce the risk of counting a single event more than once. All relevant documents are integrated into a centralized repository for drug safety input to maximize efficiency. Case Processing: Elsevier provides several tools to facilitate article pipeline management. A triage tool that operates seamlessly within the centralized document repository permits more rapid triage than a jumbled , spreadsheet and reference manager process. Articles are text mined so the most relevant information can be quickly reviewed for ADRs. Alerts about unread articles are issued to ensure that regulatory reports contain the most up-to-date information. Case Output: Elsevier enables tracking of the article review process through multiple iterations to facilitate readiness in the event of an audit. The system also provides the capacity to rapidly identify and preformat case information within relevant articles, saving time and effort. To reduce manual steps when integrating triage results, Elsevier offers automated exporting of data to case management systems through an application programming interface (API). Output Analysis: Elsevier helps companies understand new and unexpected ADRs by providing access to and mining preclinical, clinical and post-market safety data from FDA and EMA approval documents and FAERS reports, as well as published literature. To better inform safety assessments and improve study design for drugs in development, Elsevier performs searches across drug classes, target classes, ADRs and chemical substructures. To help reduce regulatory cycling, relevant drug safety data can be connected to specific regulatory concerns and recommendations. 6

7 Summary Increasing regulation and an evolving pharmaceutical business environment are placing additional demands on the pharmacovigilance function. Getting and maintaining global oversight and ensuring end-to-end pharmacovigilance are critical steps in laying the necessary foundation to protect patient safety, mitigate risk, and maintain compliance. The recommendations outlined in this paper are designed to help you to achieve these aims utilizing a practical, step-by-step approach. As an earlier PwC Health Research Institute paper highlights: The time for companies to re-examine their pharmacovigilance practices and to develop and implement effective, best-in-class solutions is now. Many organizations have already begun to evaluate and enhance their pharmacovigilance practices for efficacy and efficiency, and through that experience many have encountered significant obstacles......by concentrating on integration across the key infrastructures, companies will enable themselves to avoid the challenges companies typically face when building toward the future. They will create a sustainable infrastructure and a highly adaptive culture, both of which can lead to greatly diminished costs and risks, as well as greatly improved outcomes for patients. Unlocking the power of pharmacovigilance: An adaptive approach to an evolving drug safety environment, PwC Health Research Institute Sources 1 Vicki Page-Clark, Founder and Director of Lighthouse Pharmacovigilance Limited; Honorary Fellow of the Pharmaceutical Information and Pharmacovigilance Association (PIPA); Adjunct Lecturer for the Pharmacovigilance MSc programme at University of Hertfordshire and for the EU2P programme 2 Pharmacovigilance: Rethinking literature monitoring and review, Elsevier R&D Solutions Whitepaper 3 Unlocking the power of pharmacovigilance: An adaptive approach to an evolving drug safety environment, PwC Health Research Institute

8 LEARN MORE Contact us to discover how Elsevier s information tools and trusted content can help your company save time and gain cutting-edge insights to drive innovation. Visit or contact your nearest Elsevier office. ASIA AND AUSTRALIA Tel: sginfo@elsevier.com JAPAN Tel: jpinfo@elsevier.com KOREA AND TAIWAN Tel: krinfo.corp@elsevier.com EUROPE, MIDDLE EAST AND AFRICA Tel: nlinfo@elsevier.com NORTH AMERICA, CENTRAL AMERICA AND CANADA Tel: usinfo@elsevier.com SOUTH AMERICA Tel: brinfo@elsevier.com Copyright 2016 Elsevier B.V. All rights reserved. April 2016