The patient information leaflet

Transcription

1 core patient information leaflet (CorePIL) basics Mauricha Marcussen The patient information leaflet (PIL) is a regulated document that contains user-friendly information about a medicine, including dosing information, medical conditions and side effects. This information is packaged with a prescribed medicine and is written to be understood by a typical patient. The information in the leaflet is also meant to supplement (not replace) the advice given by health professionals. PIL content is regulated by local health authorities and it is the responsibility of the marketing authorisation holder (MAH) to create and maintain updated and accurate PIL content around the globe In 2005, the Medicines and Healthcare Products Regulatory Agency (MHRA) published a report entitled, Always Read the Leaflet: Getting the Best Information with Every Medicine 1. The report was developed by the Committee on Safety of Medicines (CSM) Working Group on Patient Information. In the foreword to this publication, Melinda Letts, Chair of the CSM Working Group on Patient Information, noted, Survey findings tell us that people want more medicines information than they get 2 5, that they want it from a range of sources 2,3, and that they value the patient information leaflet (PIL) more highly than any other source except doctors and pharmacists. PILs are there with the medicine when it is actually being used, and the information they contain is produced by the manufacturer and regulated by law. Therefore they are both easily available and authoritative. Unfortunately they are also often of poor quality and hard to understand. There are requirements in place to promote good quality in the PIL content. In Europe, for example, PILs undergo readability testing, which are rigorous requirements for the patient label. Sometimes these strict requirements are market-specific. It is key that the complex medical concepts presented in the prescribing label are written in the PIL as patient-friendly information, without changing the intent of the medical information. This is an example of where a CorePIL template is advantageous. In the US, it is important to understand that Medication Guides from the manufacturers are required, and are under Food and Drug Administration (FDA) review. However, the dispersing pharmacies in the US may create their own patient information form and give it to patients. These patient information forms from the pharmacy are not governed by the US FDA, and may present a quality issue if they are not aligned to the manufacturer s approved Medication Guide. Given the importance that patients place on PILs, as well as the health agency requirements, companies must put significant effort into creating the original user-friendly content that is reviewed and approved by the agency. The importance of this content cannot be underestimated. It represents the company s commitment to provide quality information to the patient; it represents the company s focus toward compliance; and it also represents the efforts of numerous resources in developing, reviewing and finalising the content for the PIL. This process is expected and accepted as an integral part of the practice of pharmacovigilance and safety compliance. However, gaining local market approval while updating and tracking this original content adds an entirely new dimension to the process that is less likely to be understood or controlled on a global basis. The complexity of this process Mauricha F. Marcussen (mmarcussen@auditgraph.com), CEO of Auditgraph, has worked with over 25 top pharmaceutical companies in leadership roles; as an FDA inspector and industry consultant. In her current position, she leads global regulatory affairs programs and creates sustainable technology solutions for global product labelling harmonisation, regulatory information management and international e- submissions. She is passionate about ensuring the accuracy of safety and pharmacovigilance information for prescription and patient data, while leading initiatives to support end-to-end labelling programs for tracking safety items from signal detection through product packaging. PharmacoVigilance Revıew Volume 8 Number 2 April

2 Grading of inspection findings 7 Deficiencies found during Inspections are graded in one of three ways: Critical: a deficiency in pharmacolvigilance systems, practices or processes that adversely affects the rights, safety or well-being of patients or that poses a potential risk to public health or that represents a serious violation of applicable legislation and guidelines. Major: a deficiency in pharmacovigilance systems, practices or processes that could potentially adversely affect the rights, safety or well-being of patients or that could potentially pose a risk to public health or that represents a violation of applicable legislation and guidelines. Other: a deficiency in pharmacovigilance systems, practices or processes that would not be expected to adversely affect the rights, safety or well-being of patients. Figure 1: Grading of inspection findings. may often lead to a compliance risk that is not apparent until an inspection is looming. Opportunities for content discrepancies occur as new information about a medicinal product works its way through internal finalisation processes and external health authority approval processes. Content modifications and timing and conditions of approval all impact the accuracy and relevancy of information that is presented to the end user. In addition, company communications across functions, lines of business, geographies and lack of internal tracking systems can add challenges to an already complex management task. This scenario usually results in a very timeconsuming and labour-intensive effort to attempt to track and manage alignment across global processes and potentially hundreds of documents. Even with this effort, a risk still exists that the information will not continue to be accurate nor be tracked consistently. Global health authorities have increasingly become more involved in inspection-type activities regarding the safety content harmonisation of reference safety information. In the Pharmacovigilance Inspection Metrics Report 6, for the period April 2011 to March 2012, the MHRA notes that the majority of critical findings are related to the control and maintenance of reference safety information (such as summaries of product characteristics (SPCs), patient information leaflets (PILs), investigator brochures, and company core safety information) (see Figure 1) 7. Figure 2: Types of critical findings during inspections. Reproduced from the Pharmacovigilance Inspection Metrics Report 7, April 2013 to March PharmacoVigilance Revıew Volume 8 Number 2 April 2015

3 Figure 3: Comparison of yearly findings % of critical findings categorised as reference safety information. The most recent report shows that reference safety information accounted for 42% of critical findings during the inspection period (see Figure 2). The number of critical findings in this area has increased significantly over the last four reporting periods (see Figure 3). The 2012 report also notes that Findings relating to reference safety information include failure of MAHs to ensure that the safety information in SPCs and PILs is up-to-date, that safety variations are submitted in a timely manner and that approved product information is made available to manufacturing sites; in many cases these findings have led to significant post inspection actions. Subsequently, the 2014 report states that The majority of critical findings were reported in relation to the maintenance of reference safety information, representing 42% of all critical findings identified. This is consistent with the metrics from the previous reporting period where the largest proportion of critical findings were reported in relation to activities concerning reference safety information. Compared to the previous period, The number of critical findings identified during this reporting period was slightly higher than the previous period, reporting 19 critical findings versus 18 in the previous period. The largest proportion of critical findings remained in the topic area of reference safety information, representing 42% of all reported critical findings. Critical findings associated with reference safety information were again characterised by failures and significant delays to submit safety variations to update the safety sections of SPCs and PILs. The new EU pharmacovigilance regulation is also requiring additional focus on accuracy of PIL content and scrutiny of PIL development processes. In the Medicines and Healthcare Products Regulatory Agency Annual Report and Accounts 2012/13 7, the MHRA notes, The newly-introduced Pharmacovigilance Regulation requires European Member States to make available all Summary of Product Characteristics (SPCs) and Patient Information Leaflets (PILs) for authorised medicinal products they hold. This has been a major undertaking for the Agency and by March 2013 over 17,000 SPCs and corresponding PILs have been published on the MHRA website. The new EU pharmacovigilance legislation represents a significant change in PharmacoVigilance Revıew Volume 8 Number 2 April

4 requirements. EU member states were required to implement the Directive 2010/84/EU by 21 July Financial penalties can now be assessed for various infringements, including if an MAH does not maintain up-to-date product information. Clearly, there is much work that can still be done to ensure that patient information is as up-to-date and accurate as it can be. The critical nature of the safety content requires a purposeful approach to information management and demands a process that not only pushes core information out to the markets but also collects information from those same markets. To keep the information up-to-date, gap analysis, harmonisation and adjudication efforts are the natural next step. This portion of the process is likely to be the most difficult piece to manage. Since it usually spans multiple organisations and functions, it is a relatively unknown compliance risk that must be understood at very high levels within the organisation. As with many regulatory label harmonisation initiatives, companies are looking to gain better control of information processes. To address this need, labelling professionals have developed and implemented the concept of the Company Core Data Sheet (CCDS) to track and manage regulated labelling content. The CCDS serves this purpose as it is distributed to local markets and is often considered as the one authoritative source for the company s position on the product. Some forwardthinking organisations are now applying similar concepts to the PIL development process, so that key PIL content is aligned from the start in individual local markets. The concept of a CorePIL mimics that of the CCDS in that it is based on the idea that all content comes from one authoritative source and then flows through to local processes. During interviews with major pharmaceutical companies who have implemented the CorePIL, different approaches emerged. The commonalities between these companies consider the fact that a CCDS is a necessity for the safety information of a product, as every country is required to have the prescribing information approved, but not every country is required to have the patient information. Other industry best practices include the following. l If a market has an accepted and documented deviation in the prescribing information, it should be reflected also in the Market PIL. l If the Market Prescribing Information differs from the CCDS, the Market PIL would reflect the difference; not the CorePIL. l If information is added to the CorePIL, and it is a new issue for the market, it would be covered in the Market Prescribing Information. l The Market Prescribing Information justifies why a deviation is acceptable. To support this process, the following tools can be leveraged to simplify the creation of the CorePIL. l CorePIL Template and Authoring Guide: this guide should provide authoring instructions, a list of approved headings for the PIL, relevant checklists and formatting guidance. l Glossary of Terms: the glossary should list all prescriber terms mapped to common patient terms. l CCDS: the currently approved CCDS should be referenced for this activity. l Market PILs: all currently approved Market PILs for specified regions should be used to track and manage alignment of content. l Market Prescription Labels: the corresponding approved market labels (i.e. SPC, USPI, Product Monograph) should be used to validate the safety data with respect to the patient s perspective. In a scenario where a company desires to create a CorePIL for a product currently on the market, the tools above can be used in the CorePIL development process. First, regulatory teams can begin by creating a draft CorePIL from the CCDS, supporting documents, and major Market PILs. The team can then conduct a Market PIL comparison and gap analysis which will validate each Market PIL against the draft CorePIL. The resulting content from this exercise must go through a final review process to create the approved CorePIL. Once the CorePIL has been created, the team can begin to look at global PIL content alignment across markets. 16 PharmacoVigilance Revıew Volume 8 Number 2 April 2015

5 Another approach is to generate a CorePIL once a Market PIL for a single major market exists. If this is done shortly after the CCDS is implemented, then the CCDS and the CorePIL can co-exist. This enables a fairly compliant alignment process, since any new information coming forward is considered for inclusion, and the number of deviations decrease because there are fewer deviations over time. When properly executed, the CorePIL then flows into a maintenance program, and the updates to the CorePIL are managed in sync with the related documents. Additionally, since the supporting information is available through this creation exercise, a fully annotated CCDS and CorePIL would be a logical outcome for each product. The creation of a CorePIL is also highly advantageous to support a brand new product. In this case, the CorePIL serves as a reference document, as a complement to the CCDS. As the product labelling evolves, the CCDS and CorePIL evolve in a similar manner. The tasks of aligning the content of multiple, critical safety documents are tedious yet crucial, and require a deep organisational commitment. Ensuring that the quality of PIL content is maintained is not a once and done activity. Each time a PIL is revised internally or approved by a local marketing authority, the harmonisation and update process must be initiated. When properly managed and executed, this alignment approach becomes an essential foundation for the company s pharmacovigilance compliance program. References 1. Medicines and Healthcare Products Regulatory Agency. Always Read the Leaflet: Getting the Best Information with Every Medicine. Report of the Committee on Safety of Medicines Working Group on Patient Information. London, UK: The Stationery Office; Ipsos MORI. Medicines and the British. Survey findings: MORI research sponsored by Medicines Partnership. London, UK: Ipsos MORI; October researcharchive/844/medicines-and-the-british.aspx 3. Ipsos MORI. The Public and Prescribed Medicines. London, UK: Ipsos MORI; November Schoen C, Osborn R, Huynh P T, Doty M, Davis K, Zapert K and Peugh J. Primary care and health system performance: adults experiences in five countries. Health Aff (Millwood) 2004;Jul Dec;Suppl Web Exclusives:W4-487 W Healthcare Commission. Patient Survey Report 2004: Adult Inpatients. London, UK: Healthcare Commssion; Medicines and Healthcare Products Regulatory Agency. Medicines, Medical Devices And Blood Regulation And Safety Statistics. Pharmacovigilance Inspection Metrics, 2009 to present. London, UK: The Stationery Office; September 2012 (last updated March 2015). isinsp/documents/websiteresources/ con pdf 7. Medicines and Healthcare Products Regulatory Agency. Pharmacovigilance Inspection Metrics Report April 2013-March London, UK: The Stationery Office; Medicines and Healthcare Products Regulatory Agency. Annual Report and Accounts 2012/13. London, UK: The Stationery Office; PharmacoVigilance Revıew Volume 8 Number 2 April