CCRPS

Module 4 – Resources

Chapter 35: International Pharmacovigilance Initiatives and Guidelines – EMA 

In this unit, you can access information pertaining to the major PV initiatives launched the world over, along with descriptions of their goals, scope and participating countries and regions. Initiatives listed in this chapter include the ICH (International Conference on Harmonisation), GVSI (Global Vaccine Safety Initiative), ISPE (International Society for Pharmacoepidemiology), EudraVigilance, ISO’s IDMP (International Organization for Standardization’s Identification of Medicinal Products) and numerous others.

Chapter 36: DIA Safety and Pharmacovigilance Competencies 

The section outlines the Drug Information Association’s (DIA’s) framework for assessing drug safety as well as the competencies required to maintain active pharmacovigilance during the drug development process. The DIA requires PV personnel to be able to understand and articulate all aspects of PV relevant to the drug life-cycle, outline important concepts in PV, comprehend and implement good SOPs for quality management, as well as appreciating and meeting regional and international regulatory requirements.

Chapter 37: WHO-ISoP Pharmacovigilance Resources 

The unit contains a checklist of the 15 focus areas recommended within the ISoP (International Society of Pharmacovigilance) core curriculum as topics on which PV professionals must be knowledgeable and competent. The resource can be used as a guide in searching for and reading scientific articles and book chapters to further build your PV knowledge and skills.

Chapter 38: E2E ‒ Pharmacovigilance Planning 

In this section, you will find the FDA’s ‘Guidance to Industry’ document on end-to-end pharmacovigilance planning. The guide includes safety specifications for drugs (including chemical entities, biotechnology derivatives and vaccines), as well as recommendations for structuring a pharmacovigilance plan. Finally, a brief review of PV methods is also included.

Chapter 39: GVP XVI Addendum ‒ Educational Materials

The unit reviews the EMA’s Guideline on Good Pharmacovigilance Practices (GVP) Module XVI Addendum I. The addendum provides recommendations for the design and dissemination of educational materials for building public awareness about drug safety and PV. As per these guidelines, it is the responsibility of MAHs (Market Authorization Holders, also termed clinical research sponsors) to produce educational materials meeting EMA standards and ensure their availability to the public.

Chapter 40: GVP Module I‒IV PV Systems, PSMF, Inspections & Audits 

The chapter provides an overview of the EMA’s GVP Modules I through IV that address different aspects of PV. Each module pertains to different dimensions of the PV process and lays out guidelines and recommendations for clinical research sponsors or MAHs (Market Authorization Holders) on the principles and practices that should be implemented to meet standards for PV compliance. The unit summarizes the contents of Modules I, II, III and IV.

Chapter 41: GVP I – Pharmacovigilance Systems 

This unit allows you to do an in-depth walk-through of GVP Module I. This module contains a set of contains a set of guidelines for MAHs to put in place the structures and systems essential to maintaining a high-quality PV process, including recommendations for physical facilities and equipment, staff recruitment and PV training, documentation and record management, compliance and regulatory requirements, as well as quality assurance processes and audits.

Chapter 42: GVP VIII – Post-authorisation Safety Studies 

In this chapter, the guidelines contained in Module VIII on Post-authorization Safety Studies (PASS) are covered in detail. Content addresses both interventional and non-interventional studies of drugs that are already being marketed. Recommendations span the entire PV process, from the preparation of research protocols for such studies, to the implementation of data collection, review and analysis, quality assurance and data safety, regulatory compliance, PV audits and reports, as well as reporting of research findings to regulatory authorities as well as scientific reporting.

Chapter 43: GVP III – Pharmacovigilance Inspections 

This section covers the recommendations outlined in GVP Module III, concerning PV inspections. Module III addresses product-specific inspections, pre- and post-approval inspections, routine inspections and ‘for cause’ inspections,  in addition to making recommendations for remotely conducted inspections. This module also covers pre-inspection planning as well as post-inspection follow-up actions (regulatory penalties, sanctions and so on), as well as outlining guidelines for the qualifications and training of PV inspectors.

Chapter 44: GVP IX – Methodological Aspects 

The unit gives an in-depth tutorial on the principles and guidelines laid out in Module IX, which pertains to the methodology used in analyzing and interpreting PV data. Important concepts in signal detection theory are discussed in detail, including the setting of detection thresholds, disproportionality statistics, monitoring periodicity, methods specific to patient, geriatric and pediatric populations, as well as specific techniques for analyzing DME (Designated Medical Event) and SAE data.

Chapter 45: GVP V – Risk Management Systems

Through this chapter, you will acquire a working knowledge of the recommendations and stipulations of Module V of the GVP, on risk management in PV. The module specifies in full detail the structure and contents of a comprehensive Risk Management Plan (RMP), an essential document to be created and maintained by every MAH. Contents address all domains of risk management, including responsibility for risk management, identification of different risk types as well as risk documentation. Risk documentation includes product overview, safety specification, epidemiology of risk indication and target populations – the type of users likely to be at risk from using the target drug, non-clinical profile (findings from studies on tissues, animals, etc.), as well as summarized clinical findings. RMP recommendations also include post-AE follow-up as well as risk-minimisation measures such as long-term follow-up studies and design of educational materials to improve awareness of risks.

Chapter 46: GVP IX – Signal Management 

This unit examines the GVP recommendations in Module IX on the process of signal management in PV. From defining signal management (the process of examining accruing data from various sources to identify new risks as well as to monitor changes in status for known risks), the unit lays out guidelines for signal detection and prioritisation as well as validation as well as signal quality and monitoring periodicity. Concepts addressed include non-confirmed and refuted signals, emerging safety issues, standalone signal notification and so on.

Chapter 47: GVP VIII Addendum – Requirements, Recommendations 

This section outlines the GVP VIII Addendum guidelines for conducting a PASS (Post-Authorisation Safety Study) in the context of an obligation imposed by the EU (typically in response to emerging evidence of safety risks) as well as with respect to a voluntarily conducted PASS.

Chapter 48: GVP XV – Safety Communication

Within this section, you will gain insight into the Module XV guidelines regarding communication of drug safety information. The major forms of such communication addressed here include the Summary of Product Characteristics (SmPC), package leaflet (PL), package labelling as well as public assessment reports. The scope of recommendations includes the language used, formatting as well as information content of communications targeted at different segments of the population – healthcare providers, media outlets, lay public (through social media releases, website content and so on), as well as specific correspondence with various authorities (FDA, insurance company and so forth).

Chapter 49: GVP XVI – Risk Minimization Measures 

The chapter reviews in detail Module XVI of the GVP on risk minimisation in PV. A major focus area of these guidelines is the design of educational materials on drug safety that target different segments of the population, including healthcare providers, patients and caregivers. Other risk minimisation initiatives outlined include drug distribution control (for example, through packaging that limits the number of doses bundled together) and pregnancy prevention (for drugs with teratogenic risks). The section additionally covers the module’s recommendations on assessing the effectiveness of risk minimisation initiatives.

Chapter 50: GVP II – Pharmacovigilance System Master File 

kIn this section, you will gain knowledge of GVP Module II, which addresses the concept of the PSMF (Pharmacovigilance System Master File), outlining its structure, contents and upkeep. The guidelines recommend that the PSMF must include the following:

summary of the MAH’s system (organisational structure) pertaining to PV:

-qualifications and credentials of QPPVs (Qualified Professionals for Pharmacovigilance)

-description of computerised systems and drug safety databases

-outline of sources of safety data

-details of PV process

-framework for quality assurance of safety data

In addition, the module contains recommendations for the implementation of changes in the PSMF, periodic review of PSMF and maintenance of a PSMF log-book.

Chapter 51: GVP VI – Duplicate Management 

The unit reviews Module VI of GVP, which pertains to the management of duplicate case information, which could have dangerous skewing effects on drug safety data. Guidelines in this module concern the detection, confirmation and subsequent management of duplicate information. Important concepts covered include periodic screening for duplicates, allocation of a master case number,  as well as sending nullifications to the original senders of duplicate case data.

Chapter 52: GVP IV – Pharmacovigilance Audits

The chapter provides an overview of Module IV, which addresses PV audits, including audit planning, different approaches to audits (risk-based versus routine), levels of audit planning (strategic, tactical and operational), as well as audit protocols and reports. Topics covered include the fieldwork involved in audit planning, auditor competence and audit quality management, as well as reporting of audit results to MAHs and regulatory authorities.

Chapter 53: GVP X – Additional Monitoring 

Through this section, you will acquire familiarity with the concept of ‘additional monitoring status’ for medicinal products as defined in Module X of the GVP, as well as guidelines pertaining to the implementation of additional monitoring systems. The criteria for including a product on the additional monitoring list are discussed, identification of such products (symbol of a black equilateral triangle included on product packaging), along with the scope of such monitoring, PV roles and responsibilities and the time-line for additional monitoring activities.

Chapter 54: GVP VII – Periodic Safety Update Report 

The chapter provides an in-depth review of Module VII on PSURs or Periodic Safety Update Reports. The stipulated time-line for PSURs, as well as guidelines concerning the content and presentation of a PSUR are found within this chapter. Topics addressed include cumulative and interval data summarization (respectively, summaries of all data thus far collected versus data collected since the last PSUR), summaries and tabulation of data from different sources (completed vs. ongoing trials, post-marketing data sources, non-clinical data, literature, other sources), signal evaluation and risk characterisation, changes to drug effectiveness, efficacy and safety information since last PSUR, updated benefit-risk analysis and risk-minimisation initiatives. The module also includes recommendations for the training of PSUR compilers as well as guidelines for PSUR processes meant for MAHs. Additional topics within the module cover guidelines for medicinal products authorised at national and international levels as well as for products with different marketing authorisations containing the same AS (Active Substance).

Chapter 55: GVP VI – Collection, Management and Submission of Reports 

In this unit, a detailed review is provided of Module VI pertaining to report compilation, creation and submission. The chapter covers an array of PV reports, including ICSRs, solicited as well as spontaneous reports on AEs, medicinal overdose, abuse/ misuse, reports on medication errors and occupational exposure to medicinal products, as well as reports of medicinal use in sub-populations such as pediatric, elderly, pregnant or breastfeeding women and so on. Important concepts addressed include report data and quality management, as well as report validation and follow-up action. Additional guidelines pertaining to report amendment and nullification are also reviewed.