Assignment 9 A.docx

**[Summary on Guideline on Good Pharmacovigilance Practices (GVP)-Module V (Rev 2)]** [Introduction]\ The aim of a risk management plan (RMP) is to document the risk management system considered necessary to identify, characterise and minimise a medicinal product's important risks. *Identified ris...

**[Summary on Guideline on Good Pharmacovigilance Practices (GVP)-Module V (Rev 2)]** [Introduction]\ The aim of a risk management plan (RMP) is to document the risk management system considered necessary to identify, characterise and minimise a medicinal product's important risks. *Identified risks:* the risks that are undesirable clinical outcomes and for which there is sufficient scientific evidence that they are caused by the medicinal product. *Potential Risks:* the risks that are undesirable clinical outcomes and for which there is scientific evidence to suspect the possibility of a causal relationship with the medicinal product, but where there is currently insufficient evidence to conclude that this association is causal. *Important Identified Risks:* risks that are likely to have an impact on the risk-benefit balance of the product. These risks would warrant further evaluation as part of the pharmacovigilance plan. *Important Potential Risks:* those important potential risks that, when further characterised and if confirmed, would have an impact on the risk-benefit balance of the medicinal product. *Missing Information:* refers to gaps in knowledge about the safety of a medicinal product for certain anticipated utilisation (e.g. long-term use) or for use in particular patient populations, for which there is insufficient knowledge to determine whether the safety profile differs from that characterised so far. [V.B.1. Principles of Risk Management:]\ The overall aim of risk management is to ensure that the benefits of a particular medicinal product exceed the risks by the greatest achievable margin. The primary aim and focus of the RMP remains that of appropriate risk management planning throughout a medicinal product's life cycle. The risk management system shall be proportionate to the identified risks and the potential risks of the medicinal product, and the need for post-authorisation safety data. The RMP is a dynamic document that should be updated throughout the life cycle of the product(s). [V.B.2. Responsibilities for Risk Management:]\ The principal organisations directly involved in medicinal products' risk management planning are applicants/marketing authorisation holders and the competent authorities who regulate the medicinal products. The applicant/marketing authorization holder is responsible for:\ 1. Having an appropriate risk management system in place. 2\. Ensuring that the knowledge and understanding on the product's safety profile are critically reviewed.\ There are 2 specific milestones when the marketing authorization holders are advised to review list of safety concerns:\ 1. Within the first 5 years 2\. a PSUR submission approximately 8-9 years following granting the marketing authorization. V.B.3. Overview of the format and content of the Risk Management Plan (RMP) There are 7 parts. The submitted RMP shall follow the template in IR Annex I. Part II of the RMP is subdivided into modules which generally follow the section titles of ICH-E2E. [V.B.4. RMP Part I "Product(s) Overview"]\ This should provide the administrative information on the RMP and an overview of the product(s). The information presented should be current and accurate in relation to the ongoing application as it is anticipated to appear in the marketing authorisation. Active substance information provided should include: the active substance(s), the pharmacotherapeutic group(s) (ATC code), name of the marketing authorization applicant for initial marketing authorization applications or marketing authorization holder for RMPs submitted with post-authorisation procedures, medicinal products to which the RMP refers, centralized authorization procedures, invented names in the European Economic Area (EEA), brief history of the product, eCTD Link, indications, pharmaceutical forms and strengths, dosage, additional monitoring needed. [V.B.5 RMP Part II "Safety Specification"\ ]The purpose of the safety specification is to provide an adequate discussion on the safety profile of the medicinal product(s), with focus on those aspects that need further risk management activities. It should include a summary of the important identified risks of a medicinal product, important potential risks, and missing information. It should also address the populations potentially at risk (where the product is likely to be used and any outstanding safety questions that warrant further investigation. The safety specification consists of eight RMP modules, of which RMP modules SI-SV, SVII and SVIII correspond to safety specification headings in ICH-E2E. RMP module SVI includes additional elements required to be submitted in the EU.\ [V.B.6. RMP part III "Pharmacovigilance plan (including post-authorisation safety studies)"]\ The purpose of the pharmacovigilance plan in part III of the RMP is to present an overview and discuss how the applicant/marketing authorisation holder plans to further characterise the safety concerns in the safety specification.. It provides a structured plan for:\ the investigation of whether a potential risk is confirmed as an identified risk or refuted;\ further characterisation of safety concerns including severity, frequency, and risk factors; how missing information will be sought;\ measuring the effectiveness of risk minimisation measures.\ It does not include actions intended to reduce, prevent or mitigate risks; these are discussed in RMP part V.\ [V.B.7. RMP part IV "Plans for post-authorisation efficacy studies"]\ This RMP part should include a list of post-authorisation efficacy studies (PAES) imposed as conditions to the marketing authorisation or when included as specific obligations in the context of a conditional marketing authorisation or a marketing authorisation under exceptional circumstances. If no such studies are required, RMP Part IV may be left empty.\ [V.B.8. RMP part V "Risk minimisation measures (including evaluation of the effectiveness of risk minimisation activities)"\ ]Part V of the RMP should provide details of the risk minimisation measures which will be taken to reduce the risks associated with respective safety concerns. Routine risk minimization activities apply to every medicinal product. These relate to the summary of product characteristics, labeling, package leaflet, pack size, legal status of the product. There are 2 sections here: the "Risk minimization plan" and the "Summary of risk minimization measures."\ [V.B.9. RMP part VI "Summary of the risk management plan"]\ A summary of the RMP for each authorised medicinal product shall be made publicly available and shall include the key elements of the risk management plan. The RMP summary should be updated when important changes are introduced into the full RMP. To ensure that the summary can satisfy the different needs, it should be written and presented clearly, using a plain-language approach.\ [V.B.10. RMP part VII "Annexes to the risk management plan"\ ]The RMP should contain annexes. If the RMP applies to more than one medicinal product, it is expected that the annexes will be relevant for all products.\ [V.B.11. The relationship between the risk management plan and the periodic safety update report]\ The primary post-authorisation pharmacovigilance documents for safety surveillance are the RMP and the PSUR. These two documents are complementary to each other. The main purpose of the PSUR is retrospective, integrated, post-authorisation risk-benefit assessment whilst that of the RMP is prospective pre-and post-authorisation risk-benefit management and planning.\ [V.B.12. Quality systems and record management\ ]Although many experts may be involved in writing the RMP, the final responsibility for its quality, accuracy and scientific integrity lies with the marketing authorisation applicant/holder. The marketing authorisation holder is responsible for updating the RMP when new information becomes available and should apply the quality principles detailed in GVP Module I. The marketing authorisation holder should maintain records of when RMPs were submitted to competent authorities and the significant changes between RMP versions.\ **V.C. Operation of the EU network\ **[V.C.1. Requirements for the applicant/marketing authorisation holder in the EU]\ For full initial marketing authorisation applications, all parts of an RMP should be submitted. For other types of initial marketing authorisation applications, the requirements for the RMP content follow the concept of proportionality to the identified risks and potential risks of the medicinal product, and the need for post-authorisation safety data; therefore certain parts or modules may have reduced content requirements or may be left empty, where not applicable.\ [V.C.2. Submission of a risk management plan to competent authorities in the EU\ ]For centrally authorised medicinal products, the RMP should be submitted as PDF files within the eCTD submission. The system for nationally authorised medicinal products varies across Member States and the national requirements should be followed. The initial RMP should be submitted as part of the initial marketing authorisation, or if required, for those products that do not have an RMP, through the appropriate post-authorisation procedure.\ [V.C.3. Assessment of the risk management plan within the EU regulatory network]\ Within the EU, the regulatory oversight of RMPs for medicinal products authorised centrally lies with the Pharmacovigilance Risk Assessment Committee (PRAC). For the RMP assessment, the PRAC appoints a PRAC rapporteur who works closely with the (Co-)Rapporteur(s) appointed by the CHMP and Committee for Advanced Therapies (CAT) (for ATMPs) or with the Reference Member State, as appropriate. The EMA may, on a case-by-case basis, consult healthcare professionals and patients during the assessment of RMPs to gather their input on proposed risk minimisation measures.\ [V.C.4. Transparency]\ The Agency and Member States shall make publically available, by means of the European medicines web-portal and the national medicines web-portals, public assessment reports and summaries of risk management plans. For centrally authorised medicinal products the Agency:\ makes public a summary of the RMP;\ includes tables relating to the RMP in the EPAR including the product information and any conditions to the marketing authorisation.\ The national competent authorities will provide details of how they intend to implement the transparency measures at national level.