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-===== European Medicines Agency (EMA) =====
+====== European Medicines Agency ======
-{{::ena_european_medicines_agency.png?600 |}}
+{{ ::european_medicines_agency.png?200|}}
-==== History ====
+The **European Medicines Agency (EMA)** is an agency of the [[European Union]] in charge of the evaluation and supervision of medicinal products. It is the European Union’s equivalent to the [[Food and Drug Administration]] (FDA) in the [[United States]].((https://web.archive.org/web/20180927103739/https://www.ema.europa.eu/en))
-The European Medicines Agency is an agency of the European Union in charge of the evaluation and supervision of medicinal products.
 Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or European Medicines Evaluation Agency.
-The European Medicines Agency (EMA) is a decentralized agency of the [[:European Union]] (EU) whose goal is to promote and protect human and animal health.
+==== Regulatory information on veterinary medicines ====
-The EMA is the European Union’s equivalent to the U.S. [[:Food and Drug Administration]](FDA)
+===== Partners & networks ====
-((https://web.archive.org/web/20180927103739/https://www.ema.europa.eu/en))
+{{ ::ema_stakeholder_partne_rpie_chart.png?600|}}
+The European Medicines Agency is at the core of the European Union’s (EU's) medicine and health system, and aims to protect human and animal health. To ensure that the system works effectively, the Agency works closely with its partners and stakeholders, and is a proactive member of important networks in Europe and beyond. ((https://web.archive.org/web/20201207164408/https://www.ema.europa.eu/en/partners-networks))
+==== Pharmaceutical industry ====
-Overview
+On this page, you will find information on the Agency’s activities that are most relevant to pharmaceutical industry, including news, and events. You can contribute to the Agency’s work by responding to public consultations. Learn more about how the pharmaceutical industry is actively involved in the work of the Agency. (())
-Role: EMA guarantees the scientific evaluation, supervision & safety monitoring of human & veterinary medicines in the EU.
-Executive Director: Emer Cooke
-Established in: 1995
-Number of staff: 897
-Location: Amsterdam (the Netherlands)
-Website: EMA
-The European Medicines Agency (EMA) protects and promotes human and animal health by evaluating and monitoring medicines within the European Union (EU) and the European Economic Area (EEA).
+==== EU Innovation Network ====
-What it does
-The Agency's main responsibilities are authorising and monitoring medicines in the EU. Companies apply to it for a single marketing authorisation, which is issued by the [[:European Commission]]. If granted, this enables them to market the medicine concerned throughout the EU and the EEA. Given the wide-ranging scope of the centralised procedure, most genuinely innovative medicines marketed in Europe are authorised by the EMA.
+Innovation offices in national regulatory agencies have been working informally with the EMA's [[:Innovation Task Force]] (ITF) on matters relating to emerging therapies and technologies since 2011. In 2015, EMA and the EU national competent authorities (NCAs) strengthened their collaboration to support medicine innovation and early development of new medicines in the EU by establishing the EU innovation network.
-The Agency fulfils its responsibilities by:
+EMA and the HMAs adopted the mandate of the EU-Innovation Network in October 2016
-      * facilitating the development of medicines & access to them
+=== Mandate of the European Innovation Network ===
-  *     evaluating applications for marketing authorisations
+{{ ::ema_2014_innovation.png?600|}}
-  *     monitoring the safety of medicines throughout their lifecycle
+- The [[:Innovative Medicines Initiative]] (IMI) WEB-RADR project aims to explore the use of mobile technologies and social media to further improve the collection and analysis of information on the suspected adverse drug reactions. This includes the use of mobile apps to report adverse reactions, the possibility identifying potential safety issues with medicines from user comments (posts) on social media as well as the safety information on medicines.
-  *     providing information to healthcare professionals & patients
-Who benefits
+The workshop provided an opportunity to discuss expectations with different stakeholders such as members of the European Medicines Agency (EMA) Healthcare Professionals' Working Party, the Patients' and Consumers' Working Party, the Pharmacovigilance Risk Assessment Committee, representatives of young people from the Paediatric Committee, experts in pharmacovigilance, medical ethics and data protection as well as the IMI WEB-RADR Consortium. The report on the outcome of the workshop hosted by EMA is available on the IMI website. ((https://web.archive.org/web/20181002140149/https://www.ema.europa.eu/en/events/innovative-medicines-initiative-web-radr-workshop))
-The EMA's work benefits:
+The aim of the network is to make the regulatory support for medicines developers currently available at national and EU levels more visible and attractive to innovators ((https://web.archive.org/web/20181002132519/https://www.ema.europa.eu/en/human-regulatory/research-development/innovation-medicines))
-      * patients
+=== Authorized Stakeholders ===
-  *     healthcare professionals
-  *     academics
-  *     pharmaceutical companies
-  *     medicine developers
-  *     health policymakers
-Through its scientific guidelines, scientific advice programme and incentives, it facilitates research into new medicines and encourages development, thereby translating progress in medical science into medicines with real health benefits for patients. In particular, it promotes the development of medicines for children and drugs to tackle rare diseases. ((https://web.archive.org/web/20211118020005/https://european-union.europa.eu/institutions-law-budget/institutions-and-bodies/institutions-and-bodies-profiles/ema_en))
+List of eligible industry stakeholder organisations (as of 16 May 2018) With reference to the Criteria to be fulfilled by industry stakeholder organisations involved in EMA activities, (EMA/323235/2016), the following organisations have been deemed eligible to be consulted and involved directly or to co-operate with the Agency in specific areas. All of the organisations in this list are also included in the EC Transparency Register, which provides further detailed information. ((https://web.archive.org/web/20181002140135/https://www.ema.europa.eu/en/documents/report/european-medicines-agencys-interaction-industry-stakeholders-annual-report-2017_en.pdf))
+==== Pharmacovigilance ====
-==== Regulatory information on human medicines ====
+Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem. The European Medicines Agency (EMA) coordinates the European Union (EU) pharmacovigilance system and operates services and processes to support pharmacovigilance in the EU.
-**Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products**
+Before a medicine is authorised for use, evidence of its safety and efficacy is limited to the results from clinical trials, where patients are selected carefully and followed up very closely under controlled conditions. This means that at the time of a medicine's authorisation, it has been tested in a relatively small number of selected patients for a limited length of time.
-{{ ::ema_risk_mitigation.png?600|}}
+After authorisation the medicine may be used in a large number of patients, for a long period of time and with other medicines. Certain side effects may emerge in such circumstances.
-Executive summary
-This is the first revision of the ‘Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products’. It extends the existing EU guidance to address first-in-human (FIH) and early phase clinical trials (CTs) with integrated protocols.
+It is therefore essential that the safety of all medicines is monitored throughout their use in healthcare practice.
+{{::ema_pfizer_authorize_170_patients.png?600 |}}
-The revision is intended to further assist stakeholders in the transition from non-clinical to early clinical development and in identifying factors influencing risk for new investigational medicinal products (IMPs). The document includes considerations on quality aspects, non-clinical and clinical testing strategies, study design and on conduct of FIH/early CTs. Strategies for mitigating and managing risks are given, including principles on the calculation of the starting dose to be used in humans, the subsequent dose escalations, the criteria for maximum dose and the conduct of the trial inclusive of multiple parts.
+**EU law therefore requires each marketing authorisation holder, national competent authority and EMA to operate a pharmacovigilance system.** The overall EU pharmacovigilance system operates through cooperation between the EU Member States, EMA and the [[:European Commission]]. In some Member States, regional centres are in place under the coordination of the national competent authority.
+EMA's [[:Pharmacovigilance Risk Assessment Committee]] (PRAC) is responsible for assessing and monitoring the safety of human medicines. It is made up of experts in medicines safety from regulatory authorities in Member States, plus scientific experts and representatives of patients and healthcare professionals nominated by the European Commission.
-. Introduction (background)
+EMA supports the PRAC by providing data from clinical practice available in electronic health records or prescription databases.
-The purpose of FIH trials is to evaluate an investigational medicinal product (IMP) in humans for the first time, to study the human pharmacology, tolerability and safety of the IMP and to compare how effects seen in non-clinical studies translate into humans. Traditionally FIH CTs were most associated with a single ascending dose (SAD) design, which was subsequently followed by a multiple ascending dose (MAD) CT. Since the publication of the original ‘Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products’ in 2007, integration of the non-clinical data available before FIH administration and the pharmacokinetic (PK), pharmacodynamic (PD) and human safety data emerging during a trial has evolved.
-Consequently, the increasing practice is to perform FIH and early phase CTs with integrated protocols that combine a number of different study parts (e.g. SAD, MAD and food effects). The safety and well-being of trial subjects (be they patients or healthy volunteers) should always be the priority and special consideration should be given to characterising risk and putting in place appropriate strategies to minimise risk. The guideline aims to address as far as possible the important issues that may need consideration during the process of designing a set of studies in a clinical development programme.
+The Agency is responsible for developing and maintaining EudraVigilance, a system for managing and analysing information on suspected adverse reactions to medicines authorised in the European Economic Area (EEA).
-As IMPs are widely different in their pharmacological features and intended use different parts of the guideline may be important for some and inapplicable to others. In defining an appropriate development programme for an IMP, information on safety needs to be integrated from many sources and reviewed in an iterative process. Strategies for development of a medicine and the experimental approaches used to assemble information relevant to the safety of CTs should always be science-based and decisions should be based on a rigorous interpretation of the totality of the available data.
+EudraVigilance is a single repository for reports of suspected adverse reactions seen in healthcare practice and clinical trials. It is used by Member states, the Agency and industry.
-.1. **Demonstration of relevance of the animal model**
+The PRAC evaluates safety signals from [[:EudraVigilance]] and may recommend regulatory action as a result. For more information, see Signal management.{{ ::why_was_pfizer_jab_approved_uk_gov.png?800|}}
-The relevance of the selected animal model should be justified in the CT application. The demonstration of relevance of the animal model(s) may include comparison with humans
-.2. **Nature of the target**
+EMA publishes data from EudraVigilance in the European database of suspected adverse drug reaction reports.
-Beyond the mode of action, the nature of the target itself can impact on the potential risk inherent to the initial administrations to humans. Experimental and/or literature-data should be taken into account when defining the degree of uncertainty of the IMP. This may specifically include
-.3. **Pharmacodynamics**
+Users can view the total number of individual suspected side effect reports submitted to EudraVigilance for each centrally authorised medicine.
-Primary PD studies should address the mode of action related to intended therapeutic use and provide knowledge on the interaction of the IMP with the intended target as well as with related targets. The primary and secondary PD characterisation should be conducted in vitro, using animal and human-
-derived material, and in vivo using animal models, as relevant.
-These studies might include target interactions preferably linked to functional response, e.g. receptor binding and occupancy, inhibition of
+Reports for drug substances used in nationally authorised medicines are also available since October 2014.
-enzymes, cellular response consequent to the interaction with the target, duration and (ir)reversibility of effect, dose-response relationships and physiological turn-over of the target. When defining the degree of uncertainty associated with the mode of action or effects, aspects to be
-considered may include
-.4.** Pharmaco- and toxicokinetics**
+The Pharmacovigilance Risk Assessment Committee (PRAC) is responsible for prioritising and assessing signals and issuing subsequent recommendations on medicines authorised in the European Union, including nationally and centrally authorised medicines.
-PK and toxicokinetic (TK) data, as per ICH S3, S6(R1), M3(R2) and related Q&A documents, should be available in all species used for the non-clinical safety studies conducted. These data should adequately support the interpretation of data from in vivo PD models and safety/toxicological studies before starting FIH/early CTs. Sponsors should supply a brief summary of the analytical assays used to characterise the non-clinical PK and TK, including their accuracy, precision and limits of quantification.
-Systemic exposures at pharmacodynamically active doses in the relevant animal models should be determined and considered especially when PD effects are suspected to contribute to potential safety concerns. Possible polymorphisms e.g. in metabolic enzymes should be taken into account.
+The PRAC recommendation may include one or a combination of conclusions, including:
-.5. **Safety pharmacology**
+      * No need for further evaluation or action at present;
-Standard core battery data should be available before the first administration in humans as outlined in ICH guidelines S7A, S7B, S6(R1), S9, M3(R2) and related Q&As. Additional studies to investigate effects in these and other organ systems should be conducted on a case-by-case basis where there is a cause for concern.
+  *     Need for additional information, including:
+  *         monitoring any relevant emerging information as it becomes available,;
+  *         additional analysis in EudraVigilance or other data sources;
+  *         additional data from the marketing authorisation holder in the next periodic safety update report (PSUR) or submit an ad-hoc PSUR;
+  *         a post-authorisation safety study conducted by the marketing authorisation holder;
+  *     Need for regulatory action, such as:
+  *         updating of the product information (summary of product characteristics and package leaflet) and/or risk management plan through a variation;
+  *         a referral procedure;
+  *         urgent safety restrictions. ((https://web.archive.org/web/20181223210005/https://www.ema.europa.eu/en/human-regulatory/post-authorisation/pharmacovigilance/signal-management))
-.6. **Toxicology**
-The toxicology programme should be designed taking the characteristics of the IMP and the relevant ICH guidelines S6(R1), S9 and M3(R2) into account.
-Toxicity can be the result of exaggerated pharmacological actions. These types of effects should not be ignored when establishing a safe starting dose for humans and the exposures, at which these toxicities are observed, should be considered for the definition of the dose escalation range to be investigated in humans. Primary and secondary PD data can support the generation of mechanistic hypotheses regarding the toxicities seen in vivo and help in the interpretation of the human relevance of these findings.
-An evaluation as to whether the target organs identified in the non-clinical studies warrant particular monitoring in the CT should be undertaken. Serious toxicity should lead to a more cautious approach when setting doses and applying risk mitigation strategies in the clinical setting. When serious toxicity or mortality is observed, these effects may require follow up studies to determine the cause of death or the mechanism of toxicity if this has not been possible to clarify within the studies undertaken, and if this information is relevant to the clinical trial design or safety monitoring plan.
-.2.9. **Stopping rules**
-{{ ::ema_stopping_rules.png?600|}}
-The protocol should define unambiguous stopping rules which result in an immediate stop to dosing. It should further be specified in the rule if the stop is a final end of dosing or a temporary halt. Restart is possible without a substantial amendment if review leads to a conclusion which is fully within predefined conditions for the relevant stopping criterion.
-Any submitted substantial amendment should include a rationale for the proposed dosing and for the continuation of the trial and details of any adjustments to the protocol including additional safety monitoring, if applicable. ((https://web.archive.org/web/20181002223839/https://www.ema.europa.eu/documents/scientific-guideline/guideline-strategies-identify-mitigate-risks-first-human-early-clinical-trials-investigational_en.pdf))
+==== Emergency Use ====
+The MHRA has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in place for this product at all sites responsible for the manufacture, assembly and batch release of this product.
-==== Regulatory information on veterinary medicines ====
+A Risk Management Plan (RMP) and a summary of the pharmacovigilance system have been provided with this application and are satisfactory.
-===== Partners & networks ====
+This batch, and any future batches, of COVID-19 mRNA Vaccine BNT162b2 are subject to Qualified Person (QP) certification and batch evaluation by an independent control laboratory before the vaccine is released into the UK.
+The [[:COVID-19 Vaccine Benefit Risk Expert Working Group]] (Vaccine BR EWG) have met several times to review and discuss the quality, safety and efficacy aspects in relation to batches of COVID-19 mRNA Vaccine [[:BNT162b2]]. The manufacturer, [[:Pfizer/BioNTech]], was also invited to a separate meeting with the quality subgroup of the Vaccine BR EWG to review and discuss questions related to manufacture and control of the product.
-==== Pharmaceutical industry ====
+The Vaccine BR EWG gave advice to the Commission of Human Medicines (CHM) on 11th September 2020, 8th October 2020, 27th October 2020, 28th November 2020 and 30th November 2020, regarding the requirements for authorisation for the temporary supply of COVID-19 [[:mRNA Vaccine]] BNT162b2. The requirements for quality, safety and efficacy were considered, taking into account the urgent public health need and risk to life, the pandemic situation and a lack of COVID-19 vaccines. As well as data on quality, safety and efficacy, specific mitigations and conditions on the product were discussed to ensure adequate standards of quality and safety are met.
-On this page, you will find information on the Agency’s activities that are most relevant to pharmaceutical industry, including news, and events. You can contribute to the Agency’s work by responding to public consultations. Learn more about how the pharmaceutical industry is actively involved in the work of the Agency. (())
+The CHM concluded that the proposed supply of COVID-19 mRNA Vaccine BNT162b2 for active immunisation to prevent COVID-19 caused by SARS-CoV-2 virus, in individuals 16 years of age and older, is recommended to be suitable for approval under Regulation 174 provided the company meets the conditions set out by the MHRA.
+Authorisation for the temporary supply of COVID-19 mRNA Vaccine BNT162b2 was granted in the UK on 1 December 2020. This report covers data received and reviewed for this authorisation only. This authorisation is valid until expressly withdrawn by MHRA or upon issue of a marketing authorisation.
-==== EU Innovation Network ====
+On 4 June 2021 the MHRA granted an extension of indication to ‘the active immunisation to prevent COVID-19 caused by the SARS-CoV-2 virus, in individuals 12 years of age and older’. ((https://web.archive.org/web/20220701121937/https://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19/summary-public-assessment-report-for-pfizerbiontech-covid-19-vaccine))
-Innovation offices in national regulatory agencies have been working informally with the EMA's [[:Innovation Task Force]] (ITF) on matters relating to emerging therapies and technologies since 2011. In 2015, EMA and the EU national competent authorities (NCAs) strengthened their collaboration to support medicine innovation and early development of new medicines in the EU by establishing the EU innovation network.
-EMA and the HMAs adopted the mandate of the EU-Innovation Network in October 2016
+==== Publications ====
-=== Mandate of the European Innovation Network ===
+==== EMA COVID-19 Steering Group ====
-{{ ::ema_2014_innovation.png?600|}}
-- The [[:Innovative Medicines Initiative]] (IMI) WEB-RADR project aims to explore the use of mobile technologies and social media to further improve the collection and analysis of information on the suspected adverse drug reactions. This includes the use of mobile apps to report adverse reactions, the possibility identifying potential safety issues with medicines from user comments (posts) on social media as well as the safety information on medicines.
-The workshop provided an opportunity to discuss expectations with different stakeholders such as members of the European Medicines Agency (EMA) Healthcare Professionals' Working Party, the Patients' and Consumers' Working Party, the Pharmacovigilance Risk Assessment Committee, representatives of young people from the Paediatric Committee, experts in pharmacovigilance, medical ethics and data protection as well as the IMI WEB-RADR Consortium. The report on the outcome of the workshop hosted by EMA is available on the IMI website. ((https://web.archive.org/web/20181002140149/https://www.ema.europa.eu/en/events/innovative-medicines-initiative-web-radr-workshop))
+EMA’s [[:COVID-19 Steering Group]] provides strategic oversight at EMA of the evolving scientific and regulatory challenges created by COVID-19, and other topics and emerging issues of importance, including from a political, interinstitutional or international perspective. ((https://web.archive.org/web/20220119130236/https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/emas-governance-during-covid-19-pandemic#covid-19-ema-pandemic-task-force-section))
-The aim of the network is to make the regulatory support for medicines developers currently available at national and EU levels more visible and attractive to innovators ((https://web.archive.org/web/20181002132519/https://www.ema.europa.eu/en/human-regulatory/research-development/innovation-medicines))
+===== External links =====
-==== Publications ====
+  * [[https://covidtruthinitiative.ca/en/Organizations/European-Union/European-Medicines-Agency|COVID Truth Initiative]]
+==== Links to sort ====
+  * [[https://web.archive.org/web/20181002223839/https://www.ema.europa.eu/documents/scientific-guideline/guideline-strategies-identify-mitigate-risks-first-human-early-clinical-trials-investigational_en.pdf]]