18 November 2020

EMA Risk Management approach for COVID-19 vaccines

Further to the recent good news regarding the efficacy of COVID-19 vaccine candidates, European Authorities have published new guidance documents to support Risk Management activities for these vaccines once they are authorised.

        Link to EMA News Release


Photo by Daniel Schludi on Unsplash

CoreRMP19 requirements and guidance

This includes a new guidance document published by the EMA to help companies prepare the Risk Management Plan (RMP) for their COVID-19 vaccines, which complements the existing GVP Guidelines and the associated RMP template. This document covers specific considerations for COVID-19 vaccines, including:

  • The submission by MAHs of Summary Monthly Safety Reports to the EMA, to complement PSURs. As detailed within the guidance, these reports should include interval and cumulative summary tabulations of ADR reports, exposure data, ongoing and closed signals, etc.
  • The need to adapt signal detection methods and practices to the expected large volume of ADR reports in the context of vaccination campaigns during a pandemic
  • The need to consider global efforts to define the list of Adverse Events of Special Interest (AESIs)
  • The need to consider the use of specific Follow-up Questionnaires for reports of identified safety concerns and suspected AESIs, while the burden on healthcare professionals should remain limited
  • The need to consider missing information for specific populations, including pregnant women, patients with co-morbidities, elderly and children


Photo by CDC on Unsplash


Pharmacovigilance Plan of the EU Regulatory Network

European Authorities have also produced a Safety Monitoring Plan for COVID-19 vaccines, which outlines how they intend to collect and review all relevant information once COVID-19 vaccines get authorised.

In addition to the EU GVPs, several activities will apply specifically to COVID-19 vaccines. As described above, this includes new reporting obligations for companies, who will be required to submit Summary Monthly Safety Reports to the EMA.

Transparency is an important theme of the plan, and it details the exceptional measures set up by the EMA to support public confidence and promote the uptake of COVID-19 vaccines. As an example, the EMA will publish on its website the full body of the RMP for all authorised COVID-19 vaccines, including Annex 4 presenting specific ADR follow-up forms.

        Direct link to Pharmacovigilance Plan of the EU Regulatory Network



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Thierry Hamard is a Pharmacist with more than 15 years of Global Pharmacovigilance Auditing experience and over 200 PV Audits performed since his company PV Focus was established in 2004.


Thierry is also Chief Editor of Safety Observer, a provider of Regulatory Intelligence services for Pharmacovigilance since 2005.









09 April 2020

COVID-19 Guidance: Impact for Pharmacovigilance

LAST UPDATED 18-Nov-2020:

Changes in the downloadable report are highlighted in Green.

PRIOR UPDATE 04-Nov-2020



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We are happy to share with you the result of our Regulatory Intelligence Monitoring regarding the guidance issued to address the COVID-19 pandemic.

We are highlighting the impact on Safety Reporting procedures for both Clinical Trial and Post-Marketing Pharmacovigilance activities. This information will be updated as necessary.

DISCLAIMER: This is not intended to cover all countries worldwide. For more information about the scope of our Regulatory Monitoring, please check our Q&As.



High Level Summary

Clinical Trials:

Most of the guidance documents that have been published are related to the conduct of Clinical Trials, and they are intended to protect subject safety and data validity.

The impact for Pharmacovigilance groups in the Industry is limited as compliance with existing safety reporting requirements is generally expected.
The European Commission held a webinar on 15-May-2020 to provide an overview of the most important elements of its Guidance on the management of clinical trials during the COVID-19 pandemic. Slides and Video Recording are made available.

A few National Competent Authorities (e.g. France, the UK) have however published guidance to express their understanding that safety reporting timelines may not always be met, and that SUSARs submissions should have priority over periodic safety reports.

Both the EMA and FDA have published guidance to help with the statistical analysis of trials impacted by COVID-19. 
The FDA has also issued a new guidance document to help assess the benefits of potential treatments on COVID-19-related symptoms during clinical trials.


Post-Marketing:

At the European Level, the EMA has published guidance that describes how companies can prioritise ICSR Reporting activities. This guidance has been updated to cover Pharmacovigilance Quality Management aspects including CAPAs, Audits and Inspections.
The EMA has also extended the Medical Literature Monitoring (MLM) service to include potential COVID-19 treatments.


The EMA has issued detailed guidance that provides recommendations for the processing and coding of ICSRs associated with products used for the treatment or prevention of COVID-19. The latter guidance has been revised reflect the update of MedDRA 23.0, which contains additional COVID-19- terms, which was implemented in EudraVigilance.

The MHRA has defined regulatory flexibility for certain Pharmacovigilance requirements including PSUR Submission, Safety Variations, dissemination of educational materials and DHPCs. ICSRs follow-up activities should also be prioritised to minimise the burden on Health Care Professionals. The MHRA has introduced an additional category to those defined at the EU level for the prioritization of ICSR submissions. The MHRA has also defined an urgent review procedure for the Relaxation of Risk Minimisation Measures.

The FDA and Health Canada have published guidance that provides a framework to delay the submission of some reports, including ICSRs for non-priority products. The FDA has issued an updated version of its guidance on 11-May-2020, which brought important changes for the prioritization of 15-day Alert reports that should be submitted to the FDA.
The FDA has also expressed their understanding that some REMS requirements may not be met during the Public Health Emergency.

Following positive announcements on the efficacy of some COVID-19 vaccine candidates, the EMA has published new guidance to address specific considerations for Risk Management activities. This includes new guidance on Risk Management Plans (RMPs) for COVID-19 vaccines, which complements existing GVP Guidelines and brings a new safety reporting obligation for MAHs of COVID-19 vaccines.





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Thierry Hamard is a Pharmacist with more than 15 years of Global Pharmacovigilance Auditing experience and over 200 PV Audits performed since his company PV Focus was established in 2004.


Thierry is also Chief Editor of Safety Observer, a provider of Regulatory Intelligence services for Pharmacovigilance since 2005.



22 March 2020

FDA Guidance on AE Reporting during a Pandemic

ATTENTION !!
This post was updated on 20-May-2020 to reflect the changes brought by the revised version of the Guidance Document published by the FDA on 11-May-2020. Resulting revisions are tracked (in Red & Highlighted in Yellow).



The U.S. FDA has published a new Guidance Document on 19-Mar-2020, which is entitled : “Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During a Pandemic”.

This is not exactly a new document and in reality, this represents a minor revision of the 2012 guidance on “Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During an Influenza Pandemic". The update clarifies that the guidance is applicable to any pandemic, including the current COVID-19 pandemic and not just an influenza pandemic.




Possible Impact of a Pandemic

This guidance provides recommendations to address the anticipated workforce shortage that can result from high absenteeism in the Industry and at the FDA during a pandemic, while the volume of case reports may increase due to the widespread use of medical products to face the pandemic.

Although compliance should be maintained to the maximum extent possible, the guidance brings flexibility to prioritize AE reporting responsibilities when resources become insufficient, which should be considered in Business Continuity arrangements.


Business Continuity and Prioritization

Companies that are unable to fulfill normal adverse event reporting requirements during a pandemic should maintain documentation of the declaration of a pandemic (e.g. by the WHO), and of the factors that are preventing the firm to comply with its reporting requirements, i.e. high absenteeism and/or increase in caseload. The FDA should be notified as soon as possible.

In these circumstances, the FDA will accept that certain safety reports are not submitted within the regulatory timeframes provided that delayed reports are submitted within 6 months of the restoration of AE reporting capabilities to their pre-pandemic state. However, a different timeframe may be set by the FDA (see Section D of the Guidance Document).


FDA defines Priorities for Safety Reports

The guidance includes a table that defines which reports companies should submit and which may be stored if necessary. Here is a summary for approved drug and biological products (NDA, ANDA, or BLA):
  • FDA will communicate with firms if there are products and issues that present special concerns, in which case full compliance with expedited and periodic reporting requirements is expected.
  • For all other products, Periodic Safety Reporting may be suspended.
  • Regarding Expedited Safety Reporting (i.e. 15-day Alert reports), while other reports may be stored if necessary, the following reports should be submitted within required timeframes:
1-
Reports associated to products approved for an indication related to the pathogen causing the pandemic, including pandemic vaccines targeting the pathogen or the disease, whether or not this use is included in the approved labeling
2-
Reports associated to products approved within prior three years
3-
For Biologics only All Products, Reports with a Fatal Outcome



Besides these rules for approved drug and biological products, the table provides guidance for other types of products, including Prescription drug products marketed without an approved NDA (including compounded or repackaged products), Medical Devices, Blood Products, Human Cells, Tissue, and Cellular and Tissue-Based Products (HCT/P), etc.


       Link to FDA Guidance Page




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Thierry Hamard is a Pharmacist with more than 15 years of Global Pharmacovigilance Auditing experience and over 200 PV Audits performed since his company PV Focus was established in 2004.


Thierry is also Chief Editor of Safety Observer, a provider of Regulatory Intelligence services for Pharmacovigilance since 2005.

09 January 2020

Algeria issues New GVP Guideline

Things are changing fast in Algeria: It has only been a few months since a Note was published to describe revised Safety Reporting requirements (see Post) and the Algerian Authorities have now published a full Pharmacovigilance Guide with new changes to expedited reporting requirements.

The new Guide was produced by the "Centre National de Pharmacovigilance et de Materiovigilance" (CNPM) and includes a description of the local Pharmacovigilance System in Algeria. It covers the role of the stakeholders and includes a description of the obligations applicable to the Pharma Industry.




Among other topics, the Guide describes the expectations regarding the appointment of a Local Contact Person for Pharmacovigilance and for the maintenance and provision of the Pharmacovigilance System Master File (PSMF). The topics covered also include Procedures, Audits and Inspections, RMPs and PBRERs/PSURs, as well as Signal Management.

Regarding the Safety Reporting requirements, the Note published in June 2019 (see Post) reduced drastically the number of ICSRs that required submission in Algeria by removing the obligation to include foreign ICSRs. The new Guide brings yet more changes when compared to the June 2019 Note and here is a summary of the resulting applicable ICSR reporting requirements:

- Post-Marketing ICSRs, including cases originating from Non-Interventional Studies, must be submitted to the CNPM as follows:

  • Domestic Serious ADRs: within 15 Calendar Days
  • Domestic Non-Serious ADRs: within 90 Calendar Days
  • All Foreign ADRs: through the PBRERs/PSURs


Clinical Trials ICSRs must be submitted to the CNPM and Ethics Committees as follows:


  • Domestic Fatal/Life-Threatening SARs: initial report within 7 Calendar Days
  • Other Domestic SARs: within 15 Calendar Days
  • All Foreign ICSRs: through Annual DSURs

In other words, compared to the Note published in June 2019, there is no longer a requirement to submit Domestic Fatal/Life-Threatening Post-Marketing ADRs in 7 Days.
On the other hand, the requirements for Clinical Trials ICSRs now includes all SARs, whether they are unexpected (i.e. SUSARs) or not.

The Guide produced by the CNPM is only available in French and is unfortunately not available on the website of the Agency. The copy shared here was obtained from a contact in Algeria and user of this blog, whom I would like to thank for notifying me of this new and important guidance.

   → Link to CNPM 2019 Pharmacovigilance Guide (in French)
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Thierry Hamard is a Pharmacist with more than 15 years of Global Pharmacovigilance Auditing experience and over 200 PV Audits performed since his company PV Focus was established in 2004.


Thierry is also Chief Editor of Safety Observer, a provider of Regulatory Intelligence services for Pharmacovigilance since 2005.

03 July 2019

Algeria updates Pharmacovigilance reporting requirements

ATTENTION !! UPDATE 09-Jan-2020:
This post is no longer current as the CNPM has published a new Pharmacovigilance Guide with revised ICSR reporting requirements (see New Post). The content of this post includes the resulting revisions (in Red & Highlighted in Yellow).


The Algerian Authorities have published an important revision of the Note describing the Pharmacovigilance reporting requirements in the country.

Until now, the "Centre National de Pharmacovigilance et de Materiovigilance" (CNPM) required that all Serious ICSRs and Clinical Trial SUSARs be submitted, including foreign reports. This meant that thousands of ICSRs qualified for reporting to the CNPM in Algeria, even though it is doubtful that the CNPM had sufficient resources to process such large volumes of information.

The Note published by the CNPM and dated 03-Jun-2019 will come as a relief to international companies placing medicinal products on the market in Algeria: The expedited reporting of foreign ICSRs is no longer a requirement and those cases are now only expected to be presented through the applicable periodic reports.



As a summary in English, here are the newly applicable requirements in Algeria:

- Post-Marketing ADRs, including cases originating from Non-Interventional Studies, must be submitted to the CNPM as follows:

  • Domestic Fatal/Life-Threatening ADRs: as soon as possible, within 7 Calendar Days
  • Other Domestic Serious ADRs: within 15 Calendar Days
  • Domestic Non-Serious ADRs: within 90 Calendar Days
  • All Foreign ADRs: through the PBRERs/PSURs

The Note also now clearly states that the submission of PBRERs/PSURs can be aligned with the EURD List.


- Clinical Trials SUSARs must be submitted to the CNPM and Ethics Committees as follows:

  • Domestic Fatal/Life-Threatening SUSARs: initial report within 7 Calendar Days
  • Other Domestic SUSARs: within 15 Calendar Days
  • All Foreign SUSARs: through 6-monthly Line Listings and Annual DSURs

As described in a recent article in the "Drug Safety" journal, the Algerian CNPM has not adopted the GVP Guideline for Arab countries published in 2014. With a 7-Day reporting requirement for Fatal/Life-Threatening ADRs, these new Requirements still deviate from the Arab GVPs and the underlying ICH E2D Guideline. Nevertheless, this revision represents a significant move towards international harmonization and will make compliance easier to achieve for the Industry in Algeria.

The Note issued by the CNPM is only available in French and is unfortunately not available on the website of the Agency. We obtained a copy from the CNPM, which we make available here, together with the previous version as a reference.









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Thierry Hamard is a Pharmacist with more than 15 years of Global Pharmacovigilance Auditing experience and over 200 PV Audits performed since his company PV Focus was established in 2004.


Thierry is also Chief Editor of Safety Observer, a provider of Regulatory Intelligence services for Pharmacovigilance since 2005.