who efforts to promote reliance

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Extraordinary VirtualInternational Conference of Drug Regulatory Authorities (ICDRA)

20-24 September 2021

Workshop 4

Pharmacovigilance/Medical Product Safety

Thursday 23 September 202113:00 to 14:00 (CET)

Extraordinary Virtual International Conference of Drug Regulatory Authorities (ICDRA)20-24 September 2021

Workshop 4: Agenda

• Opening remarks and introduction of panel members• Presentations Perspective from national level: Chile and the challenge of COVID-19

vaccines PV (Dr Juan Roldán) Perspective from regional level: Coordinating safety surveillance of COVID-

19 vaccines (Dr Georgy Genov) Perspective from global level: Managing risks – Assessing globally, acting

locally (Dr Shanthi Pal)• Panel discussion• Summary and closing remarks

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Workshop 4: Moderator and Panelists

Moderator:• Dr Gopa Raychaudhuri, Senior Scientist and WHO Liaison Officer, CBER, USFDA, USA

Panelists:• Dr Juan Roldán, Public Health Institute of Chile (Chile)• Dr Manal Younus, Iraqi Pharmacovigilance Centre (Iraq)• Dr Georgy Genov, European Medicines Agency (Netherlands)• Dr Hudu Mogtari, AUDA-NEPAD (South Africa)• Dr Pinelopi Lundquist, Uppsala Monitoring Centre (Sweden)• Dr Shanthi Pal, Team Lead Pharmacovigilance, WHO (Switzerland)

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Extraordinary Virtual International Conference of Drug Regulatory Authorities (ICDRA)20-24 September 2021 4

Perspective from national level:

Chile and the challenge of Covid-19 vaccines PV

Juan RoldánHead of the National Medicines Agency Department, National Institute of Health

Chile


COVID-19 situation in Chile

5Source: Statistics and Health Information Department, Ministery of Health. Date: Sep 13, 2021

Total calc. pop.:19.107.000

Since December 2020, Chilean NRA (ISP) has authorized emergency use of 6 COVID-19 vaccines: • BNT162b2/PfizerBioNTech (Dec 16, 2020)• CoronaVac/Sinovac (Jan 20, 2021) • AZD1222/OxfordAstraZeneca (Jan 27, 2021) • Ad5-nCoV/CanSino (Apr 7, 2021) • Ad26.COV2. S/Janssen (Jun 10, 2021) • Sputnik/ GAM-COVIDVAC/ ( Jul 21, 2021)

SARS-Cov-2 vaccination campaign progress by date and dose


Distribution of AEFI cases

0

1000

2000

3000

4000

5000

6000

7000

Pfizer CoronaVac AstraZeneca CanSino

Distribution of AEFI by vaccine vs seriousnessn: 10,733

Total not serious serious

10,733 AEFI received until Aug 14th96.5% of the cases are non-serious and 73,7% of thecases occurred in the female sex.The 18-39 y/o range of age was the most affected

0 1000 2000 3000 4000 5000 6000 7000

12-17

18-39

40-49

50-59

60-69

70-79

> 80

No señala

Distribution of AEFI by age range4388

5722

434 189

Number of AEFI reports by vaccine

Pfizer CoronaVac AstraZeneca CanSino

INSTITU

TO D

E SALU

D PÚ

BLIC

A D

E CH

ILE

Detection

Notification

Preliminary analysis

Follow-up of the case

Evaluation

Feedback

Send AEFI to EPI

and UMC

AEFI management

National PV Center (ARN-ISP)

EPI, SEREMI (regional ministerial secretariats), regional Health Services

Evaluation of individual cases, descriptive analysis

Collaborative analysis (feedback), informative notes, newsletters, Web page

VaccinePharmacovigilanceCommittee. Twomeeetings/month (EPI, clinical specialists)

HPC, vaccinationVarious notification systems,

most notifications are manually handled

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6

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Lack of follow-up proper data

Lack of capacity to evaluate all serious cases

Demand for responses is greater than the capacity to

generate them

Lack of informatic resources/tools to send

timely the AEFI reports to the UMC

Bottlenecks/Challenges

Manufacturers

Global levelNational level


What can be done at the national Level

•Working coordinately within the different areas of the NRA.•Working together with the Expanded Program of Immunization.•Aboard Technologic limitations in order to effectively and timely send ADR/AEFI reports to UMC.•Implement patients reporting system, if not done yet.•Keep transparency over decision making process.•Keep continuously communicating information of interest to the community

What can be done by UMC

•Support the approach on Technologic limitations in order to allow sharing ADR/AEFI reports to UMC.•Support gaps closure in order to implement a successfully patients reporting system.•Keep doing analysis of data and training activities, focused mainly in vaccines PV.

What can be done by WHO

•Keep establishing and promoting bridges for cooperation between countries.•Keep establishing and promoting bridges for cooperation between collaborating centers of WHO, regional offices and countries.•Advocate for resources, training and visibility for national PV centers work.•Keep publishing guides and TD.

Proposal for addressing some of the challenges

An agency of the European Union

Coordinating safety surveillance of COVID-19 vaccines – perspective from regional level

Extraordinary Virtual International Conference of Drug Regulatory Authorities (ICDRA) 23/09/2021

Dr Georgy Genov, Head of Pharmacovigilance, European Medicines Agency

COVID-19 Vaccines Monitoring Preparedness


Potential risk identification

• Member states’ monitoring

• EMA/EudraVigilanceregular monitoring

NEW Supplemented by increased frequency (every 2 days) of adverse events of special interestNEW International partners engagement (hot line, regular teleconferences with ICMRA and WHO)NEW Companies’ monthly safety summary reports (MSSRs)NEW EMA funded studies for prospective monitoring

Preliminary orientation

NEW EMA Task Force (ETF) on COVID-19 bi-weekly meetingsNEW Contribution to the Pharmacovigilance Risk Assessment Committee (PRAC) activities on emerging pharmacovigilance issues related to COVID-19

Risk assessment and management

• PRAC recommendations

NEW Additional data:Commissioning of independent studies following PRAC request (framework in place)NEW Core risk management plan

Communication

• PRAC Highlights• Public health

communications

NEW Monthly/ ad-hoc safety updates

NEW: ad-hoc/twice a month press briefings

Tailored pharmacovigilance process

Basis: centralised DB (EV), sharing of resources – PRAC rapporteur per products, centralised review and decision making by safety committee/PRAC and EMA communication

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More reports received with 4 vaccines than all other centrally authorised products in 1 year

Spontaneous adverse event report to EudraVigilance


From early times to expanding safety surveillance activities

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Contracts with EU PE&PV research network (UU and UMCU, NL)

Vaxzevria - Signal of Thrombosis with thrombocytopenia (TTS)

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11/12 March 2021

PRAC validated the signal

Embolic and thrombotic

event

PRAC extraordinary

meeting and the first PRAC

recommendation (DLP 17 March

2021)

18 March 2021

First communicationNo association with an increased overall risk of blood clotting disorders.

There have been very rare cases of unusual

Thromboembolic events with thrombocytopenia after vaccination. The

reported cases were almost all in women under 55.

https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-benefits-still-outweigh-risks-despite-possible-link-rare-blood-clots

Ad hoc Expert meeting To discuss hypothesis,

pathophysiological mechanisms, and possible

underlying risk factors, gaps in knowledge and additional

studies

29 March 2021

PRAC April plenarymeeting and the

second PRAC recommendation on

Thromboembolic events with

thrombocytopenia

6 -9 April 2021

Second communication: Thromboembolic events with

thrombocytopeniashould be listed as very rare side effects

of Vaxzevria The reported cases were almost all in women under 60.

7 April 2021

https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood

Dissemination of the first

DHPC in the EU/EEA

24 March 2021

22 March 2021

Update EV search DL 22/3/21

Dissemination of the second DHPC in the

EU/EEA

13 April 2021

Very rare cases of Thrombosis in combination with thrombocytopenia were identified after vaccination

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Challenges

• Rise to the challenge and demonstrate to have systems in place to rapidly detect any safety issues and minimise serious risks to patients, vaccines confidence

• Very large amount of ICSRs over short period of time, quality of the reports

• Need to address issues promptly/impact on vaccination, prioritisation of multiple assessments

• Background incidence rates ≠ predefined AESI: stratification, need for rapid generation for new signals

• Readiness/limitations of EHRs (vaccine info in early times, lagtime for data availability, outcome ascertainment)

• Case definitions, phenotypes for case finding (e.g., TTS, MIS)

Learnings

• Preparedness is key

• Business continuity planning, ringfence resources, share info and expertise, EMA framework contracts

• Importance of spontaneous reports and centralised DB

• Prompt collection of data of quality to allow meaningful analysis

• Consortia with demonstrated capacity/expertise

• International collaborations with other regulators, prompt sharing of information assessments and expertise is key

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Opportunities: the pandemic has been a powerful booster for development of tools, methods, infrastructures, sharing and international collaboration – maintain momentum


The Global Perspective

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Managing risks – assessing globally, acting locally

Dr Shanthi PalTeam Lead, Pharmacovigilance

WHO

Extraordinary Virtual International Conference of Drug Regulatory Authorities (ICDRA)20-24 September 2021 21

2018 ICDRA Recommendations

WHO should develop guidance and a toolkit to support Member States in the implementation of the Smart Safety Surveillance strategy, one that embraces a risk-based prioritization of investments, work-sharing, joint activities and reliance for maximum return on investment for all medical products.

Covid-19 vaccines: safety surveillance manual - Regulatory reliance and work-sharingTraining material_COVID-19 vaccines safety surveillance manual_ Regulatory reliance

https://www.who.int/publications/m/item/WHO-MHP-RPQ-PVG-2021.10

https://www.who.int/publications/m/item/WHO-MHP-RPQ-PVG-2021.10

https://cdn.who.int/media/docs/default-source/covid-19-vaccines-safety-surveillance-manual/training-slides_covid-19_vs_regulatory_reliance9e36329b-9758-4809-84db-a3d296a9f3b9.pdf?sfvrsn=6afe2dff_5&Status=Master


Two Types of Reliance Activities are Possible in Pharmacovigilance

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1. Reliance on processes, tools and methods developed by othersWith authorities adopting common processes and

standards; templates for safety reporting; study protocol….

2. Reliance on product-specific regulatory activities. Participation in joint safety assessments. Reliance on product information approved by

another NRAReliance on post-authorization safety study results……….This level of reliance requires that the products concerned are the same or are sufficiently similar in terms of composition, indications, conditions of use, etc.


Reliance for product and MAH information

• Under Article 57 of EU pharmaceutical legislation:- manufacturers submit and update information on authorized medicines to EMA.

• Regulators of all EU Member States can access the information;• This helps regulators to:

- Identify the company’s qualified person for pharmacovigilance (QPPV); - Submit coordinated enquiries to companies;- Organize joint PV inspections etc.

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Reliance in the context of COVID19 vaccines accessed through WHO PQ process

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• A group of countries, or a regional economic community (REC) could identify a country • to join and represent the region/REC in the WHO PQ assessment process;• to review the Risk Management Plans and PV activities in the dossiers; • to ensure local relevance of the PV plans (for their country/region).

• This would ensure that • while there is broad reliance on WHO PQ decision

• the PQ decision is appropriately adapted to the local context

Global resources exist. But national ownership and action are imperativePQ, Vigibase allow us to assess globally, and act locally


Workshop 4: Panel Discussion (Q1)

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What can be done to improve data collection and information sharing within a country? (Perspective 1)

Please discuss the roles and responsibilities of the National Regulatory Authority (NRA) and Expanded Programme on Immunization (EPI) in collecting safety data and for information sharing.



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What can be done to improve data collection and information sharing within a country? (Perspective 2)

Please discuss the role and responsibilities of the marketing authorization holder in collecting safety data and sharing the post-authorization safety findings.



Discuss the role of technology for data collection and data sharing.• How can technology assist the process of data collection and data sharing? • For LMICs, what has helped with uptake of technology relevant for PV and

what have been the challenges?

The AU 3S pilot project with participation of four countries in Africa was launched to monitor safety of COVID-19 vaccines.• What challenges in PV are being addressed through the AU-3S pilot project? • What are the gains and lessons learned so far?• How will this regional network be sustained in the long term and linked to

the global network?

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Discuss the role of reliance in pharmacovigilance –specifically:

• When is it appropriate to apply the principles of reliance at the regional level?

• What aspects of pharmacovigilance must be executed at the country level (i.e., cannot rely on others)?

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The number of adverse event reports for COVID-19 vaccines in the global database has now reached two million. UMC analyzes vaccine data with a global perspective.

• How can the global database be utilized to address safety questions that may be important at the regional or country level?

The utility and value of a global database depends on all countries submitting data into the system. Regarding submission of data to the UMC database:

• What challenges have countries faced in submitting adverse event reports to UMC?

• How has UMC addressed the challenges? What solutions have improved the process?

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Robust pharmacovigilance requires connection between country-, regional-, and global systems to share data and information, and have timely communication. Using COVID-19 as an example:• What were the challenges when it came to information flow

and timely exchange of data or information related to COVID-19 vaccine safety?

• As vaccination programs expand and additional vaccines are launched for use in different settings, what should countries and regions focus on to ensure adequate safety monitoring?

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Workshop 4: Summary

• Safety monitoring throughout product life-cycle essential for assuring continued safety and effectiveness of vaccines and other medical products‒ Strong PV systems provide assurance that safety remains a priority‒ Builds public trust and confidence in use of the product

• Benefits of implementing best practices in regulatory reliance and work sharing‒ Rely on work of trusted partners where possible; focus limited resources on activities that

must be done at local level‒ Improve regulatory efficiencies; avoid duplication; optimize use of resources‒ Reliance can be practiced by all NRAs but especially important for small or less well-

resourced countries with limited regulatory capacity‒ By pooling expertise and resources, can establish formidable regional and global capacity;

increased collaboration can result in efficiency and greater impact

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Workshop 4: Summary (con’t)

• Pharmacovigilance is a shared responsibility

‒ Role for many entities including marketing authorization holder (MAH), National Regulatory Authority (NRA), Expanded Programme on Immunization (EPI), national, regional, global networks for data collection and analysis & others

‒ Requires effective coordination, collaboration, communication and established linkages between national-, regional-, and global levels

• A few fundamental principles to consider‒ Standardization at global level is important (e.g., forms, definitions, methods, systems,

technologies etc.) -- allows easier exchange of information and pooling of data for analysis‒ Data quality is a significant issue -- need good quality data to allow meaningful analysis‒ Global databases can be used for analysis of AEFIs from global perspective and for regional or local

populations; however, regional or local analyses are possible only if countries submit AEFI data into the global (e.g., UMC) database

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Workshop 4: Summary (con’t)

Pharmacovigilance for COVID-19 vaccines

• Timeliness critical for analyzing AEFI reports and addressing potential signals• Pandemic has required regulators and other stakeholders to ‘think outside the box’

‒ Develop tools, methods, infrastructures‒ Build alliances and communication channels‒ Exercise regulatory agility based on sound scientific rationale

• Significant international collaboration among regulators with emphasis on need to share data, AEFI assessment findings and other information in a timely manner‒ Collaboration key to timely analysis and communication of potential safety signals;

leverage findings for regulatory decision-making in all regions of the world‒ ‘Assess globally, Act locally’

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THANK YOU

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who efforts to promote reliance

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