Presentation of how DADA PVD can assist you in your pharmacovigilance requirements for human or veterinary medicinal products

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Pharmacovigilance support
DADA Consultancy B.V.
2021
DADA Consultancy B.V.

2. 2
DADA Consultancy B.V.
Our aim is to provide state-of-the-art regulatory affairs and pharmacovigilance
services and to establish long-term partnerships with our international clients.
DADA Consultancy is a premier and independent consulting agency, based in
Nijmegen, The Netherlands, since 1984.
We focus on our customers and connect you to our experienced staff, who
have a scientific (biomedical) background and provide quality services in their
field of expertise.
2021
DADA Consultancy B.V.

3. 3
DADA Consultancy B.V.
DADA offers a full range of tailor-made developmental and international
regulatory affairs and pharmacovigilance services
At DADA we have a passion for detail while maintaining focus on our client’s
ultimate goal.
We have extensive experience in communicating with Health Authorities.
Covering all European Member States and related regulated markets.
Long-lasting partnerships with external experts to provide optimal support.
2021
DADA Consultancy B.V.

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Pharmacovigilance Activities
• Purpose of PV activities:
• to enable detection of new safety signals
• to enable monitoring of already detected safety issues
• to facilitate the preparation of reports to authorities
Ultimate goal:
Provide competent authorities with an up-to-date, objective overview of
the safety profile of a medicinal product.
• In this way, ensure that the product’s marketing authorization can be
maintained through early detection and proper management of safety
issues.
2021
DADA Consultancy B.V.

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Regulations and Guidelines
• The legal basis for PV:
– Council Directive 2001/83/EC (National/MRP, amended by Directive
2004/27/EC, recently by 2010/84), 2001/82/EC (replaced by Regulation
2019/6)
– Regulation 726/2004 (centralized, replaced Reg. 2309/93, recently
amended by 1235/2010)
• Guidelines:
– (Notice To Applicants Volume 9(A))
– Superseded by Good Vigilance Practices
– Volume 9B (To be superseded by Veterinary Good Pharmacovigilance
Practices)
– International Conference on Harmonization (ICH: E2A, E2B, E2B M, E2C,
E2D, M1)
– Council for International Organizations of Medical Sciences (CIOMS) I to X
– CMDh, CHMP, CVMP, HMPC, PhVWP(-V), PRAC etc.
2021
DADA Consultancy B.V.

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Pharmacovigilance System
• A pharmacovigilance system is defined as a system used by an organisation
to fulfill its legal tasks and responsibilities in relation to pharmacovigilance
and designed to monitor the safety of authorised medicinal products and
detect any change to their risk-benefit balance;
• complying with the legal requirements for pharmacovigilance tasks and
responsibilities;
• preventing harm from adverse reactions in humans arising from the use of
authorised medicinal products within or outside the terms of marketing
authorisation or from occupational exposure;
• promoting the safe and effective use of medicinal products, in particular
through providing timely information about the safety of medicinal products
to patients, healthcare professionals and the public; and
• contributing to the protection of patients’ and public health.
2021
DADA Consultancy B.V.

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QPPV
The Qualified Person for Pharmacovigilance (QPPV)
Directive 2001/83/EC (Title IX, Article 103): “The marketing authorization holder
shall have permanently and continuously at his disposal an appropriately
qualified person responsible for pharmacovigilance.”
Responsibilities (GVP Module I – PV systems and their QMSs):
• establish and maintain the Marketing Authorisation Holder’s
pharmacovigilance system;
• have an overview of the safety profiles and any emerging safety
concerns in relation to the medicinal products for which the
Marketing Authorisation Holder holds authorisations OR has applied
for an authorisation;
• act as a single contact point for the Competent Authorities on a 24-
hour basis;
2021
DADA Consultancy B.V.

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Pharmacovigilance Support
EU Qualified Person for Pharmacovigilance (QPPV)
– Within the EU, each Marketing Authorisation Holder should ensure that
they have a single point of contact, with a deputy, that is available 24/7
to act as the Qualified Person for Pharmacovigilance (QPPV).
– The QPPV must be permanently and continuously at the disposal of the
MAH and must be experienced in all aspects of pharmacovigilance. The
QPPV must reside and operate within the EEA, and a deputy may be
needed as well.
– In several countries, including the Netherlands, a local QPPV is required
or may be required depending on certain risk management activities in
the territory.
2021
DADA Consultancy B.V.

9. 9
Approach
DADA:
SOP # SOP title Topics Version Effective date Next review date WI # WI title Topics Version Effective date Next review date
WI-000 Pharmacovigilance
Glossary
Pharmacovigilance terms
glossary
14.0 30/Dec/20 Dec/23
SOP-001 Good
Pharmacovigilance
Practice
Create, update and
archive procedures;
training records, job
descriptions and other
documentation
6.0 30/Mar/18 Mar/21 WI-001 Pharmacovigilance
documentation
Record keeping, archiving 22.0 03/Apr/20 Apr/23
WI-023 Training Training 6.0 06/Apr/20 Apr/23
SOP-002 Collection and
processing of
ICSRs and
XEVPRMs
9.0 04/Oct/19 Oct/22 WI-002 Individual Case Safety
Reports Data entry and
Processing
Detection of duplicate
reports, definition of
relevant safety information
to include product defects
resulting in safety issues,
define reports from
different sources
24.0 09/Oct/20 Oct/23
WI-003 Individual Case Safety
Reports submission
Expedited reporting to
EVHUMAN and FDA, use of
EVWEB for electronic
submission, what to do in
case of system failure
(where to find paper forms
and how to use these)
24.0 29/Jan/21 Jan/24
WI-004 Individual Case Safety
Reports follow-up
Requesting and processing
of FU info
14.0 28/Feb/20 Feb/23
WI-005 Literature screening For cases and PSUR
section 11 information
19.0 30/Dec/20 Dec/23
WI-019 Management of the
XEVMPD database
Reporting of XEVPRMs, use
of EVWEB
10.0 31/Mar/20 Mar/23
WI-021 PV database
configuration
Configuration of the PV247
database for administrators
7.0 20/Jan/20 Jan/23
WI-024 Handling of medical
information
Handling of medical
information
1.0 23/May/19 May/22
WI-026 Clinical Safety Data
Management
PV activities throught the
duration of a clinical study
2.0 14/Jul/20 Jul/23
WI-027 Veterinary ICSR
management
ICSR processing, ICSR
submission
1.0 20/Jan/20 Jan/23
SOP-003 Risk Assessment Assessing safety
through risk evaluation
9.0 30/Nov/18 Nov/21 WI-006 Signal management Procedures for signal
evaluation and subsequent
management
9.0 30/Jun/20 Jun/23
WI-007 RMP Content of RMP, time lines 12.0 16/Oct/20 Oct/23
WI-008 Signal detection Evaluation, communication 12.0 02/Jun/20 Jun/23
WI-022 Post authorisation
safety study
Conducting a PASS, writing
a study protocol, abstract
and final
study report of a post-
authorisation safety study
(PASS) and the
communication of study
information to the Agency
and the national
competent authorities
3.0 28/Feb/20 Feb/23
WI-025 Health and Safety
Assessments
Review safety associated
with product quality defects
1.0 30/Dec/20 Dec-23
SOP-004 Urgent Safety
Information
Crisis management;
role of QPPV
7.0 11/Oct/18 Oct/21 WI-009 Communication with
Competent Authorities
Timelines, methods of
communication, how to
process urgent safety
restrictions and safety
variations
6.0 25/Mar/21 Mar/24
WI-010 Commitment tracking Processing of EPARs,list
with commitments per
product
6.0 31/May/18 May/21
SOP-005 Periodic Safety
Reports
Preparation of
periodic safety
(update) reports
9.0 10/Apr/20 Apr/23 WI-011 Periodic Safety Report Content of PSUR, timelines 14.0 07/Apr/20 Apr/23
WI-013 Developmental Safety
Update Reports
Content of DSUR, time
lines
7.0 13/Jul/18 Jul/21
SOP-006 Contractual
agreements
Procedure on how to
engage in such
agreements
7.0 15/Mar/21 Mar/24 WI-014 Contractual agreements Checklist, scenarios,
templates
9.0 06/Apr/20 Apr/23
SOP-007 Quality Control Ongoing and periodic
quality control/audits
9.0 07/Apr/20 Apr/23 WI-015 Quality Control Monitor performance by
QC steps and track issues
21.0 03/Apr/20 Apr/23
WI-016 Audits Internal audits, external
audits; when, by whom
12.0 09/Apr/20 Apr/23
WI-017 Business continuity Back up procedures QPPV,
business continuity
11.0 26/Jun/20 Jun/23
WI-018 Pharmacovigilance
System Master File
Writing and maintenance
of clients PSMF
10.0 13/Apr/20 Apr/23
SOP-008 Medical devices Device legislation and
requirements
4.0 06/Nov/20 Nov-23 WI-020 Medical devices
processing and reporting
Processing and reporting of
adverse events and
incidents following medical
device use
4.0 06/Nov/20 Nov-23
2021
DADA Consultancy B.V.

10. 10
Approach
DADA:
2021
DADA Consultancy B.V.

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Interaction PV – Medical /
Quality
• Triage of received information
AE
Accidental drug
intake by child
MI
Does she need
medical
treatment?
PQC
Child-proof
container
opened by child
My 2-year-old
daughter just took
two capsules from a
pot of pills that had a
child-proof container.
What should I do??
2021
DADA Consultancy B.V.

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PV Activities DADA
DADA PVD performs PV on the active substance, i.e. all relevant safety
information on the active substance is collected (independent of
marketing status) - reporting only on products for which ‘ownership’
of the client cannot be excluded.
Collecting, processing, assessing, forwarding and as necessary expedited
reporting of ICSRs (incl. SUSARs(=clinical serious unexpected ICSRs))
with a dedicated PV database
• from different origins: authorities - clinical studies - commercial partners - health care
professionals (HCPs) - patients / consumers - WW scientific literature - etc.
Electronic reporting in the EEA and US:
– Computer-to-computer talk via “.xml” files
– Compulsory since Nov 2005
– Exchange pre- and post-authorisation PV data between:
• EMA / FDA
• Competent Authorities
• Pharmaceutical Companies
– DADA has registered on behalf of client(s) with EVWEB environment for electronic
reporting of serious ICSRs
2021
DADA Consultancy B.V.

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Pharmacovigilance Activities
• Literature screening of local and worldwide published medical and
scientific literature for:
– Identification of ICSRs/case reports
– Identification of safety information from animal/clinical/post-marketing/
pharmacoepidemiological studies/safety reviews
• Ongoing Signal detection and evaluation
– Identification of underlying trends or safety issues that require notification of
Competent Authorities
– In close collaboration with RPPV and client management
• Periodic Safety/Risk Management Reports preparation
– Risk-benefit evaluation and summary of important identified safety information
– Presentation of identified signals
– Comprehensive review of all obtained safety information, set to patient exposure
estimates and assessed against established safety profile
– DADA will prepare and submit these reports on behalf of client per EU Union
Reference Dates, as applicable
2021
DADA Consultancy B.V.

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Pharmacovigilance Activities
• Writing of Addenda to the Clinical Overview for renewal procedures
• Referrals per PRAC and/or NCAs requiring answer documents
• Population and maintenance of the XEVMPD (eXtended EudraVigilance
Medicinal Product Dictionary, Article 57 Reg.)
• Responding to requests from Competent Authorities
• Set up PV Safety Data Exchange Agreements/Statements
to lay down the different responsibilities of
– distributors
– client
for the exchange of ICSRs, SUSARs, PSURs/DSURs, RMPs, line listings, opinions, etc.
including the time-frames for exchange
2021
DADA Consultancy B.V.

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• Pharmacovigilance Training
– from basic pharmacovigilance for general awareness, to dedicated training for
staff most likely to be informed of safety information
• SOP/WI writing
– assist in the preparation or review of standard operating procedures, up to the
level of
– assisting in the creation of an in-house pharmacovigilance system
• Audit of the client’s PV system, e.g. in preparation for inspections
• Pharmacovigilance Advice
• Manage Post-Authorisation Safety Study or other post-MA
commitments
Pharmacovigilance Activities
2021
DADA Consultancy B.V.

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Additional Activities DADA PVD
Medical inquiries:
– For clients who have contracted DADA PVD (either directly or through ADOH
Pharma Services) as local point of contact, any questions of a medical nature
(e.g. can I prescribe product X to patient Y, When will product Z be available
on the Dutch market?) will be processed by DADA
Product complaints:
– Similarly, being local point of contact means the DADA PV team processes
product complaints on behalf of their clients.
Local qualified person in NL and DE
2021
DADA Consultancy B.V.

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Tailormade approaches - 1
Client
Sales
R&D
QA
Website
Reception desk
Safety information
Distributor
Licensing
Co-marketing
- SDEAs
DADA
- QPPV, 24/7
availability
- signal detection
- literature screening
Competent authorities
PSURs
DSURs
ICSRs
RMPs
Contact person - RPPV
2021
DADA Consultancy B.V.

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Tailormade approaches - 3
Client’s PV dept
Sales
R&D
QA
Website
Reception desk
Safety information
Distributor
Licensing
Co-marketing
- SDEAs
- signal detection
- literature screening
Competent authorities
PSURs
DSURs
ICSRs
RMPs
- QPPV, 24/7 availability
-Local ICSR
tracking and
follow-up
- PSURs/
DSURs/RMPs/
Adds to CO
preparation
DADA
- Local literature
screening
- Local contact
point for
MI/PC/AE
2021
DADA Consultancy B.V.

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Tailormade approaches - 4
Client’s PV dept
Clients Clinical department(s)
Safety information
- SDEAs
- signal detection
- literature screening
Competent authorities
RMPs
- QPPV, 24/7 availability
- Data
monitoring
- Clinical case
processing
Client’s CRO
DADA
- Clinical Study
Report / DSUR
preparation
2021
DADA Consultancy B.V.

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Contact
• For pharmacovigilance questions, refer to:
– www.dada.nl
– +31(0)24 3730 309
– E-mail: pharmacovigilance@dada.nl
2021
DADA Consultancy B.V.