Recognizing and Reporting Adverse

Events from US Non-Interventional

Programs
Training for Non-Interventional Program Vendors
Version 2.0

Product Development Safety Risk

Management (PDS); PVOI Training

Learning Objectives

After completing this course, you will be able to:

Define Adverse Event (AE) and Special Situation Reports that
also need to
be collected and reported.
Describe the AE reporting requirements for non-interventional
programs.
Describe your roles and responsibilities for reporting AE
information to the US Pharmacovigilance (USPV) group at
Genentech.

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Adverse Event (AE) Company

Definition
To report adverse events, you must first
be able to recognize them.
An Adverse Event (AE) is any untoward
medical occurrence in a patient or
clinical investigation subject
administered a pharmaceutical drug
and which does not necessarily
have a causal relationship with this
treatment.
An Adverse Event (AE) can therefore be
any unfavorable and unintended sign
NOTE: If a patient dies this is
(including an abnormal laboratory
reportable regardless of
finding), symptom, or disease
causality.
temporally associated with the use of a
medicinal (investigational) product,
whether or not related to the medicinal
(investigational)
Recognizing and Reporting product.
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Adverse Events and Reportable Event

Categories
Definitions and Examples

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AE Reporting: Guideline

All events should be reported

regardless of:
Seriousness.
Whether or not the event was
already reported to a health
authority.
Whether or not the event is
described in product labeling.

NOTE: If a patient dies this is

reportable regardless of causality.

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Special Situation Report Definitions

(cont.)
Special Situation
Event

Overdose (with or
without AE)

Medication Error
(with or
without AE)

Misuse (with or
without AE)

Definitions

This refers to the administration of a quantity of a

medicinal product given per administration or
cumulatively, which is above the maximum
recommended dose according to the authorized product
information. Clinical judgment should always be applied.
Medication error refers to any unintentional error in
the prescribing, dispensing, or administration of a
medicinal product while in the control of the healthcare
professional, patient or consumer.
This relates to situations where the medicinal product is
intentionally and inappropriately used not in
accordance with the authorized product information.

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Special Situation Report Definitions

(cont.)
Special Situation Event
Lack of therapeutic
efficacy (with or
without AE)

Abuse (with or
without AE)

Occupational Exposure
(with or without AE)

Definition

Lack of therapeutic efficacy with or without an AE

This corresponds to the persistent or sporadic,

intentional excessive use of a medicinal product,
which is accompanied by harmful physical or
psychological effects.
This refers to the exposure to a medicinal product
as a result of ones professional or non-professional
occupation.

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Special Situation Report Definitions

Special
Situation Event

Definition
A pregnancy case where the fetus may have been
exposed to one or more Genentech drugs either:

Pregnancy (with
or without AE)

Through maternal exposure:a female (mother) took

a Genentech product before conception or during
pregnancy (i.e.,drug exposure during pregnancy).
Through paternal exposure: a male (father) took a
Genentech product before conception (i.e., pregnancy
of partner).
Note: Any data related to product use during
pregnancy is reportable.

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Special Situation Report Definitions

(cont.)
Special
Situation Event

Breastfeeding
(with or
without AE)

Definition

Report any occurrence of an infant exposed to a

Genentech product via breastfeeding.
This includes a patient who had treatment with the
Genentech product in the past, or is current receiving
Genentech product and is breastfeeding an infant.

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Special Situation Report Definitions

(cont.)
Special Situation
Event

Pediatric
Population

Suspected
Transmission of
Infectious Agents
via a Medicinal
Product (STIAMP)

Definition
Data related to product usage in
pediatric population

Data related to suspected transmission via a medicinal

product of an infectious agent

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Special Situation Report Definitions

(cont.)
Special Situation
Event

Definition

Suspected Adverse
Reaction related to
Quality Defect or
Falsified Medicinal
Products (whether
suspected or
confirmed)

Suspected Adverse Reaction related to quality defect

or falsified medicinal products (i.e., confirmed
counterfeit or suspected counterfeit)

Lawsuits

Reports from class action lawsuits

Off-label (with AEs)

This relates to situations where the medicinal product

is intentionally used for a medical purpose not in
accordance with the authorized product information.

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AE Recognition Reminders

DO
Recognize potential AEs and Special Situation reports.
Report any potential AEs occurring with any Genentech products.
Report potential AE information within 1 business day.

Note: Your reporting obligation does not require you to determine if the
event is related to the Genentech product. Your obligation is only to
recognize potentially reportable information, gather appropriate data,
and report that data to Genentech.

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Global Adverse Event Reporting

The Reporting Process

What to Report (1 of 5)

When you recognize that the reporter has

mentioned AE information, you must capture the
information and report within 1 business day.
Four minimum elements comprise an Adverse Event (AE)
report.
P R E P is a pneumonic devise you could use to
remember
these elements:
Patient
Reporter
Event
Product
Note:
If you do not have the minimum elements, you should
still report
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What to Report (2 of 5)
A Patient
When completing a report, provide a patient identifier (such as the patient's
initials, age gender, date of birth, or age group [adult, child, infant]).
If unavailable, the patient identifier should be 'patient'.

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What to Report (3 of 5)
An Identifiable Reporter
When completing a report, provide the name and all available contact
information of the person reporting the event (such as phone, fax, address, and
email).
Note: If the reporter does not provide contact information or prefers to remain
anonymous, you should still send the report indicating that the reporter wants to
remain anonymous.

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What to Report (4 of 5)
An Adverse Event
When reporting adverse event information, include a description of the event in
the words of the reporter.
Do not interpret what you think the reporter meant. State exactly what they
said verbatim.

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What to Report (5 of 5)
A Suspect Roche Product or Generic Drug
When completing a report, provide the name of the Roche drug.
Even if only given a generic name of a drug, you are still responsible for
reporting this until we receive confirmation that it is our product.

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The Reporting Process - Adverse Event

Form
Unless otherwise specified for your
program (e.g., call centers utilizing
the warm transfer process)
Provide all available information.
Forward to Genentech within 1
business day of becoming aware of
the event.
Forward available information even
if there is no identifiable patient.

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Reconciliation

Reconciliation

Definition

The process of verifying that all AEs reported by the vendor

match those received by Roche/Genentech.

Requirements

Vendor
Obligations

Reconciliation for US and global NIPs must be performed

by the vendor and USPV.
Reconciliation should take place at least annually or at
the end of the program (whichever comes first).
The reconciliation interval must be agreed upon prior to
program start.
Reconciliation is a requirement for all Roche programs.

Vendors must keep a record of all AEs sent to the USPV so

that reconciliation can be performed as required.

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Global Adverse Event Reporting AE

Reconciliation Form (Appendix 2)

Complete all requested information as applicable and provide to USPV at preagreed interval.
The information will be checked against the individual AEs collected and
forwarded to USPV to ensure all AEs reported are accounted for.
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Non-Interventional Programs Vendor

Obligations

Training

Ensure that all employees involved in

the programs on behalf of Genentech
receive annual training in recognizing
and
reporting AEs.

Reporting Timeline

Record and report to Genentech LSR

any reportable AEs within 1 business
day.

Reconciliation

Keep a record of all AEs sent to

Genentech LSR so that reconciliation
can be performed as required.
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Appendices

Appendices 1-3: Forms

Appendix 1:
AE Form (gcp_for003008)

Appendix 2:
Global AE Reconciliation Form

Appendix 3:
Individual Training Form

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Appendix 4: Frequently Asked

Questions (FAQ)
Topic

Disease
Progression

Question

Answer

Do we have to report disease

progression in the oncology
setting?

Reports of disease progression may be exempt from reporting

to the Local Safety function as individual ICSRs in real time if
this is specified in the program design as approved by
PV Approver. However, in the case of a summary line listing
of all reports of disease progression, they must be forwarded
at the conclusion of a program.
Reports of inadequate response may be exempt from
reporting to the Local Safety function as individual ICSRs in
real time if this is specified in the program design as
approved by PV Approver. However, in the case of a
summary line listing of all reports of disease progression, they
must be forwarded at the conclusion of a program.

Lack of Effect

Do we have to report lack of effect

in the oncology setting?

Competitor
Products

Do we have to report AEs of

competitor products?

NO - There is no regulatory requirement to report AEs for

competitor products in market research projects, even if there
are questions systematically asking competitor about
competitor products.

Adverse Events

Do we have to report to USPV

when no AEs are mentioned during
the market research project?

NO - You are not required to send notification to the USPV

when there are no AEs reported for a market research project
in a country.

Death

Should we forward reports of death

to USPV?

YES Although death is technically an outcome and not an

event, reports of death should always be forwarded to USPV
for further investigation.

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Appendix 5: Genentech Product List

for
AE Reporting
BioOncology

Immunology &
Ophthalmology

Metabolism &
Primary Care

Virology &
Specialty Care

Other Products

Avastin (bevacizumab)
Erivedge (vismodegib)
capsule
Herceptin
(Trastuzumab)
Perjeta (pertuzumab)
Rituxan (Rituximab)
Tarceva (erlotinib)
Xeloda (capecitabine)
ZELBORAF
(vemurafenib)

ACTEMRA
(tocilizumab)
Lucentis (ranibizumab
injection)
Rituxan (Rituximab)
Xolair (Omalizumab)
for Subcutaneous Use

Activase (Alteplase)
Boniva (ibandronate
sodium)
Cathflo Activase
(Alteplase)
Nutropin [somatropin
(rDNA origin) for
injection]
Nutropin AQ
[somatropin (rDNA
origin) injection]
Nutropin AQ NuSpin
[somatropin (rDNA
origin) injection]
Nutropin AQ Pen for us
e with Nutropin AQ Pen
Cartridge
[somatropin (rDNA
origin) injection]
TNKase (Tenecteplase)

CellCept
(mycophenolate mofetil)
Pegasys
(peginterferon alfa-2a)
Pulmozyme (dornase
alfa)
Tamiflu (oseltamivir
phosphate)
Valcyte (valganciclovir
HCL)

Anaprox (naproxen
sodium)
Cytovene (ganciclovir)
EC-Naprosyn
(naproxen)
Fuzeon (enfuvirtide)
Invirase (saquinavir
mesylate)
Klonopin
(clonazepam)
Kytril (granisetron
HCL)
Naprosyn (naproxen)
Rocephin (ceftriaxone)
Roferon-A (interferon
alfa-2a)
Romazicon
(flumazenil)
Valium (diazepam)
Xenical (orlistat)
Zenapax (daclizumab)

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Appendix 6: Contact Information for

USPV
Topic

Contact

Info

AE Reports

USPV Generic Email

Address

Reconciliation

USPV Reconciliation
Team

ctv_drugsafety@gene.com

Questions reporting
and reconciliation
processes

USPV NIP Team

nip_drugsafety@gene.com

Questions regarding
training materials and
documentation

PD Safety Risk
Management (PDS)
Training Team

pvt-gira-d@gene.com

onc_drug.safety@gene.com

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