SAFETY DATA EXCHANGE AGREEMENTS

SUBMITTED TO: Dr. Veepra Singh

SUBMITTED BY: Kunal Pariwal
 Table of Content

1. Definition of Agreement
2. Pharmacovigilance agreement
2.1 Aspect of Pharmacovigilance agreement
2.1.a. Scope
2.1.b. Aggregrate Reports
2.1.c. Product Information
2.2 Types of Pharmacovigilance agreements
2.2.a. Distributor agreement
2.2.b. Purchase agreement
2.2.c. Quality agreement
2.2.d. Safety data exchange agreement
3. Introduction of safety data exchange agreement
4. What does safety data agreement contain?
5. Who set up safety data exchange agreement?
6. Key players in safety data exchange agreement
7. Safety data sheet template
1. Definition of agreement: - A concord of understanding and intention, between two or more
parties, with respect to the effect upon their relative rights and duties, of certain past or future facts
or performances. The act of two or more persons, who unite in expressing a mutual and common
purpose, with the view of altering their rights and obligations.

2. Pharmacovigilance agreement(PVAs): - An agreement entered into by the Parties to set

forth the protocols and procedures for reporting adverse events and complying with reporting
requirements set forth by Regulatory Authorities.

Common reasons for PVAs are:

 To enable each party to be compliant with legal requirements.
 It also gives the scope for MAHs (Market Authorization Holder) to cover additional SAFETY
DATA INFORMATION.

 For the exchange of cases.

2.1 Aspect of PVAs: -

1) SCOPE
The scope is key to set the scene for the rest of the agreement. Within the scope, both the
products and territories covered by the PVA (and by which party) can be defined. However, it can
be more straightforward to have this information detailed into the agreement if the products/
territories covered are extensive and subject to frequent change. Another area which could be
included in the scope, is to define the role of each party. An example might be confirming which
party is the MAH and which is the distributor? Are the parties both MAHs but in different
territories? Or perhaps, is the distributor also the local MAH? This information will aid the
understanding of the reader when considering the requirements of each party. Another item for
inclusion within this section could also be the language that information should be exchanged.
This is an important point, as the partner companies might have offices in countries that speak
different languages. Therefore, a common language needs to be selected. The party that will
transmit the information to the regulators and the language enforced by the regulators in a
territory should also be considered.
2. EXCHANGE OF CASES: -Collecting, processing and managing individual case safety
reports (ICSRs) is a critical pharmacovigilance process. It is essential therefore, for this to
be included in the PVA.
 Firstly, the type of cases collected by each partner needs to be defined (e.g. post-
marketing, clinical studies, registries, market research), as well as whether both
serious and non-serious cases are required to be exchanged.
Similarly, it is necessary to define which party is responsible in which territory.
Equally, special situations, and the expectations for collecting cases associated
with these instances, should be clearly defined. All of the above is important to
ensure no sources of safety data are missed and conversely that there is not a
duplication of case submissions.
 Another crucial component is to define the timeline for exchange of cases,
including a definition of day zero to ensure there is no misunderstanding
between partners. This being defined in the PVA, along with how many working
or calendar days the partner has to forward the cases to the MAH, ought
to minimize late submission of cases to regulatory authorities. Including this case
exchange information, should ensure that each company will receive the reports
it needs to meet regulatory authority requirements.

3. AGGREGATE REPORTS: -
scheduling, preparing and submitting periodic safety update reports (PSURs) is another
critical pharmacovigilance process. Therefore, this is another important aspect of any
PVA. One reason for this, is the requirement to submit aggregate reports to the regulatory
authorities within certain timeframes.

 Additionally, aggregate reports are thoroughly assessed by the authorities and a

lack of safety data from partners could be detected, triggering a subsequent
authority inspection. As part of the PVA section for aggregate reports, the
responsibilities for the preparation of the report must be defined; who will write
the report, what are the responsibilities of the supporting party.
 This is important to ensure the report represents the global availability of safety
data. Finally, the party responsible for submission (and prior electronic common
technical document (eCTD) formatting if required) should be defined. Careful
 documentation of these timelines will ensure timely reporting to the regulatory
authorities.

4. PRODUCT INFORMATION
 Communicating changes in risk: benefit to healthcare professionals (HCPs) and
patients is another key process in pharmacovigilance1. Awareness of the risks
associated with products is fundamental to patient safety. One way that this is
accomplished, is through providing up to date product information (summary of
product characteristics (SmPC), patient leaflet (PL) and packaging).
 Within this section of the PVA, it should be specified whether there will be a
company core data sheet, and who will maintain it, along with who will be
responsible for updating local SmPCs.
 Another important aspect is to confirm who will be responsible for
communicating with the regulatory authorities and how the updates will be
shared (both within the partner companies and with the public/ HCPs). If the
above is not sufficiently defined, then even if the updates were completed, the
information might not reach patients and HCPs in all territories where the
product is marketed.
 In addition, if the update is driven by the regulatory authority contacting one of
the parties, timelines for notifying the other party should be defined, as well as a
clause to manage any disputes regarding the response to the regulatory
authority.

2.2 Types of pharmacovigilance agreement:-

Distributor agreement:- A distributor agreement, also known as a distribution
agreement, is a contract between channel partners that stipulates the responsibilities of
both parties. The agreement is usually between a manufacturer or vendor and
a distributor but, in some cases, may involve two distributors or a distributor and some
other channel entity.

Purchase agreement: - Legal document recording the final understanding of a

purchaser who agrees to buy and a seller who agrees to sell the specified item(s) under
stated terms and conditions.
 Quality agreement: - A Quality Agreement is a document that defines both
specific quality parameters for a project and which party is responsible for the
execution of those parameters.

Safety Data Exchange Agreement: - Safety Data Exchange Agreements are legal
written contracts ensuring that all safety data regarding a licensed product makes its

way quickly and reliably back to the marketing authorization holder so that they may

fulfil their legal obligations to aggregate safety data and to submit safety reports in a

timely manner .

Introduction of Safety Data Exchange Agreement: - Safety departments are

frequently divided in 2 groups: -

 A case management group or operations group –

-Collect safety reports.
-Feeds report into database.
-Provides aggregate listing or tables.

 A safety evaluation group (risk group)-

-Performs clinical review or individual reports.
-Perform signal detection and evaluation.
-Lead risk management activities.

For case management: - Varied professional backgrounds (language to life science).

For safety evaluation: - mix of professional+medical backgrounds.

4. What does SDEAs contain?

SDEA should allow for rapid exchange of all serious adverse events (SAEs) for
determination of whether expedited reporting is necessary. This applies to both clinical
trial and post-marketing situations as well as any special programs such as patient support
programs. Some companies want just MedWatch or CIOMS form for each case; others
want the source documents also.
All SAEs should be exchanged in less than 15 calendar days to allow an expedited report
to be submitted within the 15-day requirement in most jurisdictions.
 Deaths and life-threatening SAEs should be exchanged in less than 7 calendar days.
Non-serious AEs should be exchanged as appropriate. In clinical trials this may be only at
the end of the study (though some companies want them more frequently for signaling).
For marketed products, particularly if some non-serious cases must be submitted within
90 days in the EU, this may be monthly or even more frequently.
All follow-up data must also be exchanged.
Aggregate reports (Annual Safety Reports, DSURs, PSURs/PBRERs, PADERs, etc.) should
also be exchanged usually within a week or so of their completion or submission. Timing
should be a function of the regulatory reporting requirements.
Other: Some companies exchange signals, regulatory correspondence regarding safety
matters, IRB/EC safety comments and requirements, Data Monitoring Committee
findings, market withdrawals for safety issues, new health authority decisions or
requirements, preclinical safety issues etc.
The agreements should have some provision to ensure that the provisions in the
document are really being done correctly. This could be periodic audits, reconciliations,
meetings or teleconferences etc.
.
5. Who set up SDEAs?
Since the SDEA is a written agreement which is binding between the partners, the Legal
Department should review and approve the document. Sometimes it is included in a
master (services) contract or agreement. Sometimes it is handled as a separate document
between the drug safety groups.
Even worse is when the agreement is signed, and the safety department is not informed
about the new partner or new drug.

6. Key players in SDEAs: -

 The key players in setting up SDEAs are the lawyers. All contracts are (or certainly
should be) approved by the Legal Department. In small companies these issues are
usually not a problem as the staff all knows each other and cooperates well. In larger
companies with lawyers sitting in offices on two or more continents and with many
attorneys handling different matters it may be hard to identify the person handling
drug safety matters.

 The other key groups involved in SDEAs are the business development people. Again,
in small companies these individuals may be easily identified and educated on the PV
and safety requirements for business deals. In large companies this can be harder,
 particularly if the general manager or head of each subsidiary has the power to make
deals without necessarily telling the home office.

7. Safety data sheet template: -It covers the following areas-

1. Format of the SDEA.
2. Reporting timeframes, notification and responsibilities.
3. Analysis of safety data.
4. Notification of ongoing and planned clinical trials.
5. Notification of any known safety issues.
6. Process by which adverse events are transferred between two companies.
7. Lack of efficacy.
8. Assessment of expectedness and causality.
9. Frequency and scope of literature searches.
10. Overdose, misuse, abuse and pregnancy.
11. Which versions of MedDRA are used.
12. Responsibilities for reporting to ethics committees/IRBs and investigators.
13. How blinded reports are handled, under which circumstances the blind
reports will be broken.
THANK YOU