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i/ ~: ~ ·unded Non-lnterventional Registry Agreement with an
_':!u!1
O"'-..;t;;•1 ACADEMIC GROUP
U1CQ :"'
i'J~ ? This Agreement, dated 18 December day of 2017

REGARDING Protocol No.: ML40461 - Study on effect of antifibrotic drugs in different

subpopulations of patients with idiopathic pulmonary fibrosis - Analysis of data from the Czech
EMPIRE registry with protocol number IBA0866.

BETWEEN ROCHE s.r.o.

with its registered office at Sokolovská 685/ 136f, 186 00 Praha 8, Czech
Republic,
Registered in the commercial register maintained by the Municipal Court in
Prague, section C, file 13202
IO No.: 49617052, VAT IO: CZ49617052
(Hereinafter known as "ROCHE")

AND Masarykova Univerzita

with its registered office at Žerotínovo
nám. 9, 601 77 Brno, Czech Republic,
Faculty of Medicine
Located at: Kamenice 753/5, 625 00 Brno, Czech Republic
Represented by: prof. MUDr. Jiří Mayer, CSc., dean of the Faculty
Bank account: Komerční banka, a. s. , Account number 85636621 /0100
Masaryk University is a public university under the Act. 111/ 1998 Goll., On
universities, as amended
IO No.: 00216224, VAT IO: CZ00216224
(Hereinafter known as "GROUP")

Page 1 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

CONTENTS OF SECTIONS

1 CONDUCT OF THE REGISTRY ..................................................................................... 5

2 RESPONSIBILITIES .......................... „ ............................................... „ ... „ .. „ ... „ ............ 6
3 NIS SAFETY REPORTING OBLIGATIONS ..... „„ ..................„ .. „ ............................ „.„. 7
4 FINANCIAL SUPPORT .............. :......................................... .......................................... 7
5 LIABILITY AND INDEMNITY.......................................................................................... 8
6 INTELLECTUAL PROPERTY RIGHTS ........ „ ... „ ............. „ ... „„„ ........................... „ ... „. 9
7 CONFIDENTIALITY ........................................................................................................ 9
8 PUBLICATION AND PUBLICITY ....................................... „ ... „ ............................... „ .. 11
9 DATA DISCLOSURE ................................ „„„ .......... „„ ......................... „ ..................... 11
10 QUALITY ASSURANCE„ ............ „„ ...................................................................... „ ..... 11
11 TERM AND TERMINATION .......... „ .. „ ................................. „ .... „ ............. „.„ .. „ .......... 13
12 FORCE MAJEURE.„ .. „„„„ ............ „ ........... „„ ............... „ ............... „ ....... „„.„ .... „„.„„14
13 ENTIRE AGREEMENT ....................................................... „ .... „ .................................. 14
14 AMENDMENT............................................................................................................... 14
15 ASSIGNMENT AND SUBCONTRACTING ....................... „ .......................................... 14
16 GENERAL PROVISION„ ....... „ ....... „ .............................. „ ............................................ 14
17 APPLICABLE LAW AND JURISDICTION ................... „.„ ...................„ ...................... 15
ATTACHMENT 1 ......................................... . „ .... . . • ••• • • • ... . .••• „ „ . „ •• • ••• •• • • •....•••••• • • •.•• • • ••••••••• • • •• . „ .... 17
ATTACHMENT 2 .......... ...... „ .. . . . . ..•• ••• ••• . •.• • • •• • ••••• .. . .. . . . .. . ..••• . •... „ „ . . . . .. . . . . .. .••• • • • • ... . . . ......... ..• .. . ...• • . • 18
.............. ... .... ..... ........ „ .•. . „ ... . . . ..••••••• • • • •. „ „ . . . . • • ••• ••. ... ... • •. „ .. . „ . „ .... . • . . „ . • . . ....... 18
. ......................... ........ ..... ......................... „ . ... • .•••••••• • •.••• •. ....... . .......•. . •. . . . ....... 18
. „ • • •• . . • . „ . .. . • • ••• . • . . . . . ... . . • • . . . . . . . .. .. . . . .. • .• • • • . •• . . . .. .. . „ . „ •••••• • • .. • • • „ . „ . .. . . . .. „ . .. . . • . .. • • . . . . . 18
....................................... „ . ... ••• • • • •• • • • • • • . • •• •• • • •••• „ . .. . . . ..... ..... . . . . . .... .. .. . . . . . .. . .. „ „ .. 18
.. ......... „ „ . . ... . ••• . • . . . . ... . • .• • • . ........... . .... ... •.. . . „ „ . „ .. „ „ .. • •• • • • • • .. „ .... .... . . . . . . . . .•• ••• • • • • • 18
. ..... ... ...................... ............................. „ • . „ •••• • • • • • . .. . ... . • . . • „ „ •• • • • • • • . •. . . .. ..•• . . . . „ .. 18

...... ... ...................... ... „ . . .........•• • •.•• .. ••• . • . . . • .• • • •• • • • • . .••• . •• . • . . • •• • • • • •• • • •• • • •• • • • •.. . . . .. . . . 18

ATTACHMENT 3 .... ..... ..... „ . . . • •• • • •• •• . .. . .. .•. •• • ••••............ . •• • •••.. . . „ .......• • •• • • •• •••. . ... „ ..... „ .• • . • ..•••. „ . . .. . .. 19
ATTACHMENT 4 ......... ..... ........................ „ .••• • • • • .. . ... ... . ... .. . . . ... . . . ... . . . . . . . . . . ... . ... . . . . .. . .. . . . . . ... • • • • • •• • • • • . 20

BACKGROUND ......................... ~ ..................................................................................... 20

1. Definitions ......................................................................................................... 20
2. Single Case Management. ................... „ ... „ .••••••••••••••••••••••••••••••••••••• •••••...••••••••• 20
2.1 Collection of Single Case Reports „„„„.„ ........ „.„.„.„ ............ „„ ...... „„ ...... „.„ ....... „. 20
2.2 Tracking of Safety lnformation ........ „„.„„„ ...„ ... „.„„„ .... „„.„ ... „ ... „ ............. „„.„„„ .. 21
2.3 Exchange of Single Case Reports .... „.„„ „ „.„„.„ „ ... „„.„„„„„.„ .. „.„.„„.„„„.„.„„ .... 21
2.4 Case Transmission Verification of Single Case Reports „ ... „.„„„.„„„.„.„.„„„ ..... „ 21

Page 2 of 31
 an ACAD EMIC GROUP
Funde d Non-l nterve ntiona l Regis try Agree ment with
....................... 21
3. Repo rting to Regu lator y Auth oritie s ........................................
...................... 22
4. Quer ies ........................................................................................
.................... 22
5. Safet y Crisi s Mana geme nt ... „ ......... „ ..... „ .. „ ..... „ .... „ .. „ ..... „ ........
................... 22
6. Lang uage ........................................................................................
„ .. „„ ................. 22
7. Cont acts ...... „ ...........................................................................
„ .................... 23
8. Reco rds .. „ ........... „ ..................... „ ........ .... „ ..... „ ......... „ .... „„ .......
......... „ .. „ .......... 23
9. Com plian ce with pharm acov igila nce agree ment /audi t ........
.............. „ .......... 23
1O. Ame ndme nts ........................... „ ...... „ ......... „ .............. „ .. „ ..... „
„ ... „ ................... 23
11. Term and Term inatio n of SDEA „ ................ „ .................... „ ...
..... „ .................... 25
AP PEN DIX 1: Definitions ..... „„ .. „ ......... „ .... „ .... „ .. „ ..... „ .... „ ... „ .... „„„
........................................ 27
APPENDIX 2: Cont act Deta ils ................................................
„ ........ . „ ......... „ ... „ ... „ ... „ 29
APPENDIX 3: EMPIRE REGISTRY - CRF .„„ .. „ ... „ .......... „ ....
......... ......... ......... ...... ......... .............. ... 29
13th JULY 2016 .................... ......... .................. ..................
......... ......... .. ......... ......... ......... ........ 29
ADVERSE EVEN T ... .......... ..... ......... .................. ......... .........

Attac hmen ts:

Attac hmen t 1: Regis try Proto col versi on 1.5 valid from 1. 8. 2017
Attac hmen t 2: Sche dule of Paym ents
Attac hmen t 3: Budg et
Attac hmen t 4: Safet y Data Exch ange Agree ment

Page 3 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP
THIS AGREEMENT is made by and between the following Parties:

(1) ROCHE s.r.o., Sokolovská 685/136f, 186 00 Praha 8, Czech Republic, IO No.: 49617052,
VAT IO: CZ49617052 (hereinafter referred to as "ROCHE") ;

(2) Masarykova Univerzita, with its registered office at Žerotínovo nám. 9, 601 77 Brno,
Czech Republic, IO No.: 00216224, VAT IO: 00216224 (hereinafter referred to as
"GROUP").

WHEREAS:

(A) GROUP has already set-up a non-interventional primary data collection European registry
for IPF entitled EMPIRE (hereinafter the "Registry"). The up-to-date Registry protocol
version 1.5 is attached hereto as ATTACHMENT 1 (hereinafter the "Protocol").

GROUP shall assume the legal responsibility attached to the Sponsor capacity, as it results
from applicable laws, and from national laws and regulations, with respect to patients and
the Czech Republic health authorities for non-interventional studies carried out by GROUP.

GROUP agrees to grant ROCHE certain rights to statistical analysis data entered into the
Registry by Czech centres during the years 2017-2019 (hereinafter the "Data") and safety
data as provided for in SDEA enclosed hereto as Attachment 4.

(B) ROCHE wishes to support the Czech part of Registry and analyses of subsets of Data,
specifically Czech patients' Data. ROCHE shall therefore provide financial support to
GROUP pursuant the terms and provisions of this Agreement.

The financial support given by ROCHE to GROUP pursuant to this Agreement shall not be
exclusive. Accordingly, GROUP reserves the right to obtain additional financing from other
third parties.

Page 4 of 31
 GROUP
Funded Non-lnterventional Registry Agreement with an ACADEMIC

IT IS HEREBY AGREED THAT:

1 CONDUCT OF THE REGISTRY

in the Registry as
1.1 GROUP shall undertake and maintain or has undertaken and shall mainta
Protocol attached
the respective "Legal Sponsor" of the project as set down in the
(ATTACHMENT 1) hereto and incorporated by reference.

associated with the

1.2 GROUP is solely responsible for any legal and/or regulatory obligations
conduct of the Registry.
who participate
1.3 GROUP will ensure that all Health Care Professionals ("HCP(s)") and staff
by all applica ble terms of this
in the conduct of the Registry are informed of and abide
parts with all HCPs, who
Agreement. The GROUP is entitled to share this Agreement or its
comply with this
shall take part in fulfilling the obligations hereunder, in order to
requirement, with the exception of trade secrets as defined hereinafter.

1.4 The Registry shall be conducted by GROUP:

ln the event
1.4.1 in accordance with the Protocol and any amendments to the Protocol.
version to
the GROUP updates the Protocol, GROUP shall send this updated
, this
ROCHE. Upon receipt of the updated version of the Protocol by ROCHE
of the Protoco l and becom es an
updated protocol replaces the previous version
need to conclud e any additio nal
ATIACH MENT of this Agreement without the
written addendum to this Agreement.
vely the
1.4.2 in the participating HCP practices and academic centers (hereinafter collecti
"Centers") to be selected by GROUP.

specified in the
1.4.3 with Data collected I collated in accordance with the criteria
Protocol.
ble in the countries
1.4.4 in accordance with the requirements laici down by laws applica
where the Registry population and the Registr y are located and notably, if relevant
in the concerned country, in accordance with Good Pharm acoepidemiology
Guidelines,
Practices ("GPP"), EMA Good Pharmacovigilance Practices ("GVP")
and all applicable local regulations.

collection related to
1.5 Any changes to the Protocol that may affect processes and safety data
in particular but not
any ROCHE product under the scope of SDEA in ATTACHMENT 4,
RF_EN_AE Form"
limited to, changes to the current version of the "IBA0866_EMPIRE_C
. Should ROCH E not agree with the change,
shall require prior written consent of ROCHE
effectiv e upon receipt of notice of
ROCHE shall be entitled to terminate the Agreement
termination by GROUP.

to submit , once
1.6 During the time of duration of this Agreement, ROCHE reserves the right
the analysi s of Data
per year, to the Steering Committee relevant scientific questions for
g Comm ittee's
("Data Analysis") to be performed by GROUP and following the Steerin

Page 5 of 31
Funded Non-lntervent ional Registry Agreement with an ACADEMIC GROUP
approval. Should the Steering Committee approve Data Analysis, GROUP shall perform the
Data Analysis and provide results of the Data Analysis ("Results") to ROCHE.

2 RESPONSIBILITIES

2.1 GROUP shall:

2.1.1 be solely responsible for the Registry in accordance with Article 1 of this Agreement.

2.1.2 as GROUP will use health related data (hereinafter collectively called "Health Data")
for the Registry in the anohymized form, GROUP shall conduct the Registry and
provide Results in accordance with the applicable laws and regulations regarding
the use of such Health Data. GROUP herewith represents and warrants that the
donors of Health Data (hereinafter called "Health Data Donors") have given their
free and informed consent, as required in accordance with applicable local laws, for
the use and/or the further use of such Health Data in projects such as the Registry
hereunder, and that all requested authorizations, i.e. from the applicable Research
Ethics Committee and/or lnstitutional Review Board, have been given. GROUP
herewith represents and warrants that Results, which includes Health Data, will be
provided in an anonymized manner and that GROUP will not disclose or otherwise
make available to ROCHE any persona! data of Health Data Donors, or give access
to ROCHE to any code allowing identification of Health Data Donors. Further,
ROCHE herewith represents and warrants that it will not undertake any actions to
determine the personality or persona! data of Health Data Donors, or to get access
to any code allowing identification of the Health Data Donors.

2.1.3 define its own set of SOPs to be used for non-interventional studies.

2.1.4 be responsible for the Data management of the Registry, including the primary Data
collection of Czech patients at Czech centers (listed in Tab. 1 Participating centers
in the Czech Republic, EMPIRE Registry Protocol, ATTACHMENT 1) undertaken
with financial support of ROCHE under this agreement.

2.1.5 conclude separate site agreements with all Centers (including Czech centers) that
shall safeguard Roche's interests as provided hereunder.

2.1.6 comply with Safety Reporting obligations as detailed in Article 3.

2.1.7 set-up and maintain a Trial Master File (TMF) containing documents and written
communications essential to the management of the Registry. Ali documents to be
filed in the TMF must be clearly identifiable. The TMF must be kept in a secure
location for the duration of the Registry and archived after completion of the
Registry for a minimum of 15 years, and kept in an electronic form for a minimum of
15 yéars.

2.1.8 provide ROCHE with a copy of the Health Authorities and Ethics Committee
authorizations.

2.1.9 provide ROCHE with information on the progress of the Registry, on bi-annual
basis; including but not limited to project timelines.

2.1.1 O provide ROCHE with Results based on variables and scientific questions approved
by Steering Committee of the Registry in accordance with Art. 1.6 hereof. GROUP
shall provide ROCHE with references to statistical programs and outputs on a level

Page 6 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP
of detail sufficient to allow for subsequent research reproducibility and critical
assessment.
2.1.11 regularly update ROCHE in writing on the progress of Data Analyses as per art. 1.6
hereof.
2.1.12 allow ROCH E to review potential publications as set out in Article 8.

2.2 ROCHE shall:

2.2.1 have no obligations or responsibilities with respect to the conduct of the Registry.

2.2.2 review potential publications as set out in Article 8.

2.2.3 submit any safety queries related to Czech patients Data of the Registry collected at
Czech centers (listed in Tab. 1 Participating centres in the Czech Republic, Registry
Protocol, ATTACHMENT 1) with financial support of ROCHE under this agreement
on the respective GROUP safety query form to be provided by GROUP directly to
). A submission date and a
single ROCHE contact person must be indicated on the form.

3 NIS SAFETY REPORTING OBLIGATIONS

3.1 GROUP shall ensure that its staff, within one year prior to starting their work under this
Agreement, have completed a GVP training. GROUP agrees to provide ROCHE with an
according training certificate.

3.2 ROCHE will provide Group with training materials on the relevant GVP modules within six
months of signing this Agreement. The staff of GROUP are obliged to get acquainted with
these materials and this will be confirmed to ROCHE without undue delay. This procedure
will be repeated each year for the duration of this Agreement.
3.3 The Parties have agreed to document their. responsibilities and obligations with respect to
the procedures for collecting, processing, evaluating, reporting and exchanging safety
information related to primary Data collection of Czech patients at Czech centers (listed in
Tab. 1 Participating centers in the Czech Republic, Registry Protocol, ATTACHMENT 1)
financially supported the terms of this Agreement, in compliance with the applicable laws
and regulations pertaining to safety reporting and related activities in the Safety Data
Exchange Agreement (SDEA) enclosed as ATTACHMENT 4.
GROUP shall ensure that these obligations and corresponding timelines are communicated
to, and are complied with, by GROUP's staff and Subcontractors.
The reporting HCP or designee is responsible for collecting and reporting initial and follow-
up information for Individua! Gase Safety Reports (ICSRs) to GROUP. Reporting of
Adverse events will be performed by HCP in the registry interface thought an e-form. This
procedure will generate an e-mail in the form of an Adverse Event message sent to the
ROCHE email .

4 FINANCIAL SUPPORT
4.1 GROUP has provided a budget for the primary Data collection of Czech patients of the
Registry in Czech centres (listed in Registry Protocol, ATTACHMENT 1). A structured
financial budget with a quantification of fixed and variable costs at an annual level is given
in ATTACHMENT 3 of this Agreement. GROUP represents that the Budget is based on the
Page 7 of 3 1
 IC GROUP
istry Agreement with an ACADEM
Funded Non-lnterventional Reg own of all costs
performed, and it provides a breakd
to be
fair market value of the activities the Czech part of the
var iabl e and fixe d costs including maintenance of
and expenses for
lyses.
Registry including potential Data Ana
shall provide
of this Agr eem ent (as def ined in Article 11 below), ROCHE
During the term ount of CZ K
4.2
por t for the Cze ch par t of the Registry to GROUP in the total am
financial sup edule
g VAT , with a pay me nt sch edu le set out in ATTACHMENT 2 - Sch
includin
of Payments.
performance of this
pos e of tax calc ulat ion, the taxable fulfillment of the
For the pur paid in several
is neg otia ted as a par tial one and remuneration will be
Agreement
payments.
this Agreement enters
stage (milestone) arises on the day
Right to remuneration for the first
as a day of taxable transaction.
into effect. This day is considered
iversary of
taxa ble tran sac tion of the ann ual payments shall be on the ann
The date of the ice for the annual
ent. GROUP shall issue an invo
the entry into force of this Agreem dat e of receipt of the
ment shall be within 60 days of the
payment. The due date of the pay ROCHE.
by
invo ice
ble transaction
lied in acc ord anc e with the regulations in force at the taxa
VAT will be app by the legal
doc um ent (inv oice ) sha ll fulfill all the requirements stipulated
date. The tax 04 Coll.,
ecia lly the req uire me nts pur sua nt to Section 29 of Act No. 235/20
regulations, esp
On Value Added Tax, as amended.
s shall be the sole
am oun t pro vide d by RO CH E is final and all applicable taxe
The
responsibility of the GROUP.
financial support that
t does not include the additional
ROCHE recognizes that this amoun the latter would be
ROCHE Affiliates in the event
GROUP might obtain from other
interested in the Data.
Schedule of
fina nce the Cze ch par t of the Registry in accordance with the
4.3 ROCHE sha ll
Payments (AT IAC HM EN T 2).
of this Agreement for the
und erta kes to use the amount specified in Article 4.2
4.4 GR OU P this amount may not
t of the Reg istry only . How ever, ROCHE acknowledges that
Cze ch par in the Registry.
nt the ent iret y of the fina ncin g which may be necessary to mainta
represe
agreements with other
OUP may enter into specific
Thus, ROCHE agrees that GR may obtain additional
er legal entities so that GROUP
pharmaceutical companies or oth such pharmaceutical
the Reg istry , pro vide d that GROUP does not grant
fina ncin g for with those granted to
pan ies or lega l ent ities any rights which are not compatible
com
ROCHE under this Agreement.
P in excess of the amount
ll not be obli gat ed to make any payments to GROU
4.5 RO CHE sha eed upon in writing , the
unless such excess amount is agr
as provided for under Article 4.2, is signed by ROCHE
ma rke t valu e is rea sse sse d, and an amendment to this Agreement
fair
and GROUP.

5 LIABILITY AND INDEMNITY

ce coverage.
not providing GROUP with insuran
5.1 ROCHE is not the Sponsor and is
Page 8 of 31
 GROUP
Funded Non·lnterventional Registry Agreement with an ACADEMIC
s employees,
5.2 GROUP agrees to indemnify and hold harmless ROCHE and its Affiliate
agains t any loss, damag e, reason able costs
directors, subcontractors, and agents from and
and expens es) incurre d in connec tion
and expenses (including reasonable attorney's fees
with any claim, proceeding, or investigation arising out of this Agreem ent.
including Centres,
5.3 GROUP shall inform ROCHE of any subcontractors of GROUP,
ion may be met
("Subcontractors") performing services under this Agreement. This obligat
egistry.cz. Where GROU P contracts with
by a public declaration at http://empire.r
ent, then GROU P shall be liable
Subcontractors to perform any services under this Agreem
if GROU P had been
for Subcontractors performance of services to the same extent as
acting itself.
ent or arising
5.4 The liability of either Party to the other under or in connection with this Agreem
ent shall not extend to the loss of
in any other way out of the subject matter of this Agreem
business or profit or to any incidental or consequential losses or damag es.

6 INTELLECTUAL PROPERTY RIGHTS

Registry protocol
6.1 Ali Data-related intellectual property rights shall be provided in the
(ATTACHMENT 1).
Agreement, and its
For clarity, ROCHE, its Affiliates, as defined in Article 7.1 of this
, to use the Results for the following
collaboration partners shall be entitled , but not obliged
and filing, intellec tual property
purposes, including but not limited to, publication, registration
s, any indemn ification
purposes (e.g. patent application) and collaboration with other partner
l suppor t provide d
for the use of Results as per this Article 6.1 is included in the financia
hereunder.
applications for
6.2 Neither GROUP nor any member of GROUP shall be entitled to file patent
to ROCHE Product. Such
invention or discovery arising directly from the Results related
be solely entitled to
inventions and/or discoveries shall belong to ROCHE and ROCHE shall
d that inventors'
patent ROCHE Product-related inventions and/or discoveries, provide
rights are not infringed.

7 CONFIDENTIALITY
ntial and neither
7.1 Ali information obtained in connection with this Agreement, are confide
of the disclos ing Party or as otherwise
Party shall, without the prior written permission
third party except to the extent this
allowed for in this Agreement, disclose the same to any
not be conside red third
may be required by applicable law. Affiliates of both Parties shall
parties for purposes of this Agreement.

"Affiliates" shall mean:

ent.
a) an organization, which directly or indirectly controls a Party to this Agreem
to this
b) an organization, which is directly or indirectly controlled by a Party
Agreement.
e parent
c) an organization , which is controlled, directly or indirectly, by the ultimat
company of a Party.
t of the voting
Control as per a) to c) above is defined as owning more than fifty percen
to govern the financia l and the operating
stock of a company or having otherwise the power
policies or to appoint the management of an organization.
Page 9 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP
7.2 The Parties are aware of the current participation of Boehringer lngelheim RCV GmbH &
Co KG, located at Doktor-Boehringer-Gasse 5-11, 1120 Wien, Austria (hereinafter as "BI")
in the financial support of the Registry. Both Parties also acknowledge that BI reserved the
right to audit the GROUP for compliance with applicable law and quality requirements
agreed between GROUP and BI.

7.3 The obligations of confidentiality set out in Article 7.1 shall not apply to Confidential
lnformation which is (i) published or generally available to the public through no fault of the
receiving Party, (ii) in the possession of the receiving Party prior to the date of this
Agreement and is not subject to the duty of confidentiality; (iii) obtained by the receiving
Party from a third party and not subject to a duty of confidentiality.

7.4 The GROUP acknowledges and agrees that ROCHE will process in its interna! IT systems
and electronic databases in the context of the interna! processing of data also information
relating to the identification of the GROUP, including the wording of this Agreement, and
that ROCHE will monitor payments and benefits granted by ROCHE or ROCHE Affiliate,
including the sharing of such data with ROCHE Affiliates for cross-border collaboration with
health professionals and organisations of ROCHE Affiliates, as well as handling documents
that are the sources and proof of the above data.

7.5 ln the event that the Act No. 340/2015 Goll. , on the Special Conditions for the Effectiveness
of Certain Agreements, the Publishing of such Agreements and the Register of Agreements
("Act on the Register of Agreements") lays down an obligation to publish this Agreement
in the Register of Agreements, the Parties have agreed that the publication in the Register
of Agreements according to the Act on the Register of Agreements shall be ensured by
ROCHE no later than 15 days after the date on which this Agreement is fully executed and
in full compliance with the requirements of the Act on the Register of Agreements.

ROCHE agrees to fill in in the form for publication of the Agreement in the register of
agreements the address of the data box or e-mail of the lnstitution , so that the Register
Administrator can send a confirmation of publication to the lnstitution pursuant to Article 5
Section 4 of the Act on the Register of Agreements.

The GROUP acknowledges that ROCHE is entitled to redact those parts of the Agreement
which are excluded from publication under of the Act on the Register of Agreements before
sending it to the Register Administrator, especially those parts that constitute a trade secret
of Parties or a ROCHE Affiliate, or which are persona! data unless there is a legitimate
reason for their publication. For the purposes of publication of this Agreement in the
Register of Agreements, a trade secret shall mean, including but not limited, Attachment 1 -
the Protocol, Attachment 2 - Schedule of Payments and Attachment 3 - Budget, and the
value of this Agreement.
The GROUP is allowed to publish this Agreement in the Register of Agreements only if
ROCHE fails to ensure its publication within the period of time agreed to in this Article 7.4;
in that case, however, the GROUP is required to obtain ROCHE's consent in writing or by
e-mail with the publication of a specific form of the Agreement.

The arrangement in this Article 7.4 shall also apply mutatis mutandis to the publication of
any amendment to this Agreement or its modification.

lf the Act on the Register of Agreements does not impose the obligation to publish this
Agreement in the Register of Agreements, this Article 16 shall not apply.

Page 10 of 31
 GROUP
Funded Non-lnt erventi onal Registr y Agreem ent with an ACADEMIC
2.1 .6, the Parties
7.6 Without prejudice to the right of access to safety data provided in Article
d at any time, for instanc e to provide
hereto agree that if access to the Data is require
/questi on safety, such requested
information requested by a regulatory body or to assess
access to Data shall not be unreasonably withheld.

8 PUBLICATION AND PUBLICITY

ROCHE with any

8.1 During the time of duration of this Agreement, GROUP shall provide
tion by relevant
publication related to Data within two (2) weeks of its acceptance for publica
medium.
hereof).
8.2 The Steering Committee may publish the Results (as defined in art. 1.6
t, the GROUP
8.3 ln the event that any publication contains Data relating to any ROCHE produc
for publication. lf
shall provide the manuscript to ROCHE three (3) months prior submission
tual property of
any publication threatens or violates the possible patent claims or lntellec
ng the conten ts of the publica tion.
ROCHE, the GROUP shall consult ROCHE regardi
tual property of
8.4 lf any publication threatens or violates the possible patent claims or lntellec
BI, the GROUP might consult BI regarding the contents of the publication.
s' and/or Results
8.5 ROCHE financial support of primary Data collection of Czech patient
this agreem ent will be rightfully
originated from financial support provided by ROCHE under
ww.icm je.org/) and for
acknowledged according to international ICMJE guidelines (http://w
collection of Czech
the period of duration of ROCHE financial support of the primary Data
x-en.php).
patients' online at EMPIRE Registry website (http://e mpire.registry .cz/inde

9 DATA DISCLOSURE
y results on
9.1 GROUP shall register the Registry Protocol and post the Registr
ance with regulatory
ClinicalTrials.gov and provide the Registry results to SUKL in accord
fields. GROU P is
requirements and timelines. This posting must include all mandatory data
as per regulatory
responsible for updating posted data on any required registries
P shall provide
requirements until the main Publication by GROUP per Article 8. GROU
ROCHE with link to posting.
on EnCePP
9.2 ROCHE shall register the Registry Protocol and post the Registry results
Nl-PASS/PAES.
Register in accordance with regulatory requirements and timelines for
d to complete all
GROUP shall provide ROCHE will all necessary information require
for updatin g posted data on the required
mandatory data fields. ROCHE is responsible
main Publication by GROUP per
EnCePP Register as per regulatory requirements until the
Article 8. ROCHE will provide GROUP with link to posting.

1O QUALITY ASSURANCE
Quality Assurance
10.1 GROUP warrants that it has a Quality Assurance Group, or access to a
which GROU P will assure that its
Group, or implements quality control procedures through
rules, regulat ions, applicable
work is performed in compliance with all applicable laws,
g but not limited to GPP,
pharmacoepidemiology and pharmacovigilance guidelines, includin
industry codes of
EMA Good Pharmacovigilance Practices (GVP) Guidelines, recognized
("SOPs"). Reports
practice as well as any agreed upon Standard Operating Procedures

Page 11 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP
detailing the result of audits performed by GROUP Quality Assurance GROUP may be
inspected by ROCHE upon request.

10.2 GROUP warrants that it has and shall maintain all necessary licenses, authorizations,
approvals, permits and registrations to perform its obligations in accordance with the terms
and conditions of this Agreement and that during the term of this Agreement, all such
licenses, authorizations, approvals, permits and registrations are and shall remain current
and in good standing. GROUP agrees, upon ROCHE's request, to provide ROCHE with
copies of all relevant records for purposes of this Agreement, including without limitation
copies of all applicable licenses, authorizations, approvals, permits and registrations.

10.3 GROUP must ensure that their computer systems are complete, accurate, and reliable and
have consistent intended performance. GROUP will maintain SOPs for these systems and
their use. GROUP will ensure that the system data changes are documented (i.e. maintain
an audit trail) and have a security system that prevents unauthorized access to data.
INSTITUTION will also ensure that adequate data backup is performed. ln the event of
electronic data transfers between GROUP and ROCHE, the parties will define and
document a secure data transfer approach.

10.4 G ROUP will ensure and manage Subcontractor's satisfactory performance of services and
compliance with applicable regulations and agreed SOPs which impact the Registry.
GROUP will notify ROCHE in a timely manner of any critical and major findings at
Subcontractor's' which have a regulatory compliance impact on the Registry.

10.5 ROCHE will have the right, but not the obligation, to audit the conduct of the work under
this Agreement including that performed on behalf of GROUP by and at its Subcontractors.
ln the case of audit, GROUP or its Subcontractors will devise an action pian to address any
findings. Access to patients' charts and dossiers cannot be granted to ROCHE.

10.6 Should any local and/or national government authority conduct, or give notice of intent to
conduct, an inspection or take any other regulatory action with respect to the Registry under
this Agreement , GROUP will promptly give ROCHE notice thereof and supply all
information pertinent thereto. GROUP procures that it will include such obligations in any
Subcontractor agreements as relevant.

10.7 As part of inspection management GROUP will promptly provide ROCHE with a copy of all
communications between GROUP and any Regulatory Authority relating to the Registry.

10.8 GROUP or its Subcontractors will cooperate and assist as necessary in the implementation
of action plans resulting from the inspection findings. Corrective action or actions which
become necessary because of inspection findings which are due to Quality Standard
deviations will not be considered to be out of the scope of this Agreement, i.e. no additional
charges. ln addition GROUP will, upon ROCHE's request, provide data and information that
are relevant to such inspections.

10.9 Upon awareness, and in compliance with applicable international and local
pharmacoepidemiology and pharmacovigilance guidelines, including but not limited to GPP,
EMA GVP, GROUP must report to ROCHE any serious noncompliance or misconduct
related to the Registry occurring internally, orat any Subcontractor involved in the Registry.
A serious noncompliance issue is one which significantly and negatively impacts the
scientific integrity of the Registry. Misconduct is defined as intentional noncompliance in
connection with the conduct of a Registry including the fabrication or falsification of Registry

Page 12 of 31
 GROUP
Funded Non-lnterventional Registry Agreement with an ACADEMIC
pliance, misconduct
data. Fraud is considered to be a type of misconduct. Any such noncom
and fraud may be reported by ROCHE to relevant authorities.
in compliance with all
10.1 O GROUP shall produce all required documentation and data
e as well as the
applicable laws, rules, regulations, recognized industry code of practic
electronic data and
agreed procedura! documentation and shall store all physical and
records at a location fit for this purpose.

11 TERM AND TERMINATION

ty or by an ethics
11.1 ln the event that the Registry is not approved by a competent authori
ROCH E and the Parties shall meet
committee, if applicable, GROUP shall promptly inform
ent needs to be amended or
and discuss in good faith the extent to which this Agreem
terminated.
Agreement in the
11.2 This Agreement shall become effective upon publication of this
for 3 years, unless
Agreements Register as per 7.5 by all Parties and shall continue in force
otherwise terminated hereunder.
to the other if the
11.3 Any Party may terminate this Agreement forthwith by notice in writing
a breach capable of
other Party commits a breach of this Agreement, which, in the case of
to the Party in
remedy, shall not have been remedied within sixty (60) days of the receipt
and requirin g its remedy . Such notice to
default of a written notice identifying the breach
in questio n has been raised in
terminate this Agreement shall not be issued until the matter
writing and discussed during the said sixty (60) day period.
ent, in whole or
11.4 The Parties shall be entitled to terminate this Agreement, by mutual agreem
in part, in the following circumstances:

11.4.1 forthwith on ethical grounds.

may terminate this
ln case the Parties are not able to reach a mutual agreement each Party
Agreement.
to GROUP for
11.5 ln the event of premature termination of this Agreement, payments made
achieved milestones shall remain property of GROUP.
provide ROCHE
11 .6 Even in the event of premature termination of the Registry, GROUP shall
with Results.

obligation that may

11.7 Termination of this Agreement will not relieve any of the Parties of any
n, in the event of termination of this
have accrued prior thereto. ln particular, without limitatio
Results , discove ries and/or
Agreement, GROUP shall make available to ROCHE all
of termina tion of this
inventions generated under or as a result of the Registry until the date
Results , discove ries
Agreement in accordance with Article 6. ROCHE's rights to use such
of this Agreement
and/or inventions in accordance with Article 6 shall survive termination
for an unlimited period of time.
in farce after
11.8 Articles 3, 5, 6, 7, 8, 9, 11, 16 and 17 of this Agreement shall remain
termination of this Agreement.

Page 13 of 31
 ement with an ACADEMIC GROUP
Funded Non-lnterventional Registry Agre
12 FORCE MAJEURE
the Parties to this Agreement is prevented,
12.1 lf performance of this Agreement by one of y
e beyond this Party's control, the ether Part
hindered or delayed by reason of any caus dura tion of
ant contractual obligations for the
shall release the affected Party from its relev
the obligations hereunder are affected by such
the event of Force Majeure and to the extent
r Party without delay, and within fifteen (15)
event. The affected Party shall notify the ethe its
n of the events, explaining the reason for
days thereafter, provide a detailed descriptio perio d for whic h it is
ce and specifying the
inability to perform or its delay in performan
inue.
estimated that such inability or delay shall cont

13 ENTIRE AGREEMENT
ding of the Parties related to the subject
13.1 This Agreement constitutes the full understan
and exclusive statement of the terms of their
matter of this Agreement and a complete
ding or Agreement purporting to modify or vary
Agreement. No terms, conditions, understan by
unless hereafter made in writing and signed
the terms of this Agreement shall be binding
both Parties.

14 AMENDMENT
of
ified except by the express written consent
14.1 This Agreement cannot be amended or mod
both Parties.

15 ASSIGNMENT AND SUBCONTRACTING

ement or, subcontract any of its obligations
15.1 Neither Party shall assign or transfer this Agre
r Party. Provided, however all rights and
without the prior written consent of the ethe le
performed by its Affiliates, as defined in Artic
obligations of ROCHE may be exercised or
agree to be bound by this Agreement.
7.1 of this Agreement, provided such Affiliates

16 GENERAL PROVISION
r
renew this Agreement. ROCHE is not unde
16.1 ROCHE and GROUP have no obligation to this
Agreement with any member of GROUP at
any obligation to enter into another type of
time or in the future.
full right
and represent to the ether that both have the
16.2 Both ROCHE and GROUP warrant
are unaware of any impediment that would
and authority to enter into this Agreement and
hereunder. ·
inhibit their ability to perform their obligations
shall be
benefit of ROCHE under this Agreement
16.3 Ali rights vested in or created to the , as defin ed in
to any of ROCHE's Affiliates
deemed to benefit to and to be assignable
Article 7.1 above.
product
t or logo of the ether in any press release or
16.4 Neither Party shall use the name, cres writt en cons ent of the
ose without the prior
advertising or for any ether commercial purp
ether.
een the
te, imply or evidence any partnership betw
16.5 Nothing in this Agreement shall crea
ipal and agent.
Parties or the relationship between them of princ
tions
in addition to ROCHE as far as these collabora
16.6 GROUP can work with ether partners ges of the
Registry design, substantial chan
do not result in a change of the agreed
Page 14 of 31
 GROUP
Funded Non-lnterventional Registry Agreement with an ACADEMIC
ration partners
Protocol, and GROUP agrees to inform ROCHE about the other collabo
involved.

16.7 Legal notices under this Agreement should be addressed to:

For ROCHE:
ROCHE s.r.o.
Sokolovská 685/136f,
Karlín, 186 00 Praha 8,
Česká republika
DIČ : CZ49617052
For GROUP:

Faculty of Medicine
Masaryk University
Kamenice 753/5,
625 00 Brno
Czech Republic
force and effect as
16.8 Ali ATTACHMENTs form part of this Agreement and will have the same
if set out in the body of this Agreement.

17 APPLICABLE LAW AND JURISDICTION

accordance with the
17.1 This Agreement will be governed by and construed for all purposes in
to its choice of law principles.
substantive laws of the Czech Republic without giving effect
connection with the
17 .2 The Parties shall attempt to settle all disputes arising out of or in
t should fail , the
present Agreement in an amicable way. ln the event that such attemp
exclusive jurisdiction for both Parties lies in the Courts of Prague City.

s have caused this

IN WITNESS WHEREOF, the Parties by their duly authorized representative
Agreement to be executed as of the date first above written .

Made in two (2) original copies for and on behalf of:

Signed on behalf of: 1 /}

ROCHE: ROCHE s.r.o'~ 1 B-12 - ~

Date: 18/ 12/2017

dd MON yyyy

Page 15 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

Signed on behalf of:

GROUP: Masarykova Univerzita
19 -12- 2017
.„ „ .. Date: . „ .. „ .. „ . . . . ... „ .......... „ .. .

prof. MUDr. Jiří Ma , CSc. dd MON yyyy

Authoriz ed signator y

MASA'";'{'<0'
I
I"' l'. ,, - . A

625 OJ [ 1 -
5

Page 16 of 31
;

ACADEMIC GROUP
Funde d Non-ln terven tional Regis try Agree ment with an
ATTA CHM ENT 1

SEE FINA L REGI STRY PROT OCOL

Do Not Write Below

This space

intentionally left

blan k

Page 17 of 31
 ATIAC HMEN T2

SCHEDULE OF PAYMENTS

Page 18 of 3 1
SRD-012011 3 (V1.0)
 EMIC GROUP
Funded Non-lnterventional Registry Agreement with an ACAD

ATTA CHME NT 3

BUDG ET

Page 19 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

ATTACHMENT 4

SAFETY DATA EXCHANGE AGREEMENT

BACKGROUND

A. ML-40461 - Study on effect of antifibrotic drugs in different subpopulations of patients with

idiopathic pulmonary fibrosis. Analysis of data from the Czech EMPIRE registry, with protocol
number IBA0866 ("the STUDY").
ROCHE shall provide financial support for the Czech part of the Registry according to timelines and
milestones as per Study Agreement ("NISA").

B. This Safety Data Exchange Agreement (hereinafter referred to as "SDEA") describes the
procedures 9.nd time frames and defines the responsibilities that both Parties will employ for
ensuring compliance with the applicable laws and regulations pertaining to safety reporting and its
related activities, as well as related activities for the Study.

C. The terms and conditions of the NISA are incorporated and made part of this SDEA. To the
extent the terms and conditions of this SDEA conflict or are inconsistent with any terms or
conditions of the NISA, the terms and conditions of the NISA shall take precedence unless
otherwise agreed by both Parties in writing.

D. The relevant lnternational Council for Harmonisation (ICH) guidelines, the latest European
Union Pharmacovigilance guidelines and applicable European Union legislation, the United States
(US) Code of Federal Regulations, Title 21, and relevant local regulations form the basis of the
information to be exchanged between the Parties and to be reported to the regulatory authorities, as
applicable.

NOW, THEREFORE, the Parties agree the following terms:

1. Definitions

Ali acronyms and capitalized terms not otherwise defined in the body of this SDEA are set forth in
Appendix 1.

2. Single Case Management

2.1 Collection of Single Case Reports

Page 20 of 31
 EMIC GROUP
Funded Non-lnterventional Registry Agreement with an ACAD
Events (AEs). lt is understood and
Masaryk University will be responsible for collecting all Adverse
ce with regard to obtaining follow-
agreed that Masaryk University will perform adequate due diligen
is not responsible for not receiving
up information on incomplete AE reports . Masaryk University
to obtain them.
follow-up reports , provided that adequate efforts have been made
Ali AEs must be collected for patients receiving a Roche product.

ilance section according to the

Masaryk University shall amend the EMPIRE protocol Pharmacovig
effective date of this Agreement.
changes stipulated in section 2 hereof within 6 months of the
s about their PV obligations by email
Masaryk University shall notify investigators and Czech center
within 2 weeks of the effective date of this Agreement.

2.2 Tracking of Safety lnformation

Masaryk University will track all safety reports collected as
per Section 2.1 (Collection of Single
Gase Reports), originating from the Study for the Product.

2.3 Exchange of Single Case Reports

d Roche Product(s), will be sent to
AE Reports, where the patient has been exposed to the studie
in the format described below.
the Roche contact specified in Appendix 2 of this SDEA
nically via email and within the
Transmission of these reports (initial and follow-up) will be electro
timelines specified below:
• Adverse events
o Ali AE reports will be performed by HCP in the registry
interface through an e-form.
Event message sent
This procedure will generate an e-mail in the form of an Adverse
HCP to the email
immediately after filling the pre-defined fields in the e-form by
contacts listed in APPENDIX 2.

2.4 Case Transmission Verification of Single Case Reports

adequately received by Roche , via
The Parties will ensure that all single case reports have been
enting single case reports sent by
Masaryk University emailing Roche a monthly line-listing docum
. The periodic line-listing will be
Masaryk University to Roche in the preceding time period
time period .
exchanged within seven (7) calendar days of the end of the agreed
ar days of receipt.
Confirmation of receipt should be received within seven (7) calend
which have not been received by
Following Gase Transmission Verification, single case reports
five (5) calendar days from request
Roche shall be forwarded by Masaryk University to Roche within
by Roche.

3. Reporting to Regulatory Authorities

for the reporting of individua! case

Roche as the Marketing Authorization Heider will be responsible
iance with applicable regulations.
safety reports from the study to the regulatory authority in compl
to report Adverse Drug Reactions
However, this does not impact the individua! HCP's responsibility
in line with the applicable local legislation.

Page 21 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

4. Queries

Queries related to the Study will be answered by Masaryk University. However, responses to all
safety queries from regulatory authorities related to Roche Product or for publications will be
discussed and coordinated between the Parties. The Parties agree that Roche shall have the final
say and control over safety queries relating to the Roche Product. Masaryk University agrees that it
shall not answer such queries from regulatory authorities and other sources relating to the Roche
Product independently but shall redirect such queries to Roche.

Both Parties will use all reasonable effort to ensure that deadlines for responses to urgent requests
for information or review of data are met. The Parties will clearly indicate on the request the reason
for urgency and the date by which a response is required.

5. Safety Crisis Management

ln case of a safety crisis, e.g.,

• where safety issues have a potential impact on the indication(s), on the conduct of the
Study,
• may lead to labeling changes or regulatory actions that limit or restrict the way in which the
Product is used, or
• where there is media involvement,
the Party where the crisis originates will contact the other Party as soon as possible.

The Parties agree that Roche shall have the final say and control over safety crisis management
issues relating to the Roche Product. Masaryk University agrees that it shall not answer such
queries from media and other sources relating to the Product but shall redirect such queries to
Roche. For contact details see APPENDIX 2.

6. Language

English will be used as the common language for all safety information exchanged between the
Parties.

7. Contacts

Ali transfer of safety information between the Parties will be made through the designated or
alternate contact person(s) listed in APPENDIX 2, will be reviewed annually and updated
accordingly as agreed by the Parties by e-mail correspondence. The Parties shall inform each other
of changes in the contact details affecting critical processes such as single case management and
safety crisis.

Page 22 of 31
 GROUP
Funded Non-lnterventional Registry Agreement with an ACADEMIC

8. Records

copies of these documents)

Ali Parties will maintain reports and all related documentation (or true
territories for which they are
for a time period required by the applicable laws and regulations in the
responsible, taking into account the minimum archiving period worldw ide.

9. Compliance with pharmacovigilance agreement/audit

g timelines.
The Parties shall follow their own procedures for adherence to AE reportin
other Party regarding AE
Each Party shall monitor and, as applicable, request feedback from the
agree to provide written
report timeliness in accordance with its own procedures. The Parties
ng AE reports received
responses in a timely manner to inquiries from the other Party regardi
of trends of increasing or
outside the agreed upon Agreement timelines. lf there is any detection
ent, both Parties agree
persistent non-compliance to transmission timelines stipulated in this Agreem
to conduct ad hoc or institute a regular joint meetin gs to addres s the issue.
exchange timelines, with
ln case of concerns related to non-compliance of processes, other than
rate on clarifyin g and resolving the issues
this Agreement, the Parties will jointly discuss and collabo
mplian t Party to solve the non-
causing non-compliance. Every effort will be made by the non-co
tative actions taken.
compliance issues and inform the other Party of the corrective and preven
calendar days, an audit
Upon justified request, given sufficient notice of no less than sixty (60)
The Parties will then
under the provisions of this Agreement can be requested by either Party.
execution of the audit. The
discuss and agree in good faith upon the audit scope, agenda and
requesting Party will bear the cost of the audit.

1O. Amendments

ed lega! or regulatory
The Parties agree to revise this SDEA to comply with new or amend
r, that no subsequent
requirements as necessary, or as and when required; provided, howeve
shall be binding upon the Parties hereto
alteration, amendment, change or addition to this SDEA
tive authori zed personnel of
unless in writing, with reference to this SDEA and signed by the respec
the Parties.

11. Term and Termination of SDEA

executes the NISA and

This SDEA becomes effective on the date upon which the last Party
under applicable laws and
remains in full force and effect as long as the reporting obligations
regulations for the Parties exist.

Page 23 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

IN WITNESS WHEREOF, the Parties by their duly authorized representatives have caused this
Safety Data Exchange Agreement to be executed as of the date first above written.

Made in two (2) original cop ies for and on behalf of:

Signed on behalf of:

GROUP: Masaryk University, Faculty of Medicine, prof. MUDr. Jiří Mayer, CSc., Dean of the
Faculty

19 -12- 2017
Date:
DD/MMMNYYY
Authorized signatory

MASf\'<':<',.."'ll !I• I

I
625 Úu t 11 „ I ~11~-'3 5

Page 24 of 31
 t with an ACADEMIC GROUP
Funded Non-lnterventional Registry Agreemen

APPENDIX 1: Definitions

nal Council for Harmonisation (ICH) guidelines and

The definitions below are based on the lnternatio to
s. The use of italic font in this section refers
Food and Drug Administration (FDA) regulation itions relate
FDA and EMA regulations. Other defin
definitions taken from the ICH guidelines and/or
edures Glossary.
to the company specific Global Processes and Proc

• Adverse Event (AE)

nt or clinica/ tria/ subject administered a
''.Any untoward medica/ occurrence in a patie
ly have a causa/ relationship with this
medicina/ product and which does not necessari
be any unfavorab/e and unintended sign
treatment. An Adverse Event (AE) can therefore
tom, or disease temporally associated with
(including an abnormal laboratory finding), symp
idered related to the medicina/ product."
the use of a medicina/ prod uct, whether or not cons
Definitions and Standards for expedited
(Source: Clinical Safety Data Management:
Reporting, ICH E2A, 1994)

• Awareness Date
tes or agents acting on behalf of either
The date any Party (including employees of affilia
elements as defined by ICH E2A guideline.
Party), first has knowledge of the minimum data
ded for a case to be considered as valid:
At the very least, the following data must be provi
o an identifiable reporter*,
ber, patient/subject number, initials,
o an identifiab/e patient**(i.e. , eithe r CRF num
gend er, date of birth, age or age group),
o a drug/counterfeit drug,
t).
o an adverse event (or a special situation repor
ed contact details (e.g., email address) are
*For AE reports from social media sources, verifi
considered an identifiable reporter.
patient" is considered an identifiable patient
**For reports from healthcare professionals, "a
criterion.
initially prior to transmitting the information
The minimum data elements should be obtained
rt is lacking minimum data elements, this
to the ether Party . ln the event that an AE repo
until all the minimum data elements are
report should not be forwarded to the ether Party
pt follow-up as necessary.
gathered. The originating Party will ensure prom

• European Medicines Agency (EMA)

the European Union (EU) member states.
The centralized European regulatory authority for

• European economic area (EEA)

and Norway.
European Union (EU) plus lceland, Liechtenstein

Page 25 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

• Food and Drug Administration (FDA)

The agency within the U.S. Department of Health and Human Services protecting the public
health by assuring the safety, effectiveness, quality, and security of human and veterinary
drugs, vaccines and other biological products, and medical devices.

• lnternational Council for Harmonisation (ICH)

lnternational Council for Harmonization of Technical Requirements for Registration on
Pharmaceuticals for Human Use.

• Non-interventional study (NIS)

NIS are carefully designed and conducted epidemiological studies, specifically observational
(non-interventional, non-experimental) . ln observational studies, the physician "observes and
evaluates results of ongoing medical care without 'controlling' the therapy beyond normal
medical practice."
Note: The prescription of the medicine is clearly separated from the decision to include the
patient in the study.
For EEA Affiliates, please refer to the definition below from EMA GVP Module VIII: ''.A non-
interventional study is a study fulfilling, cumu/atively, the following requirements:
1. The medicina/ product is prescribed in the usual manner in accordance with the terms of
the marketing authorization;
2. The assignment of the patient to a particular medical treatment is not decided in
advance by a tria/ protoco/ but fal/s within current practice;
3. No additional diagnostic or monitoring procedures are applied to the patients above
those applied in course of routine clinical practice; and 4. epidemio/ogica/ methods are
used for the analysis of col/ected data.
(Sources: CIOMS, Current Challenges in Pharmacovigilance: Pragmatic Approaches. Report
of CIOMS Working Group V. Geneva; World Health Organization [WHO], 2001 and FDA
Guidance for lndustry E2E Pharmacovigilance Planning, 2005).

• Product
The Roche product that is the subject of the study as defined in the corresponding protocol.

• Single case reports

A document providing the most complete information related to an individua! case at a
certain point of time. An individua! case is the information provided by a primary source to
describe adverse events/special situation reports following the administration of one or more
medicina! products to an individua! patient at a particular point of time.

Page 26 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

APPENDIX 2: Contact Details

Roche Contacts:

ENTER NAME OF External NIS lnitiator Contacts:

Page 27 of 3 1
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

Page 28 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

APPENDIX 3: EMPIRE REGISTRY - CRF

131hJULY201 6

ADVERSE EVENT
•!• Basic information
~ Type of report (selection)
• lnitial
• Follow-up
~ Race of patient
• Asian
• Black
• White
• Other
~ Weight
~ Height
~ Pregnancy (yes/no)
~ Weeks
•!• Type of adverse event
~ Type of adverse event (selection)

• Nausea

• Dyspepsia

• Emesis

• Diarrhoea

• Anorexia nervosa

• Photosensitive reaction

• Rash

• Dizziness

• Fatigue

• Fever

• Weight loss

• Weight gained

• Obstipation

• Abdominal pain

• Dyspnoea

• Cough
Page 29 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

• Elevated liver enzymes

• Liver failure

• Bleeding

• Loss of appetite

• Other
);:> Please specify
);:> Grade
• 1- Mild

• 2- Moderate

• 3 - Severe

• 4 - Life threatening
• 5 - Death
•!• Adverse event
);:> Onset date of the adverse event (dd.mm.yyyy) (date)
);:> Stop date of the adverse event (dd.mm.yyyy) (date)
);:> Was the adverse event serious (SAE)? (yes/no)
);:> Specify serious adverse event (checkbox)
• Death
• Life-threatening event
• Patient required hospitalisation or existing hospitalisation was prolonged
• Persistent or significant disability/incapacity
• Congenital birth defect
• Required intervention to prevent permanent impairment or damage
);:> ls there a reasonable causal relationship with the drug administered? (selection)
• Yes
• No
• Cannot be excluded
);:> What is the indication of this drug? (selection)
• IPF
• Non-IPF
);:> Type of non-IPF medication (text)
);:> IPF medication (selection)

• N-acetylcysteine

• Protein pump inhibitors

• Corticosteroids

• Azathioprine

• Pirfenidone

• Nintedanib

Page 30 of 31
Funded Non-lnterventional Registry Agreement with an ACADEMIC GROUP

• lnvestigational drug (specify)

• Other
~ Please specify
~ Who is the marketing authorization holder? (selection)
• Boehringer lngelheim
• Roche
• Trommsdorff
• Zentiva
• Mundipharma
• Bristol-Meyers
• Aspen Pharma
• Other
~ Please specify
~ ls the patient treated with this drug within the clinical trial (CT)? (yes/no)
~ ls the patient treated with this drug within the compassionate use program (CUP)? (yes/no)
~ Was the Adverse event already reported within the CUP or CT? (yes/no)
;... Please insert CUP/CT number and sponsor (text)
~ Please insert site number in this CT/CUP (text)
~ Please insert patient ID in this CT/CUP (text)
•!• Assessment of the adverse event
;... AE treatment (yes/no)
~ Type of treatment (text)
;... Formulation (text)
;... Total daily dose at onset {dose, unit) (text)
;... Route of administration (text)
;... Start date of treatment of AE (dd.mm.yyyy) (date)
~ End date of treatment of AE (dd.mm.yyyy) (date)
~ lndication for use (text)
~ Concomitant therapy (relevant) (text)
;... ls there a reasonable causal relationship between the event and the concomitant therapy?
(yes/no)
~ Concomitant diagnoses (relevant) (text)
~ Outcome of AE (selection)
• The AE completely subsided
• The condition improved
• The condition worsened
• Unknown
;... Action taken with suspect drug dueto event (selection)
• Continued
• Reduced
• Discontinued
• lncreased
• Completed according to protocol
• Discontinued and reintroduced
• Not applicable
;... Comments (text)
Please insert telephone number and email in case any further details are needed (text)

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