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Working document QAS/17.704
page 1
Working document QAS/17.704 1
March 2017 2
Draft for comment 3
Prepared by EMP/RSS 4
5 6
COLLABORATIVE PROCEDURE IN THE ASSESSMENT AND 7
ACCELERATED NATIONAL REGISTRATION OF PHARMACEUTICAL 8
PRODUCTS APPROVED BY STRINGENT REGULATORY AUTHORITIES 9
(March 2017) 10
DRAFT FOR COMMENT 11
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_____________________________________________________________________________________ 21
© World Health Organization 2017 22
All rights reserved. 23
This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft may not be 24 reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any form or by any means 25 outside these individuals and organizations (including the organizations' concerned staff and member organizations) without the permission 26 of the World Health Organization. The draft should not be displayed on any website. 27
Please send any request for permission to: 28
Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies Standards and Norms, Department of Essential Medicines and 29 Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland. Fax: (41-22) 791 4730; email: [email protected]. 30
The designations employed and the presentation of the material in this draft do not imply the expression of any opinion whatsoever on the 31 part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the 32 delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full 33 agreement. 34
Should you have any comments on the attached text, please send these to: Dr Luther Gwaza, Department of
Essential Medicines and Health Products, World Health Organization, 1211 Geneva 27, Switzerland;
email: [email protected]; fax: (+41 22) 791 4730; with copies to Mrs Ksenia Finnerty (finnertyk@who)
and to Mrs Wendy Bonny ([email protected]), by 17 May 2017.
Working documents are sent out electronically and they will also be placed on the Medicines website
for comment. If you do not already receive directly our draft guidelines please let us have your email
address (to [email protected]) and we will add it to our electronic mailing list.
.
Working document QAS/17.704
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The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the 35 World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of 36 proprietary products are distinguished by initial capital letters. 37
All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. However, the 38 printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and 39 use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. 40
This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 41 42
Working document QAS/17.704
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SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT QAS/17.704: 43
Collaborative procedure in the assessment and accelerated national registration 44
of pharmaceutical products and vaccines approved by stringent regulatory 45
authorities 46
Development of the proposal for piloting the collaborative
procedure of pharmaceutical products approved by stringent
regulatory authorities
June 2014
Proposal discussed with some national medicines regulatory
authorities at a meeting in Swakopmund, Namibia for the pilot
procedure
December 2014
Presentation of the proposal to the fifty-first meeting of the WHO
Expert Committee on Specifications for Pharmaceutical
Preparations (ECSPP)
October 2016
Finalization of the draft collaborative procedure November 2016
Proposal discussed at the 4th Annual meeting on Collaborative
Registration in Capetown, South Africa
December 2016
Mailing and posting of the working document on the WHO
website for the 2nd public consultation March 2017
Compilation of comments received May 2017
Review of comments by an expert working group May 2017
Mailing and posting of the revised working document on the WHO
website for 2nd public consultation June 2017
Compilation of comments received August 2017
Presentation to fifty-second meeting of the WHO ECSPP October 2017
Further follow-up action as required
47
48
49
Working document QAS/17.704
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NOTE: 50
This document has been prepared for the purpose of inviting comments and suggestions on the 51
proposals contained therein, which will then be considered by the Expert Committee on 52
Specifications for Pharmaceutical Preparations (ECSPP). 53
This guideline was developed based on the outcomes of the pilot process that was conducted from 54
2015 to 2017 and consensus of the WHO meetings held in December 2015 and December 2016 with 55
participants from national regulatory authorities and feedback from the manufacturers and 56
stakeholders. The text in its present form does not necessarily represent an agreed formulation of the 57
ECSPP. Written comments proposing modifications to this text MUST be received by 17 May 2017 58
in the Comment Form available separately and should be addressed to the World Health 59
Organization, 1211 Geneva 27, Switzerland, attention: Department of Essential Medicines and 60
Health Products (EMP). Comments may also be submitted electronically to the Responsible Officer: 61
Dr Luther Gwaza at email: [email protected]. 62
The outcome of the deliberations of the Expert Committees will be published in the WHO Technical 63
Report Series. The final agreed formulation of the document will be edited to be in conformity with 64
the "WHO style guide" (WHO/IMD/PUB/04.1). 65
66
67
Working document QAS/17.704
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ACRONYMS ........................................................................................................................................ 6 68
GLOSSARY.......................................................................................................................................... 7 69
1. BACKGROUND INFORMATION ........................................................................................... 8 70
2. PRINCIPLES OF FACILITATED REGISTRATION ............................................................ 9 71
ABSTRACT .......................................................................................................................................... 9 72
PRINCIPAL ROLES OF THE PARTICIPATING PARTIES ............................................................................ 10 73
3. PHARMACEUTICAL PRODUCTS ....................................................................................... 10 74
SUBMISSIONS FORMAT AND CONTENT ............................................................................................... 11 75
REGISTRATION PROCESS ACCORDING TO THE PROCEDURE ................................................................ 12 76
77
Annex 1: Agreement of NMRA to participate in the pilot of the SRA collaborative registration 78
procedure 79
Annex 2: Example of information included in the list of participating SRAs 80
Annex 3: Standard document package to be submitted to NMRA for the purpose of national 81
registration in line with the Procedure 82
Annex 4: Requirements for provision of a "bridging" report for SRA-approved medicines for 83
consideration of registration in non-SRA settings 84
Annex 5 QIS-SRA Procedure 85
Annex 6: Declaration of the applicant to the NMRAs to initiate registration in line with the 86
Procedure 87
Annex 7A: The model content of the company consent to SRA with information-sharing 88
Annex 7B: The model content of the request to SRA to agree with assessment and inspection 89
reports sharing 90
Annex 8: Confidential disclosure agreement among participating company and WHO-PQT to 91
access the data shared by company with participating NMRAs 92
Annex 9: Notification of an outcome of the national registration provided by the participating 93
company to WHO-PQT 94
95
96
97
98
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Acronyms 99
API active pharmaceutical ingredient 100
CEP certificate of suitability 101
CTD common technical document 102
FPP finished pharmaceutical product 103
GMP good manufacturing practices 104
ICH International Council for Harmonisation of Technical Requirements for 105
Pharmaceuticals for Human Use 106
NDA new drug application 107
NMRA national medicine regulatory authority 108
PQT Prequalification Team 109
QIS quality information summary 110
SRA stringent regulatory authority 111
WHO World Health Organization 112
113
114
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Glossary 115
facilitated registration procedure of SRA-approved medicines (Procedure). Registration 116
procedure in which assessment and national registration of pharmaceutical products approved by 117
stringent regulatory authorities (SRAs) is facilitated and accelerated by sharing of detailed 118
assessment and inspection outcomes generated by a SRA. 119
participating authority or participating national medicines regulatory authority. 120 National medicines regulatory authority (NMRA) that voluntarily agrees to implement this 121
collaborative procedure and accepts the task of processing applications for registration of medicines 122
approved by SRAs in accordance with the terms of the Procedure. A list of participating authorities 123
is posted on the WHO/PQT website (http://www.who.int/prequal/). 124
participating company. Pharmaceutical company, which is a holder of marketing 125
authorization granted by SRA for a medicine that is intended to be submitted, has been submitted or 126
has been granted a national registration by participating NMRAs in line with principles of the 127
Procedure. 128
participating stringent regulatory authority. SRA that agrees with provision of outcomes 129
of its regulatory expertise (especially assessment and inspection reports) to applicants/authorization 130
holders or inspected manufacturers, does not object to sharing of these documents with national 131
medicines regulatory authorities and provides under specified conditions in line with principles of 132
the Procedure a support to other parties involved in the Procedure. 133
stringent regulatory authority.1 A regulatory authority which is: 134
a. a member of the International Council for Harmonisation of Technical Requirements for 135
Pharmaceuticals for Human Use (ICH), being the European Commission, the US Food and Drug 136
Administration and the Ministry of Health, Labour and Welfare of Japan also represented by the 137
Pharmaceuticals and Medical Devices Agency (as before 23 October 2015)); or 138
b. an ICH observer, being the European Free Trade Association, as represented by Swissmedic, and 139
Health Canada (as before 23 October 2015 ); or 140
c. a regulatory authority associated with an ICH member through a legally-binding, mutual 141
recognition agreement, including Australia, Iceland, Liechtenstein and Norway (as before 23 142
October 2015) 143 . 144
145
1 Clarification with Respect to a Stringent Regulatory Organization as Applicable to the Stringent Regulatory
Authority (SRA) Guideline. WHO PQT: medicines;
https://extranet.who.int/prequal/sites/default/files/documents/75%20SRA%20clarification_February2017_0.pdf.
Working document QAS/17.704
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1. Background information 146
Management of diseases known to be of major public health relevance in countries with limited 147
regulatory resources is often jeopardized by delayed access to new or otherwise needed therapies. 148
Although many medicines successfully passed regulatory review process by internationally respected 149
regulatory bodies, also known as stringent regulatory authorities (SRAs), or even in addition were 150
prequalified by the World Health Organization (WHO), local regulatory approvals tend to consume 151
additional time, workload and resources of national medicine regulatory authorities (NMRAs) before 152
these therapies can be available to patients. 153
In order to address this issue, WHO proposes a scheme for NMRAs and pharmaceutical companies 154
(manufacturers) to facilitate registrations of medicines approved by SRAs.2 WHO recognizes the 155
scientific evaluation of pharmaceutical products by SRAs as they apply similarly stringent standards 156
for quality, safety and efficacy to those recommended by WHO. 157
Based on WHO experience with the Collaborative Registration of WHOPrequalified Pharmaceutical 158
Products,3 it is possible to facilitate and accelerate national registration processes by provision of 159
detailed assessment and inspection outcomes generated by respected regulatory bodies.4 Assessment 160
and inspection reports of SRAs made available in addition to the registration dossiers can facilitate 161
adoption of national regulatory decisions by assuring NMRAs about positive risk/benefit of a 162
product and its identical quality with the product already approved elsewhere. Normally, publicly 163
available versions of assessment and inspection outcomes do not provide sufficiently detailed 164
information to adopt regulatory decisions and therefore detailed assessment and inspection outcomes 165
that include commercially sensitive data must be shared. To make such information-sharing possible 166
is up to interested pharmaceutical companies, who have to provide consent with information 167
exchange among reference SRA and NMRAs, to which a product is submitted for regulatory 168
approval. Pharmaceutical companies benefit from accelerated and facilitated regulatory process. On 169
the other side, it is up to interested NMRAs to provide sufficient assurance that shared data will be 170
treated with necessary care and confidentiality. 171
It should be stressed that the decision to apply the process for specific medicines is up to respective 172
NMRAs, which retain the prerogative to conclude their assessment through sovereign decisions on 173
medicine registration within their national jurisdiction. 174
In addition to facilitation of regulatory decisions on needed medicines and faster access to patients, 175
the process also represents an avenue for harmonization of regulatory requirements and capacity 176
building. 177
The Procedure is designed for chemical medicines, irrespective if these are of innovative or generic 178
nature. Extension to other categories of medicines can be considered in future. 179
2 In addition to medicines approved by conventional marketing authorization process, the Procedure is applicable
to special “approval” mechanisms like the scientific opinion process according to Art.58 of Regulation (EC) No.
726/2004 in the EU. 3 Collaborative procedure between the World Health Organization Prequalification of Medicines Programme and
national medicines regulatory authorities in the assessment and accelerated national registration of WHO‑prequalified
pharmaceutical products, WHO Technical Report Series, No. 981, 2013, Annex 4, pp 155–188. 4 In case of the Collaborative Registration of WHO‑Prequalified Pharmaceutical Products the assessments and
inspections are organized by WHO, although WHO cannot be considered as a regulatory body.
Working document QAS/17.704
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2. Principles of facilitated registration 180
Abstract 181
The process is applicable both to SRA-approved innovative and generic medicines. Participation of 182
all parties is voluntary and should be performed in compliance with relevant applicable legislation. 183
All SRAs, NMRAs and holders of authorization for medicines considered to be therapeutically 184
important by participating NMRAs are welcome to participate. 185
WHO plays a facilitating role in this process and monitoring of its use and improvement of detailed 186
conditions. 187
The general approach is similar to principles of Collaborative Registration of WHO-Prequalified 188
Products in terms of information sharing, utilization of shared information, management of 189
confidentiality and timeframe. Instead of the WHO Prequalification Team (PQT), SRAs are the 190
generators of the basic regulatory expertise in this procedure. 191
The dossiers submitted for national registrations are organized in globally harmonized common 192
technical document (CTD) format to maximize use of data already submitted to SRAs. In case of 193
generic medicines the technical part of dossier is equivalent to the WHO/PQ prequalification dossier 194
requirements. For innovative products (i.e. new drug applications (NDA) or self-standing 195
applications) a submitted dossier consists of a rather simplified version of SRA dossier (unless 196
informed otherwise by the respective NMRA) in order to reduce the volume of submissions to 197
practically manageable extent, but include all data essential for national assessment. Such pragmatic 198
simplification also reduces the risk of unnecessary dissemination of highly sensitive commercial 199
information and can make the process more acceptable for pharmaceutical companies. 200
The key role in the process is given to the pharmaceutical companies to carry on the procedure and 201
organize provision of relevant regulatory information generated by reference SRAs to participating 202
NMRAs. Conditions, under which individual SRAs agree with availability of assessment and 203
inspection reports for this purpose have to be confirmed with each SRA. It is planned that WHO will 204
summarize positions of willing SRAs as regards availability of assessment and inspection reports and 205
post it on its website, similarly like the list of NMRAs that agreed to apply the piloted procedure in 206
principle. It is expected that SRAs that issued the reference marketing authorization will provide a 207
certain degree of support and cooperation, if necessary (e.g. authentication of submitted documents 208
in case of doubt). In general, to save the resources of reference authorities, the role of SRAs in the 209
proposed process is minimized. 210
It is up to participating NMRAs to recognize individual medicines as being eligible for the 211
registration under this procedure considering relevance of the respective medicine for public health 212
and existing NMRA capacity. 213
Confidentiality of shared data is assured by mechanisms applied by participating parties (NMRAs, 214
SRAs, companies, WHO). Participating NMRAs provide a special comittment in the respect that any 215
information and documentation provided to it by applicants and SRAs (possibly mediated by WHO) 216
pursuant to this procedure will be treated as confidential and an access to this information will be 217
allowed only to persons involved in the individual registrations who are bound by confidentiality 218
Working document QAS/17.704
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undertakings (Annex 1). Authorities that provided such a commitment and agree to apply the 219
principles of the Procedure will be publicly listed by WHO. 220
After initiation of the Procedure, switch to normal registration process is possible, provided that 221
involved parties inform each other of this decision. 222
Principal roles of the participating parties 223
Participating NMRAs express their interest to participate in the Procedure, their commitment to 224
respect principles of the Procedure and their confirmation of confidential treatment of commercially 225
sensitive information by forwarding to WHO a completed Annex 1 to this procedure. A focal person 226
to communicate on issues relevant for the Procedure will be designated in each participating NMRA. 227
A list of participating authorities is posted on the WHO/PQT website (http://www.who.int/prequal/). 228
Participating SRAs do not object to share their assessment reports and inspection reports with 229
applicants/authorization holders to support access to needed medicines in line with principles of the 230
Procedure. Conditions and mechanisms, by which the information will be shared, and what can be an 231
extent of additional support to participating NMRAs are notified to WHO. A list of SRAs that agree 232
to share outcomes of their regulatory expertise in line with principles of the Procedure and detailed 233
conditions of information sharing are posted on the WHO/PQT website 234
(http://www.who.int/prequal/). Example of such a listing is provided in Annex 2. 235
Participating companies submit applications to NMRAs and provide assistance necessary to finalize 236
the application in line with the Procedure. The participating companies applying for registration have 237
a major role in the national registration process and in the post-registration phase by carrying on the 238
procedure and providing additional requested information. 239
WHO assists in the execution and maintenance of the Procedure, posts lists of participating NMRAs 240
and SRAs (including SRA conditions with information sharing) on its website and collects 241
information about performance of the Procedure. Should the medicine be highly therapeutically 242
relevant for WHO-supported treatment programmes, WHO actively facilitates information exchange 243
among involved SRAs and participating NMRAs. 244
3. Pharmaceutical products 245
Both innovative and generic medicinal products approved by SRAs are eligible for the Procedure. 246
The products can be prequalified by the WHO SRA-prequalification route, but non-prequalified 247
medicines are also eligible. The medicines submitted for registration to participating NMRAs should 248
be identical with medicines approved by SRAs. Within the context of this Procedure, identical 249
products are characterized by descriptions listed below. It is important to note that should there be 250
any deviations from this definition of “sameness”, these must be notified (e.g. different supply chain, 251
specifications, stability or medical claims, etc.) and such deviations can be the reason for non-252
applicability of the Procedure. 253
The same medicinal product for the purpose of the Procedure is characterized by: 254
the same qualitative and quantitative formulation; 255
the same manufacturing site(s), chain, processes, control of materials and final product; 256
Working document QAS/17.704
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the same active pharmaceutical ingredient (API) and finished pharmaceutical product (FPP) 257
specifications; 258
the same essential elements of product information.5 259
Submissions format and content 260
The dossiers submitted for national registrations are organized in International Council for 261
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) CTD 262
format and contain data specified in Annex 3. Scope of submitted technical data for innovators 263
(i.e. NDA or self-standing applications) represents subset of data submitted to SRAs that 264
provides sufficient assurance about product identity, quality, safety and efficacy and is pragmatic 265
for NMRAs. As much as possible API quality is confirmed by existing certification schemes (e.g. 266
certificate of suitability (CEP)). In principle, only nonclinical and clinical summaries (ICH 267
Module 2, parts 2.6 and 2.7) are submitted instead of extensive full ICH modules 4 and 5. 268
However, the applicants are committed to submit these modules or requested nonclinical and 269
clinical data if asked by a participating NMRA. It may be advantageous to submit in addition to 270
existing overviews a “bridging report” which provides the summarized evidence about positive 271
risk/benefit and justification of relevance of the product for the countries of submission (Annex 272
4). 273
In case of generic medicines the technical part of a dossier corresponds in module 3 to full scope 274
of quality data on finished dosage form (3.P part) and data on API correspond to an open part of 275
the API master file. Demonstrations of bioequivalence and biowaiver criteria are equivalent to 276
the WHO-PQT prequalification dossier requirements (www.who.int/prequal). 277
In addition to technical data the applicants provide NMRAs with: 278
‒ valid assessment and inspection reports issued by SRA; 279
‒ quality information summary (QIS)-SRA (Annex 5); and 280
‒ a declaration assuring the identity of the product with the medicinal product approved by 281
the SRA, consent to communicate in the product-related matters freely with the reference 282
SRA and additional commitments as specified in Annex 6. 283
Should the local applicant be a different legal entity from a holder of SRA marketing authorization 284
(or scientific opinion), the relationship should be clarified and agreements assuring information flow 285
should be adjusted to this situation. 286
Translation of documents required in national language is under the responsibility of the individual 287
company. The method and extent of verification of translation accuracy is a matter of decision of 288
individual NMRAs. 289
5 The essential elements of product information include in particular the indications, contraindications, posology
(dosing), special warnings and precautions for use, adverse reactions, storage conditions, primary packaging and shelf
life. For pharmaceutical products differences in brand name, the name of the applicant, language, format and degree of
detail of the product information, labelling of internal and external packaging, among others, are not considered essential
for the purposes of this Procedure. The language of the product information may be different as long as the information
content is the same as that approved by the SRA.
Working document QAS/17.704
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Samples, if required, should be used for control of appearance or packaging. Laboratory testing of 290
registration samples is not recommended and random sampling and testing should be rather planned 291
in the post-registration period. Graphical design of package labelling (mock-up) is an acceptable way 292
for presentation of texts and symbols on the packaging. 293
It should be noted, however, that participating authorities may require applicants to comply with 294
specific additional national requirements. Each participating authority is encouraged to reduce the 295
scope of specific national requirements for the sake of the Procedure and harmonize with 296
international format and content of regulatory dossier. Specific national requirements should be 297
made public. 298
Registration process according to the Procedure 299
1. Pre-submission phase: 300
a. Companies considering registrations according to the Procedure select familiarize 301
themselves with principles of the Procedure, NMRAs that are prepared to participate 302
in the Procedure and conditions, under which SRA that have authorized their 303
medicinal product agrees with information-sharing and provides additional 304
prospective support. 305
b. Best, if a participating company confirms with participating NMRA(s) its interest to 306
apply the Procedure for the given medicine before the submission. 307
c. The company also provides the reference SRA with its consent to share the regulatory 308
relevant information with participating NMRA(s). The model content of the consent 309
is proposed (Annex 7A), but it is up to individual applicants and SRAs to agree on 310
detailed wording. 311
d. In case that the company does not have available valid assessment and inspection 312
reports, these should be requested from the respective SRA. Should the company 313
need to obtain an agreement of SRA before sharing the assessment and inspection 314
reports, such agreement should be requested. The model content of the request is 315
proposed (Annex 7B). 316
e. In case of medicines that are relevant for WHO treatment programmes, the company 317
agrees with WHO the extent of WHO coordination and support. 318
f. The company prepares the QIS SRA (Annex 5) and the QIS should be verified and 319
endorsed by the respective SRA that issued the marketing authorization. 320
2. Submission for registration 321
a. The company submits the registration application to the participating NMRA. 322
Specific national requirements must be respected, but it is up to NMRAs to minimize 323
national deviations from the internationally acceptable dossiers as much as possible. 324
Application fees are applicable according to national requirements. 325
b. The registration dossier is organized in CTD format and consists of data sets as 326
specified in Annex 3, including valid assessment and inspection reports issued by the 327
SRA and a company/applicant’s declaration. 328
c. In case of submissions coordinated with WHO, the company informs WHO about 329
applications submitted to individual NMRAs and comes to an agreement with WHO 330
as regards access to the shared data (Annex 8). 331
3. NMRAs’ acceptance of products for registration in line with the Procedure and registration 332
phase 333
a. Participating NMRA decides whether or not to apply the procedure for each specific 334
case and informs promptly the applicant in this respect. 335
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b. Should NMRA have doubts about authenticity or validity of submitted assessment 336
and inspection reports, it can ask respective SRA for a confirmation. The way by 337
which the confirmation is organized can vary between SRAs. The practical way is to 338
share recent assessment and inspection reports as archived by SRA. 339
c. The NMRA processes an application, benefiting from shared SRA regulatory 340
outcomes and assurance about the identity of the medicine with the one approved by 341
SRA. It is up to individual NMRAs to which extent accept, verify or reassess the 342
provided information before coming to a decision. A pragmatic approach is to verify 343
product identity and assess only those areas which relate to use of the product in the 344
country concerned and where failure to comply with regulatory standards could pose 345
specific health risks. In the other areas the outcomes of trusted authorities are 346
proposed to be adopted. 347
d. Participating SRAs can be approached for additional explanation or justification, 348
depending on the extent of individual SRA’s commitment to support the process. In 349
case of medicines prioritized by WHO, WHO can organize responses to questions, 350
discussion via tele- or video-conferences or joint meetings with SRA experts to 351
facilitate the process. 352
e. Participating NMRAs issue a decision within 90 days from acceptance of the 353
submission for processing according to the Procedure. 354
f. Achievement of registrations processed according to this Procedure is notified by the 355
company to WHO in order to monitor the Procedure performance. Information about 356
registered medicine, deviations from SRA decision, dates of submission and 357
experience is notified according to Annex 9. 358
4. Post-registration management 359
a. Participating companies commit to inform NMRA(s) concerned about relevant 360
variations or regulatory actions and submit corresponding applications for variations 361
in line with national requirements. 362
b. Notification of completion of post-authorization commitments agreed with reference 363
SRA is subject to specific agreements with individual participating NMRAs. 364
c. Concerned NMRAs are entitled to approach reference SRAs in case of doubt for the 365
most updated information about the conditions of SRA product approval. 366
367
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368
369
Figure 1: A summary of the scheme of steps in the Procedure and corresponding documentation. 370 371
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ANNEX 1 372
Agreement of NMRA to participate in the Collaborative Procedure in 373
Assessment and Accelerated National Registration of Pharmaceutical Products 374
Approved by Stringent Regulatory Authorities 375
Coordinated by the World Health Organization 376
377
Details of national medicines regulatory authority (NMRA) 378
Name of NMRA: Click here to enter text. ________________________ (“the NMRA”) 379
Postal address: Click here to enter text. _____________________________________ 380
Country: Click here to enter text. _____________________________ (“the Country”) 381
Telephone number (please include codes): Click here to enter text. _______________ 382
Email: Click here to enter text. ____________________________________________ 383
Scope of agreement 384
Applicants for national registration of a pharmaceutical product approved by a stringent regulatory 385
authority (SRA) (hereafter referred to as “Applicants”) may express their interest to the NMRA for the 386
assessment and accelerated registration of this product (“the Product”) in the Country under the 387
“Collaborative Procedure in Assessment and Accelerated National Registration of Pharmaceutical Products 388
Approved by Stringent Regulatory Authorities” (hereafter referred to as “the Collaborative SRA Procedure” or 389
“the Procedure”).6 390
Subject to the NMRA agreeing to participate in the Procedure and conduct such assessment and 391
consider such accelerated registration of the Product under the Procedure, the NMRA hereby confirms for 392
each such Product that it will adhere to, and collaborate with, the Applicant of the Product and if relevant with 393
respective SRA and the WHO in accordance with, the terms of the Procedure. 394
Confidentiality of information 395
Any information and documentation relating to the Product and provided by the Applicant or SRA to 396
the NMRA under the Procedure may include but shall not necessarily be limited to: 397
‒ the registration dossier as defined by the Procedure 398
‒ the full SRA assessment and inspection outcomes (reports); 399
6 If the applicant for national registration is not the same as the SRA registration/marketing authorization holder, the SRA
registration holder must confirm to the NMRA by an authorization letter that the applicant is acting for, or pursuant to rights derived from, the SRA registration holder, and that the SRA registration holder agrees with the application of the Procedure in the country concerned.
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‒ information and documentation on variations, as well as information and documentation on any 400
actions taken by SRA post-national registration of the Product; 401
‒ all such data, reports, information and documentation being hereinafter referred to as “the 402 Information”. 403
As regards sharing the outcomes of assessments and inspections, full SRA assessment and inspection 404
reports are shared by Applicants with participating NMRAs with an agreement of respective SRA. Should any 405
data in assessment and inspection report be hidden from whatever reason, nature and scope of missing data 406
will be clearly indicated. Sharing of any data by SRAs is subject to consent of data owner. 407
The Applicant and SRA agree to make the Information available to the NMRA exclusively for the 408
purpose of the assessment and accelerated registration of the Product in the Country and any postregistration 409
processes that may be required, in accordance with and subject to the terms of the Procedure (“the Purpose”). 410
The NMRA agrees to treat any Information provided by the Applicant and SRA as aforesaid as strictly 411
confidential and proprietary to Applicant, parties collaborating with Applicant and/or SRA as relevant. In this 412
regard, the NMRA agrees to use such Information only for the Purpose and to make no other use thereof. 413
Thus, the NMRA undertakes to maintain the Information received from Applicant and SRA in strict 414
confidence, and to take all reasonable measures to ensure that: 415
■ the Information received from the Applicant or SRA shall not be used for any purpose other than 416
the Purpose; 417
■ the Information shall only be disclosed to persons who have a need to know for the aforesaid 418
Purpose and are bound by confidentiality undertakings in respect of such information and 419
documentation which are no less stringent than those contained herein. 420
The NMRA warrants and represents that it has adequate procedures in place to ensure compliance with 421
its aforesaid obligations. 422
The obligations of confidentiality and restrictions on use contained herein shall not cease on completion 423
of the Purpose. 424
The obligations of confidentiality and restrictions on use contained herein shall not apply to any part of 425
the Information which the NMRA is clearly able to demonstrate: 426
■ was in the public domain or the subject of public knowledge at the time of disclosure by 427
Applicant or SRA to the NMRA under the Procedure; or 428
■ becomes part of the public domain or the subject of public knowledge through no fault of the 429
NMRA; or 430
■ is required to be disclosed by law, provided that the NMRA shall in such event immediately 431
notify SRA and the Applicant in writing of such obligation and shall provide adequate 432
opportunity to SRA and/or the Applicant to object to such disclosure or request confidential 433
treatment thereof. 434
Upon completion of the Purpose, the NMRA shall cease all use and make no further use of the 435
Information disclosed to it under the Procedure, and shall promptly destroy the Information received from 436
Applicant and SRA, which is in tangible or other form and is not archived in accordance with NMRA 437
established archival procedures. The Purpose for each product shall be deemed completed as soon as: 438
Working document QAS/17.704
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the SRA authorization holder/Applicant discontinues participation in the Procedure for the particular 439
product; 440
the Product is deregistered by the NMRA and/or loses SRA authorization. 441
The NMRA agrees that it has no right in or to the Information and that nothing contained herein shall 442
be construed, by implication or otherwise, as the grant of a licence to the NMRA to use the Information other 443
than for the Purpose. 444
Should WHO staff or external experts independent on the Applicant or NMRA be provided with an 445
access to the Information in order to co-ordinate the Collaborative SRA procedure or provide an expert 446
opinion, an access to the Information shall be subject to a confidentiality undertaking. 447
Timelines 448
In respect of each Product which the NMRA accepts to assess and consider under the Procedure, the 449
NMRA undertakes to abide by the terms of the Procedure, including but not limited to the timelines 450
designed for processing each application. 451
Miscellaneous 452
The NMRA agrees that WHO may list its name on the WHO/PQT website as a participant in the SRA 453
Procedure. Except as provided hereinbefore, neither party shall, without the prior written consent of the other 454
party, refer to the relationship of the parties under this Agreement and/or to the relationship of the other party 455
to the Product, the Information and/or the Purpose, in any statement or material of an advertising or 456
promotional nature. 457
This Agreement shall not be modified except by mutual agreement of WHO and the NMRA in writing. 458
The NMRA furthermore undertakes to promptly inform WHO/PQT of any circumstances or change in 459
circumstances that may affect the implementation of this Agreement and its participation in the Procedure. 460
This Agreement can be invalidated by a written note of NMRA to WHO. Validity of this Agreement expires 461
at termination of the Procedure, which will be publicly announced. 462
Focal point(s) for communication 463
The NMRA has designated the person(s) listed below to act as a communication focal point (s) 464
concerning the Procedure. 465
466
Title …………………………………… 467
Name ………………………………………………………………………………. 468
Position ……………………………………………………………………..……… 469
Email ………………………………….. 470
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Telephone ………………………………….. 471
472
Title …………………………………… 473
Name ………………………………………………………………………………. 474
Position ……………………………………………………………………..……… 475
Email ………………………………….. 476
Telephone ………………………………….. 477
478
479
Agreed and accepted 480
For the NMRA 481
482
Signature: _____________________________________________________________ 483
Name: Click here to enter text. ____________________________________________ 484
Title: Click here to enter text. _____________________________________________ 485
Place and date: Click here to enter text. _____________________________________ 486
487
488
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ANNEX 2 489
Example of information included in the list of participating SRAs 490
491
Acronyms 492
SRA stringent regulatory authority as stipulated in WHO 493
MAH marketing authorization holder 494
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495
(Blank page) 496
497
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NMRA national
medicines regulatory
authority
The Procedure -
Collaborative Procedure in
Assessment and
Accelerated National
Registration of
Pharmaceutical Products
Approved by Stringent
Regulatory Authorities
Details of SRA agreeing to
proceed, in principle, in
line with conditions of the
Procedure
Provision of consent or “no objection
statement” to share the assessment and
inspection reports issued by the SRA
Agreement to authenticate the SRA issued assessment and
inspection reports on request of NMRAs, which have received
an application for registration according to the Procedure
Provision of additional
explanation with scientific
justification of granted
authorization to NMRAs, which
have received an application for
registration according to the
Procedure
SRA position to post-
registration management
of medicinal product
registered by NMRA
using the Procedure
Name and address of SRA
Focal point for
communication in matters
related to the Procedure
Example 1: (EMA - current situation)
EMA does not object to MAHs of centrally
authorised medicinal products and holders of
scientific opinions according to Article 58
using final assessment and inspection reports
in support of national registrations. However,
when documents are provided to authorities in
third countries by the MAH or holder of
scientific opinion, personal information need
to be redacted.
The ‘no objection statement’ is provided by
EMA on request of individual MAHs. The
request has to specify each NMRA with which
the assessment and inspection reports will be
shared.
The ‘no objection statement’ is normally
issued within 10 days.
Example 1: (EMA - current position)
It is expected that requests for authentication of documents will be
exceptional.
Subject to previous agreement with MAH (See Annex 3 of the Procedure) the EMA can provide to requesting NMRA the full
assessment reports or other relevant assessment documents. As
regards inspection reports, it is expected that the applicant in the third country to the EU will forward the latest inspection report(s)
for the manufacturing site(s) to the concerned authority.
Communication with the relevant Member State authority might be necessary to confirm authenticity.
Possible, on the understanding
that these situations are
exceptional and that request is channeled by WHO or the
respective NMRA, not by the
company.
E.g.:
EMA supports the obligation of MAHs to
keep national regulators
informed of due major variations or line
extensions, however for the
Procedure EMA would suggest to focus on initial
applications.
Example 2: (hypothetical SRA)
SRA does not object to MAHs of centrally
authorised medicinal products and holders of
scientific opinions according to Article 58
using final assessment and inspection reports
Working document QAS/17.704
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in support of national registrations. However,
when documents are provided to authorities in
third countries by the MAH or holder of
scientific opinion, personal information need
to be redacted.
The general statement confirming SRA
position and conditions for sharing of the final
assessment and inspection reports are made
publicly available at
www………………………………………….
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498
(Blank page) 499
500
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ANNEX 3 501
Proposed documentation for collaborative registration process for 502
SRA-approved medicinal products 503
504
Notes: 505
The format of the documentation corresponds to CTD in accordance with ICH format/content. From 506
practical reasons non/clinical (Module IV) and clinical data (Module V) are replaced by summaries 507
included in Module II. Should there be a need of more extensive data from Module IV and Module V, 508
these are available on request. 509
Confidentiality of submitted data and no-disclosure to a third party is – in addition to relevant 510
national legislation and organizational measures applied by NMRs participating in the Procedure – 511
assured by a commitment on confidentiality that represents integral part of the Procedure7 (Annex 1), 512
is signed by representatives of participating NMRAs and archived by WHO. 513
514
7 Collaborative Procedure in Assessment and Accelerated National Registration of Pharmaceutical Products Approved by Stringent
Regulatory Authorities, facilitated by WHO.
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515
ADAPTED MODULE 1 516
Documentation to be provided Comments
1.0 Letter of application Cover letter in
English or French as
applicable to the
region
Attachments to the Letter:
Annex 4A of the
SRA procedure
Annex 4B of the
SRA procedure
Annex 5 Includes information as
specified in Commitment
letter 1 (additional
administrative data) and
Commitment letter 2
(additional stability data for
climatic zones). Any
differences in dossier
submitted to SRA should be
explained, including
differences in Product
Information.
Submitted in English
or French as
applicable to the
region
1.1 Comprehensive Table of
Contents
Comprehensive TOC
including Module 1
information
1.2 Quality Information
Summary (QIS-SRA)
This will be included instead
of a country-specific
application form
Refer to Annex 9 for
the QIS–SRA
template
To be included in the
adapted Module 1
1.3 Product Information
1.3.1 Package Insert or SmPC Product information as
applicable for region where
application will be submitted
Submitted in English
or French as
applicable to the
region
1.3.2 Patient Information Leaflet
or Package leaflet
Mock-ups Submitted in English
or French as
applicable to the
region
1.3.3 Labelling Mock-ups Language and
information to reflect
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Documentation to be provided Comments
national requirements
1.4 Marketing Authorization
from SRA
1.4.1 Marketing Authorization
from SRA
YES
1.4.2 Assessment report from SRA
(Access to the full
assessment report from the
SRA used as reference
country, if available)
Agreement from the company
to allow SRA to share the
report with WHO and NRAs.
Prior to sharing, the SRA and
company should agree on the
content of the document that
is shared. If fully justified,
sentences referring to highly
confidential information
and/or highly sensitive data
and/or not related to the
product assessment data could
be masked
Please note that this
time of document is
available only if
product registered in
Europe, via
Centralized Procedure
Public reports are
preferred as they
already contain all
useful information
except those
considered to give a
competitive
advantage.
The sharing process is
facilitated by WHO,
between SRA and
NRAs.
1.5 GMP Certification
1.5.1 Copy of the GMP certificate
of the API supplier, if
available
YES
If not available, statement
signed by drug product site
QP to be provided
Not always available
for the time being.
No legalization is
required…
1.5.2 Copy of the GMP certificate
of the FPP manufacturer(s)
YES No legalization is
required
1.5.3 GMP inspection report of the
manufacturing site(s) (FPP)
from any SRA
Agreement from the company
to allow SRA to share the
report with WHO and NRAs.
Prior to sharing, the SRA and
company should agree on the
content of the document that
is shared. If fully justified,
sentences referring to highly
confidential information
and/or highly sensitive data
and/or not related to the
Public reports are
preferred as they
already contain all
useful information
except those
considered to give a
competitive
advantage.
The sharing process is
facilitated by WHO,
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Documentation to be provided Comments
product assessment data could
be masked
between SRA and
NRAs.
1.6 Other documentation
If generic dossier:
Full GCP inspection report
of the bioequivalence study
from any SRA, if any
Agreement from the company
to allow SRA to share the
report with WHO and NRAs.
Prior to sharing, the SRA and
company should agree on the
content of the document that
is shared. If fully justified,
sentences referring to highly
confidential information
and/or highly sensitive data
and/or not related to the
product assessment data could
be masked
Public reports are
preferred as they
already contain all
useful information
except those
considered to give a
competitive
advantage.
The sharing process is
facilitated by WHO,
between SRA and
NRAs.
517
518
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ADAPTED MODULE 2 519
Documentation to be
provided/comments
comments
2.3 Quality Overall Summary YES In accordance with
ICH CTD format (and
not WHO PQP
template)
2.6 Non clinical summary * YES No submission of 2.4
Module 2.6 identical
to the one submitted to
the SRA
*See documentation
requirement for line
extensions below
2.7 Clinical Summary ** YES No submission of 2.5
Module 2.7 identical
to the one submitted to
the SRA
520
* In case of line extension, since 2.6 is usually not available (since we cross refer to the initial 521
NDE) we do provide 2.4 and 2.5 and 2.7 (if available). 522
**In the case of generic medicines where a Clinical Summary is not available, the Clinical 523
Overview (Module 2.5) should be included. 524
525
MODULE 3 CMC DOCUMENTATION 526
3.2. BODY OF DATA (CTD
FORMAT)
To be provided/comments comments
For each active substance
3.2.S DRUG SUBSTANCE Corresponding to the open
part of the APIMF
3.2.S.1 General Information YES
3.2.S.1.1 Nomenclature YES
3.2.S.1.2 Structure YES
3.2.S.1.3 General Properties YES
3.2.S.2 Manufacture YES
3.2.S.2.1 Manufacturer(s) YES
3.2.S.2.2 Description of
manufacturing process and
YES
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3.2. BODY OF DATA (CTD
FORMAT)
To be provided/comments comments
process controls
3.2.S.2.3 Control of materials YES
3.2.S.2.4 Controls of critical steps and
intermediates
YES
3.2.S.2.5 Process validation and/or
evaluation
YES
3.2.S.2.6 Manufacturing process
development
YES
3.2.S.3 Characterization YES
3.2.S.3.1 Elucidation of structure and
other characteristics
YES
3.2.S.3.2 Impurities YES
3.2.S.4 Control of drug substance YES
3.2.S.4.1 Specification YES
3.2.S.4.2 Analytical procedures YES
3.2.S.4.3 Validation of analytical
procedures
YES
3.2.S.4.4 Batch analyses YES
3.2.S.4.5 Justification of Specification YES
3.2.S.5 Reference standards or
materials
YES
3.2.S.6 Container closure system YES
3.2.S.7 Stability YES
3.2.S.7.1 Stability summary and
conclusions
YES
3.2.S.7.2 Post-approval stability
protocol and stability
commitment
YES
3.2.S.7.3 Stability data YES
3.2.P DRUG PRODUCT
3.2.P.1 Description and composition
of the drug product
YES
3.2.P.2 Pharmaceutical development YES
3.2.P.2.1 Components of the Drug
Product (name, dosage form)
YES
3.2.P.2.1.1 Drug Substance (name,
dosage form)
YES
3.2.P.2.1.2 Excipients (name, dosage
form)
YES
3.2.P.2.2 Drug Product (name, dosage
form)
YES
3.2.P.2.2.1 Formulation Development
(name, dosage form)
YES
3.2.P.2.2.2 Overages (name, dosage YES
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3.2. BODY OF DATA (CTD
FORMAT)
To be provided/comments comments
form)
3.2.P.2.2.3 Physicochemical and
Biological Properties (name,
dosage form)
YES
3.2.P.2.3 Manufacturing Process
Development (name, dosage
form)
YES
3.2.P.2.4 Container Closure System
(name, dosage form)
YES
3.2.P.2.5 Microbiological Attributes
(name, dosage form)
YES
3.2.P.2.6 Compatibility (name, dosage
form)
YES
3.2.P.3 Manufacture YES
3.2.P.3.1 Manufacturer(s) YES
3.2.P.3.2 Batch formula YES
3.2.P.3.3 Description of
manufacturing process and
process controls
YES
3.2.P.3.4 Controls of critical steps and
intermediates
YES
3.2.P.3.5 Process validation and / or
evaluation
YES
3.2.P.4 Control of excipients YES
3.2.P.4.1 Specifications YES
3.2.P.4.2 Analytical procedures YES
3.2.P.4.3 Validation of analytical
procedures
YES
3.2.P.4.4 Justification of
specifications
YES
3.2.P.4.5 Excipients of human or
animal origin
YES
3.2.P.4.6 Novel Excipients (ref to A 3) YES
3.2.P.5 Control of drug product YES
3.2.P.5.1 Specification(s) YES
3.2.P.5.2 Analytical procedures YES
3.2.P.5.3 Validation of analytical
procedures
YES
3.2.P.5.4 Batch analyses YES
3.2.P.5.5 Characterization of
impurities
YES
3.2.P.5.6 Justification of
specification(s)
YES
3.2.P.6 Reference standards or
materials
YES
3.2.P.7 Container closure system YES
3.2.P.8 Stability if zone III – IV are not
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3.2. BODY OF DATA (CTD
FORMAT)
To be provided/comments comments
available, commitment and
protocol will be joined; and
if any, any preliminary data
will be provided for these
conditions (see commitment
letter)
3.2.P.8.1 Stability summary and
conclusions
YES
3.2.P.8.2 Post approval stability
protocol and stability
commitment
YES
3.2.P.8.3 Stability data YES
3.2.A APPENDICES
3.2.A.1 Facilities and equipment -
3.2.A.2 Adventitious agents safety
evaluation
YES
3.2.A.3 Excipients -
3.2.R REGIONAL
INFORMATION
Copy of the certificate of
analysis of the finished
product
YES
3.3 LITERATURE
REFERENCES
If any
527
528
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ANNEX 4 529
Requirements for provision of a “bridging” report for SRA-approved 530
medicines for consideration of registration in non-SRA settings 531
532
It is expected and general practice that medicines authorized for use by SRAs are approved for the 533
conditions of use relevant for the respective SRA territory. When a SRA-approved product is 534
submitted for the regulatory approval in a country where conditions of use or benefit-risk profile of 535
the medicine can differ, it is assumed that the applicant for registration (marketing authorization) is 536
able to support the application by providing evidence justifying positive benefit-risk profile for 537
proposed conditions of use also for this country. Since SRA assessments do not always confirm 538
availability of data and questions relevant for use in other environments, the SRA assessment reports 539
can be considered in this respect to be incomplete. Currently it is only EMA’s scientific opinion 540
according to EU Regulation (EC) No 726/2004 EU Art 58, which may be considered to significantly 541
address these questions. 542
543
Differences in target population, epidemiology and other features of the disease, concomitantly used 544
drugs and hence the interaction potential, local treatment and diagnostic modalities and other factors 545
can substantially affect benefit-risk of a medicinal product. There can be also issues related to certain 546
quality parameters, especially in relation to the stability under different climatic conditions. 547
Therefore, in order to provide regulators in target countries with information relevant for use of the 548
product in their countries it is proposed to develop a bridging report supplementing the SRA 549
assessment report (quality, safety) and the quality and clinical overviews provided in Module 2 of the 550
CTD. 551
552
Such a bridging report should especially provide the applicant’s with the justification of the: 553
relevance of studied population for the target population (ethnicity, gender representation, age 554
groups, …) as regards demonstration safety and efficacy, 555
relevance of SRA-approved conditions of use as regards epidemiology and disease pattern in 556
the target countries as well as other implications for efficacy and safety, e.g. feasibility of 557
monitoring and precautionary measures (e.g. resistance testing or therapeutic drug 558
monitoring), 559
food and drug-drug interactions relevant for target countries that are not discussed in the SRA 560
assessment report, 561
therapeutic role of a product and its recommended use according to relevant national and 562
international treatment guidelines, 563
other related quality issues, including but not limited to, storage conditions and conditions of 564
administration and use. 565
566
Such report is justified in the case that SRA assessment report does not cover these elements of 567
assessment to sufficient extent. Provision of a bridging report should not be mandatory, but can 568
substantially facilitate conduct of the regulatory assessment, reduce extent of potential regulatory 569
questions and shorten duration of regulatory approval process. Such report can be valid for more than 570
one country, where conditions of use of the medicine are seen in principle similar. Similarly like in 571
the case of overviews submitted in Module 2, the bridging report should be prepared by expert(s) 572
contracted by an applicant, who will attach the professional CV(s). 573
574
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AANNNNEEXX 55 575
QQUUAALLIITTYY IINNFFOORRMMAATTIIOONN SSUUMMMMAARRYY OOFF TTHHEE FFPPPP 576
AAPPPPRROOVVEEDD BBYY TTHHEE RREEFFEERREENNCCEE SSRRAA ((QQIISS--SSRRAA)) 577 FOREWORD 578
Reference: Collaborative Procedure in the Assessment and Accelerated National Registration of 579 Pharmaceutical Products Approved by Stringent Regulatory Authorities 580
Acronym: SRA Collaborative Registration Procedure 581
The WHO Guidelines on submission of documentation for prequalification of finished pharmaceutical 582 products approved by stringent regulatory authorities define a template of simplified Quality Information 583 Summary (QIS) to summarize the key quality parameters of a product approved by a Stringent Regulatory 584 Authority (SRA) for WHO prequalification. It was realized that this simplified QIS can be a useful instrument 585 to share (under condition of confidentiality) the essential quality parameters characterizing each medicinal 586 product approved by Stringent Regulatory Authorities in order to accelerate national decisions on registration. 587 However, experience from the pilot of the SRA Collaborative Registration Procedure revealed that the 588 simplified WHO QIS does not contain certain data which would facilitate verification of ‘sameness’ of the 589 product for the purpose of the collaborative registration of SRA-approved medicines. Therefore the 590 information content of the template was extended to the form of ‘QIS-SRA’. 591
The QIS-SRA template should be completed by the applicant and verified by the reference SRA, optimally in 592 the initial stage of the collaborative process, when the applicant (MAH) requests the SRA cooperation and 593 grants consent with information sharing. Should data in application for national registration deviate from data 594 approved by the reference SRA, this should be clearly indicated and summarised in section B10. The QIS-595 SRA should be submitted as a part of the application for national registration together with other documents 596 stipulated by the SRA Collaborative Registration Procedure. A copy should also be provided in Word format. 597
Whenever any variation to the FPP that affects the QIS-SRA has been approved by the reference SRA, the 598 QIS-SRA should be revised (using track change mode) and resubmitted to relevant regulatory authorities in 599 Word format together with the regulatory letter or other relevant document confirming approval of the 600 respective variation. 601
602
The QIS-SRA is specifically designed for the purpose of SRA Collaborative Registration Procedure and 603 should not be confused with other formats of Quality Information Summaries that are used for the 604 purpose of WHO prequalification. 605
When completing the QIS-SRA template, this covering Foreword should be deleted. 606
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(Blank page) 607
608
609
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QUALITY INFORMATION SUMMARY OF THE FPP 610 APPROVED BY THE REFERENCE SRA (QIS-SRA) 611
A. Medicinal product subject to SRA Collaborative Registration Procedure 612
A.1 Reference stringent regulatory authority
A2. Product SRA registration/authorisation number
613
Information as currently approved by the reference SRA Information as submitted in the application(s) for national
registration(s)
Deviation
ref#8
A3. Proprietary name of finished pharmaceutical product (FPP) in the
SRA country/region
A3. Proprietary name of finished pharmaceutical product (FPP) in the
application
A4. Innovator or multisource (generic) FPP A4. Innovator or multisource (generic) FPP
A5. Name of the holder of the SRA Marketing Authorization and official
address
A5. Name of the applicant for the national registration and official
address
A6. INN of active pharmaceutical ingredient(s) [API(s)], including form
(salt, hydrate, solvate, etc)
A6. INN of active pharmaceutical ingredient(s) [API(s)], including form
(salt, hydrate, solvate, etc)
A7. Dosage form and strength A7. Dosage form and strength
8 In the case that there are differences between national application and data approved by the reference SRA, assign a reference number and discuss/Explain/ each deviation
in the part B10.
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A8. Product description (as in Product Information, e.g. White, film-
coated, capsule shaped tablets debossed with ‘X’ and score line on one
side and plain on other side.)
A8. Product description (as in Product Information)
A9. Primary and secondary packaging material(s) and pack size(s) (all
pack types)
A9. Primary and secondary packaging material(s) and pack size(s) (all
pack types)
A10. Storage conditions (as in Product Information) A10. Storage conditions (as in Product Information)
A11. Shelf-life of FPP (including in-use periods, where applicable) A11. Shelf-life of FPP (including in-use periods, where applicable)
A12. Names of all approved manufacturers of FPP, physical address(es)
of manufacturing site(s) (and unit if applicable), including intermediates,
primary packaging site and release testing (indicate function of each site)
A12. Names of all applied for manufacturers of FPP, physical address(es)
of manufacturing site(s) (and unit if applicable), including intermediates,
primary packaging site and release testing (indicate function of each site)
A13. FPP storage conditions and duration over which stability, as
reported to the SRA, was established (e.g. 30±2°C/75±5%RH for 24
months, 40±2°C/75±5%RH for 6 months):
A13. FPP storage conditions and duration over which stability is
demonstrated in the application (e.g. 30±2°C/75±5%RH for 24 months,
40±2°C/75±5%RH for 6 months)
Long term (real time in months) Long term (real time in months)
Intermediate (duration in months) Intermediate (duration in months)
Accelerated (duration in months) Accelerated (duration in months)
614
615
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616
B. Information that is considered confidential 617
Information as currently approved by the reference SRA Information as submitted in the application(s) for national
registration(s)
Deviation
ref#1
B1. Names of all approved API manufacturers, physical address(es) of
manufacturing site(s) (and unit if applicable), incl. intermediates,
contractors and release testing (indicate function of each site)
B1. Names of all applied for API manufacturers, physical address(es) of
manufacturing site(s) (and unit if applicable), incl. intermediates,
contractors and release testing (indicate function of each site)
B2. APIMF/DMF version number(s) and date(s), if relevant B2. APIMF/DMF version number(s) and date(s), if relevant
Name of API API manufacturer APIMF/DMF version
number(s) and date(s)
Name of API API manufacturer APIMF/DMF version
number(s) and date(s)
B3. API specifications of the FPP manufacturer B3. API specifications of the FPP manufacturer
Standard (e.g. Ph.Int., Ph.Eur., BP, USP, in-house) Standard (e.g. Ph.Int., Ph.Eur., BP, USP, in-house)
Specification reference number and version Specification reference number and version
Test Acceptance criteria Analytical procedure
(Type/Source/Version)
Test Acceptance criteria Analytical procedure
(Type/Source/Version)
Description Description
Identification Identification
Impurities Impurities
Assay Assay
etc. etc.
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B4. API container closure system and re-test period B4. API container closure system and re-test period
Container closure system Storage statement Re-test period9 Container closure system Storage statement Re-test period
2
618 619 620 B5. FPP composition (formulation) information B5. FPP composition (formulation) information
Component and
quality standard
Function Unit composition Batch composition
(largest approved size)
Component and
quality standard
Function Unit composition Batch composition
(largest approved size)
Quantity per
unit or per ml
% Theoretical
quantity/batch
% Quantity per
unit or per ml
% Theoretical
quantity/batch
%
<complete with appropriate title e.g. core tablet, contents of capsule, powder for injection>
Subtotal 1 Subtotal 1
<complete with appropriate title e.g. film-coating>
Subtotal 2 Subtotal 2
Total Total
Batch size in number of units, where applicable Batch size in number of units, where applicable
Additionally approved batch sizes – in number of units
or kg, where applicable (add as many rows as necessary)
Additionally approved batch sizes – in number of units or
kg, where applicable (add as many rows as necessary)
9 Indicate if a shelf life is proposed in lieu of a re-test period (e.g. in the case of labile APIs).
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Composition of all components purchased as mixtures (e.g. colorants, coatings,
capsule shells, imprinting inks):
Composition of all components purchased as mixtures (e.g. colorants, coatings,
capsule shells, imprinting inks):
B6. FPP manufacture B6. FPP manufacture
Master production document reference
number and version
Master production document reference
number and version
B7. FPP specifications B7. FPP specifications
Standard (e.g. Ph.Int., BP, USP, in-house) Standard (e.g. Ph.Int., BP, USP, in-house)
Specification reference number and version/ effective date Specification reference number and version/ effective date
Test Acceptance criteria
(release)
Acceptance criteria
(shelf-life)
Analytical procedure
(type/source/version)
Test Acceptance criteria
(release)
Acceptance criteria
(shelf-life)
Analytical procedure
(type/source/version)
Description Description
Identification Identification
Impurities Impurities
Assay Assay
etc. etc.
B8. Pharmacokinetic / safety / efficacy related information used for SRA
approval of multisource products. Indicate:
B8. Pharmacokinetic / safety / efficacy related information submitted in
the application for national registration of multisource products. Indicate:
Type of study “X” in appropriate box Comparator product Type of study “X” in appropriate box Comparator product
Bioequivalence Bioequivalence
BCS-based biowaiver BCS-based biowaiver
Other (specify) Other (specify)
No study No study
Notes / clarifications Notes / clarifications
621 622
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B9. List of variations pending in the SRA to the date of verification
Variation
number
Variation Type of variation according
to SRA regulations
623
B10. Discussion of differences between national application and data approved by the reference SRA
Deviation
ref #
Data submitted for national registration which deviates from data
approved by the reference SRA presented above. Mention also
deviations in content of Product information, especially those related
to indications, contraindications and posology.
Explanatory note
624 625
C1. Confirmation of content and verification by the reference SRA
Date of completion by the applicant Name of person representing the
applicant who completed the
QIS-SRA
Position in the organization
Date of verification by the reference
SRA
Part B10 is exempted from verification
Person representing the
reference SRA who verified the
QIS-SRA information
Position in the organization
626 627
628
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Change History to QIS-SRA and Product Information 629
Date of revision
(reported variation*) Revision/variation description
* Variations approved by the SRA after national registration of the FPP and affecting only the QIS-SRA and/or Product Information should be reported in the change 630 history. 631
632
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(Blank page) 633
634
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ANNEX 6 635
Date:……………………………………………………. 636
637
To: ………………………………………………………. 638
639
RE: declaration to the <National Medicines Regulatory Authority (NMRA)> to initiate and proceed 640
with registration of <Product> in line with the Procedure 641
642
643
Dear <NMRA>, 644
645
On behalf of <Company>, the <Marketing Authorization Holder> in <Stringent Regulatory 646
Authority country / region > of the medicinal that is registered with the <Stringent Regulatory 647
Authority> under the <Reference number>, and solely for the purpose of the “Collaborative 648
Procedure in the Assessment and Accelerated National Registration of Pharmaceutical Products 649
Approved by Stringent Regulatory Authorities” (The Procedure - <date; version>) organized by 650
WHO. 651
I, <Company representative name > certify that: 652
1. The Product submitted for registration is identical in all aspects of manufacturing and quality 653
to that currently approved by the <Stringent Regulatory Authority (SRA)> under the 654
<Reference number>, including formulation, method and site(s) of manufacture, sources of 655
active and excipient starting materials, quality specifications and control methods of the 656
Product and starting material, packaging, shelf-life and product information. 657
658
If applicable: 659
The only exception(s) from the conditions approved by the <Stringent Regulatory Authority 660
(SRA)> are: 661
<Deviations from current SRA approval, explanations and related commitments> 662
663
2. Submitted Assessment and Inspection Reports are complete reports as issued by the 664
<Stringent Regulatory Authority (SRA)>. The <Stringent Regulatory Authority (SRA)> has 665
been authorized by the <Company> to share with <NMRA focal point > in full extent all 666
Working document QAS/17.704
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<Product> related regulatory information, including information of a confidential nature. A 667
copy of the authorization letter to the <Stringent Regulatory Authority (SRA)> is attached as 668
an <Appendix No 1>. 669
670
If applicable: 671
The only data hidden in the Assessment and/or Inspection Report of the <Stringent 672
Regulatory Authority (SRA)> concern <nature and scope of missing data> and are hidden 673
because of <reason>. 674
675
3. Information included in the registration dossier is identical with data currently approved by 676
the <SRA>. As for the purpose of The Procedure, the Module IV of the registration dossier in 677
CTD format containing nonclinical data and the Module V containing clinical data are 678
replaced by respective summaries included in the Module II, the <Company> commits to 679
submit without delay the non-submitted data on request of the <NMRA>. 680
681
4. On behalf of <Company>, the <Marketing Authorization Holder> in <Stringent Regulatory 682
Authority country/region> of the above-referenced regulated product, I hereby commit to 683
a. Supplying any additional administrative information in accordance with local 684
regulations or upon request from the <National Regulatory Authority> as soon as 685
possible during the process. 686
b. Should the registration be granted, submitting in accordance with local regulations 687
without delay all relevant variations as approved by the <Stringent Regulatory 688
Authority country/region> . 689
c. Supplying in accordance with local regulations any information about <Stringent 690
Regulatory Authority> regulatory actions relevant to the <Product> , including 691
suspension or termination of registration, should it happen from whichever reason. 692
693
694
695
Signature 696
<Appendix No 1>: Copy of the authorization letter to the <Stringent Regulatory Authority 697
(SRA)> 698
699
700
701
If appropriate: 702
Working document QAS/17.704
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Current storage conditions approved by the <Stringent Regulatory Authority country/region> 703
are <Storage conditions approved by SRA>. On behalf of <Company>, the <Marketing 704
Authorization Holder> in <Stringent Regulatory Authority country/region> of the above-705
referenced regulated product, I hereby commit to supplying within <time period> results of 706
stability data applicable to Zones III-IVa or IVb should any of these stability zones be 707
applicable to your country. 708
In addition, <National Regulatory Authority> will be informed of any Out Of Specification 709
(OOS) results during the study and protocol for the relevant applicable zones. 710
711
The WHO Collaborative registration processional/s <Name/s> has/have been provided with 712
the <Product> dossier to facilitate The Procedure and is/are authorized by the <Company> to 713
communicate on the Product related issues with <NMRA representatives >. By this letter the 714
<NMRA> is authorised to share with WHO in full extent all <Product> related regulatory 715
information and communicate for the purpose of The Procedure on the <Product> related 716
regulatory issues, including exchange of confidential information. 717
718
Should the local applicant be different legal entity from a holder of SRA marketing 719
authorization or from a holder of scientific opinion in case of EU Article 58 procedures, the 720
relationship should be clarified and agreements assuring information flow should be adjusted 721
to this situation. 722
723
724
Working document QAS/17.704
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725
ANNEX 7A 726
727
Date: 728
729
To 730
731
RE: <Stringent Regulatory Authority> Sharing of Non-Public Information 732
concerning <Product> with the <National Regulatory Authority> and the World 733
Health Organization (WHO)10
734
735
Dear [<Stringent Regulatory Authority>], 736
On behalf of <Company>, the <Marketing Authorization Holder> in <Stringent Regulatory 737
Authority country/region> of the above-referenced regulated product, I authorize the 738
<Stringent Regulatory Authority> to share the information described below (“Information”) 739
only with <National Regulatory Authority focal point – contact person/function> and the 740
World Health Organization (WHO) <contact person/function> solely for the purpose of the 741
“Collaborative Procedure in Assessment and Accelerated National Registration of 742
Pharmaceutical Products Approved by Stringent Regulatory”<date; version>. 743
Confidentiality agreements are in place between <Company> and WHO. 744
I understand that the Information may contain confidential commercial or financial 745
information or trade secrets that are exempt from public disclosure. I agree to hold 746
<Stringent Regulatory Authority> harmless for any injury caused by <Stringent Regulatory 747
Authority>'s sharing of the Information with the <National Regulatory Authority> and the 748
WHO under the terms set out herein. 749
Information authorized to be shared with the <National Regulatory Authority and/or WHO: 750
all available quality data on <Product>; 751
all available non-clinical data on <Product>; 752
all available clinical data on <Product>; 753
10 During the Facilitated Process in National Registration of Pharmaceutical Products
approved by stringent Regulatory Authorities <date; version>, WHO plays a facilitating
role in process.
Working document QAS/17.704
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any other document reasonably requested by the <National Regulatory Authority or 754
WHO> during the evaluation procedure; 755
all other information regarding GxP inspections and <Product> assessment. 756
757
Authorization is given to <Stringent Regulatory Authority> to provide the Information 758
without deleting confidential, commercial or financial, or trade secret information. 759
As indicated by my signature, I am authorized to provide this consent on behalf of 760
<Company> and my full name, title, address, telephone number and email address are set 761
out below for verification. 762
763
764
765
Sincerely, 766
767
768
Name 769
Title 770
Address 771
Company 772
Email: 773
Telephone number: 774
Fax number: 775
776
777
Cc: 778
779
Working document QAS/17.704
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ANNEX 7B 780
Date: 781
782
<Company> 783
784
RE: Request to <Stringent Regulatory Authority> for a Permission to <Company> To 785
Share <Stringent Regulatory Authority>’s Non-Public Information concerning 786
<Product> with the <National Regulatory Authority/ies> and the World Health 787
Organization1 788
789
Dear <SRA>, 790
<Company> as a <Marketing Authorization Holder> of the <Stringent Regulatory 791
Authority> authorized <Product> (product for which has been given an opinion according 792
to Art 58 …), hereby requests the <SRA> permission to share <Stringent Regulatory 793
Authority> owned Non-Public Information concerning <Product> for the purpose of the 794
“Collaborative Procedure in Assessment and Accelerated National Registration of 795
Pharmaceutical Products Approved by Stringent Regulatory Authorities Assisted by the 796
WHO” 797
The information to be shared consists of 798
<Stringent Regulatory Authority> final GxP inspection reports for Product <date; version>; 799
<Stringent Regulatory Authority> Product assessment reports; and 800
<Stringent Regulatory Authority> Product owned documents/reports that may be needed in 801
the context of this Procedure. 802
The information will be shared with the <National Regulatory Authority/ies> and the 803
World Health Organization (“WHO”). 804
805
Sincerely, 806
807
808
809
810
Working document QAS/17.704
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Name 811
Title 812
Stringent Regulatory Authority 813
Address 814
Email: 815
Telephone number: 816
817
818
819
Cc: 820
821
822
1During the Facilitated Process in National Registration of Pharmaceutical Products 823
approved by stringent Regulatory Authorities <date; version>, WHO plays a facilitating 824
role in process. 825
826
827
828
Working document QAS/17.704
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AANNNNEEXX 88 829
830
CCOONNFFIIDDEENNTTIIAALL DDIISSCCLLOOSSUURREE AAGGRREEEEMMEENNTT 831
832
833
This Agreement, effective as from the last date of signature, is between 834
835
………………………………………………….., of the one part, 836
837
and 838
839
WORLD HEALTH ORGANIZATION (“WHO”), 20 Avenue Appia, 1211 Geneva 27, 840
Switzerland, of the other part. 841
842
WHEREAS, …… has developed certain information and data relating to …. which it considers to 843
be confidential and its proprietary property (such confidential information and data being hereinafter 844
collectively referred to as the “Information”). 845
846
WHEREAS, ........ is willing to release the Information to WHO, to enable WHO to assess such 847
Information and discuss the merits of a possible collaboration with ........ (the “Purpose”), provided 848
that WHO undertakes to regard the Information as confidential and the property of ........, and release 849
it only to persons who are bound by like obligations of confidentiality and non-use, as are contained 850
in this Agreement. 851
852
NOW IT IS HEREBY AGREED as follows: 853
854
1. The Parties hereto agree that any disclosure of Information by ........ to WHO will be subject to 855
the following terms and conditions. 856
857
2. Any Information which is supplied by ........ in written or other tangible form shall be marked 858
by ........ as “confidential”. Any Information which is disclosed by ........ in oral form shall be 859
confirmed by it in written summary form within thirty (30) days from the date of oral 860
disclosure. 861
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862
3. In accepting the Information, WHO agrees with ........ as follows: 863
864
(a). WHO shall regard the Information disclosed by ........ as confidential and the property 865
of ......... In this regard, WHO agrees to use such Information only for the Purpose (as 866
defined above) and to make no other use thereof, unless and until a further agreement is 867
executed with …………….. governing the use thereof; 868
869
(b). nothing in this Agreement shall prevent …….. from disclosing the Information to any 870
third party; and 871
872
(c). WHO has no right in or to the Information of …….. 873
874
4. WHO undertakes to maintain the Information received from…….. in confidence. In connection 875
with the foregoing, WHO shall take all reasonable measures to ensure that the Information 876
received from…….. shall not be used for any purpose other than the Purpose (as defined above) 877
and shall not be disclosed to any person who does not have a need to know for the aforesaid 878
Purpose and is not bound by similar obligations of confidentiality and restrictions on use as 879
contained in this Agreement. 880
881
The obligations of confidentiality and restrictions on use contained in this Agreement shall 882
continue for a period of five (5) years from the date of disclosure by…….. to WHO. 883
884
5. The obligations of confidentiality and restrictions on use contained in this Agreement shall not 885
apply to any part of the Information which WHO is clearly able to demonstrate: 886
887
(a). was lawfully in its possession and known to it prior to disclosure by…….. hereunder, as 888
evidenced by documents antedating the date of disclosure; or 889
890
(b). was in the public domain or the subject of public knowledge at the time of disclosure 891
by…….. hereunder; or 892
893
(c). becomes part of the public domain or the subject of public knowledge through no fault of 894
WHO; or 895
896
(d). becomes available to WHO from a third party not in breach of a legal obligation of 897
confidentiality to…….. in respect thereof; or 898
Working document QAS/17.704
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899
(e). was subsequently and independently developed by or on behalf of WHO, as shown by 900
written records, by persons who had no knowledge of such Information; or 901
902
(f). is required to be disclosed by law, provided that WHO shall in such case immediately 903
notify…….. in writing of such obligation and shall provide adequate opportunity to…….. 904
to object to such disclosure or request confidential treatment thereof (provided always, 905
however, that nothing contained herein shall be construed as a waiver of the privileges 906
and immunities enjoyed by WHO and/or to submit WHO to any national court 907
jurisdiction). 908
909
6. WHO undertakes that it will disclose the Information only to those persons who need to 910
receive the Information of…….. for the Purpose (as defined above). 911
912
7. WHO undertakes to ensure that all persons who receive the Information disclosed to WHO 913
hereunder shall be bound by similar obligations of confidentiality and restrictions on use as 914
contained in this Agreement. 915
916
8. Nothing contained in this Agreement shall be construed, by implication or otherwise, as an 917
obligation to enter into any further agreement relating to any of the Information or as the grant 918
of a license to WHO to use t……………'s Information other than for the Purpose (as defined 919
above). 920
921
9. Upon completion of the aforesaid Purpose and in the absence of any further written agreement 922
between the Parties, WHO shall cease all use, shall make no further use of the Information 923
disclosed to it hereunder, and shall, upon written request from…….., promptly return to…….. 924
all of the Information received which is in tangible form, except that WHO may retain one 925
copy of the Information in its files to determine any continuing obligations hereunder. 926
927
10. This Agreement constitutes the entire understanding of the Parties hereto with respect to the 928
subject matter hereof and shall not be modified except by mutual agreement in writing. 929
930
11. Without the prior written consent of the other Party, neither Party shall, in any statement or 931
material of an advertising or promotional nature, refer to the relationship of the Parties under 932
this Agreement, or to the relationship of the other Party to the Information and/or the Purpose. 933
934
12. Any matter relating to the interpretation or the execution of this Agreement which is not 935
covered by its terms shall be resolved by reference to the laws of Switzerland. Any dispute 936
relating to the interpretation or application of this Agreement shall, unless amicably settled, be 937
subject to conciliation. In the event of failure of the latter, the dispute shall be settled by 938
arbitration. The arbitration shall be conducted in accordance with the modalities to be agreed 939
Working document QAS/17.704
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upon by the Parties or, in absence of agreement, with the rules of arbitration of the 940
International Chamber of Commerce. The Parties shall accept the arbitral award as final. It is 941
agreed furthermore that nothing contained in this Agreement shall be construed as a waiver of 942
any of the privileges and immunities enjoyed by WHO under national and international law, 943
and/or as submitting WHO to any national court jurisdiction. 944
945
946
947
Made in two (2) original copies, 948
949
………………………. World Health Organization 950
951
952
953
By: By: 954
Title: Title: 955
________________________ 956
Date: 957
____ Date: 958
959
960
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ANNEX 9 961
962
Notification of an outcome of the national registration provided by the 963
participating company to WHO 964
965
Details of pharmaceutical company using the Procedure11
966
Company: Click here to enter text. _______________________________________________________ 967
Country: Click here to enter text. ________________________________________________________ 968
Address: Click here to enter text. ________________________________________________________ 969
Focal point: Click here to enter text. _____________________________________________________ 970
Telephone number (please include codes): Click here to enter text. _____________________________ 971
Email: Click here to enter text. __________________________________________________________ 972
Details of medicinal product (the Product) subject to the Procedure 973
Name of the Product: Click here to enter text. ______________________________________________ 974
Active principle(s): Click here to enter text. _______________________________________________ 975
Strength: Click here to enter text. ________________________________________________________ 976
Dosage form: Click here to enter text. ____________________________________________________ 977
978
Course of the Procedure 979
Country: Click here to enter text. ________________________________________________________ 980
Regulatory authority: Click here to enter text. ______________________________________________ 981
Date of submission of the application: Click here to enter text. _________________________________ 982
Date of acceptance of the application (if differs from submission date): Click here to enter text. ______ 983
Date of issuance of a decision: Click here to enter text. _______________________________________ 984
Length of process interruption/clock-stop (if applicable)12
: Click here to enter text. ________________ 985
986
Decision on registration 987
Granted, rejected, withdrawn: Click here to enter text. _______________________________________ 988
Registration number (if applicable): Click here to enter text. __________________________________ 989
Registration granted in line with the SRA decision or with deviations, please comment: 990
Click here to enter text. ________________________________________________________________ 991
11 Collaborative Procedure in Assessment and Accelerated National Registration of Pharmaceutical Products Approved
by Stringent Regulatory Authorities – facilitated by WHO
12 Time provided by NMRA to the applicant to complete data or respond regulatory questions.
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992
Compliance with the Procedure, other observations and recommendations 993
In the course of the Procedure following deviations were observed and recorded: 994
Click here to enter text. _______________________________________________________________ 995
996
997
998
Any other observations and recommendations: Click here to enter text. __________________________ 999
1000
1001
1002
1003
1004
1005
For the company 1006
1007
1008
Signature: ____________________________________ 1009
1010
Name: Click here to enter text. _________________ 1011
1012
Title: Click here to enter text. _________________ 1013
1014
Place and date: Click here to enter text. _________________ 1015
1016
1017 *** 1018