COLLABORATIVE PROCEDURE IN THE ASSESSMENT ......115 Glossary 116 facilitated registration procedure of SRA-approved medicines (Procedure). Registration 117 procedure in which assessment
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
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
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)
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
page 3
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
page 4
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
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
Working document QAS/17.704
page 6
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
Working document QAS/17.704
page 7
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
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
page 9
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
page 10
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
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
page 12
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
Working document QAS/17.704
page 13
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
Working document QAS/17.704
page 14
368
369
Figure 1: A summary of the scheme of steps in the Procedure and corresponding documentation. 370 371
Working document QAS/17.704
page 15
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.
Working document QAS/17.704
page 16
‒ 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
page 17
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
Reference: Collaborative Procedure in the Assessment and Accelerated National Registration of 579 Pharmaceutical Products Approved by Stringent Regulatory Authorities 580
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
Working document QAS/17.704
page 34
(Blank page) 607
608
609
Working document QAS/17.704
page 35
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.
Working document QAS/17.704
page 36
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
Working document QAS/17.704
page 37
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.
Working document QAS/17.704
page 38
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).
Working document QAS/17.704
page 39
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
Working document QAS/17.704
page 40
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
Working document QAS/17.704
page 41
Change History to QIS-SRA and Product Information 629
* 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
Working document QAS/17.704
page 42
(Blank page) 633
634
Working document QAS/17.704
page 43
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
page 44
<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
page 45
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
page 46
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
page 47
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
page 48
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
page 49
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