COLLABORATIVE PROCEDURE IN THE ASSESSMENT ......115 Glossary 116 facilitated registration procedure...

Working document QAS/17.704

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Working document QAS/17.704 1

March 2017 2

Draft for comment 3

Prepared by EMP/RSS 4

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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.

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mailto:[email protected]





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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


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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

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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

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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

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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

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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

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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.


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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.


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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


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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

http://www.who.int/prequal/

http://www.who.int/prequal/


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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.


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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


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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


page 18

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


page 19

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


page 20

495

(Blank page) 496

497


page 21

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


page 22

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………………………………………….


page 23

498

(Blank page) 499

500


page 24

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.


page 25

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


page 26


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












Public reports are

preferred as they

already contain all

useful information

except those


competitive

advantage.


facilitated by WHO,


page 27



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













be masked

Public reports are

preferred as they

already contain all

useful information

except those


competitive

advantage.


facilitated by WHO,

between SRA and

NRAs.

517

518


page 28

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


page 29


FORMAT)


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


page 30


FORMAT)


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


page 31


FORMAT)


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


page 32

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


page 33

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


page 34

(Blank page) 607

608

609


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.


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


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.


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).


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


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


page 41

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


page 42

(Blank page) 633

634


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


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


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


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.


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


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


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

role in process. 825

826

827

828


page 50

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


page 51

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


page 52

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


page 53

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


page 54

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.


page 55

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

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