1 guidance on good practices for desk ......91 registration procedures, delegates recommended that...

Working document QAS/17.713

May 2017

Document for comments

1

GUIDANCE ON GOOD PRACTICES FOR DESK ASSESSMENT 2

FOR COMPLIANCE WITH GOOD MANUFACTURING 3

PRACTICES, GOOD LABORATORY PRACTICES AND GOOD 4

CLINICAL PRACTICES 5

FOR MARKETING AUTHORIZATION OF MEDICAL 6

PRODUCTS 7

(May 2017) 8 9

DRAFT FOR COMMENTS 10

11

© World Health Organization 2017 12

All rights reserved. 13

This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft may 14 not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any form or by 15 any means outside these individuals and organizations (including the organizations' concerned staff and member organizations) 16 without the permission of the World Health Organization. The draft should not be displayed on any website. 17

Please send any request for permission to: 18

Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies Standards and Norms, Department of Essential Medicines 19 and Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland. Fax: (41-22) 791 4730; email: [email protected]. 20 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion whatsoever 21 on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or 22 concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there 23 may not yet be full agreement. 24

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by 25 the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the 26 names of proprietary products are distinguished by initial capital letters. 27

All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. 28 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility for 29 the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages 30 arising from its use. 31

This draft does not necessarily represent the decisions or the stated policy of the World Health Organization.32

Should you have any comments on the attached text, please send these to: Dr Sabine Kopp, Group Lead,

Medicines Quality Assurance, Technologies Standards and Norms, World Health Organization, 1211

Geneva 27, Switzerland; email: [email protected]; fax: (+41 22) 791 4730; and to Mrs Xenia Finnerty

([email protected] by 15 July 2017.

Working documents are sent out electronically and they will also be placed on the Medicines website

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SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT QAS/17.713: 33

GUIDANCE ON GOOD PRACTICES FOR DESK ASSESSMENT FOR COMPLIANCE WITH 34

GOOD MANUFACTURING PRACTICES, GOOD LABORATORY PRACTICES AND 35

GOOD CLINICAL PRACTICES FOR MARKETING AUTHORIZATION OF MEDICAL 36 PRODUCTS 37

Recommendation to develop a guidance on assessment of GxPs

based on desk review in lieu of inspections during a World Health

Organization (WHO) training symposium for national medicines

Regulatory Authorities held in Kenya

September 2016

Development of a draft outline of this text based on the experience

gained and the feedback during the above mentioned workshop by

PQT Inspection group

September–October

2016

Presentation of the proposal in a concept paper to the fifty-first

meeting of the WHO Expert Committee on Specifications for

Pharmaceutical Preparations (ECSPP)

October 2016

Drafting of the draft best practices for desk assessment in order to

verify and confirm compliance with good manufacturing practices,

good laboratory practices and good clinical practice

by Mrs Kate S. Kikule, Head, Drug Inspectorate Services,

National Drug Authority, Kampala, Uganda

January–March 2017

Review of the draft by East African Community inspectors and

finalization of the draft by Mrs Kate S. Kikule

March 2017

Draft discussed and reviewed at the informal consultation on Good

Practices for health products manufacture and inspection held in

WHO in Geneva, amendments of draft based on the feedback

received by Mrs Kate S. Kikule

25–28 April 2017

Mailing and posting of the working document on the WHO website

for public consultation May 2017

Compilation of comments received July 2017

Review of comments by an expert working group July 2017

Mailing and posting of the revised working document on the WHO

website for 2nd public consultation August 2017

Compilation of comments received October 2017

Presentation to fifty-second meeting of the WHO ECSPP 16–20 October 2017

Further follow-up action as required

38


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Contents 39

[Note from Secretariat: page numbers will need to be adjusted] 40

page 41

42 1. Background ......................................................................................................................................... 4 43 2. Introduction ........................................................................................................................................ 4 44 3. Aim and objectives of the guidance .................................................................................................... 6 45 4. Scope of the guidance ......................................................................................................................... 6 46 5. Definitions .......................................................................................................................................... 7 47 6. Essential elements of desk assessment ............................................................................................... 8 48

6.1 High-level support and cooperation ......................................................................................... 8 49 6.2 Commonality of quality management systems in inspectorates ............................................... 9 50 6.3 Convergent standards of good practices ................................................................................... 9 51 6.4 Reliability and accuracy of information ................................................................................... 9 52 6.5 Management tools to support consistent and objective assessment ....................................... 10 53 6.6 Risk-based assessment of available information .................................................................... 10 54 6.7 Mutual trust and confidence among inspectorates ................................................................ 10 55 6.8 Quality assurance of the desk assessment process ................................................................. 10 56 6.9 Communication of assessment outcomes ............................................................................... 11 57

7. Sources of good information and related challenges ........................................................................ 11 58 7.1 Official websites with databases ............................................................................................ 11 59 7.2 Authenticity of documents ..................................................................................................... 11 60 7.3 Failure to submit documentary evidence ................................................................................ 12 61

8. Submission and assessment of documentary evidence and information .......................................... 12 62 8.1 Submission of application for desk assessment and documentary evidence .......................... 12 63 8.2 Assessment of documentary evidence and information ......................................................... 12 64 8.3 General requirements for documents ...................................................................................... 18 65

9. Regulatory actions and reporting of serious non-compliances ......................................................... 19 66 9.1 Communication and information exchange ............................................................................ 20 67

10. Responsibilities of the applicant ....................................................................................................... 20 68 Annex A. Model report format for desk assessment for finished pharmaceutical products and active…..29 69

pharmaceutical ingredients manufacturers 70 Annex B. Model report format for desk assessment for quality control laboratories…………………….25 71 Annex C. Model report format for desk assessment for contract research organizations and clinical…...37 72

trial sites 73 References 74 75

TABLES 76

Table 1. Type of facility and evidence documents required for desk assessment………………………..14 77 Table 2. Documentary evidence requirements……………………………………………………………15 78

79

80

81


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1. BACKGROUND 82 83 In recent years both the formal and informal collaboration among national regulatory authorities 84 (NRAs) has significantly improved and has strengthened drug regulatory systems, thereby 85

improving the availability of good quality, safe and effective medical products for patients. A 86 number of regional and supra-regional groupings of NRAs are developing. 87 88 During a recent World Health Organization (WHO) training symposium for national medicines 89 regulatory authorities held in Kenya in September 2016, on the subject of collaborative 90

registration procedures, delegates recommended that this lack of common guidance on best 91 practice for performing desk assessment should be filled. It was proposed that WHO in 92

collaboration with regulators from Member States develop guidance that NRAs might leverage 93 in their national regulatory practice and decision-making. 94 95 Currently, there is no general guidance on approaches and best practices for desk assessment in 96

order to verify and confirm compliance with good manufacturing practices (GMP), good 97 laboratory practices (GLP) and good clinical practice (GCP) of foreign facilities for manufacture 98

of finished pharmaceutical products (FPP) and active pharmaceutical ingredients (APIs), quality 99 control laboratories (QCL) and contract research organizations (CROs)/clinical trial sites. 100 101

The critical analysis of this method of assessment to provide advantages and potential risks has 102 not been documented. 103

104

2. INTRODUCTION 105 106 NRAs worldwide use systems for the authorization and post-marketing surveillance of medical 107

products that depend upon the assessment of submitted dossiers, variations files and the 108 inspection of FPP and API manufacturers, QCLs and CROs in the development, manufacture 109 and distribution of the product. These inspections are performed for dossier data verification and 110

to provide evidence that the FPP and APIs manufacturers, QCLs and CROs/clinical trial sites are 111 in compliance with the relevant good practice (GxP) guidelines and requirements. 112

113 The performance of on-site inspection of manufacturing, testing and clinical trials as well as the 114

supply and distribution chain outside the NRA’s domestic territory is a resource-intensive 115 activity and one that often lies on the critical path to regulatory decision-making. Furthermore, 116

the hosting of multiple regulatory inspections and audits is also a significant overhead for the 117 sites inspected that adds to the cost of producing the products. Even the best resourced NRAs 118 face resource limitations and therefore it is regulatory best practice to use quality risk 119 management in prioritizing inspection activities. In order to best use the limited inspection 120 resources and minimize multiple and repeated inspections, it is therefore good practice for 121

national authorities to leverage available and reliable evidence of compliance and noncompliance 122 with good practice requirements as part of their risk-based inspection planning process, such that 123 there is no on-site inspection without well-founded cause. 124 125

Verification and confirmation of GMP compliance of a manufacturer of an FPP or API in a 126 foreign country may be based on the assessment of evidence of GMP compliance that includes a 127


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recent inspection of the manufacturer by a competent regulatory authority and other 128 internationally recognized institutions. 129 130 One element of this risk-based approach is the desk assessment of inspection information from 131

reliable and trusted sources by national or regional authorities in order to decide whether to 132 perform a further inspection before reaching a final decision on marketing authorization or 133 renewal of marketing authorization or other regulatory action. Whereas the use of a desk 134 assessment process for GMP and GCP verification and confirmation has been a method of 135 assessment by some organizations and agencies like the WHO Prequalification Team (PQT), 136

European Medicines Agency (EMA) and the Australian Therapeutic Goods Administration 137 (TGA) for some years, for others it is an emerging consideration. 138

139 Such agencies have relied on regulatory decisions made by other agencies basing on bilateral or 140 multilateral agreements depending on the decision made independently by each individual 141 authority. A range of international and regional formal agreements may be utilized to facilitate 142

the effective management of regulatory decisions in order to increase access to good quality, safe 143 and effective products on the market but are not a prerequisite. These include mutual recognition 144

agreements (MRA), cooperation agreements (CA) and memoranda of understanding (MoU). 145 146 Mutual recognition works well if there are common technical standards that are used, good 147

regulatory practices, clear procedural legislation in form of agreement, tracking tools to support 148 the process, trust and political will with no interference in technical decisions. On the other hand, 149

cooperation agreements or MoU should be pursued where there is minimal legal obligation. It is 150 also possible to perform desk assessments without a formal agreement. 151

152 The desk assessment pathway may be used by an NRA to grant GMP/GLP/GCP compliance for 153

facilities that manufacture finished pharmaceutical products, APIs; to CROs/clinical trial sites 154 and outsourced QCLs, where there is an established MRA, CA or MoU or recognition of a 155 decision made by a competent NRA; Pharmaceutical Inspection Co-operation/Scheme (PIC/S) 156

member, or where WHO prequalification exist. 157 158

The procedure to apply for the desk assessment will depend on whether the facility was 159 previously inspected by one of the competent NRA, PIC/S member or WHO Prequalification 160

Scheme; or if an MRA, CA, or MoU exist. 161 162

The desk assessment process involves submission of documentary evidence by the applicant, 163 usually a manufacturer or representative, to the NRA in order to demonstrate the conformity of 164 the FPP or API manufacturer, outsourced QCL, or CRO/clinical trial site to GMP or GLP/GCP. 165 The evidence provided is assessed to determine the level of compliance based on the accepted 166 standard and the scope of the application. The outcome of the assessment process is used to 167

make a regulatory decision that serves as a prerequisite to determining the marketing 168 authorization of a medical product. 169 170 Acceptance of data from clinical trials/CROs to support marketing authorization application will 171

rely upon conformance with GCP, including review and approval by an institution ethics 172


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committee where the study was conducted and obtaining and documenting informed consent of 173 the study subjects. 174 175 The option to undertake the desk assessment process does not preclude an on-site inspection in 176

cases where the outcome of the assessment shows non-compliance to the stipulated practices. 177 The confirmation may be granted for a specified period of time and the process may be subjected 178 to recovery of costs. It is important to determine the number of cycles for performing desk 179 assessments before conducting a physical inspection. 180 181

3. AIM AND OBJECTIVES OF THE GUIDANCE 182 183

This guidance aims at providing an approach for use by NRAs in order to assess GMP/GLP/GCP 184 confirmation using the desk assessment pathway thus reducing the necessity for duplication and 185 frequency of inspections while relying on authentic and reliable documentary evidence from 186 other regulatory authorities. It may also be used by NRAs for assessment of national sites and 187

defining inspection programmes. 188 189

The guidance also provides key documents to be provided by other regulatory authorities and/or 190 manufacturers that offer reliable information about the status of compliance to good practices in 191 manufacturing, quality control and clinical trials of a specified medical product. 192

193 The guidance outlines a set of essential information and documents to be available to conduct the 194

desk assessment in relation to the most relevant GxPs namely GMP, GLP, and GCP. 195 196

The objective of this document is to: 197 198

ensure that a standardized procedure is followed for desk assessment of inspection reports 199 issued by trusted, competent regulatory bodies and corrective actions from inspected 200 sites; 201

to facilitate a convergent approach and model for exchange and use of inspection 202 information in national and regional decision-making processes concerning the necessity 203 to perform preapproval and surveillance inspections. 204

205

4. SCOPE OF THE GUIDANCE 206 207 This guidance applies to FPPs and API manufacturers, CROs/clinical trial sites and outsourced 208 QCLs that are subjected to GxP inspections in foreign countries. However, the local NRA may 209 use desk assessments to set up risk-based inspection plans without loss of regulatory oversight 210 through physical inspections. 211

212 Although the guidance has general geographical applicability, it is most relevant to regulatory 213 authorities in low- and middle-income countries in order to support ongoing harmonization 214 initiatives and optimum use of limited resources. 215

216


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The guidance covers the information and evidence required to undertake a desk assessment 217 process and excludes the process of on-site inspection except the process of tracking and review 218 of completion of corrective action and preventive action (CAPA). On-site inspection is covered 219 in a separate WHO guidance document. 220

221 Desk assessment procedures cannot be applied to sites that have failed GxP inspections. The 222 NRA takes the ultimate decision whether it is appropriate to perform a desk review. 223 224

5. DEFINITIONS 225 226 The definitions given below apply to the terms used in this guidance. They may have different 227

meanings in other contexts. 228 229

agent or local technical representative. Every applicant who is not resident in the 230 country of the national regulatory authority (NRA) should appoint a person in that country and 231

authorized by the NRA to deal in medical products to be an agent (local technical 232 representative). The appointment should be notified to the NRA by submitting a letter of 233

appointment supported by powers of attorney duly notarized in country of origin, and registered 234 with the registrar of companies in the country of the NRA. 235

applicant. An applicant is a person who applies for marketing authorization of a medical 236

product to the national regulatory authority, who must be the owner of the product. The applicant 237

may be a manufacturer or a person to whose order and specifications the product is 238 manufactured. After the product is registered, the applicant becomes the marketing authorization 239 holder. 240

bioequivalence. Two pharmaceutical products are bioequivalent if they are 241 pharmaceutically equivalent or pharmaceutical alternatives, and their bioavailabilities, in terms 242

of rate (Cmax and tmax) and extent of absorption (area under the curve), after administration of 243 the same molar dose under the same conditions, are similar to such a degree that their effects can 244 be expected to be essentially the same. 245

clinical trial/study. Any investigation in human subjects intended to discover or verify 246 the clinical, pharmacological and/or other pharmacodynamic effects of an investigational 247

product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to 248 study absorption, distribution, metabolism and excretion of an investigational product(s) with the 249 object of ascertaining its safety and/or efficacy. The terms clinical trial and clinical study are 250 synonymous. 251

competent regulatory authority. This is any organization that has a legal authority or 252 power to perform a designated regulatory function for authorization of a medical product. 253

cooperation agreement. This is a formal business document outlining the basic terms of 254 an agreement with another individual, group or entity. Also called a memorandum of 255 understanding or cooperation contract, it's one of the first steps toward a more detailed contract. 256

desk assessment. This is the evaluation of prior documentary evidence by a competent 257

regulatory authority recognized by the national regulatory authority for compliance to the 258

required good practices (good manufacturing practices, good laboratory practice and good 259 clinical practice) in support of marketing authorization. 260


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good clinical practice. In this context the term means standard for design, conduct, 261 performance, monitoring, auditing, recording, analysis and reporting of clinical trials in a way 262 that provides assurance that the data and reported results are credible, accurate and that the 263 rights, safety and well-being of trial subjects are protected. 264

information sharing. This is defined as exchange of data between individuals or entities 265 outside the traditional organizational boundaries, to achieve a common goal in terms of better 266 policies and deliver better services that otherwise would not be possible without the exchange of 267 data. This may mean that one party is disclosing information while the other is collecting the 268 information or both parties are mutually disclosing and collecting information. 269

manufacture. All operations of purchase of materials and products, production, quality 270

control, release, storage, distribution of medicinal products and the related controls. 271

manufacturer. A manufacturer is a natural or legal person who holds a manufacturing 272 authorization and has responsibility for manufacturing of a medical product or active 273 pharmaceutical ingredient. 274

marketing authorization (product license, registration certificate). A legal document 275

issued by the competent regulatory authority that establishes the detailed composition and 276 formulation of the product and the pharmacopoeial or other recognized specifications of its 277

ingredients and of the final product itself and includes details of packaging, labelling and shelf 278 life. 279

memoranda of understanding. A memorandum of understanding (MoU) is a formal 280

agreement between two or more parties. Companies and organizations can use MoUs to establish 281

official partnerships. MoUs are not legally binding but they carry a degree of seriousness and 282 mutual respect, stronger than a gentlemen's agreement. 283

mutual recognition agreement. This is defined as the reciprocal adoption or acceptance 284

of regulatory decisions or outcomes in other partner states as valid in form of a legal basis – law 285 or regulations or agreements. 286

287 Pharmaceutical Inspection Co-operation Scheme (PIC/S). This is a non-binding, 288

informal cooperative arrangement between regulatory authorities in the field of good 289

manufacturing practices of medicinal products for human or veterinary use. 290

291 quality system. The sum of all that is necessary to implement an organization's quality 292

policy and meet quality objectives. It includes organizational structure, responsibilities, 293 procedures, systems, processes and resources. Typically these features will be addressed in 294 different kinds of documents as the quality manual and documented procedures. 295

296

6. ESSENTIAL ELEMENTS OF DESK ASSESSMENT 297 298

6.1 High level support and cooperation 299 300

The legal framework and governance structure for the NRA should have provisions for support 301

and collaboration with other agencies in making regulatory decisions. Legal provisions (laws and 302

regulations) that allow for the reliance on foreign NRA inspections and enforcement actions 303 based on well-defined criteria should be established and implemented. 304


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305 Such recognition can be in the form of MRAs, CAs or MoU between collaborating inspectorates 306 and could entail agreements to enable bilateral or multilateral commitment and exchange of 307 information on specified manufacturing sites. 308

309 MRAs are usually binding and may require inspectorates at the same level of development with 310 the appropriate organization and funding to fulfill the responsibility of protecting and promoting 311 public health. 312 313

Where such recognition exists, the requirements to determine compliance with GMP, GLP and 314 GCP of foreign manufacturing sites, CROs and outsourced QCLs may be less, given the level of 315

cooperation and trust established. 316

317 6.2 Commonality of quality management systems in inspectorates 318 319

There should be a quality system in place based on recognized international standards namely 320 WHO quality management system (QMS) or International Organization for Standardization 321

(ISO) QMS standards. The quality management system should be established, implemented and 322 maintained throughout the period of the recognition or reliance. 323 324

The primary purpose of a QMS is to ensure that adequate quality standards are maintained. 325 Adopting common standards for quality system requirements helps to achieve consistency in 326

inspection standards between GMP national pharmaceutical inspectorates (WHO standards or 327 equivalent) and thus to facilitate mutual recognition and mutual confidence. 328

329

6.3 Convergent standards of good practices 330 331 WHO has over the years published standard requirements of compliance to GMP and other good 332 practices including GLP and GCP. These serve as a measure of the standard in relation to what 333

the manufacturers have established in order to deliver and supply a good quality and safe 334 product. The NRA should have similar standards of GxP in order to facilitate uniform desk 335

assessment. 336 337

6.4 Reliability and accuracy of information 338 339

Organizations have the responsibility to ensure that information used in desk assessment is 340 reliable and not false or misleading. 341 342 Mechanisms and controls should be established to ensure the information provided by the 343 applicant is authentic, legible, current and accurate. 344

345 There should be high confidence that the information provided relates to the same strength and 346 specifications of the product and to the same site, workshop or production line (consider use of 347 unique facility identifiers); and should accurately relate to the product under assessment without 348

any false information. 349 350


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Controls should be established by the NRA to ensure that the information provided by the 351 applicant is secured and remains confidential. 352 353

6.5 Management tools to support consistent and objective assessment 354 355

There should be well structured and up-to-date assessment tools and procedures to enable 356 uniform and consistent objective assessment of the documents provided. Personnel involved in 357 the assessment process should be adequately trained to utilize the assessment tools and 358 procedures consistently without bias, and be able to detect inconsistent and inaccurate 359

information regarding the product under assessment. 360 361

Validated electronic assessment tools (software applications) may be used to perform the desk 362 assessments; however, paper systems may also be utilized. 363 364

6.6 Risk-based assessment of available information 365 366 The principles of quality risk management should be employed to perform desk assessment 367

considering the management of resources in terms of time, funding and personnel in the NRA. 368 The aim of the assessment process should be understood in order to provide a quality product in 369 a timely manner without putting the patient at risk. 370

371 Based on the fact that other competent and trusted inspectorates have inspected the site of 372

manufacture and in some cases several products manufactured on site, the assessment should 373 take into consideration and focus on the critical products and critical processes in the 374

manufacture of a specified product in relation to patient risk. 375 376

Key factors to consider include the origin of the information, the authenticity of the information 377 provided, location of the site of manufacture, complexity and type of the product (whether sterile 378 or biological) and the risk to the patient. 379

380

6.7 Mutual trust and confidence among inspectorates 381 382 Joint inspections may be conducted together by countries within the same region or those where 383

an agreement exists. Through such interactions regulators may be able to build confidence, share 384 information and experiences in order to rely on their inspection outcomes and regulatory 385

decisions. Joint inspections also serve as a basis for desk assessments by means of building 386 mutual trust and identifying barriers towards reliance on other regulators' inspection outcomes 387 and devise solutions to overcome them. 388 389

6.8 Quality assurance of the desk assessment process 390 391 Quality assurance of the desk assessment process involves providing confidence that the 392 requirements of the assessment process will be fulfilled. This should require compliance of the 393 inspectorate function to a quality management system (e.g. ISO/International Electrotechnical 394

Commission (IEC) 17020 Conformity Assessment - Requirements for the Operation of Various 395


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Types of Bodies Performing Inspection, or PIC/S Quality management system for inspectorates) 396 over a period of three to five years. 397 398

6.9 Communication of assessment outcomes 399 400 Communication of the outcome of the desk assessment process should be carried out in a 401 transparent and timely manner. The outcome of the desk assessment should be communicated to 402 the applicant whether an approval, a deferment or a rejection of an application for GxP 403 assessment is made. 404

405 In case of a rejection leading to a regulatory decision to conduct an on-site inspection, a 406

statement of the reasons should be provided which details the documents, information and 407 regulatory requirements taken into account in reaching the decision. An appeal mechanism 408 should also be in place giving a chance to the applicant to defend their case. The NRA reserves 409 the right to conduct an inspection of any site. 410

411

7. SOURCES OF GOOD INFORMATION AND RELATED CHALLENGES 412 413 Trusted sources of information are available either in the public domain or from the NRAs. 414 Information provided may vary in detail due to restrictions and rights to the owners. Information 415

provided may include but not limited to non-compliant facilities, market complaints and product 416 recall on websites of NRAs. 417

418 Certificates and reports issued by stringent regulatory authorities (SRAs) also serve as evidence 419

of the information about a specified manufacturer, CROs and outsourced QCLs. 420 421

7.1 Official websites with databases 422 423 NRAs and organizations such as WHO and EMA have websites where information on compliant 424

and non-compliant facilities to GxP is provided. Some websites provide GMP certificates and 425 inspection reports and other information about medicine manufacturing facilities and medicines 426

such as results of sample testing, including samples that failed analysis, product recalls and rapid 427 alerts. The website should be current and updated regularly. Certificates presented by applicants 428

for marketing authorization should be verified using the information available on websites of 429 NRAs or by directly contacting the relevant NRA. The NRA is responsible to check that 430

information is current and complete 431 432

7.2 Authenticity of documents 433 434 It is important that documentary evidence provided upon which is the basis for granting a 435

GMP/GLP or GCP approval be current, accurate and authentic. It is the responsibility of the 436 applicant to ensure that the information provided is authentic and accurate. 437 438 NRAs may request that information such as inspection reports and certificates granted by NRAs 439

be notarized or be certified. 440 441


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Submission of inaccurate or false information may result in declaration of the manufacturer, 442 QCL or CRO as non-compliant. 443 444

7.3 Failure to submit documentary evidence 445 446 If the applicant is unable to provide adequate documentary evidence, including ongoing 447 information on current compliance or submit the documents within a specified timeline, or fails 448 to submit documents as required, the application for desk assessment may be rejected leading to 449 a decision to conduct an on-site inspection. In such circumstances, GMP/GLP approval should 450

only be granted after the on-site inspection has been conducted and manufacturer, the 451 CRO/clinical trial site or outsourced QCL found compliant. 452

453

8. SUBMISSION AND ASSESSMENT OF DOCUMENTARY EVIDENCE AND 454 INFORMATION 455

456

8.1 Submission of application for desk assessment and documentary evidence 457 458

Prior to assessment an application for each site should be submitted to the NRA for desk 459 assessment. Applications are required for renewals, changes to scope, changes to processes and 460 major facility changes. 461

462

8.2 Assessment of documentary evidence and information 463 464 Desk assessment involves a detailed assessment of the specified documentary evidence supplied 465

by the applicant. 466 467

The assessment will include an assessment of recent inspection reports of the relevant 468 manufacturing site undertaken by a competent regulatory agency together with other available 469 regulatory information. Desk assessment for compliance of manufacturing facilities for FPPs and 470

APIs to GMP/GLP/GCP can be used where the NRA has an agreement or understanding for 471 exchange of information, such as an MRA, CA or MoU. 472

473 In accordance with international agreements with certain countries, the NRA may accept 474

compliance of a foreign site with the GMP requirements based on a current GMP certificate 475 issued by the regulatory agency of the other party to the MRA. 476

477 Authorization may be granted by the NRA on the basis of a current GMP certificate issued 478 within the scope of a MRA agreement. The scope of the manufacturing activities indicated in the 479 application should be within the scope of the activities covered by the GMP Certificate. 480 481

Where an MRA has been established: 482 483

a) a copy of the manufacturing authorization granted by local authorities together with a 484 certified translation where this is not in English, may suffice. 485

486


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Where a CA or other bilateral or multilateral arrangements have been established, the document 487 above in a) should be provided in addition to the following essential documents: 488 489

b. site master file (Annex 14, WHO Technical Report Series, No. 961) that is not older than 490

one year from its approval date and any forecasted modifications, including legible 491 coloured printouts of water treatment, air-handling systems, including pipeline and 492 instrumentation drawings (P&IDs) in A3 or A2 format; 493

c. list of all the products manufactured on site. The list should include proprietary names 494 and international nonproprietary names (INN); 495

d. copy of the last inspection report issued by the local regulatory authority with a certified 496

translated copy where this is not in English and GMP certificates with a certified 497

translated copy where this is not in English (production-line specific); 498

e. full inspection report(s) for inspections performed by competent NRAs in the last three to 499 five years; 500

f. CAPA and proof of CAPA implementation related to the last inspection report 501

observations/deficiencies or any warning letter or equivalent regulatory action 502 (production-line specific); 503

g. the most recent product quality review(s) (PQR)(s) of the concerned product(s); 504 PQR(s) (WHO Technical Report Series, No. 986, Annex 2) or equivalent documentation 505 covering all required subsections and trend results should be presented; 506

h. the completed batch manufacturing/packaging record(s) including the analytical part for 507

the most recent released batch of relevant product(s); 508

i. a list of any recalls in the last three years related to quality defective products. 509

510

The following documents may be evaluated while performing desk assessments: 511 512

a) a confirmation by the senior quality assurance representative that a full self-inspection or 513

external audit dedicated to the product(s) has been performed and all matters dealt with; 514

b) master batch manufacturing/packaging record(s) of the product(s) of interest; 515

c) a copy of any warning letter or equivalent regulatory action issued by any authority to 516

which the site provides or has applied to provide the product; 517

d) out-of-stock situations. 518 519

The evidence documents required for desk assessment of each type of facility are mentioned in 520 Table 1 below.: 521 522

523


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Table 1. Type of facility and evidence documents required for desk assessment 524

525

Type of facility Where a MRA

exists

Where a CA/MoU

exists; or member of

PIC/S; or SRA

regulator; or WHO

Prequalification

Scheme

Where no MRA, CA,

MoU; or member of

PIC/S; or SRA regulator;

or WHO Prequalification

Scheme exists

Non-sterile products

facilities

FPP

API

Evidence List A

Evidence List B On-site GMP inspection

Sterile products facilities

FPP

API

biotech

Evidence List A and

certification to

relevant ISO

Standards for

sterilization

facility.1

Evidence Lists B and C On-site GMP inspection

Outsourced (contract)

testing laboratory; and

outsourced sterilization

Evidence List A Evidence List D On-site laboratory

inspection

On-site GMP inspection

CRO

1) Clinical facility

2) Clinical laboratory

3) Bioanalytical

laboratory

4) Company

performing

pharmokinetics

statistical analysis.

Evidence List E Evidence List E and F On-site GLP/GCP

inspection

526

A list of the documents that should be provided for desk assessment is given in Table 2. The 527 documents below are required for the manufacturing sites desk assessment. For CROs and QCL 528 desk assessment, the inspector should choose the documents that are relevant to CROs and QCLs 529 desk assessment as indicated in Table 2. 530 531

532

1 If applicable to the manufacturing facility or activity.


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Table 2: Documentary evidence requirements 533 534

Required evidence Comments/Exclusions

Evidence List A Current GMP certificate.

(GLP or ISO/IEC 17025

certification for outsourced

laboratory

Certificates must be sufficient to cover the

scope of the GMP compliance application

Evidence List B

Current GMP certificate GMP agreements may be requested if the

foreign manufacturer performs the release for

supply function

Current manufacturing license The manufacturing license should show the

scope of products and activities approved the

local NRA

Regulatory inspections conducted

within the past three years and a

copy of the most recent inspection

report issued by authorities stated

under Table 1 above

Provide a list of all inspection reports

applicable to the scope of the application.

These may be sent to the NRA directly from

the manufacturer

Processing can be expedited if reports for two

or more of the above inspections are provided

Corrective action and preventive action

evaluation report for the recent inspection

report should be provided

Market complaints register For previous three years, including one

investigation report for one of the complaints

classified as high risk to public health

The complaint register should be applicable to

the products applied for

Details of any regulatory actions

in past three years

For example, product alerts, warning letters,

import alerts, recalls due to defects

Site master file, quality manual or

equivalent

Site master file (refer to WHO Technical

Report Series, No. 961, Annex 14, for

guidelines for writing site master file)

Site mater file not required if the scope of the

application is only for the step of release for

supply


page 16


List of products intended for

supply in the recipient country

a) PQR report;

b) Process validation report; and

c) Batch records (batch

manufacturing, packaging and

testing) for each product

applied for marketing

authorization

The PQR reports should be provided for each

product. In case of multiple products provide

one PQR report from each FPP dosage form

applied for

The batch records of a product for each FPP

dosage form manufactured in the last 6 to 12

months; and the corresponding process

validation reports and annual product quality

review reports

Evidence List C

Validation master plan Not required if the scope of the application is

only for the step of release for supply

Aseptic processing and filling

validation reports

Required for products applied for that are not

terminally sterilized

Evidence List D

Current GMP certificate or

ISO/IEC accreditation certificate

or WHO prequalification

For outsourced testing laboratories, a GLP

certificate issued by a recognized regulatory

authority or a current ISO/IEC 17025

accreditation certificate or prequalification of

the laboratory by WHO

For outsourced sterilization facilities

certification to applicable ISO sterilization

standards (e.g. ISO 11137, ISO 11135)

Quality manual/laboratory manual

or equivalent

The quality manual/laboratory manual should

be written as per the WHO good practices for

pharmaceutical quality control laboratories,

or as per the ISO/IEC 17025 General

requirements for the competence

of testing and calibration laboratories


page 17


Contract or agreement between the

FPP or API manufacturer and the

outsourced testing laboratory or

sterilization institution

A copy of the contract or agreement clearly

describing the roles and responsibilities of the

manufacturer and the testing laboratory or

sterilization institution should be submitted

A list of tests a laboratory is

authorized to perform as per the

scope of its accreditation to the

ISO/IEC 17025 or WHO

prequalification

For botanical ingredients,

evidence that authenticated

standard reference materials are

used

The scope of activities of the outsourced

laboratory should include the type, range and

volume of testing and/or calibration, validation

and verification activities it undertakes

Evidence List E Current GCP/GLP certificate Issued by the NRA

Evidence List F Clinical trial approval by the NRA

Provide a list summarizing the approved trials

and their outcome

Provide complete study report if no

application has been submitted for marketing

authorization of a product

Where applicable reports from data safety

monitoring board /independent safety monitors

should be provided

Copy of IRB/IEC clinical trial

approval

Provide approved protocol and consent form.

Provide list of committee members of the

IRB/IEC

Quality manual or equivalent Quality manual (refer to guidelines for writing

quality manual)

Responsibilities of the sponsor and clinical

investigator should be provided

Management and assessment of subcontracted

vendors should be provided


page 18


Deviation management and procedures for

handling the investigational product

Regulatory inspections conducted

within the past three years and a

copy of the most recent inspection

report amongst those stated under

Table 1 above

Provide a list of all inspection reports

applicable to the scope of the application.

These may be sent to the NRA directly from

the manufacturer or CRO

Processing can be expedited if reports for two

or more of the above inspections are provided

Provide the following inspection reports:

a) by the NRA;

b) study monitory report by the CRO;

c) study monitoring report by the sponsor,

except where the CRO and sponsor are the

same

Concerns/alerts raised by the NRA

and any other responsible

authority

Provide details of investigation of any non-

compliances and how they were addressed

535

536 8.3 General requirements for documents 537

Documents to be submitted to NRAs as evidence of compliance should adhere to the following 538

general requirements: 539

a) all certificates and other supporting documents should be in English or in nationally 540

accepted language; 541

b) where the document is not in English or a nationally accepted language, it should be 542 submitted with a certified translation; 543

c) translated documents must be accompanied by a signed and dated statement, by the 544 certified translator, stating that it is a true and accurate translation of the original 545

document; 546

d) documents must be the most recent and reflect current activities and practices and dated 547 (expired/superseded documentation cannot be used); 548

e) documents must provide sufficient information to cover the scope of activities for which 549 GxP compliance is sought; and 550


page 19

f) all documents are to be submitted electronically (DVD, CDs, etc.) and are not required to 551 be certified as original copies unless requested by the NRA. Certification of a document 552 may be requested if, for example, there is concern over the validity of the supplied 553 documents. 554

The NRA can request certified copies of original documents at any time. Certified copies must 555 be legible and authenticated as true copies by any one of the following: 556

a) an official of the regulatory agency of a country that is a party to an MRA, or a partner to 557 an MoU or a CA, WHO prequalification or SRA regulator; or 558 559

b) a public notary (include details of the relevant practice certificate or license number). 560

The following is an example of a declaration that should appear on the front page of the 561

document being certified: 562

Declaration of authenticity 563

I, the undersigned, as a ...............for the state of ................, country.............. 564

declare that the attached copy of the document issued by .................................. and certified by 565

me, is a true and accurate copy of an original document presented to me for certification. 566

____________________________ ______________ Date: /.........../.......... 567

Full Names [Signature] Day/Month/Year 568

569

9. REGULATORY ACTIONS AND REPORTING OF SERIOUS NON-COMPLIANCES 570 571

Regulatory actions should be taken by NRAs in response to the reporting of serious non-572 compliance. 573 574

The impact of the non-compliance should be assessed by the NRA to ascertain the potential risk 575

to public health, supply and availability of affected medicines. This assessment should take into 576 consideration the risk of exposure of national shortages and divergent actions. 577 578 The following are some of the actions taken by the NRA in response to reported serious non-579 compliance: 580

581 1) issuance of a rapid public alert to collaborating partners; 582 2) issuance of non-compliance letter; 583 3) suspension of marketing authorization; 584 4) withdrawal/cancellation of the GMP certificate; 585

5) suspension of certificate of suitability; 586

6) institution of a recall; 587

7) suspension of supply or importation; 588


page 20

8) prosecution. 589 590

9.1 Communication and information exchange 591 592

There should be a mechanism for exchange of information among inspectorates, for example, a 593 shared web-based portal for communication serious non-compliances in a timely manner. 594 595 Facilities with serious non-compliances to GMP, GLP/GCP guidelines should be communicated 596 to stakeholders and partners The regulatory decision and action taken should be explained to the 597

stakeholders including analysis of the risk and threats to the patient. 598 599

10. RESPONSIBILITIES OF THE APPLICANT 600

The main responsibilities of an applicant for GMP/GLP/GCP desk assessment are listed below. 601

1) Ensuring that all required evidence documents are submitted with applications for GMP 602 desk assessment. Incomplete applications may be rejected. 603

2) Remitting all application fees at the time of lodging an application for GMP desk 604 assessment. 605

3) Submitting applications for renewal of a GMP certificate prior to the expiry of the current 606 certificate within a timeline specified by the NRA. 607

4) Promptly submitting any additional information that may be requested by the NRA 608 during an assessment. Failure to provide required documents in the time may result in the 609

application being rejected. 610

611


page 21

Annex A 612

613

Model report format for desk assessment for finished pharmaceutical products and active 614

pharmaceutical ingredient manufacturers 615

616

Part 1. General information

a) Particulars of the applicant (Name of applicant, physical

address, postal address of

applicant (if different from

physical address), 24-hour

telephone numbers, fax, email

address)

b) Particulars of the manufacturer

(Name of manufacturer, physical

address of manufacturer, postal

address of manufacturer (if

different from physical address),

24-hour telephone number(s),

fax, email address, contact

person)

c) Activities performed on the site

(For example, manufacture of

APIs, manufacture of FPPs,

intermediates or bulk packaging,

laboratory testing, batch release,

warehousing, primary and

secondary packaging)

d) Date of last inspection by the NRA

(Date when the last inspection

was carried out, Name of the

national drug regulatory

authority that carried out the

inspection)

e) Production and packaging lines applied for

(For FPP: dosage form line,

category: beta lactam, non-beta

lactam, biologicals, vaccines,

hormones, cytotoxic products)

(For API: name of API)

f) Authorized representative of marketing

authorization holder in the recipient country

(For example, representative,

agent)

617


page 22

618

Part 2. Documentary evidence (comment on adequacy of information provided)

a) Current site master file

(Comment on date, completeness and

adequacy in accordance with WHO or

PIC/S guideline for writing site master

file)

b) List of all regulatory inspections carried

out in the past three to five years

(Name of regulatory authority that

carried out the inspection, dates when the

inspection was carried out, inspection

outcome)

c) Copy of valid manufacturing license

granted by the NRA together with a

certified translation attached if not in

English

(Number of manufacturing license, name

of regulatory authority that granted the

license and validity of the manufacturing

license and scope)

d) Copy of valid GMP certificate granted by

the national drug regulatory authority

together with a certified translation

attached if not in English

(Number of GMP certificate, name of

NRA that granted the certificate and

validity of the GMP certificate and scope)

e) List of products manufactured at the site

and those to be exported to the country of

import

(List of products, dosage form (where

applicable), list of registered product and

those to be registered)

f)

Notarized copy of inspection report (s)

from the national drug regulatory

authority and/or that from WHO

prequalification (whichever is applicable)

carried out within the past three to five

years.

(Name of the regulatory authority that

carried out the inspection, dates of the

inspection, scope of inspection, findings

and recommendations, list of non-

compliances, conclusion)

(CAPA reports submitted and found

satisfactory for the most recent inspection

(adequacy of CAPA, timelines))

g) Performance of the company’s products

on the market within the past review

period

(Any product alerts, warning letters,

market complaints, product failure or any

product recall, (note any unacceptable

findings))

h) PQR reports

(For products seeking or renewing

marketing authorization. Assess the

consistency of the processes, trends,


page 23

specifications, process changes, recall,

returns, market complaints, deviations on

critical parameters, in-process controls,

quality control tests, stability study

data)(select product of interest)

i) Validation master plan

(Validation policy, utilities qualification,

equipment qualification, procedures,

protocols, reports, cleaning, personnel

qualification, process validation,

analytical method validation, computer

validation, revalidation, requalification,

validation matrix)

j) Process validation for one of the products

marketed product marketed or to be

registered in the country of import

(Comment on adequacy)

k) One batch manufacturing record (BMR)

for each production line together with the

master batch record including the packing

and analytical part (certified translation of

original BMR where applicable); BMR

should refer to a product marketed or to

be registered in the country of import


l) Out-of-specifications (OOS) procedure:

three OOS including at least one assigned

to laboratory error

m) List of reprocessed or reworked product

batches in last year (or two years)

619

Part 3. Recommendation

1. Recommended for a GMP compliance approval?

(Provide recommendation basing on the assessment done in Parts 1 and 2)

2. If Yes, production lines/product/pharmaceutical active ingredient recommended:

3. If No, state reasons below:

620


page 24

Part 4. Evaluation team 621

First assessor 622 623 Signed:

Date:

Name: Position:

(BLOCK CAPITALS)

624 Second assessor 625 626 Signed:

Date:

Name:

Position:

(BLOCK CAPITALS)

627

628


page 25

Annex B 629

630

Model report format for desk assessment for quality control laboratories 631

632

Part 1. General information

a) Particulars of the applicant

(Name of applicant, physical address,

postal address of applicant (if different

from physical address), 24-hour

telephone numbers, email address)

b) Particulars of the QCL

(Name of QCL, physical address of QCL,

postal address of the laboratory (if

different from physical address), 24-hour

telephone number(s), email address,

contact person)

c) Date of last inspection by SRA, WHO or

accreditation body for ISO/IEC 17025

(Name of NRA or accreditation body that

carried out the inspection, dates when

the inspection was carried out, the

inspection outcome

Part 2. Documentary evidence (comment on adequacy of information provided)

a) Copy of appropriate certificate or

approval granted by a recognized

regulatory authority or accreditation

certificate granted by accreditation body

for ISO/IEC 17025 together with a

certified translation attached if not in

English

(Number/Reference of appropriate

certificate or approval or ISO/IEC

17025 certificate, name of regulatory

authority that granted the certificate and

validity of the certificate)

b) Scope of accreditation

(Indicate the analytical

methods/techniques)

c) Current quality manual/laboratory

manual or an equivalent

(Comment on adequacy) (refer to WHO

Good Practice for pharmaceutical

quality control laboratories, WHO

Technical Report Series, No. 957, 2010)

d) Contract between the manufacturer and

contract laboratory and its

subcontractors if applicable (where

(Comment on adequacy of agreement

stating responsibilities of the parties)


page 26

testing is outsourced)

e) List of all inspections carried out in the

past three years by regulatory authority

or accreditation body

f) Copy of inspection report (s) from

regulatory authority or accreditation body

and/or that from WHO Prequalification

(whichever is applicable) carried out

within the past three to five years

(Name of the regulatory authority or

accreditation body that carried out the

inspection, dates of the inspection, scope

of inspection, findings and

recommendations, list of non-

compliances, conclusion)

g) CAPA reports submitted and found

satisfactory for the most recent

inspection


h) a. Register of OOS, OOS procedure

and investigation reports of at

least three OOS assigned to

laboratory error in past one year

handled


Part 3. Recommendation

1. Recommended for a GMP compliance approval?


2. If Yes, laboratory testing activities/product analysed:


633

634


page 27

Part 4. Evaluation team 635


Date:

Name: Position:

(BLOCK CAPITALS)

638 639 Second assessor 640 641 Signed:

Date:

Name: Position:

(BLOCK CAPITALS)

642

643

644

645


page 28

Annex C 646

647

Model report format for desk assessment for contract research organizations and clinical trial 648

sites 649

650

Part 1 (i). General information - study

a) Particulars of the applicant

(Name of applicant, physical address,

postal address of applicant (if different

from physical address), 24-hour

telephone numbers, email address)

b) Particulars of the organization

(Name of research organization,

physical address, Postal address (if

different from physical address), 24-hour

telephone number(s), fax, email address)

c) Title of the study

d) Particulars of the bioanalytical laboratory

(Name of bioanalytical laboratory,

physical address of bioanalytical

laboratory, postal address of the

laboratory (if different from physical

address), 24-hour telephone number(s),

fax, email address)

e) Particulars of the sponsor

(Name of sponsor, 24-hour telephone

number(s), fax, email address, contact

person)

Part 1 (ii). General information - site quality management system

a) Date of last inspection by NRA (if

applicable)

(Dates when the last inspection was

carried out, name of the national drug

regulatory authority that carried out the

inspection)

b) Particulars of the investigator’s current

CV and/or qualifications

651


page 29

Part 2 (i). Documentary evidence - study

a) Copy of institutional review board

(IRB)/independent ethics committee

(IEC) clinical trial/bioequivalence (BE)

study approval

b) Copy of clinical trial/BE approval

granted by a competent national drug

regulatory authority a certified translation

attached if not in English

(Name of the approving authority,

validity of approval) (study)

c) Copy of clinical trial/BE/bioavailability

study protocol, amendments

(Comment on the trial design, selection

and withdrawal of subjects, treatment of

subjects, assessment of efficacy,

assessment of safety, statistics, data

handling and record keeping, ethics,

financing and insurance, quality control

and quality assurance, publication

policy)

d) Copy of investigator’s brochure

(Confidentiality statement, physical

chemical and pharmaceutical properties

and formulation, non-clinical studies,

effects in humans, summary of data and

guidance for the investigator)

e) Copy of clinical trial/BE reports

including safety reports

(Comment on adequacy and compliance

with the protocol) (study)

f) Copy of study monitoring report by the

CRO

Part 2 (ii). Documentary evidence - site quality management system

a) Copy of current GCP/GLP certificate

b) Number of clinical trials/BE study

approvals granted by a national

medicines regulatory authority in the past

five years, a certified translation attached

if not in English

(State number of approved clinical

trials/BE studies and their outcomes,

name of the approving authority, validity

of approva

c) Copy of current clinical trial master file

(make reference to the quality assurance

mechanism for CRO) (SQMS)

(Comment on adequacy deviation

management and procedures for

handling investigational product)


page 30

Responsibilities of the sponsor and

clinical investigator, management and

assessment of sub contracted vendors

should be provided

d) List of all regulatory inspections carried

out in the past three to five years

e) Copy of inspection report (s) from

national drug regulatory authority and/or

that from WHO prequalification

(whichever is applicable) carried out

within the past three to five years.

(Including bioanalytical method

validation and compliance with GLP)

f) Provide evidence of NRA oversight

including concerns/alerts raised, if any

g) Copy of study monitoring report by the

sponsor (where applicable)

Part 3: Recommendation

1. Recommended for a GCP compliance approval?


2. If Yes, study/clinical trial site recommended:


652

653


page 31

Part 4: Evaluation team 654

(Indicate names of 1st and 2nd assessor, signature and date) 655


Date:

Name: Position:

(BLOCK CAPITALS)

658 659 660 Second assessor 661 662 Signed:

Date:

Name:

Position:

(BLOCK CAPITALS)

663

664

665

666

667

668

669

670

671

672

673

674

675

676


page 32

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1. Australian Regulatory Guidelines Good Manufacturing Practice (GMP) Clearance for

Overseas Manufacturers, 17th

Edition, version 1.0 May 2011.

2. Good assessment practices: guidelines for national and regional regulatory authorities.

In:WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-

ninth report. Geneva, WHO Technical Report Series, No. 992, 2015, Annex 9.

3. Guidance for site master file. WHO Technical Report Series, No. 961, Annex 14. In:

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-fifth

report. Geneva, World Health Organization, 2011.

4. Guidelines for Good Clinical Practice E6(R1), Current Step 4 Version, 10 June 1996;

available online at:

http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E

6_R1_Guideline.pdf.

5. Guidelines for good clinical practice for trials on pharmaceutical products (1995)

WHO Technical Report Series, No. 850, Annex 3, 1995.

6. Guidance for organizations performing in vivo bioequivalence studies (revision) (2016)

WHO Technical Report Series, No. 996, Annex 9, 2016.

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Pharmaceutical Preparations. Forty-seventh report. Geneva, WHO Technical Report

Series, No. 981, 2013, Annex 2.

8. Guidelines on submission of documentation for prequalification of finished

pharmaceutical products approved by national regulatory authorities (“SRA guideline”)

(WHO Technical Report Series, No. 986, 2014, Annex 5).

Further reading

ICH Efficacy Guidelines; available online at:

http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html.

ISO 11135:2014: Sterilization of Healthcare products – Ethylene oxide – Requirements for the

development, validation and routine control of a sterilization process for medical devices.

ISO 11137-1:2006, Sterilization of Healthcare products- Radiation- Part 1: Requirements for

development, validation and routine control of sterilization process for medical devices.

ISO 11137-2:2013, Sterilization of Healthcare products- Radiation- Part 2: Establishing the

sterilization dose.

ISO 9001:2015, Quality Management Systems - Requirements.

ISO/IEC 17020:2012, Conformity Assessment - Requirements for the Operation of Various

http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf

http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf

http://apps.who.int/medicinedocs/en/d/Js5516e/19.11.html

http://www.who.int/medicines/publications/pharmprep/WHO_TRS_996_annex09.pdf?ua=1

http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html


page 33

Types of Bodies Performing Inspection.

ISO/IEC 17025:2005, General requirements for the competence of testing and calibration

laboratories.

Outline of a Procedure for Coordinating the verification for the GMP Status of manufacturers in

Third Countries, July 2005 European Medicines Agency.

Pharmaceutical Inspection Co-operation Scheme: Recommendation on Quality System

Requirements for Pharmaceutical Inspectorates, PI 002-3, 2007.

WHO good manufacturing practices for pharmaceutical products: main principles. In: WHO

Expert Committee on Specifications for Pharmaceutical Preparations. Forty-eighth report.

WHO Technical Report Series, No. 986, Annex 2. Geneva, World Health Organization, 2014.

WHO good practice for pharmaceutical quality control laboratories. In: WHO Expert Committee

on Specifications for Pharmaceutical Preparations. Forty-fourth report. WHO Technical Report

Series, No. 957, Annex 1. Geneva, World Health Organization, 2010.

WHO guidance on good manufacturing practices: inspection report. In: WHO Expert Committee

on Specifications for Pharmaceutical Preparations. Fiftieth report. WHO Technical Report


WHO Guidelines on variations to a prequalified product. In: WHO Expert Committee on

Specifications for Pharmaceutical Preparations. Forty-seventh report. WHO Technical Report


678

*** 679