Buenas Prácticas Regulatorias WHO

Working document QAS/16.686/Rev.
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August 2020
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3 DRAFT WORKING DOCUMENT FOR COMMENTS
4
5 Good regulatory practices

6 for regulatory oversight of medical
7 products
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Please send your comments to Dr Marie Valentin, Technical Officer, Regulatory Convergence and Networks,
Regulation and Safety ([email protected]), with a copy to Mrs Carolyn Doucelin ([email protected]) by
11 September 2020. Please use our attached Comments Table for this purpose.
Our working documents are sent out electronically and they will also be placed on the WHO Medicines
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11 © World Health Organization 2020
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15 This is a draft. The content of this document is not final, and the text may be subject to revisions before publication. The
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17 in whole, in any form or by any means without the permission of the World Health Organization.
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19 Please send any request for permission to:
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21 Dr Sabine Kopp, Team Lead, Norms and Standards for Pharmaceuticals, Technical Standards and Specifications, Department
22 of Health Products Policy and Standards, World Health Organization, CH-1211 Geneva 27, Switzerland, email: [email protected].
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24 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion
25 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or
26 of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate
27 border lines for which there may not yet be full agreement.
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30 recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors
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Working document QAS/16.686/Rev.3
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41 SCHEDULE FOR DRAFT WORKING DOCUMENT QAS/16.686/Rev.3

42 Good regulatory practices for regulatory oversight
43 of medical products
44
45
Description of activity Date
Concept Paper on Good Regulatory Practices. October 2013
Concept development workshop – India. July 2014
Draft development workshop – China. October 2015
Public consultation of the first draft document. May- December 2016
Internal consultation meeting. July 2017
Presentation to 53rd Expert Committee on Specifications for September 2018

Pharmaceutical Preparations (ECSPP) on the way forward.
Consultation with National Regulatory Authorities and regulatory 19 September 2019

organizations – Switzerland.
Update on the proposed plan for a high-level document for Good 14-18 October 2019
Regulatory Practices to the 54th ECSPP.
Development of the high-level Good Regulatory Practice high-level Until 31 July 2020
document.
Second public consultation. Until 11 September 2020
Consolidation of comments received and revision of the working September 2020

document by WHO.
Presentation to the 55th ECSPP with a proposal for adoption. 12-16 October 2020
46
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47 Good regulatory practices

48 for regulatory oversight
49 of medical products
50
51 Contents
52 Acronyms
53 Executive summary
54 1. Introduction
55 2. Background
56 3. Puprpose
57 4. Scope
58 5. Objectives
59 6. Key considerations
60 7. Overview of regulatory system for medical products
61 8. Principles of good regulatory practices
62 8.1 Legality
63 8.2 Consistency
64 8.3 Independence
65 8.4 Impartiality
66 8.5 Proportionality
67 8.6 Flexibility
68 8.7 Clarity
69 8.8 Efficiency
70 8.9 Transparency
71 9. Enablers for good regulatory practices
72 9.1 Political and government-wide support
73 9.2 Effective organization and good governance supported with leadership
74 9.3 Inter-and-intra-organizational communication, collaboration and coordination
75 9.4 A robust and well-functioning quality management system
76 9.5 Sufficient and sustainable financial resources
77 9.6 Competent human resources
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78 9.7 Pre-set organizational ethics and values

79 9.8 Science- and data-driven decision-making process
80 10. Implementing good regulatory practices
81 Acknowledgements
82 Glossary
83 References
84
85
86
87
88
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89 Acronyms
90
91 APEC Asia-Pacific Economic Cooperation
92 ASEAN Association of Southeast Asian Nations
93 GGP Good Governance Practices
94 GRP Good Regulatory Practices
95 GRelP Good Reliance Practices
96 GRevP Good Review Practices
97 OECD Organisation for Economic Co-operation and Development
98 QMS Quality Management System
99 QRM Quality Risk Management
100 WHO World Health Organization
101 WLAs WHO-Listed Authorities
102
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103 Executive summary

104
105 A fundamental role of government is to protect and promote the health and safety of the public,
106 including the delivery of health care. A well-functioning health care system depends upon the
107 availability and affordability of medical products that are safe, effective and of consistently assured
108 quality.
109
110 The medical products sector is one of the most regulated of all industries as a consequence of the
111 impact of the diverse range of medical products on health, the difficulty in assessing their quality, safety
112 and efficacy, and the complexities associated with their development, production, supply and
113 surveillance. It is therefore essential that the interests and safety of the public be entrusted to a
114 regulatory body responsible for ensuring that only products in legal trade are available and that
115 marketed products are safe, perform as claimed and are of assured quality.
116
117 Regulatory authorities have a duty to ensure that they regulate in a manner that achieves public policy
118 objectives. A coherent legal framework should be established and implemented that provides the
119 required level of oversight while also facilitating innovation and access to safe, effective and quality
120 medical products. This also means building the necessary flexibilities and responsiveness to manage
121 public health emergencies, address new technologies and practices and promote international
122 regulatory cooperation.
123
124 Governments incur costs by establishing and maintaining regulatory systems to protect and promote
125 the health of its citizens. Regulated parties incur costs in complying with regulation. However,
126 additional impacts (health system, socio-economic and economic impacts) can accrue from inefficient
127 regulatory systems - with potentially significant implications for disease morbidity/mortality, health
128 care costs and the economy.
129
130 A sound legal framework, the adoption of international norms and standards and the recruitment and
131 development of competent staff are necessary but not sufficient conditions to ensure ‘good regulatory
132 oversight’. These measures must be combined with good regulatory practices (GRP) that guide all
133 individuals within organizations entrusted to regulate in the application of requirements and the
134 formulation of decisions so that they are clear, consistent, impartial, proportionate, timely and based
135 on sound science and legislation.
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136 GRP can be defined as a set of principles and practices that are applied to the development,
137 implementation and maintenance of regulatory instruments – including laws, regulations and
138 guidelines – in order to achieve a public health policy objective in the most efficient way.
139
140 The successful application of GRP is the hallmark of a modern, science-based and responsive regulatory
141 system that translates the practice of regulation into desired outcomes. GRP provide a means of
142 establishing and implementing sound, affordable and efficient regulatory oversight of medical products
143 as an important part of health system performance and sustainability.
144
145 This document is intended to present Member States with widely-recognized principles of GRP. The
146 principles presented in this document derive from an extensive review of public documents developed
147 by governments and multi-lateral organizations on the subject, as well as many consultative workshops,
148 benchmarking exercises and interactions with Member States. The nine principles presented in this
149 document, such as, legality, consistency, independence, impartiality, proportionality, flexibility, clarity,
150 efficiency and transparency, are relevant to all authorities responsible for the regulatory oversight of
151 medical products, irrespective of resources, sophistication or regulatory model.
152
153 GRP serve as a foundation within a suite of related guidance documents on best regulatory practices.
154 Taken together, this expanding set of guidance documents is intended to provide regulatory authorities
155 comprehensive guidance on improving their performance. This document will be supplemented by
156 practical ‘how to’ guides and tools designed to facilitate the implementation of GRP.
157
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158 1. Introduction
159
160 This document responds to requests from national authorities responsible for the regulatory oversight
161 of medical products for guidance in addressing common gaps in regulatory practices identified during
162 benchmarking exercises.
163
164 This document draws upon documents from multilateral bodies such as the Asia-Pacific Economic
165 Cooperation (APEC), the Organisation for Economic Co-operation and Development (OECD), the World
166 Bank and the Association of Southeast Asian Nations (ASEAN) (1) (2) (3) (4) (5) as well as guides
167 published by a number of governments. The document also takes account of earlier World Health
168 Organization (WHO) documents that touch on aspects of GRP (6) (7) (8) (9) (10) (11) (12) (13) (14) and
169 from WHO experience in applying the WHO Global Benchmarking Tool (GBT) and promoting the various
170 principles of good regulatory practices (GRP).
171
172 When the principles of GRP are properly implemented through the GRP enablers across the regulatory
173 system, desired regulatory outcomes and impact can be achieved.
174
175 2. Background
176
177 A fundamental role of government is to protect and promote the health and safety of the public,
178 including in the delivery of health care. A well-functioning health care system depends upon the
179 availability and affordability of medical products that are safe, effective and of assured quality.
180
181 Medical products are essential to the prevention, diagnosis and treatment of disease and the
182 consequences of substandard and falsified medical products can be therefore life-threatening. This
183 reality is of particular concern as users of medical products are typically not in a position to judge their
184 quality. It is therefore essential that the interests and safety of the public be entrusted to a regulatory
185 body or bodies responsible for ensuring that only products in legal trade are available and that
186 marketed products are safe, perform as claimed and are of assured quality.
187
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188 The regulatory oversight of medical product has become increasingly complex given the globalization
189 of product development, production and supply, coupled with the rapid pace of technological and social
190 change in a context of limited financial and human resources.
191
192 The importance of robust regulatory systems was recognized by the Sixty-Seventh World Health
193 Assembly in endorsing Resolution WHA 67.20 Regulatory system strengthening for medical products.
194 The Resolution notes that “effective regulatory systems are an essential component of health system
195 strengthening and contribute to better public health outcomes”, that “regulators are an essential part
196 of the health workforce”, and that “inefficient regulatory systems themselves can be a barrier to access
197 to safe, effective and quality medical products” (15).
198
199 A sound system of oversight requires that regulatory authorities are supported by an effective
200 framework of laws, regulations and guidelines, and that they have the competence, capacity and
201 science-based knowledge to conduct their mandate in an efficient and transparent manner. The degree
202 to which the regulatory framework fulfils policy objectives depends on the quality of its development
203 and implementation processes.
204
205 GRP are critical to the efficient performance of the regulatory system and, consequently, to the public’s
206 confidence in the system. A sound regulatory framework, including the adoption of international norms
207 and standards and the recruitment and development of competent staff, are necessary but not
208 sufficient conditions to ensure ‘good oversight’. These measures must be combined with GRP that
209 guide all individuals from regulatory authorities to set appropriate requirements and formulate
210 decisions that are clear, consistent, impartial, proportionate, timely and based on sound science.
211
212 3. Purpose
213
214 This document presents the high-level principles of GRP. The principles are intended to serve as a
215 benchmark and thereby assist Member States in the application of good practices for the regulatory
216 oversight of medical products. This document is also meant to assist Member States in prioritizing the
217 functions of a regulatory system based on available resources, national goals, medical products policies
218 and the medical product environment.
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219 This principles-based document will be supplemented by practical ‘how to’ guides and tools designed
220 to facilitate the implementation of GRP within organizations responsible for the regulatory oversight of
221 medical products.
222
223 This foundational document is complemented by a suite of related guidance on best regulatory
224 practices, including but not limited to good governance practices (GGP) (16), good reliance practices
225 (GRelP) (17), good review practices (GRevP) (18) and the implementation of quality management
226 systems (QMS) for national regulatory authorities (NRAs) (19). Taken together, this expanding body of
227 work is intended to provide regulatory authorities with comprehensive guidance on improving
228 performance.
229
230 4. Scope
231
232 This document is relevant to all regulatory authorities irrespective of resources, maturity or regulatory
233 model. These GRP high-level principles are equally applicable to regulatory systems that are
234 supranational (e.g. regional), national and/or subnational in nature, or involve multiple institutions
235 charged with regulating certain products or activities within a country or jurisdiction.
236
237 This document presents principles and considerations in the development and implementation of
238 regulatory instruments which underpin regulatory activities. Broader practices and attributes are
239 presented that define well-performing regulatory systems for medical products.
240
241 This document is intended for a number of related audiences: institutions and policy-makers
242 responsible for the formulation of health policies, laws, regulations and guidelines; institutions that,
243 together, form national or supranational systems for regulatory oversight of medical products;
244 regulatory networks and parties affected by or otherwise interested in regulatory frameworks; for
245 example, industry or other developers of medical products.
246
247 5. Objectives
248
249 GRP provide a means of establishing sound and effective oversight of medical products as an important
250 part of health system performance and sustainability. If consistently and effectively implemented, they
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251 can lead to higher quality regulation, improved regulatory decision-making and compliance, increased
252 efficiency of regulatory systems, and better public health outcomes. They help to ensure that
253 regulatory systems remain current as technologies and the systems in which they are used continue to
254 evolve.
255
256 Within the context of an increasingly complex and interconnected regulatory environment, GRP are
257 also an important enabler in promoting trust between regulatory authorities and thereby facilitating
258 international cooperation and the adoption of more effective and efficient approaches to ensuring the
259 quality, safety and efficacy of medical products within the global regulatory community.
260
261 The ultimate aim of GRP is to serve and protect public health and patients’ interest, respecting all
262 applicable ethical principles.
263
264 6. Key considerations

265
266 The medical products sector is one of the most regulated of all industries as a consequence of the
267 impact of the diverse range of medical products on health and society, the difficulty in assessing their
268 quality, efficacy and safety, lessons learned from public health tragedies, and the complexities
269 associated with developing, producing, supplying and monitoring medical products to ensure they
270 consistently perform as intended. This has led many countries to put into place an increasingly
271 sophisticated set of laws, regulations and guidelines that control all aspects of the medical product life-
272 cycle.
273
274 While providing the necessary authorities, prohibitions and tools necessary to fulfil publicly entrusted
275 mandates, regulatory authorities have a duty to ensure that they regulate in a manner that achieves
276 public policy objectives. This means establishing and implementing a coherent regulatory framework
277 that provides the required level of oversight and control while also facilitating the innovation and access
278 to safe, effective and quality medical products. It also means building the necessary flexibilities and
279 responsiveness to manage public health emergencies, address new technologies and best practices,
280 and promote international regulatory cooperation.
281
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282 Increasingly, policy makers and regulatory authorities must adopt modern and responsive models of
283 regulation that consider resource constraints in the face of the challenges posed by scientific
284 development, globalization, rising public expectations and public health emergencies.
285
286 Weak or inefficient regulatory systems can be a barrier to access to safe, effective and quality medical
287 products and a threat to public health. At the same time, countries strengthen regulatory capacity
288 regulatory systems need to be science-based, respect international standards and to adopt an approach
289 that leverages the work of other trusted regulatory authorities and institutions whenever possible.
290 Towards this end, countries are encouraged to formulate and implement policies and strategies that
291 promote convergence, harmonization, information and work-sharing, and reliance as part of GRP (17).
292 An ongoing initiative at WHO aims at establishing and implementing a framework for evaluating NRAs
293 and regional regulatory systems as well as designating those that meet a specific standard as WHO-
294 Listed Authorities (WLAs) (20).
295
296 For reasons of public health protection noted earlier in the document, the need for regulatory controls
297 over medical products is fully acknowledged. The issue is more how to regulate in an effective, efficient
298 and transparent manner, such that the interests of the health care system are served. The consistent
299 application of GRP in all aspects of oversight is essential in ensuring that these interests are met and
300 providing the foundation on which a well-performing, respected regulatory system is built.
301
302 GRP can be defined as a set of principles and practices that are applied to the development,
303 implementation and maintenance of regulatory instruments – including laws, regulations and
304 guidelines – in order to achieve a public health policy objective in the most efficient way.
305
306 GRP is about instilling a culture of best practices across institutions responsible for regulatory oversight
307 to ensure that regulation is fairly, consistently and effectively applied.
308
309 7. Overview of regulatory system for medical

310 products
311
312 Definitions are essential to a common understanding of concepts. While a more extensive set of terms
313 is provided in the Glossary, an elaboration of the terms regulatory framework, legal framework,
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314 regulatory authority, regulatory system, and regulatory outputs is provided below to ensure a proper
315 understanding of their usage in this document.
316
317 Components of the regulatory framework
318
319 In this document, the terms “law” and “regulation” are used for the components of the legal framework
320 (binding legislation). It is acknowledged that other terms may be used in different jurisdictions, such as
321 “act” (instead of law) or “ordinance” (instead of regulation).
322
323 Laws are generally used to set out at a high level the roles and responsibilities of institutions;, in this
324 case, the regulatory authority, the ministry of health and other relevant organizations. They define the
325 products, persons and activities that are to be regulated and state what is permitted and what is not.
326 More importantly, laws authorize the institution to make lower level (or subordinate) regulations.
327
328 Regulations are a diverse set of instruments by which governments place requirements on enterprises
329 and citizens. The regulations usually state at high level the conditions to be met and detail the
330 requirements defined in the laws.
331
332 For instance, a law may prohibit the manufacturer, importation or sale of a medical product in the
333 absence of specific authorisation. The regulations would set out the conditions for obtaining
334 authorisation; for example, the need to provide certain types of information - such as clinical trial and
335 manufacturing and control data - that would allow the regulatory authority to establish the quality,
336 safety and efficacy of a medical product.
337
338 Guidelines (and other guidance documents) provide further detail on how the regulated stakeholders
339 can comply with the laws and regulations. Guidelines may also provide details on the processes that
340 enforce the respective legislation (laws and regulations). Within a regulatory framework for medical
341 products, these documents are usually non-binding and are generally more detailed and scientific in
342 nature. This makes them appropriate for describing approaches generally considered suitable for
343 satisfying regulatory requirements but unsuitable to be embedded into legislation.
344
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345
346 Figure 1: Architecture of a Regulatory Framework

347
348 Components of the regulatory system
349
350 A regulatory authority is a public institution(s) or governmental body/bodies authorized by law to
351 independently exercise regulatory powers concerning the development, production, marketing and
352 surveillance of medical products. Although the term implies that a single organization is responsible
353 for all regulatory functions, indeed these functions may be undertaken by one or more institutions
354 reporting to the same or different senior official. The regulatory authority plays a critical role in
355 ensuring the quality, safety, efficacy and performance of medical products as well as the relevance and
356 accuracy of product information.
357
358 The regulatory framework is the collection of laws, regulations, guidelines and other regulatory
359 instruments through which a government and a regulatory authority controls particular aspects of a
360 specific activity.
361
362 The legal framework is the part of the regulatory framework that refers to (binding) pieces of legislation,
363 such as laws and regulations.
364
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365 Regulatory outputs are the results or products coming from the regulatory authority
366 (e.g. inspection/assessment reports, decisions, product label, and so on).
367
368 The term regulatory system is used to describe the combination of the institutions, processes,
369 regulatory framework and resources which, taken together, are integral to the effective regulatory
370 oversight of medical products in a given country or multi-country jurisdiction. GRP should be
371 considered and applied for the whole regulatory system.
372
August 2020
373
374 Figure 2: Principles and enablers of Good Regulatory Practices (GRP) and Components of the regulatory system
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375 When looking at the overall regulatory system, three main components (inputs) can be seen as the
376 main contributors to regulatory functions and activities: (1) regulatory framework composed of legal
377 framework (laws and regulations) along with guidelines and other guidance documents, (2) regulatory
378 institutions which may be represented by one or more entities including the national regulatory
379 authority (NRA), the national control laboratory, pharmacovigilance centre(s), research ethics
380 committee(s) and others, and (3) all types of resources including human and financial resources,
381 infrastructure and equipment and information management systems. There are several regulatory
382 outputs depending on the concerned functions and activities (e.g. regulatory and marketing
383 authorization inspection/assessment reports). The concepts and principles of GRP cover and address
384 the overall regulatory system as explained above. For the purpose of application and implementation
385 of GRP, several enablers are essential (see 10. Enablers for Good Regulatory Practices). When the
386 principles of GRP are properly implemented through the enablers, a desired regulatory outcome and
387 impact can be achieved.
388
389 WHO classifies the spectrum of regulatory activities according to seven common regulatory functions
390 applicable to the regulation of all medical products: clinical trials oversight, registration and marketing
391 authorization, vigilance, market surveillance and control, licensing establishments, regulatory
392 inspection and laboratory testing (21). In addition, a number of non-common functions apply to certain
393 medical products, such as official lot release for vaccines and other biologicals.
394
395 The term regulatory authority implies that a single organization is responsible for all regulatory
396 functions. This is not always the case. For example, different organizations may be legally responsible
397 for the regulation of medicines and vaccines as compared to medical devices. Even when one body is
398 responsible for all regulatory functions, aspects critical to certain functions may lay outside the
399 authority, such as those performed by pharmacovigilance centres that have a formal relationship with
400 the authority in collecting adverse event reports. Certain regulatory functions may also be undertaken
401 by third parties, as in the case of auditing organizations in relation to medical devices.
402
403 Regulatory activities may also be undertaken at a supranational (e.g. regional), national and/or
404 subnational level. Examples include the supranational evaluation of certain products for the purpose
405 of granting a marketing authorization valid across multiple countries, or the GMP inspections of multi-
406 source medicines performed at the state level.
407
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408 8. Principles of good regulatory practices

409
410 There is no universal model for the regulatory oversight of medical products. Each approach will reflect
411 national health policies and priorities, the country’s level of socioeconomic development, the
412 availability of resources and infrastructure, the health system, the national legal system, the research
413 and development capacity, as well as the local production capacity. Nonetheless, as in other regulated
414 sectors, there is a growing international consensus on best practices that may be applied to regulatory
415 oversight.
416
417 A review of public documents (1) (4) (5) (22) on GRP reveals common themes that should be adopted
418 by all institutions responsible for or involved in the regulatory oversight of medical products. These
419 principles apply equally to the development and implementation of regulatory oversight and to daily
420 regulatory business.
421
422 GRP are guided by overarching principles. There are nine principles which are listed below and are
423 described in this section, together with considerations relevant to the regulatory oversight of medical
424 products.
425
426 Further elaboration of the principles, practices and examples is foreseen in supplemental ‘how to’
427 guidance complementing this document.
428
429
Principles of Good Regulatory Practice
Legality Regulatory systems and the decisions that flow from them must have a
sound legal basis.
Consistency Regulatory oversight of medical products should be consistent with

existing government policies and legislation and be applied in a
consistent and predictable manner.
Independence Institutions executing regulatory oversight of medical products should

be independent.
Impartiality All regulated parties should be treated equitably, fairly and free from
bias.
Proportionality Regulation and regulatory decisions should be proportional to risk and

the regulator’s capacity to implement and enforce.
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Flexibility Regulatory oversight should not be prescriptive but rather allow for
flexibility in responding to a changing environment and unforeseen
circumstances. Responsiveness in a timely manner to public health
emergencies should be built into the regulatory system.
Clarity Regulatory requirements should be accessible to and understood by

users.
Regulatory systems should achieve their goals within the required time
Efficiency
and at reasonable effort and cost. International collaboration
promotes efficiency by allowing the best use for resources.
Transparency Regulatory systems should be transparent; requirements and

decisions should be made known, and input sought on regulatory
proposals.
430
8.1 Legality
Regulatory systems and the decisions that flow from them must have a sound legal basis.
Key elements:
• The regulatory framework should provide the necessary authorities, scope and flexibilities
to safeguard and promote health.
• The delegation of power and responsibilities to different levels of the regulatory system
should be clear and explicit.
• Regulatory frameworks should support and empower regulatory authorities to contribute
to and benefit from international cooperation.
• Systems should be in place to ensure that regulatory decisions and sanctions can be
reviewed.
• Regulatory framework should afford for the integrity of the regulatory system with clear
scope and lines of authority of institutions forming the regulatory system.
• A legal framework must hold the regulatory authority accountable to the public, those
regulated and the government for their actions and decisions.
431
432 The principle of legality means that the regulatory system is structured so that all regulatory actions
433 and decisions are based on clear legal authority, thus respecting the “rule of law”.
434
435 A regulatory body exists to achieve objectives deemed by the government to be in the public interest.
436 It must operate within and in accordance of the powers conferred by the legal framework (23). The
437 law or act establishing the regulatory authority should be clear on the objectives of the enabling
438 legislation, the powers of the authority, the scope of products and general activities the authority is
439 mandated to regulate, and the provisions for making regulations.
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440 The delegation of power and responsibilities to different levels of the regulatory system should be
441 explicit and clear. When more than one institution or level of government is involved in the regulation
442 of medical products, the functions and responsibilities of the various institutions should be clear and
443 complementary (see 9.2 Consistency).
444
445 Given the need for all regulatory authorities to cooperate to manage increasingly complex and
446 cross-jurisdictional issues, it is essential that a modern legal framework for medical products supports
447 and encourages such cooperation in all its forms - including convergence, harmonization, information-
448 and work-sharing, reliance and recognition. Ideally, this would take the form of explicit provisions in
449 law and/or regulations, with further operational detail provided in policies and procedural guidance.
450 At a minimum, the legal framework should not prohibit all forms of regulatory cooperation, including
451 the use of assessments and decisions of other trusted regulatory authorities and institutions in
452 performing its own work. Cooperation does not alter the sovereign responsibility and accountability of
453 each regulatory authority to protect the health and safety of its citizens but allows for the exchange of
454 good practices and may help save resources and avoid duplication.
455
456 Legislation has to be in place to control and perform all required regulatory activities under common
457 and non common regulatory functions. Policies, guidelines and procedures cannot compensate for the
458 absence of legislation.
459
460 A legal framework should support the integrity of the regulatory system with clear authority, power,
461 roles and responsibilities of institutions forming the regulatory system. Conflict in organizational
462 authority or responsibilities should be avoided.
463
464 All regulatory authorities must be accountable to the public, those regulated, and the government for
465 their actions and decisions as part of good governance and accountability frameworks. Within the
466 context of GRP, accountability means that regulatory authorities are: (i) responsible for acting according
467 to certain standards and commitments; (ii) answerable for their actions; and (iii) willing to face the
468 consequences when standards or commitments are not met.
469
470 Regulatory actions and decisions should be consistent with authorities and controls provided for by the
471 legal framework. Processes should therefore be put in place for the review of regulatory decisions.
472 This includes internal appeal mechanisms and the right to judicially appeal decisions of regulators –
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473 including on the grounds of procedural fairness and due process – in addition to scientific and
474 administrative grounds.
475
8.2 Consistency
Regulatory oversight of medical products should be consistent with existing government policies
and legislation and be applied in a consistent and predictable manner.
Key elements:
• The regulatory framework for medical products should fit coherently into the national legal
and policy framework.
• New regulations should complement, and not conflict with, existing regulatory
instruments.
• Regulatory requirements should be consistently implemented and enforced across medical
product sectors and stakeholders.
476
477 Regulatory oversight of medical products must be performed in the context of, and in ways coherent
478 with, the national legal framework, general government policies and public health policy objectives.
479 This also includes any treaties, conventions and regional or international agreements to which the
480 country is a party as well as any supranational legislation having an effect on constituent Member States.
481
482 Overlap and conflicts with existing laws and regulations should be avoided since this causes confusion
483 and the duplication of mandates, unnecessary regulatory burden and the likelihood of noncompliance.
484 Manufacturers, importers, distributors and other stakeholders should be able to consistently identify
485 which authority is responsible for what.
486
487 This is especially important where the regulation of medical products is decentralized – when, for
488 instance, there may be central and state/provincial-level authorities. Effective systems of mutual
489 consultation, cooperation and coordination between the different levels of government should be put
490 in place in order to promote the national uniformity of regulatory requirements while respecting local
491 responsibilities. It is essential that all the different regulatory functions and activities are efficiently
492 integrated allowing for the uniformity of the regulatory system.
493
494 The same considerations are equally important when more than one institution or department within
495 the same level of government is responsible for different, or the same, regulatory functions and
496 products – a situation which is not uncommon. The problems associated with unclear or conflicting
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497 mandates and requirements can and do result from complex regulatory systems, compounded by
498 challenges in effective communication and coordination.
499
500 In all instances, formal mechanisms should be established to ensure proper coordination during the
501 drafting and execution of the regulatory instruments and the ongoing operations of bodies charged
502 with the regulatory oversight of medical products.
503
504 Consistency in regulatory actions and decisions means that the same or similar circumstances should
505 lead to the same or similar outcomes. It is therefore important for the regulatory system to build an
506 institutional memory to keep records of decisions made in order to offer similar and fair treatment to
507 future similar situations. Consistency is supported when the regulatory framework provides for
508 appealing regulatory decisions through an impartial appeals process. The enforcement of such, and
509 corrective measures, should also be consistent across sectors.
510
511 Consistency is also supported by having sufficient and clear regulatory guidance based, whenever
512 possible, on international guidelines; the orientation and training programmes for staff; and regular
513 discussions with regulated parties and other key stakeholders that serve as mechanisms for the
514 identification and resolution of issues.
515
516 The application of a well-functioning quality management system that spans all regulatory activities (24)
517 is critical for achieving regulatory consistency. This includes, among others, the adoption of a process
518 approach involving the systematic definition and management of regulatory processes, and their
519 interactions, so as to achieve the intended results in accordance with the quality policy and strategic
520 direction of the organization.
521
522 Performance based indicators, internal reviews and external audits can also play an important role in
523 ensuring consistency in the application of regulations and regulatory operations.
524
8.3 Independence
Institutions executing regulatory oversight of medical products should be independent.
Key elements:
• The regulatory system must operate, and be seen to operate, in an independent and
authoritative manner, discharging its duties independently from politicians, government
and regulated entities.
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• Regulatory activities and decisions should avoid improper and undue influence from
stakeholders (also known as regulatory capture).
• The appropriate funding and clarity on funding processses is essential.
• Independence of leadership should be put in placein order to support independent
behaviour while in employment and upon exiting.
525
526 According to an OECD publication entitled Creating a culture of independence (20) “regulatory agencies
527 (authorities) often find themselves under various pressures from different stakeholders and interest
528 groups which can subject them to different forms of influence. To ensure they conduct their activities
529 correctly and achieve the right policy outcomes they must take on board legitimate interests and
530 protect themselves from inappropriate or undue influence”.
531
532 Good governance and anti-corruption measures (16) should be built into the regulatory framework to
533 avoid actual or perceived conflicts of interest, unfounded bias or improper influence by stakeholders
534 (also known as regulatory capture). To maintain public confidence, the regulatory authority must
535 operate, and be seen to operate, in an independent, authoritative and impartial manner, discharging
536 its duties independently of those regulated entities (e.g. independence from researchers and
537 industries).
538
539 For regulators that are funded through fees, an appropriate cost-recovery mechanism is essential to
540 set the “right” fee and avoid a regulator that is under-funded, captured by industry or undermined by
541 the executive. It can be easier to influence a regulator funded through general government revenues
542 by reducing the resources at its disposal. Annual appropriations can make it easier to influence the
543 regulator than multi annual appropriations that are less susceptible to short-term shocks, such as
544 political/electoral imperatives. Adequate safeguards can protect the budget process from being used
545 to unduly direct the regulator.
546
547 The nomination and appointment of the regulator’s leadership should be based on transparent and
548 accountable processes. Clear conflict of interest rules should be in place to support independent
549 behaviour while in employment and upon exiting.
550
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8.4 Impartiality
All regulated parties should be treated equitably, fairly and free from bias.
Key elements:
• Regulatory activities and decisions should avoid conflicts of interest or unfounded bias.
• The regulatory system must operate in an impartial manner.
• The regulatory authority should not be engaged in activities it regulates nor be at a
hierarchal level that is subordinate to institutions that perform regulated activities.
• Regulatory decision should be science- and evidence-based and the decision-making
process should be robust, according to defined criteria.
551
552 Regulatory instruments must be written so that regulatory activities and decisions made on the basis
553 of such instruments are legitimate, evidence-based and ethical. Public and private bodies, domestic
554 and foreign entities should all be regulated equitably using the same principles and framework so that
555 competitive neutrality is achieved.
556
557 The regulatory authority must operate in an impartial manner, discharging its duties independently of
558 those regulated entities (see 9.3 Independence).
559
560 This principle also extends to researchers and other experts sitting on scientific and advisory
561 committees convened to provide recommendations to the regulatory authority on matters related to
562 regulatory policy or the authorisation of medical products. Declarations of interest have to be
563 completed and reviewed, and rules for withdrawal need to be defined prior to discussions to maintain
564 the integrity and impartiality of the committee and its recommendations.
565
566 Furthermore, the regulatory authority should not be engaged in the activities it regulates nor be at a
567 hierarchal level that is subordinate to those institutions that perform regulated activities, including the
568 procurement of medical products by a ministry of health or other government institution.
569
570 Regulators can avoid actual or perceived influence by being open and transparent about their decisions
571 and decision-making process. This will help ensure impartiality, better regulatory outcomes and
572 increased public confidence in the use of the regulated products.
573
574 Regulatory activities and decisions should be science-driven, evidence-based and predictable. While
575 there will always be a need for good regulatory judgement and discretion in enforcement, actions and
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576 decisions should be based on regulatory requirements and on the evidence or circumstances of the
577 situation (also supports 9.2 Consistency).
578
8.5 Proportionality
Regulatory oversight and regulatory decisions should be proportional to risk and the regulator’s
capacity to implement and enforce.
Key elements:
• Regulatory oversight should be adequate to achieve the objectives without being
excessive.
• Regulatory measures should be proportionate to the risk of the product or activity or
service.
• Regulation should not exceed the national capacity to implement and enforce the
regulation.
• The assessment of medical products should be based on a benefit/risk evaluation and
continuous monitoring of the benefit/risk profile through a robust vigilance system.
579
580 The principle of proportionality means that an action does not go beyond what is needed to achieve an
581 intended objective. This principle should be applied to all elements of a regulatory system. Regulation
582 should be created only when necessary and should be adequate to the aim being pursued without
583 being excessive. The content and form of regulation should be appropriate to both the issue being
584 addressed and the risk it poses. For instance, extensive pre-clinical and clinical studies are needed to
585 support the safety and efficacy for the marketing authorization of a new medicine, whereas, limited
586 safety/efficacy studies, usually in a form of a single in vivo bioequivalence study or, where appropriate,
587 in vitro studies, are sufficient for generic medicines.
588
589 Regulatory enforcement and inspection regimes should also be proportionate to the risk and severity
590 of the infraction with an aim to reduce or mitigate the health risk posed by the infraction. A
591 proportionate, risk-based approach allows the regulator to allocate resources where the need is greater.
592 It also ensures that the cost of complying with regulation is proportionate to the nature of the risk.
593
594 The principle of proportionality also applies to the policies and processes by which regulation is made.
595 The regulation-making process should be flexible and proportionate to the complexity and/or impact
596 of the problem that it addresses. For instance, a rigorous cost/impact analysis may be required for a
597 new complex regulatory framework but not for simple regulations or where the policy alternatives are
598 limited.
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599 Regulation should not exceed national capacity to implement and enforce the regulation. “If there are
600 no strategies, facilities and resources for implementation and enforcement, legislation on its own will
601 achieve nothing. A law with modest aims and objectives that is properly enforced is preferable to a
602 more comprehensive one that cannot be implemented”(12). Furthermore, the lack of resources or
603 ability to implement and enforce represents a liability for the government.
604
605 The assessment of medical products should be based on a benefit/risk evaluation. All the demonstrated
606 benefits from the medical products should be weighed against the identified risks in order to determine
607 if the benefit outweighs the risks. Regulatory systems should have appropriate vigilance processes in
608 place in order to monitor the benefit/risk profile and to take any regulatory actions if required.
609
8.6 Flexibility
Regulatory oversight should allow for flexibility in responding to a changing environment and
unforeseen circumstances.
Key elements:
• The regulatory system, including regulatory frameworks, should provide sufficient flexibility
to reflect/respond to changes in the regulated environment, including evolving science and
technology.
• The regulatory system should be prepared and provide for timely response to urgent
situations, including public health emergencies and shortages of medical products.
• The language of regulation should be performance-based whenever possible, allowing for
alternative approaches that achieve the same result.
• The regulatory system should provide the flexibility to apply good judgement.
610
611 Flexibility is essential to ensure that regulatory frameworks and regulatory systems remain “fit for
612 purpose”. This requires the appropriate design and use of regulatory instruments.
613
614 In developing a meaningful, understandable and enforceable regulatory framework, there is a need to
615 provide sufficient detail to ensure clarity. At the same time, the regulatory framework should allow
616 flexibility to respond to new technologies and innovation, to changes in the regulated environment and
617 to enable a timely response to unforeseen public health threats. It should provide for the regulator’s
618 administrative and enforcement discretion – that is, the flexibility to apply good judgement within the
619 regulatory framework. This discretion must be subject to the appropriate controls and oversight.
620 Flexibility in regulatory oversight should also be risk-based and must not compromise the ability to
621 ensure the quality, safety and efficacy and performance of the product (19).
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622 Responsiveness is an extended principle of flexibility, however slightly different. Responsiveness is

623 time-bound and temporary in nature due to the fact that it addresses urgent situations such as public
624 health emergencies, serious shortages of medical products with no alternatives, unmet medical needs
625 and rare disorders, and the use for compassionate and donation purposes. Regulatory systems should
626 be well prepared and equipped with the necessary regulatory instruments to respond to and manage
627 these unforeseen situations. Flexible and responsive provisions are critical for providing the authority
628 with the ability to make decisions based on best available science and benefit/risk considerations, often
629 in the face of less-than-complete information (e.g. compassionate use, emergency use authorization or
630 listing). The lack of necessary regulatory tools and the flexibilities they afford can pose real and
631 significant impediments to public safety, particularly in times of public health emergencies.
632
633 During times when regulatory responsiveness is urged, a regulatory authority should consider the
634 prioritization of its activities using a risk-based approach. The involvement of policy and decision-
635 makers, as well as regulatory collaboration and coordination within the international regulatory
636 community, significantly contributes to regulatory responsiveness.
637
638 Flexibility and responsiveness within regulatory framework should aim to accommodate continuing
639 evolution in science and technology. The language of the regulations that support the law should
640 normally be performance-based rather than prescriptive (6), thus allowing regulated parties to use
641 alternative approaches that achieve the same outcome.
642
643 Guidelines and other guidance documents are the most detailed, most flexible and most amendable of
644 the regulatory framework instruments. These attributes allow the regulatory framework to respond to
645 new risks in a timely manner and allow for the possibility that an unforeseen technology may be used
646 in a future medical product. Unlike laws and regulations, guidelines in themselves usually do not have
647 the force of law. However, guidelines are very effective if appropriately anchored to the regulation and
648 used to describe how compliance with the regulation may be achieved. They should also allow for other
649 scientifically justified approaches to compliance. Alternate approaches to the principles and practices
650 described in a guidance may be acceptable provided they are supported by adequate scientific
651 justification. The flexibility and amendable attributes that guidelines offer is lost if such detailed texts
652 are put into regulation.
653
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654 In circumstances where science is rapidly evolving and not sufficiently mature to justify the
655 development of regulatory guidelines, ‘points to consider’ type documents can provide useful
656 principles-based guidance and definitions that promote best practices, a common regulatory
657 understanding, international convergence, and prepare the ground for eventual guidelines. Existing
658 international guidelines and standards should always be considered when new guidance documents
659 are being developed.
660
661 The regulation of medical products is complex and ever-evolving. New technologies and practices will
662 continue to pose challenges to regulatory systems and redefine the boundaries of what can and should
663 be regulated. Prior to the possible development of regulations designed to deal with new technologies
664 or address certain practices, regulators will often need to generate the necessary regulatory flexibility
665 through the appropriate interpretation of existing legislation and regulations.
666
8.7 Clarity
Regulatory requirements should be accessible to and understood by users.
Key elements:
• Regulatory instruments should be written in language that is understood by users.
• Terminology should be defined and consistent with international norms whenever possible.
• Consultation, education and training on new requirements contribute to clarity and
compliance.
• Guidelines and good guidance practices are instrumental to proper interpretation of
regulations.
• The process and basis for taking regulatory decisions and enforcement actions should be
clear.
667
668 The compliance with and consistent application of regulatory requirements and processes require a
669 clear understanding of what is expected. Both the regulator and the regulated party should understand
670 the conduct that is expected and the consequences of non-compliance.
671
672 Proposed regulatory instruments should be written in language that can be understood by intended
673 users. This will require the collaboration of regulatory programme personnel and legal drafters, taking
674 into consideration the objectives of the legal instrument, the intended audience and other potentially
675 impacted stakeholders, as well as feedback from internal and external consultations. Clear,
676 unambiguous and precise instruments that are drafted in a language and form consistent with other
page 29
677 laws and regulations reduce the potential for disputes or misinterpretation and also promote
678 compliance.
679
680 As an initial step in the process, the authority drafting medical product regulations should conduct a
681 review to identify areas that lack clarity and resolve any inconsistencies – whether within the regulation
682 itself or between regulations. This also serves as an opportunity to review the “regulatory stock” – the
683 accumulated body of applicable regulations – to identify the need for future updating and better
684 integration of regulatory requirements with a view to eliminating inconsistencies, redundancies and
685 complexity or adapting to new requirements.
686
687 Providing interested parties, including the public, the opportunity to be informed of and contribute to
688 the process of regulatory development and regulatory impact analysis is critical to improving the quality
689 and language of the regulatory instrument, promoting a clear understanding of what is intended, and
690 increasing the likelihood of buy-in and future compliance. The means by which interested parties can
691 contribute should be made clear.
692
693 Regulatory impact analysis is a valuable tool for systematic assessment of the expected effects of
694 regulatory proposals. It is usually undertaken by the policy analysts of the regulatory departments,
695 agencies or ministries that sponsor the proposal and is primarily aimed at assisting decision-makers in
696 their consideration of a recommended proposal. The product of the regulatory impact analysis process
697 is a document that summarizes the regulatory proposal, the potential alternatives and the
698 implementation aspects and impacts of the proposal.
699 Terminology should be defined whenever possible to avoid ambiguity or misinterpretation. Where
700 possible, terminology should be consistent with established international norms, standards and
701 harmonized guidelines. As noted, international standards and guidelines are particularly important as
702 vehicles to promote a common regulatory language, convergence and international cooperation.
703
704 The principle of clarity is equally important and applicable to the development of regulatory and
705 administrative guidelines which are instrumental in interpreting and providing operational clarity to
706 regulations. Guideline development should follow good guidance practice to ensure that guidelines are
707 written in a clear and concise manner and are consistent with other guidelines and the underlying
page 30
708 regulations. This includes the use of standard templates and formats, writing style guides, editors, and
709 experts with a good knowledge of the regulatory framework.
710
711 Draft guidelines, as with regulations, should be subject to internal and external consultation.
712 Consultation will help confirm if language is clear or if it requires some refinement to improve
713 comprehension. Plain language and simple sentence structure should be the goal as well as to give
714 illustrative examples where possible.
715
716 Education, awareness sessions and training, along with clear timelines for the adoption of new
717 regulations and guidelines, should also be considered as tools to promote clarity and compliance when
718 introducing or amending regulations and guidelines, particularly when complex in nature.
719
720 Regulations and supporting guidelines should be reviewed periodically to ensure that they still reflect
721 the authority’s current practices and expectations, are adapted to the scientific and technological
722 developments, and are aligned with current international standards and guidelines, where applicable.
723 When reviewing and revising any guideline, one must consider the consequential changes in other
724 existing guidelines that will need simultaneous revision.
725
726 From an operational perspective, the process and basis for taking regulatory decisions and enforcement
727 actions should be clear and accessible to those directly impacted or otherwise affected (see 7.9
728 Transparency).
729
730 In summary, clarity is essential in all aspects of regulatory oversight (requirements, procedures,
731 decisions and communications) if regulatory programmes are to have the desired effect.
732
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8.8 Efficiency
Regulatory systems should achieve the intended results within the required time and at reasonable
effort and cost.
Key elements:
• Efficient regulatory oversight are those that achieve the intended public health goals.
• A sound regulatory framework, competent staff and the effective use of resources and
information from other authorities are the key elements of an efficient regulatory system.
• Policy-makers should seek the most efficient and least burdensome means of achieving
their regulatory purposes and confirm actual effectiveness once implemented.
• In considering a regulatory approach, the total burden and resource needs of cumulative
regulation should be evaluated.
• Regulatory authorities should continually explore ways of improving efficiency in fulfilling
their mandate.
• Alignment of regulatory requirements with other countries and international collaboration
promote efficiency.
• Regulated entities play a critical role in contributing to the efficiency of regulatory systems.
• The efficiency of regulatory instruments and regulatory operations should be assessed
using performance-based indicators.
733
734 An efficient regulatory system must be science- and evidence-based, apply the principles of risk
735 assessment and management, and embed a strategy of international regulatory cooperation into daily
736 business. A regulatory system that is unable to make sound decisions in a timely and consistent fashion
737 is not effective. This is not only a matter of having sufficient resources but also having the right
738 resources and using them effectively, irrespective of size. In this context, lack of integrity of the overall
739 regulatory system is a barrier to regulatory efficiency.
740
741 Less resourced regulatory systems can be as effective as more resourced systems if risk-based and if
742 advantage is taken of the work and decisions of other regulatory authorities while focusing resources
743 on essential, value-added activities which only the regulatory authority is in a position to perform (17).
744
745 Regulatory oversight cannot be considered efficient if it creates unjustified barriers to access, trade and
746 international regulatory cooperation. The successful establishment of effective regulatory controls on
747 medical products depends on a number of factors as previously described, including:
748 • The analysis of options that includes the results of consultation with stakeholders. Regulations
749 are more likely to be effective if those impacted have provided input.
750 • Regulations that are proportional to perceived risk.
page 32
751 • Early-stage planning for implementation and the practicalities of future enforcement.
752 Application and enforcement should not be after-thoughts.
753
754 When new regulatory instruments are being developed and subjected to regulatory impact analysis,
755 the regulatory authority should develop “strategies for education, assistance, persuasion, promotion,
756 economic incentives, monitoring, enforcement, and sanctions” (24). The authority must decide which
757 compliance strategies will be established and whether or not consumer awareness and market forces
758 can reasonably be used, in addition to the threat of penalties. The role of civil society in monitoring
759 adherence to regulation should also be considered, if appropriate.
760
761 Co-regulation may also be considered in certain circumstances. In such situations, a government would
762 issue regulations and enter into a non-statutory agreement with a body to develop and administer a
763 compliance program. While a government works with and through the body in regulating the activity,
764 it has not delegated its oversight of the activity.
765
766 The use of third parties can also be considered by regulatory authority to conduct their activities, a
767 model prevalent in the regulation of medical devices; for example, the use of recognized auditing
768 organizations to conduct audits of manufacturers’ quality managements systems to an international
769 standard and applicable regulatory requirements. Regulatory resources are directed at establishing
770 and maintaining oversight of audit organizations, providing more effective use of limited regulatory
771 resources (25).
772
773 A government incurs costs by establishing and maintaining regulatory systems. Industry and other
774 regulated parties incur costs in complying with regulation; for example, in undertaking studies,
775 preparing application dossiers, maintaining records and paying fees – the cost of doing business.
776
777 Additional costs accrue from inefficient regulatory systems. If the cost of complying with regulation is
778 disproportionately high, companies may decide against placing products on the market. For instance,
779 a mandatory requirement to conduct local clinical trials as a condition for marketing authorisation could
780 be a disincentive to enter a market, especially if trials conducted elsewhere reflect the patient profiles
781 of the intended market and demonstrate safety and efficacy of the product. Similarly, lengthy product
782 review times translate into lost revenue and unnecessary delays in the availability of products for
783 patients – with potentially significant negative implications in terms of morbidity/mortality, health care
784 costs and the economy (healthy economies require healthy people).
page 33
785 Inefficiency also costs regulatory authorities in terms of sub-optimal impact for available resources,
786 reputation, job satisfaction and time spent addressing complaints related to performance. Regulatory
787 frameworks reflecting the principles of proportionality, flexibility and consistency are more likely to be
788 effective. They allow for resources to be allocated to the regulatory activities where they are most
789 needed.
790
International collaboration. Regulatory frameworks that are consistent and aligned with those of
other countries and regions encourage the investment needed to bring appropriate and affordable
products to that market. Internationally consistent frameworks also enable the regulatory
authority to participate in work-sharing networks and other forms of regulatory cooperation
(including convergence, harmonization, information- and work-sharing, reliance and recognition).
When properly anchored in the regulatory framework, reliance on the work of other authorities
eliminates or reduces the inefficient duplication of regulatory evaluations of medical products and
the inspection/audit of facilities.
791
792 Regulatory authorities should continually explore the means of improving efficiency while maintaining
793 standards for evaluating the quality, safety and efficacy/performance of medical products. For example,
794 this could include the introduction or refinement good review practices (18) and a quality management
795 system (19); greater and more effective use of information technology; consultations with industry on
796 common deficiencies and how best to address them; risk-based criteria for scheduling and conducting
797 inspections; addressing gaps in guidance; performance measurement; and – as highlighted above –
798 regulatory cooperation and reliance.
799
800 Industry also plays a critical role in contributing to the efficiency of regulatory systems. As an example,
801 high quality applications for marketing authorization reduce the overall review time by reducing the
802 number of deficiencies and review cycles. Similarly, a manufacturer with a good compliance record
803 should not require the same frequency and depth of inspection as a poorly performing manufacturer.
804 Consultations and training can be effective complements to enforcement actions in achieving the
805 desired level of compliance.
806
807 As part of the regulatory impact analysis process, policy-makers should seek the most efficient and least
808 burdensome means of achieving their regulatory purposes at a minimum reasonable cost, including
809 non-regulatory options. In considering a regulatory approach, there should be consideration of the
810 total burden and resource needs of cumulative regulation.
811
page 34
812 Periodic performance assessments should evaluate the actual efficiency of regulatory instruments that
813 are implemented in order to ensure that the foreseen benefits have been achieved and, if so, what the
814 direct and indirect costs are.
815
8.9 Transparency
Transparency is the hallmark of a well-functioning regulatory system and essential to building
public trust and enabling international cooperation.
Key elements:
• Transparency requires investment and a culture of openness, supported by government
policy, commitment and action.
• The process of developing new or revising existing regulatory instruments should include
stakeholder consultation.
• Regulatory requirements, processes, fees, assessments, decisions and actions should be
accessible as much as possible.
• The regulatory authority’s disclosure policies should be consistent with national laws on
access to information.
816
817 “Informed opinion and active co-operation on the part of the public are of the utmost importance in
818 the improvement of the health of the people.” - World Health Organization Constitution
819
820 Transparency is a hallmark of a well-functioning regulatory system. It is in the interests of patients,
821 consumers, governments, health care workers and manufacturers as it increases the level of public
822 trust and confidence in the regulatory oversight of medical products. Transparency in regulatory
823 requirements and actions allows for better-informed investment decisions in the public and private
824 sectors and discourages discriminatory, corrupt or abusive practices.
825
826 Transparency means that all affected and potentially interested parties – domestic, foreign, public and
827 private – have meaningful opportunities to be informed of new or amended regulations and guidelines
828 and to make their views known before they are enacted.
829
830 Transparency means that, once adopted, medical product regulations and guidelines are readily
831 available and accessible to stakeholders and the general public. Relevant laws, regulations and
832 guideline documents should be posted on the authority’s website. Additionally, national industry and
833 professional associations will often work with regulatory authorities to disseminate new regulatory
834 texts or to provide opportunities for the exchange of relevant information.
835
page 35
836 The assessments, decisions (positive and also, when possible, negative ones) and actions of the
837 regulatory authority should be documented and made publicly available. Such information is important
838 to a broad range of stakeholders - including industry, researchers, health professionals, patients and
839 consumers - who will use the information for a variety of purposes. It is also an essential element to
840 building trust and confidence in the regulatory system.
841
842 Regulated parties should be able to access the full product assessment or site inspection reports that
843 pertain to them. In addition to providing an insight into the basis for comments and decisions, it also
844 serves as an educational tool that can help improve regulatory compliance and the quality of future
845 submissions. This practice can also be beneficial to the regulatory authority by fostering a culture of
846 transparency and accountability at the operational and management level. Furthermore, it can lead to
847 higher quality reports by ensuring that reports clearly explain how such assessments led to decisions.
848
849 Transparency requires investment and a culture of openness that, in turn, must be supported by
850 government policy, commitment and action. While it may not be possible for all regulatory authorities
851 to implement the full range of measures that define an optimally transparent regulatory system, a step-
852 wise approach can be adopted. Given the prevalence of smart devices and the internet, efforts could
853 be directed towards establishing and maintaining an up-to-date, searchable public website that
854 contains certain basic information, including:
855 • Information on the regulatory authority – roles, responsibilities, organization, and contact
856 information.
857 • Access to laws, regulations, guidelines and procedures necessary to satisfy regulatory
858 requirements and improve the safety and quality of medical products.
859 • A searchable product registry of approved, suspended and withdrawn products.
860 • Product information for health care professionals and patients.
861 • Licensing status of manufacturing sites.
862 • Health advisories, safety information, quality or substandard and falsified medical product
863 alerts, recalls and other time-sensitive information of public health interest.
864 • Performance targets/results and annual reports.
865 • Proposed new regulatory instruments, including comment periods and how to provide input.
866
867 The findings of all audits or oversight reviews of the performance and functioning of the regulatory
868 authority should be made public. Such reviews are an important element of public accountability, as is
page 36
869 the establishment and ongoing reporting of performance against regulatory targets and the publication
870 of annual reports.
871
872 As it fulfils its responsibilities, the regulatory authority will necessarily create or come into possession
873 of proprietary or confidential information. Examples include personal identifiable information from
874 clinical trials or reports of adverse events, specifications of medical product compounds or materials,
875 and key manufacturing processes. Measures should be established to prevent the inappropriate
876 disclosure of such specific information. There should be a mechanism to address instances when the
877 proprietary nature or confidentiality of the information is in dispute.
878
879 In general, national law and regulation should favour transparency and public access in both the process
880 and the criteria of regulatory decision-making. The regulatory authority’s disclosure policies should be
881 consistent with the national laws on public access to government information or “freedom of
882 information”. Procedures and contact points to obtain information held by the regulatory authority
883 should be accessible and clear.
884
885 Transparency is a key enabler to adopting new, more efficient ways of conducting regulatory operations.
886 It is incumbent upon regulators to practice transparency in regulatory operations and decisions as a
887 fundamental principle of GRP but also towards building trust and maximizing opportunities for
888 cooperation and reliance as part of a shared regulatory community responsibility.
889
890 9. Enablers for good regulatory practices

891
892 An enabling environment will facilitate a successful implementation of GRP. The non-exhaustive list of
893 GRP key enablers include:
894
895 9.1 Political and government-wide support

896
897 A sustained support at the highest political and government levels, including policy makers, is essential
898 for the proper implementation of the concept and principles of GRP.
899
900 GRP should form an integral part of government-wide policies on regulatory system and, in addition,
901 be backed by strong political support.
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902 9.2 Effective organization and good governance supported with

903 leadership
904
905 The structure and line of authority among and within all institutions of the regulatory system should be
906 well defined. The integrity of the overall regulatory system is critical to the effective and efficient
907 performance of all institutions composing the regulatory system. If more than one institution is
908 involved in the regulatory system, the legislation or institutional regulation should provide for clear
909 coordination and avoid an overlap of the regulatory activities. Leadership is critical for setting and
910 carrying out the organizational vision, mission, policies and strategies which in turn significantly
911 contribute to organizational efficiency.
912
913 9.3 Inter-and-intra-organizational communication, collaboration

914 and coordination
915
916 Adequate and effective communication plays a fundamental role for exchanging information within and
917 outside the institutions forming the regulatory system. When regularly communicating both internally
918 and externally, regulatory authorities remain more transparent and accountable. Communicating
919 correct information prevents the potential misunderstandings and dissemination of misleading
920 information to patients and the public. Communication is a powerful tool for collaboration and
921 coordination with relevant stakeholders at national and international levels which in turn feed into an
922 effective and efficient use of resources and better regulatory outcomes.
923
924 9.4 A robust and well-functioning quality mangement system

925
926 QMS (19), which includes the application of quality risk management (QRM) principles, is a valuable
927 tool that helps regulatory authorities to achieve greater credibility for their decisions, and greater
928 stability and consistency in their operations. QMS contributes to systematic planning, control and
929 improved quality in all processes throughout all regulatory functions and ensures a comprehensive
930 approach for all.
931
932
page 38
933 9.5 Sufficient and sustainable financial resources

934
935 Investment in regulatory systems is critical to a well-functioning health care system. Securing financial
936 resources to effectively carry out the regulatory mandate and to continuously improve the performance
937 of regulatory activities is an essential enabler for regulatory system independence, impartiality,
938 consistency and efficiency. The financial resources of all institutions of the regulatory system should
939 be sustainable, apart from donors’ or philanthropic entities donations.
940
941 9.6 Competent human resources

942
943 An array of knowledge and the skills of regulatory staff contribute to the development, implementation
944 and maintenance of a regulatory system for medical products. Personal and career development
945 policies and measures (e.g. training programmes, competitive remuneration schemes) are critical for
946 regulatory authorities to attract and recruit competent staff and, in addition, to retain staff in the
947 service.
948
949 9.7 Pre-set organizational ethics and values

950
951 Regulatory activities should abide by ethical principles, organizational values, and professionalism. All
952 regulatory staff should be made aware and be trained on the ethics and values as set by the regulator
953 authorities (e.g. code of conduct). A system should be established, within or external to the regulatory
954 system, to manage situations of departure from the organizational ethics and values.
955
956 9.8 Science- and data-driven decision-making process

957
958 Regulatory decisions, along with their making process, should be based on scientific foundations and
959 accurate data rather than intuitions or arbitrariness. Science-based decisions provide for the
960 consistency and predictability of regulatory outcomes.
961
962 The above-listed enablers do not work in a stand-alone mode. Rather, they work in harmony to realize
963 the application and implementation of GRP; for example, the sufficient and sustainable financial
964 resources contribute to the recruitment, development and maintenance of competent human
965 resources. Similarly, financial resources shall be managed following good governance practices.
page 39
966 10. Implementing good regulatory practices

967
968 WHO Member States are encouraged to implement GRP in their regulatory systems with due
969 consideration to their legal and regulatory system realities. Transparent and predictable processes
970 should aim to develop high-quality regulatory oversight that achieves intended objectives while also
971 minimizing negative impact and costs.
972
973 At the same time, there should be sufficient flexibility to allow the processes to be applied
974 proportionately to the scope, magnitude and complexity of the issue. Sustained support at the highest
975 levels, along with adequate resourcing, is essential.
976
977 Further guidance will be developed to assist Member States both in establishing new regulatory
978 systems for medical products and in updating existing ones.
979
980 Acknowledgements
981
982 WHO wishes to acknowledge all the authors, stakeholders and organizations who contributed to the
983 preparation of this document.
page 40
984 Glossary
985
986 The definitions given below apply to the terms as used in this document. They may have different
987 meanings in other contexts. Readers are also encouraged to consult related WHO guidances for a more
988 complete set of definitions relevant to best regulatory practices (see References).
989
990 public health emergency. A public health emergency (the condition that requires a governor to declare
991 a state of public health emergency) is defined as "an occurrence or imminent threat of an illness or
992 health condition, caused by bioterrorism, epidemic or pandemic disease, or (a) novel and highly fatal
993 infectious agent or biological toxin that poses a substantial risk of a significant number of human
994 facilities or incidents or permanent or long-term disability (WHO/DCD, 2001). The declaration of a state
995 of public health emergency permits a governor to suspend state regulations and change the functions
996 of state agencies (26).
997
998 quality management system (QMS). An appropriate infrastructure encompassing the organizational
999 structure, procedures, processes and resources and systematic actions necessary to ensure adequate
1000 confidence that a product or service will satisfy given requirements for quality.
1001
1002 recognition. The acceptance of the regulatory decision of another regulator or other trusted institution.
1003 Recognition should be based on evidence of conformity that the regulatory requirements of the
1004 reference regulatory authority is sufficient to meet the regulatory requirements of the relying authority.
1005
1006 regulatory convergence. A voluntary process whereby the regulatory requirements in different
1007 countries or regions become more similar or “aligned” over time. The process results from the gradual
1008 adoption of internationally recognized technical guideline documents, standards and scientific
1009 principles, common or similar practices and procedures, or the establishment of appropriate domestic
1010 regulatory mechanisms that align with shared principles to achieve a common public health goal (27).
1011
1012 regulatory cooperation. A practice between regulatory authorities aimed at the efficient and effective
1013 regulation of medical products. Regulatory cooperation can be practised by an agency or institution
1014 or on a government-wide basis. The range of formal mechanisms include the creation of joint
1015 institutions and treaties and conventions such as mutual recognition agreements, while less formal
1016 practices include the sharing of information, scientific collaboration, common risk assessment, joint
page 41
1017 reviews and inspections and the development of standards. Regulatory cooperation may also include
1018 work with international counterparts to build regulatory capacity or provide technical assistance, thus
1019 contributing to the improvement of international regulatory governance practices (28) (29) (30) (31).
1020
1021 regulatory harmonization. The process whereby technical guidelines are developed in order to be
1022 uniform across participating authorities in multiple countries (32).
1023
1024 regulatory impact analysis. The process of examining the likely impacts of a proposed regulation and
1025 alternative policy options to assist the policy development process (33).
1026
1027 regulatory stock. The collection or inventory of accumulated regulations.
1028
1029 regulatory system. The combination of institutions, processes and the regulatory framework through
1030 which a government controls the particular aspects of an activity (34).
1031
1032 reliance. The act whereby the NRA in one jurisdiction may take into account and give significant weight
1033 to assessments performed by another NRA or trusted institution, or to any other authoritative
1034 information in reaching its own decision. The relying authority remains independent, responsible and
1035 accountable regarding the decisions taken, even when it relies on the decisions and information of
1036 others.
1037
1038
1039
page 42
1040 References
1041
1. APEC-OECD Co-operative Initiative on Regulatory Reform. APEC-OECD integrated checklist on

regulatory reform. Paris: Organisation for Economic Co-operation and Development; 2005
(http://www.oecd.org/regreform/34989455.pdf, accessed 30 June 2020).
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Economic Co-operation and Development; 1997 (http://www.oecd.org/gov/regulatory-
policy/2391768.pdf, accessed 30 June 2020).
3. OECD guiding principles for regulatory quality and performance. Paris: Organisation for
Economic Co-operation and Development; 2005 (www.oecd.org/fr/reformereg/34976533.pdf,
accessed 30 June 2020).
4. Better Regulation for Growth. Governance frameworks and tools for effective regulatory
reform. Washington (DC): The World Bank; 2007
(http://documents1.worldbank.org/curated/en/955811468330978599/pdf/556350WP0Box03
10Governance01PUBLIC1.pdf, accessed 30 June 2020).
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2009
(http://www.asean.org/wpcontent/uploads/images/2012/Economic/sectoral_aem/standards_
conformance/ASEAN%20Good%20Regulatory%20Practice%20(GRP)%20Guide.pdf, accessed
30 June 2020).
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Reference to Multisource (Generic) Products, A manual for National Medicines Regulatory
Authorities NMRAs)
(https://apps.who.int/iris/bitstream/handle/10665/44576/9789241501453_eng.pdf;jsessionid
=52D37F5BD27B9BB5055CF9DA79453B5B?sequence=1, accessed 30 June 2020).
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WHO Expert Committee on Specifications for Pharmaceutical Preparations: thirty-fifth report.
Geneva: World Health Organization; 1999: Annex 8 (WHO Technical Report Series, No. 885)
(https://www.who.int/medicines/technical_briefing/tbs/National_drug_regulatory_legislation_
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8. Regulation of vaccines: building on existing drug regulatory authorities. Geneva: World Health
Organization; 1999 (Document WHO/V&B/99.10;
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June 2020).
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(https://apps.who.int/iris/bitstream/handle/10665/42470/9241562064.pdf?sequence=1&isAll
owed=y, accessed 28 July 2020).
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Organization; 2003
(http://www.who.int/medical_devices/publications/en/MD_Regulations.pdf, accessed 30 June
2020).
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Pan American Health Organization; 2001
(http://new.paho.org/hq/dmdocuments/2009/AmodelRegulatoryProgramforMedicalDevices_
AnInternalGuide.pdf?ua=1, accessed 30 June 2020).
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28 July 2020).
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(generic) products: a manual for national medicines regulatory authorities (NMRAs), second
edition. Geneva: World Health Organization; 2011
(http://www.who.int/medicines/areas/quality_safety/regulation_legislation/blue_book/en/,
14. Global model regulatory framework for medical devices including IVDs. Geneva: World Health
Organization; 2017
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eng.pdf?sequence=1, accessed 30 June 2020).
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World Health Assembly, Geneva, 19−24 May 2014. Resolutions and decisions: resolutions.
Geneva: World Health Organization; 2014
(http://apps.who.int/gb/ebwha/pdf_files/WHA67/A67_R20-en.pdf, accessed 30 June 2020).
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(http://www.who.int/medicines/areas/governance/ggm_modelframe_updated/en/, , accessed
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principles and recommendations 8 Draft. Geneva: World Health Organization; 2020 (working
document QAS/20.851
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1042
1043 ***

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Working document QAS/16.686/Rev.

5 Good regulatory practices

41 SCHEDULE FOR DRAFT WORKING DOCUMENT QAS/16.686/Rev.3

Concept Paper on Good Regulatory Practices. October 2013

Concept development workshop – India. July 2014

Draft development workshop – China. October 2015

Public consultation of the first draft document. May- December 2016

Internal consultation meeting. July 2017

Presentation to 53rd Expert Committee on Specifications for September 2018

Consultation with National Regulatory Authorities and regulatory 19 September 2019

Second public consultation. Until 11 September 2020

Consolidation of comments received and revision of the working September 2020

47 Good regulatory practices

78 9.7 Pre-set organizational ethics and values

103 Executive summary

264 6. Key considerations

309 7. Overview of regulatory system for medical

346 Figure 1: Architecture of a Regulatory Framework

408 8. Principles of good regulatory practices

Consistency Regulatory oversight of medical products should be consistent with

Independence Institutions executing regulatory oversight of medical products should

Proportionality Regulation and regulatory decisions should be proportional to risk and

Clarity Regulatory requirements should be accessible to and understood by

Transparency Regulatory systems should be transparent; requirements and

622 Responsiveness is an extended principle of flexibility, however slightly different. Responsiveness is

890 9. Enablers for good regulatory practices

895 9.1 Political and government-wide support

902 9.2 Effective organization and good governance supported with

913 9.3 Inter-and-intra-organizational communication, collaboration

924 9.4 A robust and well-functioning quality mangement system

933 9.5 Sufficient and sustainable financial resources

941 9.6 Competent human resources

949 9.7 Pre-set organizational ethics and values

956 9.8 Science- and data-driven decision-making process

966 10. Implementing good regulatory practices

1. APEC-OECD Co-operative Initiative on Regulatory Reform. APEC-OECD integrated checklist on

6. WHO “Blue Book” on Marketing Authorization of Pharmaceutical Products with Special

13. Marketing authorization of pharmaceutical products with special references to multi-sourced

26. WHO definitions: emergencies (https://www.who.int/hac/about/definitions/en/, accessed 28

33. Best practice regulation handbook. Canberra: Australian Government; 2007

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