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WHO GLOBAL BENCHMARKING TOOL (GBT) FOR 2

EVALUATION OF NATIONAL REGULATORY SYSTEM OF 3

MEDICAL PRODUCTS 4

FACT SHEETS FOR CLINICAL TRIALS OVERSIGHT 5

(DRAFT REVISION VI VERSION 1) 6

(DECEMBER 2017) 7

DRAFT FOR COMMENTS 8

Should you have any comments on the attached text, please send these to: Country Regulatory Support 9 (CRS) Group , Regulatory Systems Strengthening (RSS), World Health Organization, 1211 Geneva 10 27,Switzerland; Alireza Khadem ([email protected]); fax: (+41 22) 791 4856; and to Laura 11 Brown ([email protected]) by 28 February 2018. Working documents are sent out electronically and they 12 will also be placed on the Medicines website for comment. 13

14 © World Health Organization 2017 15

All rights reserved. 16

This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. 17 The draft may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part 18 or in whole, in any form or by any means outside these individuals and organizations (including the organizations' 19 concerned staff and member organizations) without the permission of the World Health Organization. The draft 20 should not be displayed on any website. 21

Please send any request for permission to: 22

Dr Alireza Khadem Broojerdi, Scientist, Country Regulatory Support, Regulatory Systems Strengthening, 23 Department of Essential Medicines and Health Products, World Health Organization, CH-1211 Geneva 27, 24 Switzerland. Fax: (+41 22) 791 4856; email: [email protected]. The designations employed and the 25 presentation of the material in this draft do not imply the expression of any opinion whatsoever on the part of the 26 World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or 27 concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines 28 for which there may not yet be full agreement. 29

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or 30 recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. 31 Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. 32

All reasonable precautions have been taken by the World Health Organization to verify the information contained in 33 this draft. However, the printed material is being distributed without warranty of any kind, either expressed or 34 implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the 35 World Health Organization be liable for damages arising from its use. 36

This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 37

WHO global benchmarking tool rev. VI ver. 1, CT

08-CLINICAL TRIALS OVERSIGHT (CT) 1

2

National Regulatory Authorities (NRAs) should have the legal mandate to authorize and regulate clinical 3 trials, including terminate clinical trials if necessary. They should develop the necessary requirements, 4 guidelines, procedures and forms in line with major international guidelines on clinical trials including the 5 Declaration of Helsinki and WHO Good Clinical Practices guidelines. Clinical trials oversight is aimed 6 to: protect the safety and rights of human subjects participating in clinical trials, ensure that trials are 7 adequately designed to meet scientifically sound objectives and prevent any potential fraud and 8 falsification of data. NRAs are responsible at two stages for the critical evaluation of the documentation 9 supporting clinical studies: when clinical trials are being proposed for authorization and when the results 10 are submitted in an application for marketing authorization. Clinical trials protocols should be reviewed 11 and approved by Independent Ethics Committees before they are submitted to the NRA for authorization. 12 A clinical trial review committee composed of members with the appropriate medical and scientific 13 knowledge, experience and skills, who are also free of conflicts of interest, should review the protocols 14 and may require where necessary, protocol revisions. They will be also responsible for the review of the 15 trials results. In order to ensure the quality and safety of investigational products they should be 16 manufactured in compliance with Good Manufacturing Practices (GMP) for investigational medical 17 products; the supporting preclinical studies should be in compliance with Good Laboratory Practices 18 (GLP) and the importation, storage, use, and/or destruction of investigational products should follow the 19 national requirements. Qualified and experienced inspectors should carry out on-site inspections of the 20 clinical trial sites to verify compliance with Good Clinical Practices (GCP), ethical principles and 21 regulatory requirements, including the quality and reliability of the data obtained, with due concern for 22 the confidentiality. The legal provisions should allow the NRA to recognize and/or rely on relevant 23 clinical trials decisions, reports or information from other NRAs, or regional and international bodies. 24 They should also allow in special circumstances (e.g. for public-health interest) that the NRA does not 25 follow the routine clinical trials procedures. Transparency in the process is fundamental to ensure the 26 safety of patients and to ensure that no product that has failed clinical trials will be made available to the 27 public. 28

29

Indicator: CT01 LEGAL PROVISIONS, REGULATIONS AND 30

GUIDELINES REQUIRED TO DEFINE REGULATORY 31

FRAMEWORK OF CLINICAL TRIALS OVERSIGHT. 32

Rationale: 33

The objective of this indicator is to assure that the NRA has the legal mandate to both authorize and 34 suspend the implementation of Clinical Trials (CTs). The mandate will ensure, amongst others, that 35 regulations and guidelines are in place to protect the safety and rights of the subjects participating in a 36 trial, and to ensure that trials are adequately designed to meet scientifically sound objectives. 37

Category: Legal provisions, regulations and guidelines 38

Sub-Indicator: CT01.01: LEGAL PROVISIONS AND/OR REGULATIONS FOR 39

CLINICAL TRIALS (CT) OVERSIGHT EXIST. 40

Scope: All 41


Maturity: 1 1

Requirement: 2

Legislation on CT oversight 3

Rationale: 4

The objective of this sub-indicator is to assure the legal provisions and /or regulations that require 5 authorization from NRA for conducting clinical study prior to study exist. The NRA should review the 6 protocol and other relevant documentation to be sure that all required aspects such as safety of 7 participants are considered and it is according Good clinical practices. 8

Description: 9

The assessor should verify that the legal provisions and/or regulations for clinical trials oversight exist, 10 are enacted and implemented. The legal provisions should clearly specify the entity (ies) with the mandate 11 for clinical trial oversight and the extent of their mandate (s), as well as shared responsibilities 12 among/between the entity (ies). 13

The assessor should verify the legal provisions and/or regulations that require authorization from NRA for 14 conducting clinical study prior to study exist, are enacted and implemented. The assessor should review 15 all provided documentation such as importation licensing/control of investigational medical products 16 (IMPs) with GMP certificate, on-site inspections mandate for ensuring the location is acceptable and the 17 product quality is maintained during storage, as well as review informed consent forms and investigator 18 brochure. The assessor should verify that provided information and documentation are following GCP. 19 The assessor should be guided by the existing law and regulation before applying the scoring. 20

Evidence to review: 21

The assessor should request for and review: 22

1. Legal provisions and/or regulations that grants the NRA the legal mandate for CT oversight. 23

2. The sections in the law that define the extent/scope of the CT mandate allocated to the NRA and 24 other entity (ies) involved in CT related activities. 25

3. Relevant sections of the law on CT that require authorization from NRA for conducting clinical 26 study prior to study. 27

4. The guidelines on the format and content of protocol, as well as the submission procedure as well 28 as timeframe for review of application. 29

Framework: 30

Structure/Foundation/Input 31

Rating Scale: 32

N: There is no legal provisions and/or regulations for clinical trials (CT) oversight. 33

OI: The NRA has recently drafted and adopted legal provisions for clinical trials (CT) oversight but it has 34 not yet been followed. 35

WHO global benchmarking tool rev. VI ver. 1, CT PI: The NRA has legal provisions for conducting clinical trials (CT) oversight and has been applying it 1 for less than two years. 2

Y: The NRA has legal provisions for conducting clinical trials (CT) oversight supported with enough 3 documented evidences. 4

Limitations and remarks: 5

Related indicators: 6

References: 7

1. 3- WHO TRS 858, Annex 1, 1995 8

2. 40- WHO TRS 850, Annex 3, 1995 (Chapter 1.5, 2,4.7, 4.8,11) 9

Sub-Indicator: CT01.02: LEGAL PROVISIONS AND/OR REGULATIONS REQUIRE 10

AUTHORIZATION FROM NRA AND NOTIFICATION TO THE NRA ON 11

CHANGES/VARIATIONS (AMENDMENTS) IN THE ORIGINAL PROTOCOL AND 12

RELEVANT DOCUMENTS OF THE CT. 13

Scope: All 14

Maturity: 2 15

Requirement: 16

Changes/variations to already approved (original protocol) CT protocols 17

Rationale: 18

The objective of this sub-indicator is to assure that legal provisions and /or regulations require that the 19 NRA should be notified of changes/variations (amendments) to the original protocol, and should 20 authorize changes /variations to the original protocol before they are implemented. 21

Description: 22

The assessor should verify that legal provisions and/or regulations on changes/variations to the original 23 (approved) CT protocols exist, are enacted and implemented. It should clearly state that the NRA should 24 be notified of any changes/variations to the original protocol, and authorization from the NRA is required 25 before the changes /variations (amendments) are implemented. The assessor should note that some 26 amendments to protocol may not require authorization from the NRA prior to implementation. Some may 27 require either a notification prior to implementation or implementation before notification. The assessor 28 should be guided by the existing law, regulation and regulation before applying the scoring. 29



1. Relevant sections of the legal provisions (laws, decrees, regulations or any legal binding 32 document) on CT with emphasis on the requirement for either notification or authorization prior to 33 implementation of changes/variations to original protocol and relevant documents. 34


2. The guidelines on the format and content preparation on changes /variations to original protocol, 1 including the submission procedure as well as timeframe for review of variations. 2

Framework: 3


Rating Scale: 5

NI: There are no legal provisions and/or regulations requiring authorization from and notification to the 6 NRA on changes/variations (amendments) in the original protocol of the CT. 7

OI: The NRA has recently drafted or adopted this legal provision but it has not yet been followed. 8

PI: The NRA has legal provision and has been applying it for less than two years. 9

I: The NRA has legal provisions and/or regulations requiring authorization from NRA and notification to 10 the NRA on changes/variations (amendments) in the original protocol of the CT supported with 11 documented evidences. 12


References: 14

1. 39- WHO TRS 987, Annex 2, 2014 15


3. 38-WHO TRS 1004, Annex 9, 2017 17

4. 119- WHO TRS 987, Annex 2, 2014 18

Sub-Indicator: CT01.03: LEGAL PROVISIONS AND/OR REGULATIONS 19

REQUIRING RESEARCH CENTRES, RESEARCHERS, SPONSORS, CLINICAL 20

RESEARCH ORGANIZATIONS (CROs) AND ALL RELEVANT INSTITUTIONS IN 21

THE CLINICAL TRIAL TO COMPLY WITH GOOD CLINICAL PRACTICE (GCP) 22

Scope: All 23

Maturity: 2 24

Requirement: 25

Stakeholder acting in compliance with GCP 26

Rationale: 27

The objective of this sub-indicator is to assure the legal provisions and /or regulations that mandates 28 stakeholders, including research centers, researchers, sponsors, Clinical Research Organizations (CROs) 29 and everyone involved in clinical trials to comply with Good Clinical Practice (GCP) exist. It will ensure 30 all stakeholder, including research centers, researchers, sponsors, Clinical Research Organizations 31 (CROs) and everyone involved CTs operate within set globally acceptable standards for the conduct of 32 biomedical research on human subjects. 33

Description: 34

WHO global benchmarking tool rev. VI ver. 1, CT The assessor should verify the legal provisions and /or regulations that request stakeholders, including 1 research centers, researchers, sponsors, Clinical Research Organizations (CROs) and everyone involved 2 in clinical trials to comply with the principle of Good Clinical Practice (GCP) exist, are enacted and 3 implemented. Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 4 designing, conducting, recording and reporting trials that involve the participation of human subjects. 5 Compliance with this standard provides assurance that the rights, safety and well-being of trial subjects 6 are protected consistent with the principles established in the Declaration of Helsinki, and that clinical 7 trial data are credible. The legal provisions should be supported by detailed and published regulatory 8 requirements for GCP. The published GCP principles should be current and up to date with information 9 on inspections, suspension and/or stoppage of trials among others. In the event of adoption or reference of 10 GCP, there should be documentation to demonstrate recognition. The assessor should verify that Ethics 11 Committees and NRA conduct evaluation according to GCP. 12



1. The legal provisions(laws, decrees, regulations or any legal binding document) that require 15 stakeholders involved in CT comply with GCP principles. 16

2. The current GCP requirements for all CTs. The requirement should be published and easily 17 accessible. 18

3. Guidelines and/ or similar documents (e.g., checklist, SOPs, etc.) used for guidance in the 19 application of the legal provision and/or regulation. 20

Framework: 21


Rating Scale: 23

NI: There are no legal provisions and/or regulations requiring research centers, researchers, sponsors, 24 clinical research organizations (CROS) and everyone involved in the clinical trials to comply with good 25 clinical practice (GCP) 26

OI: The NRA has recently drafted or adopted this legal provision and/ or regulation but it has not yet been 27 followed. 28

PI: The NRA has developed this legal provision and has been applying it for less than two years, or not all 29 involved organizations have fully followed this regulation. 30

I: The NRA has legal provisions and/or regulations requiring research centers, researchers, sponsors, 31 clinical research organizations (CROS) and everyone involved in clinical trials to comply with good 32 clinical practice (GCP) supported with documented evidence. 33

Limitations and remarks: The assessor should consider legal binding of existent written documents. 34


References: 36

1. 40- WHO TRS 850, Annex 3, 1995(Chapter 1.5, 2,4.7' 4.8,11) 37


2. 3- WHO TRS 858, Annex 1, 1995 1

3. 38-WHO TRS 1004, Annex 9, 2017 2

4. 119- WHO TRS 987, Annex 2, 2014 3

Sub-Indicator: CT01.04: LEGAL PROVISIONS, REGULATIONS AND/OR 4

GUIDELINES REQUIRING THAT INVESTIGATIONAL MEDICAL PRODUCTS 5

(IMPs) COMPLY WITH GOOD MANUFACTURING PRACTICE (GMP) FOR IMPs 6

Scope: All 7

Maturity: 3 8

Requirement: 9

Investigational medical products (IMPs) good manufacturing practice (GMP) requirements 10

Rationale: 11

The objective of this sub-indicator is to assure that legal provisions, regulations and guidelines that 12 mandate IMPs to be used in CTs comply with GMP requirements exist. 13

Description: 14

The assessor should verify that legal provisions, regulations and/or guidelines on IMPs GMP compliance 15 exist, are enacted and implemented. It should clearly state that only IMPs produced in compliance with 16 current GMP standards for IMPs will be used in CTs, and that trial’s applicant or sponsor is responsible 17 for supplying IMPs produced in accordance with GMP principles. The legal provision should be 18 supported with regulation and or guidelines that clearly present the applicable GMP 19 standards/requirements and the type of evidence to present (e.g., certificate, summary product release 20 documents, others). The assessor should note that some NRAs may not require a GMP certificate when 21 the IMP is already licensed or registered in the country of origin. However, per good regulatory practices, 22 a current GMP certificate from the national regulatory authority of the country of origin should be 23 required when the IMP has a marketing authorization in the country of origin or has a marketing 24 authorization but the original indication is modified for the purpose of the trial. 25



1. The legal provisions(laws, decrees, regulations or any legal binding document) and /or guidelines 28 requiring that IMPs used in CTs are produced in compliance with the principles of GMP for IMPs. 29

2. The legal provisions/ regulations and /or guidelines that states that it is the responsibility of the 30 sponsors / applicants to supply IMPs produced in compliance with the principles of GMP for IMPs. 31

3. Format of IMPs GMP certificate requirement prior to CT authorization. The GMP certificate 32 should be issued by the national competent authority of the country of origin of the IMP. 33

Framework: 34


Rating Scale: 36

WHO global benchmarking tool rev. VI ver. 1, CT NI: There is no evidence of existence of legal provisions, regulations and/or guidelines requiring that 1 investigational medical products (IMPS) comply with good manufacturing practice (GMP) for IMPs. 2

OI: The NRA has recently drafted or adopted this legal provisions, regulations and or guidelines but they 3 have not yet been implemented. 4

PI: The NRA has legal provisions, regulations and or guidelines and has been applying them for at 5 minimum two years. 6

I: The NRA has legal provisions, regulations and or guidelines requiring that investigational medical 7 products (IMPs) comply with good manufacturing practice (GMP) for IMPs. 8



References: 11

1. 51- WHO TRS 986, Annex 2, 2014 12


3. 120- WHO TRS 863, Annex 7, 1996 14

Sub-Indicator: CT01.05: THERE ARE LEGAL PROVISIONS OR REGULATIONS 15

COVERING CIRCUMSTANCES IN WHICH THE ROUTINE CT EVALUATION 16

AND PROCEDURE MAY NOT BE FOLLOWED (E.G. FOR PUBLIC-HEALTH 17

INTERESTS) 18

Scope: All 19

Maturity: 2 20

Requirement: 21

Exemptions from routine CT application evaluation and procedures 22

Rationale: 23

The objective of this sub-indicator is to assure legal provisions and/or regulations are established to allow 24 the NRA/ responsible regulatory authority (ies) apply non-routine CT procedures such as fast-track or 25 expedite receipt, evaluation, and authorization of a CT application in certain situations/circumstances (e.g. 26 Public health emergencies). This sub-indicator will establish whether there is an abridge route other than 27 the normal CT application route for CT authorization. 28

Description: 29

The assessor should verify that legal provisions and/or regulations that allows the NRA to apply non 30 routine CT procedures such as fast-track or expedite receipt, screening, evaluation/review, and 31 authorization (taking a decision on) of a CT application in certain situations/circumstances (e.g. public 32 health emergencies) exist, are enacted and implemented. The legal provisions and / or regulations should 33 provide clear statements /directives on the circumstances/instances where the fast-track CT authorization 34 should apply. It should provide guidance on the relationship between the fast-track CT authorization and 35 the mandate of the IEC. It should be supported with guidelines that would provide guidance on the 36


content (e.g. critical requirements) and format of the CT application for fast-track authorization, as well as 1 the scope of the evaluation/review process (screening, verification, etc.). It should also provide guidance 2 on how CTs authorized through the fast-track procedure should be managed (e.g. the number of GCP 3 inspections (random, announced/scheduled, responsive, etc.), reports. The supporting guidelines may 4 provide clarity on whether a CT application rejected through the fast-track procedure could be re-5 submitted through the routine procedure. In addition, there should be a guidance document to provide 6 direction to the NRA on how to justify application of the non-routine procedure to the CT. 7

The assessor should verify that the proposed procedure meet targeted timeframe for public health 8 emergency or any other unmet medical need. 9


There is need for clarification when and how the CT conducted faster manner, for example authorization 11 procedures 12


1. Guidelines or similar document that provides the list of situation where the routine CT procedures 14 should not be followed. 15

2. Legal provisions(laws, decrees, regulations or any legal binding document) that cover 16 circumstances /instances where non-routine CT procedures such fast-track CT authorization is 17 required/applied. The legal provisions should be published and implemented. 18

3. The supporting guidelines and /or regulations. 19

4. The content and format of CT application requiring non- routine CT procedures such as fast-20 track. 21

5. The scope of the evaluation process (screening or verification, etc.). 22

6. Regulatory actions post-authorization. The assessor should verify and discriminate between the 23 routine procedure and the fast-track procedure. 24

Framework: 25


Rating Scale: 27

NI: There are no legal provisions and/or regulations to cover circumstances in which the routine CT 28 application evaluation may not be followed (e.g. for public-health interests) 29

OI: The NRA has drafted or adopted this legal provision and/ or regulation, but it has not yet been 30 followed. 31

PI: The NRA has legal provision and/ or regulation and has been applying it for less than two years. 32

I: The NRA has legal provisions and/or regulations covering circumstances in which the routine CT 33 application evaluation may not be followed (e.g. for public-health interests). 34

Limitations and remarks: Thea assessor should consider any kind of legal document that address this 35 requirement. 36

WHO global benchmarking tool rev. VI ver. 1, CT Related indicators: 1

References: 2


2. 121- EUAL for candidate medicines for use in the context of a public health emergency. WHO; 4 2015 5

3. 122- EUAL for candidate vaccines for use in the context of a public health emergency. WHO; 6 2015 7

Sub-Indicator: CT01.06: LEGAL PROVISIONS, REGULATIONS AND/OR 8

GUIDELINES EXIST FOR NRA TO INSPECT, SUSPEND AND/OR STOP CT 9

Scope: All 10

Maturity: 3 11

Requirement: 12

Legal provisions, regulations and /or guidelines to inspect, suspend and/or stop CTs 13

Rationale: 14

The objective of this sub-indicator is to assure legal provisions and/or regulations are established to give 15 the NRA enforcement powers to inspect, suspend and /or stop CTs. 16

Description: 17

The assessor should verify that legal provisions and/or regulations regarding the NRA enforcement 18 powers to inspect, suspend and /or stop CTs should exist, are enacted and implemented. It should be 19 supported with clear regulation and/or guidance on when (i.e., routine, randomly and/or for specific 20 reasons) and how to inspect, suspend and/or stop CT. Clear guidance on what to inspect e.g., quality and 21 reliability of data obtained or reported results, subjects, equipment, protocols, environment, among others 22 should also be included. 23



1. The legal provisions (laws, decrees, regulations or any legal binding document) that give the 26 NRA the enforcement power to inspect, suspend and/or stop CTs. 27

2. When, how and whom to inspect, suspend and/or stop CTs. 28

3. List of CTs inspected, suspended and/or stopped. 29

Framework: 30


Rating scale: 32

NI: There are no legal provisions , regulations and/or guidelines for NRA to inspect, suspend and/or stop 33 CT 34


OI: The NRA has recently drafted or developed the regulations and/or guidelines, but these have not yet 1 been followed. 2

PI: The NRA has legal provisions, regulations and/or guidelines and has been applying it for less than two 3 years or the guideline or regulation is not fully implemented for all CTs applications. 4

I: The NRA has legal provisions, regulations and/or guidelines to inspect, suspend and/or stop CT and 5 these are implemented and followed for all approved CTs applications. 6

Limitations and remarks: The assessor should consider if there is no clinical trial ongoing, the assessor 7 can score as implemented by reviewing guidelines or other required documentation. 8


References: 10

1. 38-WHO TRS 1004, Annex 9, 2017 11

2. 39- WHO TRS 987, Annex 2, 2014 12

3. 40-WHO TRS 850, Annex 3, 1995. (Chapter 1.5, 2,4.7,4.8,11) 13

4. 119- WHO TRS 987, Annex 2, 2014 14

Sub-Indicator: CT01.07: THERE ARE LEGAL PROVISIONS AND /OR A 15

REGULATIONS THAT REQUIRE THE ESTABLISHMENT OF AN INDEPENDENT 16

ETHICS COMMITTEE (IEC) 17

Scope: All 18

Maturity: 2 19

Requirement: 20

Establishment of independent ethic committee (IEC) 21

Rationale: 22

The objective of this sub-indicator is to assure regulations are in place requiring the establishment of an 23 IEC to review the CTs. The IEC should verify that safety, integrity, and human rights of participating 24 subjects in a particular CT are protected, and should consider the general ethics of the trial, thereby 25 providing public reassurance. 26

Description: 27

The assessor should verify that regulations requesting the establishment of an IEC exist, are issued and 28 implemented. The regulation should be clear on the authority that should host and assist the IEC to 29 successfully discharge its duties/mandate. It should also provide guidance on what it is meant by 30 independent, and provide supporting regulations and /guidelines to sustain the IEC’s independence. The 31 objectives, functions and composition of the IEC should be clearly presented and documented, as well as 32 the general policy on potential conflicts of interest for IEC members. The assessor should note that there 33 may be more than one legally established IEC in a country. The assessor should therefore be particular 34 about the legal mandate of the IEC in question and the scope of their activity (ies). 35


WHO global benchmarking tool rev. VI ver. 1, CT The assessor should request for and review: 1

1. Legal provisions (laws, decrees, regulations or any legal binding document) requesting the 2 establishment of the independent EC. 3

2. The identity of the designated authority mandated to host and assist the IEC in discharging its 4 duties. 5

3. The selection criteria for the members of the IEC and the number of members, as well as their 6 term of office. 7

4. The mechanisms and structures to ensure the independence of the IEC, as well as the code of 8 conduct for its members. 9

5. The general policy on potential conflicts of interest for members of the IEC. 10

Framework: 11


Rating Scale: 13

NI: There are no legal provisions and /or regulations requiring the establishment of an independent ethics 14 committee (IEC). 15

OI: The legal provisions and /or regulations that require the establishment of an independent ethics 16 committee (IEC) have recently defined or drafted, but these have not yet been implemented. 17

PI: The legal provisions and /or regulations requiring the establishment of an independent ethics 18 committee (IEC) have been developed and the IEC has been established for less than two years. 19

I: The NRA has legal provisions and /or regulations requiring the establishment of an independent ethics 20 committee (IEC)and the IEC is established. 21



• CT04.02 24

• CT04.05 25

• CT04.07 26

References: 27

1. 41- Handbook for good clinical research practice (GCP): guidance for implementation. WHO; 28 2002 (Principle 3 : GLP; Principle 5) 29

2. 40- WHO TRS 850, Annex 3, 1995. (Chapter 1.5, 2,4.7, 4.8,11) 30

Sub-Indicator: CT01.08: Legal provisions, regulations and /or guidelines that require 31

authorization for the import, export and destruction of investigational medical products 32

Scope: All 33


Maturity: 2 1

Requirement: 2

Legal provisions, regulation and /or guidelines to import, export and destroy IMPs 3

Rationale: 4

The objective of this sub-indicator is to assure legal provisions, regulations and /or guidelines exist 5 requiring the NRAs / responsible regulatory authority (ies) to authorize import, export or destruct of 6 IMPs. 7

Description: 8

The assessor should verify that the legal provisions, regulations and/or guidelines requiring the NRA 9 authorize import, export and destruction of IMP sexist. The assessor should verify this regulation is 10 enacted and implemented as well. It should be supported with regulation and /or guidelines that provide 11 guidance on the permitted quantities to export or import. The assessor should note that the quantities to 12 import, export or destroy should be justified in relation to the timelines and /or use of the IMPs discussed 13 in the protocol. It should provide guidance on the import, export or destruction process, including the 14 roles and responsibilities of the various stakeholders, including the sponsor, principal investigator (PI), 15 others. The guidelines should discuss procedures to follow for NRA assistance, the acceptable /allowable 16 quantities of IMPs to import or export and the appropriate destruction methods (by the NRA or 17 supervised by the NRA), and the feedback mechanism to inform the NRA on quantities left over after CT. 18 The guideline and application forms should be developed and easily available to the sponsor and other 19 stakeholders. The processes and procedures to seek authorization for import, export or destruction should 20 be published and easily available. 21



1. Legal provisions(laws, decrees, regulations or any legal binding document) and / or guidelines on 24 the import, export and destruction of IMPs. The assessor should verify whether IMPs imported and/or 25 exported for the purposes of CT application submissions require authorization. 26

2. The guidance documents and application forms for requesting assistance from the NRA to import 27 export or destroy IMPs, as well as the processes executed upon receipt of an application. 28

3. Records of IMPs imported, exported or destroyed since the last NRA inspection. 29

4. Guidelines or similar documents providing guidance on the justifiable quantities of IMPs that 30 should be imported and /or exported relative to the timelines in the CT protocol, as well as the stage in the 31 CT application process where IMPs may be imported or exported. 32

Framework: 33


Rating Scale: 35

NI: There are no legal provisions, regulations and /or guidelines that require authorization for the import, 36 export and destruction of investigational medical products. 37

WHO global benchmarking tool rev. VI ver. 1, CT OI: The legal provisions and /or regulations or guidelines that require authorization for the import, export 1 and destruction of investigational medical products exist, but these have not yet been implemented. 2

PI: The legal provisions and /or regulations or guidelines that require authorization for the import, export 3 and destruction of investigational medical products have been established for less than two years. 4

I: The NRA has legal provisions, regulations and /or guidelines that require authorization for the import, 5 export and destruction of investigational medical products and applies for all IMPs. 6



References: 9


2. 38-WHO TRS 1004, Annex 9, 2017 11

3. 39- WHO TRS 987, Annex 2, 2014 12

4. 119- WHO TRS 987, Annex 2, 2014 13

Sub-Indicator: CT01.09: THERE ARE REQUIREMENTSON MONITORING 14

ADVERSE EVENTS/ REACTIONSAND REPORTINGDURING CONDUCTING CT. 15

Scope: All 16

Maturity: 2 17

Requirement: 18

Monitoring and reporting adverse reactions/events 19

Rationale: 20

The objective of this sub-indicator is to assure requirements that mandate investigators and /or sponsors to 21 monitor all subjects involved in CTs exist including obligation to report to the NRA/ responsible 22 regulatory authority (ies) all adverse and /or serious adverse reactions and /or events within the approved 23 time frame for reporting. 24

Description: 25

The assessor should verify that the requirements on monitoring and reporting adverse and/reactions 26 should be in existence and implemented. It should clearly provide guidance on monitoring adverse 27 reactions and follow up. It should provide clarity on the roles/responsibility/duties of all stakeholders, 28 including the NRA, as well as the exact requirement for monitoring, such as data collection and 29 evaluation, and reporting adverse reactions/ events during the period of the CT. It should provide the 30 type/nature/form of adverse reaction and/or event to report. The sequence of report in the event of 31 reporting to more than one NRA or authority and other stakeholders, e.g. sponsor, should be indicated. 32 The guideline should be supported by a form for monitoring and reporting adverse reaction/events. 33




1. The guidelines and / or regulations on monitoring adverse events/ reactions and reporting, as well 1 as follow up. The assessor should verify if the guidelines have been implemented. 2

2. The exact roles/responsibilities/duties of each stakeholder, and compare with the WHO 3 recommendations or other international standards. 4

3. The NRA recommendations to the sponsor /investigator on the procedures for monitoring adverse 5 events/ reactions and reporting. The assessor should verify if the recommendations are in line with WHO 6 or other international standards. 7

4. Committee responsible for reviewing adverse reactions/events reports, the composition of the 8 committee and specialties of committee members. 9

5. The timelines allocated for investigating adverse reactions/events on the part of the 10 investigator/sponsor and generating a report on the adverse reaction and /or event to the NRA. 11

6. Records of the completed form sent to the NRA. The assessor should verify the format and 12 content to assure compliance with the guidelines. 13

Framework: 14


Rating Scale: 16

NI: There are no requirements and guidance on monitoring adverse event/reactions and reporting. 17

OI: The requirements on monitoring adverse event/ reactions and reporting are drafted or defined, but 18 these have not yet been followed. 19

PI: The requirements and guidance on monitoring adverse event/reactions and reporting have been 20 developed less than two years or there are no reports from all CTs. 21

I: The requirements and guidance on monitoring adverse event/reactions and reporting exist and all 22 sponsors are following them. 23

Limitations and remarks: The assessor should score this sub-indicator as implemented if there is no 24 record due no ongoing CT study. 25


References: 27

1. 41- Handbook for good clinical research practice (GCP): guidance for implementation. WHO; 28 2002(Principle 3 : GLP; Principle 5) 29


Sub-Indicator: CT01.10: THERE ARE GUIDELINES ON THE FORMAT AND 31

CONTENT OF CLINICAL TRIAL APPLICATIONS 32

Scope: All 33

Maturity: 2 34

Requirement: 35

WHO global benchmarking tool rev. VI ver. 1, CT Format and content of CT applications 1

Rationale: 2

The objective of this sub-indicator is to assure the existence of a clear guidance document that guides the 3 applicant/sponsor on the information to be included in the application pack (content and format) and the 4 procedure for submitting the application to the NRA for evaluation. Its content should be sufficient to 5 facilitate CT activities. 6

Description: 7

The assessor should verify that the guidelines on the format and content of CT applications should be in 8 existence, issued and implemented. It should clearly provide guidance on the format and content (list of 9 requirements/documents) of the CT application dossier to be submitted to the NRA. The content may 10 include but not limited to ;CT registration with a registry that is approved/recognized by the NRA, 11 covering letter addressed to head of the NRA, completed CT application forms that should be signed by 12 an authorized person(s) and dated, CT Protocol, investigator’s brochure (IB), investigational product 13 dossier, good manufacturing practice (GMP) certificate, ethics committee / evidence of institutional 14 review board approval, , evidence of insurance cover (from a recognized insurance company), 15 statement/evidence of financial support/declaration, data safety monitoring board membership (DSMB) 16 and signed charter, evidence of sponsor-PI contractual agreement, sample of informed consent form, 17 assent forms (if applicable), statistical analysis plan (SAP), professional profile of potential PI, study 18 pharmacist and local monitor (i.e. qualification, experience/ expertise, evidence of excellent knowledge of 19 local CTs regulatory requirements, past CTs managed), others. The guidelines should also provide 20 guidance on the sequence of events to be complied with before the actual submission (e.g. meetings, 21 workshops, seminars, IEC, etc.). The guidelines may provide guidance on choosing a CT site and 22 selection of subjects. 23



1. The guidelines on the format and content of the CT application are available, implemented and 26 published on the NRA’s website. 27

2. Accessory documents such as CT application forms and other CT related forms exist, are issued 28 and used. 29

3. The form/nature of CT application pack submission (i.e. electronic or face-to-face, hard or soft 30 copies and the number of copies. 31

4. List of critical documents that should be included in the application pack. 32

Framework: 33


Rating Scale: 35

NI: There is no guidelines on the format and content of clinical trial applications. 36

OI: The guidelines on the format and content of clinical trial applications drafted or adopted, but it has not 37 yet been implemented. 38


PI: The format and content of clinical trial applications has been established and it has been applying for 1 less than two years. 2

I: The NRA has guidelines on the format and content of clinical trial applications and it is followed for all 3 received CTs application. 4



References: 7

1. 38-WHO TRS 1004, Annex 9, 2017 8


3. 41- Handbook for good clinical research practice (GCP): guidance for implementation. WHO; 10 2002 (Principle 3 : GLP; Principle 5) 11

4. 39- WHO TRS 987, Annex 2, 2014 12

5. 119- WHO TRS 987, Annex 2, 2014 13

Sub-Indicator: CT01.11: LEGAL PROVISIONS AND/OR REGULATIONS ALLOW 14

THE NRA TO RECOGNIZE AND/OR USE RELEVANT CLINICAL TRIAL 15

DECISIONS, REPORTS OR INFORMATION FROM OTHER NRAS, OR REGIONAL 16

AND INTERNATIONAL BODIES. 17

Scope: All 18

Maturity: 1 19

Requirement: 20

Recognition and/ reliance on CT application decision/information 21

Rationale: 22

The objective of this sub-indicator is to assure legal provisions and/ or regulations exist to allow the NRA 23 to recognize and/or use relevant CT decisions, reports or information from other NRAs, or regional and 24 international bodies. 25

Description: 26

The assessor should verify that the legal provisions and/or regulations that allow the NRAs to recognize 27 and/or use relevant CT decisions, reports or information from other NRAs or regional and international 28 bodies should be in existence, enacted and implemented. The legal provision and /or regulation should 29 provide guidance on the modalities/processes and procedure to recognize and/or use relevant CT 30 decisions, reports or information from other NRAs or regional and international bodies, as well as 31 guidance on the conditions (when/how) to recognize and/or use relevant CT decisions, reports or 32 information from other NRAs, or regional and international bodies. The legal provision and/ or regulation 33 should also provide clear directives on the scope or extent of recognition and/or use of the CT decisions, 34 reports or information from other NRAs, or regional and international bodies. 35

WHO global benchmarking tool rev. VI ver. 1, CT Evidence to review: 1


1. The legal provisions(laws, decrees, regulations or any legal binding document) that permits the 3 NRA to recognize and/or use relevant CT decisions, reports or information from other NRAs or regional 4 and international bodies. 5

2. The scope /extent of recognition and /or use of relevant CT decisions, reports or information from 6 other NRAs, or regional and international bodies. 7

3. Instances or situations that permit recognition and/or use relevant CT decisions, reports or 8 information from other NRAs or regional and international bodies. 9

4. List of NRAs or regional and international bodies whose relevant decisions, reports or 10 information may be used to influence a CT application decision, and whether those NRAs, or regional and 11 international bodies are aware that their relevant CT decisions, reports or information on certain CTs may 12 be used (aware of the legal provision). 13

Framework: 14


Rating Scale: 16

NI: There are no legal provisions and/or regulations that allow the NRA to recognize and/or use relevant 17 clinical trial decisions, reports or information from other NRAs, or regional and international bodies. 18

OI: The legal provisions and/or regulations that allow the NRA to recognize and/or use relevant clinical 19 trial decisions, reports or information from other NRAs, or regional and international bodies are drafted or 20 pending for adoption. 21

PI: Legal provisions and/or regulations allowing the NRA to recognize and/or use relevant clinical trial 22 decisions, reports or information from other NRAs, or regional and international bodies have been 23 established and the NRA has been applying them for less than two years. 24

I: There are legal provisions and/or regulations allowing the NRA to recognize and/or use relevant 25 clinical trial decisions, reports or information from other NRAs, or regional and international bodies, 26 supported with adequate documentation such as criteria for selection or list of other NRAs. 27


References: 29

1. 112-Good regulatory practices: guidelines for national regulatory authorities for medical 30 products. Working document QAS 16.686 31

Indicator: CT02 ARRANGEMENT FOR EFFECTIVE 32

ORGANIZATION AND GOOD GOVERNANCE 33

Rationale: 34

The objective of this indicator is to assure that there is a legal basis for the organizational structure and 35 governance that allows for the smooth exchange of information within and outside the entity responsibly 36


for CT (NRA, ECs, CROs, others) as appropriate. The arrangement should establish the responsible roles 1 and persons within the entity responsible for the various sectors within the CT, and how their roles relate 2 to the governance structure of the organization, as well as other CT – related NRAs/ competent regulatory 3 authority(ies) without the entity for CT. It will ensure that the NRA responsible for CT has complete 4 control of all the information related to CT, including, on-going CTs, new directives, new authorizations, 5 suspensions and rejections etc. 6

The objective of this indicator is to establish that structures are in place at the organizational and 7 governance levels to promote effective intra- and inter NRA relationships where information traffic is 8 efficiently managed. 9

Category: Organization and governance 10

Sub-Indicator: CT02.01: THERE IS A DEFINED STRUCTURE WITH CLEAR 11

RESPONSIBILITIES TO CONDUCT CLINICAL TRIAL OVERSIGHT ACTIVITIES 12

Scope: All 13

Maturity: 2 14

Requirement: 15

Structure and Responsibilities 16

Rationale: 17

The objective of this sub-indicator is to assure there are structures in place, with clearly defined roles and 18 responsibilities for each structural and governance level for CT activities. 19

Description: 20

The assessor should verify that the defined structure with clear responsibilities to conduct CT activities 21 exist and are implemented. It should be supported by legal provisions, regulations and guidelines, and 22 clearly delineating roles, responsibilities and duties of all stakeholders within the NRA and outside of the 23 NRA. The scope/extent of their role/responsibilities within the NRA in relation to CT activities, as well as 24 their reporting lines should be clearly established. The structure of the entity (ies) or authority relative to 25 relationships and ranks, as well as information exchange / flow within and outside (e.g. IEC) the entity 26 (ies) or authority (ies) should be established and implemented. Guidelines for the establishment of 27 advisory committees, such as technical experts committees, external experts among others, with clear 28 objective/functions, composition, terms of reference, others should be established and implemented. 29



1. The roles/responsibility (ies) /duties of the entity (ies) responsible for CT within the NRA and 32 their placement on the organizational chart in relation to other entities involved in CT. 33

2. The regulation and/or guidelines mandating such entity (ies) or authority (ies) with the 34 responsibility to conduct CT activities within the NRA. 35

3. A clearly defined policy on conflict of interest. 36

WHO global benchmarking tool rev. VI ver. 1, CT 4. The operational manual or similar document of the entity (ies). The manual should contain all the 1 authorized /approved guidelines (published or not), application form (published or not), and SOPs or 2 similar documents. 3

5. Published CT application processing flow diagrams and corresponding timelines, as well as the 4 fees and charges schedule. 5

Framework: 6


Rating Scale: 8

NI: There is no defined structure with clear responsibilities to conduct clinical trial oversight activities. 9

OI: The NRA has recently drafted a defined structure with clear responsibilities to conduct clinical trial 10 oversight activities. 11

PI: The NRA has established a defined structure with clear responsibilities to conduct clinical trial 12 oversight activities, however there is the need to improve this function by providing required support for 13 effective implementation and coordination. 14

I: The NRA has established a defined structure with clear responsibilities to conduct clinical trial 15 oversight activities that is fully supported with required resources. 16



References: 19

Sub-Indicator: CT02.02: DOCUMENTED PROCEDURES ARE IMPLEMENTED TO 20

ENSURE THE INVOLVEMENT AND COMMUNICATION BETWEEN ALL 21

STAKEHOLDERS RELEVANT TO CT 22

Scope: All 23

Maturity: 3 24

Requirement: 25

CT stakeholders interactions 26

Rationale: 27

The objective of this sub-indicator is to assure there are documented procedures and /or structures/ 28 mechanisms in place to ensure proper inter- and intra-relationships between and within entities involved 29 in CT in order to ensure effective and efficient exchange of information amongst stakeholders. 30

Description: 31

The assessor should verify the documented procedures that promote involvement and communication 32 between all stakeholders should be in existence and are implemented. The procedure should provide clear 33 directives on the regulatory divisions and guidance on how to implement the operational procedures to 34 ensure the involvement and communication between all stakeholders within and outside the NRA such as 35


the CT entity, IEC, GCP inspectorate, sponsors/IP, etc. It should be clear on the scope/extent of the role/ 1 responsibilities of each stakeholder. In addition, the procedure should be supported by information and/or 2 documentation transfer policy to ensure that directives/ information and/or documentation reach the 3 intended recipients and feedbacks are received. SOPs or similar documents and guidelines should be 4 approved, authorized and implemented. 5



1. Whether procedures are documented and implemented, and the impact of the implementation is 8 periodically assessed. 9

2. Standard Operating Procedures (SOPs) or similar documents that guide and/or inform effective 10 communication and collaboration between stakeholders. 11

3. The CT application guidelines that captures the duties/roles and responsibilities of the various 12 stakeholders involved in CT activities and whether the document is known to the relevant organizations, 13 institutions, and/or departments. 14

4. The CT application processing flow that captures the roles/duties and responsibilities of the 15 various stakeholders and the corresponding timelines allocated to the various levels 16

5. The feedback mechanism in the information and /or documentation transfer policy (ies) among 17 the various stakeholders. 18

Framework: 19

Process 20

Rating Scale: 21

NI: There are no procedures to ensure involvement and communication with all stakeholders relevant to 22 CT. 23

OI: The NRA has recently drafted procedures to ensure involvement and communication between all 24 stakeholders relevant to CT. 25

PI: The NRA established the procedures to ensure involvement and communication between all 26 stakeholders relevant to CT but these have not been fully incorporated and are not consistent with relevant 27 guidance. 28

I: The NRA has implemented procedures to ensure involvement and communication with all relevant 29 stakeholders including required documentation and records of communication, as well as feedback. 30



References: 33


Indicator: CT03 HUMAN RESOURCES TO PERFORM CLINICAL 1

TRIALS OVERSIGHT ACTIVITIES. 2

Rationale: 3

The objective of this indicator is to assure to that all entity (ies) within an NRA that is/are adequately 4 resourced with trained, experienced and skilled workforce, as well as empowered to fully perform clinical 5 trials oversight activities. This will ensure that clinical trials oversight activities are performed in 6 accordance with international best practices. 7

The objective of this indicator is to evaluate the human resource capacity of the entity (ies) with respect to 8 the number of personnel, their composition, their skill set and experience, as well as their specific areas of 9 expertise to perform the clinical trials oversight activities. The assessor should consider that some NRAs 10 may outsource CT activities. 11

Category: Resources (HR,FR, infrastructure and equipment) 12

Sub-Indicator: CT03.01: ENOUGH COMPETENT STAFF (EDUCATION, 13

TRAINING, SKILLS AND EXPERIENCE) ARE ASSIGNED TO PERFORM 14

CLINICAL TRIALS OVERSIGHT ACTIVITIES. 15

Scope: All 16

Maturity: 3 17

Requirement: 18

Enough number of competent human resources in charge of clinical trials oversight activities. 19

Rationale: 20

The objective of this sub-indicator is to assure the existing human resources for clinical trials oversight 21 activities is adequate in terms of numbers, their experience and their specific competences to perform all 22 the activities along the entire clinical trials oversight activities 23

Description: 24

The assessor should verify that the human resources assigned to perform clinical trials oversight activities 25 should be enough in terms of numbers and are competent with the requisite skills, education, experience 26 and training. There should be technical documents and /or SOPs that provide guidance on the required 27 background for CT activities taking into account the educational background, competencies/skills, and 28 experience and training requirements. 29

The assessor should verify that the NRA estimated the adequate number of staff required to effectively 30 and efficiently perform CT function and such number is actually recruited. In addition, the assessor 31 should verify that these competency requirements are well set and maintained by the NRA Metrics and 32 statistics on the different activities performed as well as performance indicators can be used for estimating 33 the adequacy of the number of the assigned staff. The assessor should also verify that the competency of 34 the assigned staff is built, maintained and improved through induction as well as continuous on-the-job 35 training. 36




1. The number of human resources involved in each of the documented activities along the entire 2 clinical trials oversight activities for adequacy 3

2. The systems/structures in place to ensure appropriate placement of staff with respect to 4 competence and skills, and whether the system or structures have been implemented including the records 5 of staff review. 6

3. The professional profiles of the human resources engaged in the clinical trials oversight activities 7 for appropriateness of education, and skills/expertise to perform a particular function along the clinical 8 trials oversight chain including the list the requisite skills and training 9

4. Recruitment plan. 10

Framework: 11


Rating Scale: 13

NI: The NRA does not have enough competent staff (education, training, skills and experience) to 14 perform CT oversight activities. 15

OI: The NRA has recently developed the plan to recruit adequate competent staff, however the plan has 16 not been implemented. 17

PI: The NRA has initiated the implementation of the human resources development plan, however there is 18 need to complete competency profile. 19

I: The NRA has adequate number of competent staff (education, training, skills and experience)assigned 20 to perform CT oversight. 21

Limitations and remarks: The adequacy and appropriateness of the number of staff is quite subjective 22 and shall be linked to some process and/or output indicators. The assessor should consider the workload, 23 backlog, and delay in delivery based on established timeframes for estimation of staff adequacy. 24


References: 26

1. 1- WHO TRS 885, Annex 8, 1999 27

Sub-Indicator: CT03.02: DUTIES, FUNCTIONS ANDRESPONSIBILITIES OF THE 28

STAFF, IN CHARGE OF CT OVERSIGHT ACTIVITIES ARE ESTABLISHED AND 29

UPDATED IN THE RESPECTIVE JOB DESCRIPTIONS 30

Scope: All 31

Maturity: 3 32

Requirement: 33

Duties, roles and responsibilities of the staff relevant to perform CT oversight activities. 34

WHO global benchmarking tool rev. VI ver. 1, CT Rationale: 1

The objective of this sub-indicator is to assure clear and well defined duties and responsibilities of the 2 staff and their job descriptions are up to date with their current duties, functions, and responsibilities, and 3 adequately documented. 4

Description: 5

The assessor should verify that a current and updated structure for job description should be in place. In 6 addition, it should address staff current duties, responsibilities and the requisite competence. Such format 7 and content should be established and implemented for all staff. The procedure should be supported with 8 a guidance document that provide direction on when and how to update the information, and where the 9 information is kept for easy access. It should present the appropriate duties/responsibilities that are 10 assigned to roles for each member of the entity (ies) involved in CT oversight activities. Thus, the 11 professional profiles of staff are reflected in their respective roles and/ or responsibilities within the NRA. 12 There should be procedures to guide responsible persons to document up to date revised duties/functions 13 and responsibilities. In addition, procedures to guide the keeping and/or documenting of up to date work 14 schedule and, and enforcing the implementation of the documented guidelines /procedures should be 15 available. 16



1. The procedure and /or guidelines that guide placement of staff members within the NRA; 19

2. The professional profiles of staff(Job descriptions), and relate it to their current roles/duties; 20

3. The professional profiles of the external experts for completeness, in relation to their composition 21 as prescribed in the legal provision; 22

4. Procedures to guide the documentation of up to date duties and work schedules, and enforcing 23 the implementing of the documented guidelines /procedures; 24

5. Job description of designated staff 25

Framework: 26


Rating Scale: 28

NI: There is no evidence of defined or establishment of duties, functions, responsibilities, respective job 29 descriptions and necessary required competencies. 30

OI: The NRA has recently drafted or developed the role and responsibilities document but it has not yet 31 been in place. 32

PI: The NRA has initiated implementation of this requirement but has not defined or followed for all staff 33 or the role and responsibility document including staff job descriptions are not up to date. 34

I: The NRA has defined and established of all required duties, functions, responsibilities and respective 35 job descriptions. 36




References: 3

1. 1- WHO TRS 885, Annex 8, 1999 4

2. 4- ISO standard 9001:2015 sub-clause 5.1.1 5

3. 5- WHO TRS 790, Annex 6, 1990. Chapter 1.4 and 1.8 (b) 6

4. 7- Effective Drug Regulation; 2002.Chapter 4.4 7

Sub-Indicator: CT03.03: TRAINING PLAN DEVELOPED, IMPLEMENTED AND 8

UPDATED AT LEAST ONCE A YEAR 9

Scope: All 10

Maturity: 3 11

Requirement: 12

Implementation of training plan 13

Rationale: 14

The objective of this sub-indicator is to assure training plan for staff exist, and whether it is implemented 15 and annually updated. Through the training plan, NRA can be sure that competency of staff in charge of 16 CT activities is maintained and enhanced. 17

Description: 18

The assessor should verify that the training plans are developed, implemented and updated at least once 19 every year to reflect current situation by considering education and experience of the staff. The training 20 plan should be complemented with guidelines or similar documents to guide the development and 21 implementation of training plans. The assessor should ensure planning and implementation of induction 22 training for new staff as well as continued on-the-job for staff. There should be procedures to approve 23 training plan and budget allocated for the training plan, as well as updating the plan. The plan should 24 present clearly defined training goals. This should involve learning certain topics and /or skills to address 25 deficiencies. Learning objectives, training methods/activities, documentation / or evidence of learning and 26 evaluation / assessment of training should be documented. This will confirm whether the learning 27 objectives were achieved and they have been designed to address weakness within the entity (ies). 28 Procedures should be in place to ensure that a training plan is developed, implemented and updated at 29 least once every year. Measuring training effectiveness is another aspect which the assessor should 30 check. The assessor should verify that there is a system in place for monitoring the implementation and 31 effectiveness of the training plan along with the skills acquired in training activities for internal and 32 external experts. 33



WHO global benchmarking tool rev. VI ver. 1, CT 1. The guideline for development, implementation and update of the training plan at least once 1 every year as well as mechanism to measure effectiveness of training. 2

2. The system/structures used to approve the training plan as well as the budget allocated to the 3 training activities for the purposes of adequacy. 4

3. The current/existing training plan/matrix of staff, and relate it to their respective job 5 descriptions. 6

4. SOP for developing and maintaining the training plan. 7

5. Collection and/or investigation of training needs. 8

6. List of trainings performed. 9

7. Example records for training activities. 10

Framework: 11

Process 12

Rating Scale: 13

NI: There is no systematic training programme including training matrix/plan to perform CT oversight 14 activities. 15

OI: The NRA has recently drafted or developed training plan but there is no evidence of implementation. 16

PI: The NRA has developed and initiated the training plan implementation. However, the NRA has not 17 fulfilled all required planned training and has been applying it for less than two years. 18

I: The NRA has an updated training plan developed and supported by adequate records to demonstrate 19 effective plan implementation, including induction training for new staff and routine on-the-job training 20 for recruited staff. 21

Limitations and remarks: Training plans must be updated regularly, expectedly on annual basis, but not 22 beyond biennial (once every two years). 23


References: 25

1. 1- WHO TRS 885, Annex 8, 1999 26




5. 8- WHO TRS 902, Annex 8, 2002. Chapter 5.2 (d) 30

Sub-Indicator: CT03.04: THE NRA PERFORMS AND MAINTAINS RECORDS OF 31

STAFF TRAINING ACTIVITIES 32

Scope: All 33


Maturity: 3 1

Requirement: 2

Training records 3

Rationale: 4

The objective of this sub-indicator is to assure that trainings organized by the NRA/ responsible 5 regulatory authority (ies), and the training records are adequately documented, and maintained/kept. Staff 6 training records as an integral part of staff file is a tool for measuring and tracking staff competency and 7 development and adequacy. 8

Description: 9

The assessor should verify that the records on staff training performed/organized by the NRA exist, are 10 implemented and regularly updated. The activity should be supported with guidelines to guide the NRAs 11 to perform and maintain records of staff training activities. Procedures to document and propose staff 12 training needs as well as to allocate a budget for continuous staff capacity building/development should 13 be in place. The assessor should check there is an evaluation/ assessment mechanism to verify the quality 14 of learning, and to confirm whether learning objectives are achieved. An inventory (soft and/or hard) 15 system to document all impactful and non- impactful trainings, and members of staff who participated. A 16 system to measure /estimate impact of trainings should be established. 17



1. Guidelines or similar documents to guide the NRA to perform and maintain records of staff 20 training activities; 21

2. Training effectiveness evaluation; 22

3. The training inventory, and how the inventory is completed; 23

4. Records keeping or staff training archives and archiving system. 24

Framework: 25

Output 26

Rating Scale: 27

NI: There is no evidence of that the NRA performs and maintains records of staff training activities. 28

OI: The NRA has recently planned or initiated to perform, document and keep records of staff training 29 activities however is not followed yet. 30

PI: The NRA has recently established planned or initiated to perform, document and keep records of staff 31 training activities but it is not fully followed for all training activities or it is established for less than two 32 years. 33

I: The NRA performs and maintains records of staff training activities. 34

WHO global benchmarking tool rev. VI ver. 1, CT Limitations and remarks: The assessor should note that some NRAs out-source training including staff 1 capacity development activities. In this case the assessor should request for the identity, as well as the 2 provide revaluation status. The assessor may request for the professional profiles of tutors or resource 3 persons used to offer training, as well as the records and archiving systems in place. 4


References: 6

1. 1- WHO TRS 885, Annex 8, 1999 7




Indicator: CT04 PROCEDURES ESTABLISHED AND 11

IMPLEMENTED TO PERFORM CLINICAL TRIALS OVERSIGHT. 12

Rationale: 13

The objective of this indicator is to assure that the NRA/ responsible regulatory authority have 14 documented procedures establishing how CT should be implemented. The documented procedures should 15 be efficiently designed to assist in the preparation of the CT application, receipt and evaluation of the 16 enclosed information. The procedures should present an overview of the activities to be carried out, the 17 steps to be followed, the resources required, the processes to be followed to evaluate the documents 18 submitted, the interrelationship between the various documents, and verify that all procedures follow and 19 address all legal principles. The established procedures will give guidance on how CT applications are 20 handled to ensure efficient CT. 21

The objective of this indicator is to establish whether procedures have been established and implemented 22 to effectively perform CT activities. 23

Category: Regulatory process 24

Sub-Indicator: CT04.01: NRA HAS ACCESS TO AN ADVISORY COMMITTEE 25

FOR REVIEWING OF CT APPLICATIONS AND/ORPOST APPROVAL SAFETY 26

AND COMPLIANCE ISSUES. 27

Scope: All 28

Maturity: 4 29

Requirement: 30

Advisory committee for CT 31

Rationale: 32

The objective of this sub-indicator is to assure the NRA has option of using an advisory committee in the 33 review of CT applications and post approval safety and compliance issues if needed especially in the 34 event of new/emerging technology. 35


Description: 1

The assessor should verify that the involvement of an advisory committee in the review of CT 2 applications is documented and supported by a legal provision and / or regulations. The legal provision 3 and/or regulation for the establishment and use of an advisory committee in the review of CT applications 4 should be established and implemented. There should be clear guidance on when and how to use the 5 committee, and the scope /extent of the use of their expertise in the CT application review and post 6 approval safety and compliance issues. The terms of reference of the members of the committee should be 7 available and documented. There should be documented objectives and functions of the committee, and 8 each member of the committee. Professional profile of the committee members should be available and 9 the composition of the committee should be guided by a legal provision or regulation. In addition, 10 supporting guidelines should clearly define the roles/ responsibilities of each member of the committee in 11 relation to the review of CT application. The code of conduct and a general policy on conflict of interest 12 for the committee members should also be documented and available. The assessor should note that some 13 NRAs /responsible regulatory authorities may not involve the advisory committee only in the review of 14 the submitted CT application. Some NRAs may refer to advisory committees in the regard of adverse 15 event/reactions and / or serious adverse events for direction. 16



1. Legal provisions(laws, decrees, regulations or any legal binding document) for the establishment 19 and use of advisory committee in the review of CT applications 20

2. The terms of reference of the committee and members of the committee including their signed 21 updated conflict of interest form. 22

3. The composition of the advisory committee, and whether it is in line with the directive prescribed 23 in the legal provision and/or regulations 24

4. The scope /extent of their advisory contributions in the review of CT applications. 25

5. SOPs for their activities. 26

6. Records of reports 27

Framework: 28

Process 29

Rating Scale: 30

NI: The NRA does not have access to an advisory committee involved in the review of CT applications 31 and/or post-approval safety and compliance issues. 32

OI: The NRA has drafted a proposal to establish the advisory committee that is involved in the review of 33 CT activities. 34

PI: The advisory committee is established less than two years or is not involved in all required CT 35 activities. 36

I: The advisory committee is established, officially endorsed and involved in all required CT activities. 37

WHO global benchmarking tool rev. VI ver. 1, CT Limitations and remarks: 1

In the case the NRA has all required internal resources for CT activities, this sub-indicator can be scored 2 as not applicable. 3

The assessor should consider this sub-indicator as implemented, if the NRA can provide adequate 4 evidence of access to advisory committees in case of need. 5


References: 7

Sub-Indicator: CT04.02: THE EXISTENCE OF THE ETHICS COMMITTEES (ECs) 8

WITH CLEAR DEFINED COMPOSITION. 9

Scope: All 10

Maturity: 3 11

Requirement: 12

Existence, performance and composition of ethic committee 13

Rationale: 14

The objective of this sub-indicator is to assure there is a defined and documented composition of the 15 ethics committees for CT activities. 16

Description: 17

The assessor should verify the legal provisions and / or regulations that provide guidance on the 18 composition of the ethics committees should exist, are enacted and implemented. The legal provisions 19 and/ or regulation should direct that the composition of the ECs should be multidisciplinary and multi-20 sectorial and should include relevant scientific expertise, balanced age and gender distribution, and 21 laypersons/proletariats representing the interests and the concerns of the community. It should be 22 supported with guidelines and / or SOPs that provide guidance on selection of members and the terms of 23 reference, as well as selection of the committee chair. The legal provision and / or regulation should also 24 provide direction on how the activities of the ECs should be regulated. 25



1. Legal provisions(laws, decrees, regulations or any legal binding document) that provides 28 guidance on the composition of the ECs 29

2. The terms of reference for each member, including the selection process. The assessor should 30 review the ToR and SOPs that provide guidance. 31

3. Professional profiles for members of the ECs for balance in terms relevant expertise, gender, age 32 and representation. 33

4. Current and up to date list of the EC members. 34

Framework: 35



Rating Scale: 2

NI: Ethics committees are not established for CT activities. 3

OI: The composition of the ethics committees has been recently drafted but the committees have not been 4 implemented. 5

PI: The ethics committees are established but are not officially approved or are not routinely involved in 6 CT activities. 7

I: The ethics committees are established, officially endorsed and routinely involved in CT activities. 8

Limitations and remarks: The assessor should note that in most cases, the NRA will not be the agency 9 that host the EC, and as a result may not be able to provide sufficient information to address this sub-10 indicator. The assessor may have to consult the Ministry of Health (MoH) or the relevant Ministry or 11 institution for more information. Failure to secure information should justify the “not or partial 12 implemented” of the scoring. 13


• CT01.08 15

References: 16

1. 38-WHO TRS 1004, Annex 9, 2017 17

2. 39- WHO TRS 987, Annex 2, 2014 18

3. 119- WHO TRS 987, Annex 2, 2014 19

Sub-Indicator: CT04.03: NON-CLINICAL DATA IS CONSIDERED WITHIN CT 20

APPLICATION REVIEW. 21

Scope: All 22

Maturity: 3 23

Requirement: 24

Preclinical data as part of CT application 25

Rationale: 26

The objective of this sub-indicator is to assure that data from preclinical studies will give sufficient 27 insight into potential safety issues that may influence eventual clinical application of the IMP. The 28 objective of the sub-indicator is to establish whether preclinical data is part of the application pack, and 29 the data submitted is reviewed per a documented procedure. 30

Description: 31

The assessor should verify that the regulation and /or guidelines on the requirements for CT application 32 should be in existence and implemented. It should clearly states that the CT application requirements 33 include preclinical data which is generated in accordance with the principles of Good Laboratory 34

WHO global benchmarking tool rev. VI ver. 1, CT Practices (GLP). It should provide guidance on the type and scope of data to submit to support the CT 1 application. 2



1. The regulation / guidelines that states that non-clinical data is a requirement in a CT application, 5 and satisfactory review of the preclinical data is a pre-requisite for CT authorization. 6

2. SOPs that provide guidance during the review of the non-clinical data submitted for the purposes 7 of CT applications. 8

3. Record of CT application form. 9

Framework: 10

Process 11

Rating Scale: 12

NI: The NRA does not require and review the non-clinical data within CT application. 13

OI: The NRA has recently drafted guideline or similar documents to consider non-clinical data as part of 14 CT application. 15

PI: The NRA considers non-clinical data as part of CT application however there is no systematic review, 16 records or capacity to review these data. 17

I: The NRA requires and reviews the non-clinical data within CT application. 18



References: 21


2. 39- WHO TRS 987, Annex 2, 2014 23

Sub-Indicator: CT04.04: THERE ARE DEFINED ROLES FOR ECs AT ALL LEVELS 24

Scope: All 25

Maturity: 3 26

Requirement: 27

Defined roles for ECs 28

Rationale: 29

The objective of this sub-indicator is to assure whether there are defined roles for the ECs at all levels 30

Description: 31


The assessor should verify that the legal provisions, regulations and /or guidelines establishing the EC, 1 provide direction on the composition, and their roles and responsibilities at each level and up to date. The 2 regulation and /or guidelines should provide the objective and functions, the mandate, mission, roles and 3 responsibilities of the ECs as well as each member. In addition, the scope /extent of their mandate should 4 be clarified. There is need to define and document the interaction between different level of ECs. 5



1. The legal provisions(laws, decrees, regulations or any legal binding document) and/or guidelines 8 that provides defined roles of the EC at each level of the CT activities including guidance on information 9 sharing and interaction with relevant stakeholders. 10

2. Guidelines detailing the objectives, functions, roles and responsibilities of the EC at each level of 11 the CT activities. 12

3. Whether their legally mandated scope of work is acceptable per the WHO guidelines 13

4. Records of interaction between different ECs level. 14

Framework: 15

Process 16

Rating Scale: 17

NI: The role and responsibilities of all levels of ECs have not been defined. 18

OI: The role and responsibilities of ECs have been drafted at all levels however is not yet followed. 19

PI: The role and responsibilities of ECs have been assigned at all levels however less than two years or is 20 not fully documents. 21

I: The role and responsibilities of ECs have been established and documented at all levels and followed 22 by all relevant parties. 23


. 25


• CT01. 02 27

• CT01.08 28

References: 29

1. 39- WHO TRS 987, Annex 2, 2014 30

2. 38-WHO TRS 1004, Annex 9, 2017 31

3. 119- WHO TRS 987, Annex 2, 2014 32


Sub-Indicator: CT04.05: DOCUMENTED AND IMPLEMENTED PROCEDURES 1

EXIST TO REVIEW CT APPLICATIONS 2

Scope: All 3

Maturity: 3 4

Requirement: 5

Document procedures to review CT applications 6

Rationale: 7

The objective of this sub-indicator is to assure uniform evaluation of CT applications is devoid of bias. 8 There should be regulation /guidelines instituting defined set of criteria for the NRAs / responsible 9 regulatory authority (ies) to adhere to in the discharge of their duties to avoid bias. 10

Description: 11

The assessor should verify that the guidelines and / or SOPs needed to provide guidance during the 12 review of the CT application exist, and are implemented. The guidelines and /or SOPs should provide 13 guidance on how to review the various components of the CT application, and should be supported by a 14 checklist or CT application review form that would be completed during the review process. Such a 15 form/checklist should be used to generate the review report that would capture the recommendations and 16 /or comments to justify authorization, rejection and deferral of the CT application. The review procedure 17 should be a single set of established criteria applicable to all CT applications. 18



1. The guidelines and /or SOPs that establishes the criteria for reviewing CT application. 21

2. Whether the guidelines and /or SOPs are implemented during the review process. The assessor 22 should request for a completed review report and compare with the guidance note for compliance. 23

Framework: 24

Process 25

Rating Scale: 26

NI: There are no documented procedures to review CT applications. 27

OI: The NRA has drafted or adopted the documented procedures to review CT application. 28

PI: the NRA has developed and officially approved the documented procedures to review CT applications 29 for less than two years or there is no evidence to demonstrate the implementation of this procedure for all 30 the applications. 31

I: The NRA has developed and implemented the documented procedures to review CT application and 32 followed for all CT applications by adequate evidence. 33




References: 1

Sub-Indicator: CT04.06: THERE ARE PROCEDURES FOR EC RESPONSIBILITY 2

FOR CLEARANCE AND FOLLOW UP UNTIL COMPLETION OF THE CLINICAL 3

TRIAL 4

Scope: All 5

Maturity: 3 6

Requirement: 7

Documented procedures for the EC along the entire CT authorization chain 8

Rationale: 9

The objective of this sub-indicator is to assure the NRAs/ responsible regulatory authority (ies) have 10 established procedures on the responsibilities of the EC from CT clearance until the completion of the 11 study. 12

Description: 13

The assessor should verify that the procedures that provide guidance for the EC’s responsibility for 14 clearance and follow-up until completion of the CT exist, are documented and implemented. The 15 documentation of procedures should be in the form of guidelines or SOPs, and should provide detailed 16 guidance on the roles and responsibilities of the EC in the clearance and follow-up processes until 17 completion of the CT. The guidelines should provide the scope/extent of the EC’s activity in the CT 18 activities and the corresponding timelines for each activity, as well as guidance on the expected outcomes 19 of their activities, and its impact on the entire CT activity until CT completion. 20



1. The regulations, guidelines and /or SOPs detailing the role and responsibilities of the EC in the 23 clearance and follow-up process of CTs until completion. The assessor should verify whether the 24 procedures have been appropriately documented and are implemented. 25

2. The documented scope/extent of responsibility (ies) at each level of the CT. 26

3. The processes and procedures guiding the operations /activities at each level/stage of the CT. 27

Framework: 28

Process 29

Rating Scale: 30

NI: There are no procedures to define EC responsibility for clearance and follow up until completion of 31 the clinical trial. 32

OI: There are drafted or adopted procedures to define EC responsibility for clearance and follow up until 33 completion of the clinical trial. 34

WHO global benchmarking tool rev. VI ver. 1, CT PI There are procedures to define EC responsibility for clearance and follow up until completion of the 1 clinical trial however it has not been implemented. 2

I: The defined procedures regarding EC responsibility for clearance and follow up until completion of the 3 clinical trial are implemented and supported with documented evidences. 4

Limitations and remarks: The assessor should note that some EC may have limited mandate along the 5 entire CT chain in accordance to the existing regulations. In such cases, the assessor should be guided by 6 the existing law or regulation. The scoring may be partial or not applicable depending on the country 7 regulation. 8


• CT01. 02 10

• CT01.08 11

References: 12

Sub-Indicator: CT04.08: THE SAME POLICYARE USED FOR THE EVALUATION 13

OF CT APPLICATIONS REGARDLESS OF THE APPLICANT (E.G. DOMESTIC, 14

FOREIGN, PUBLIC/PRIVATE SECTOR) 15

Scope: All. 16

Maturity: 3 17

Requirement: 18

Uniform criteria and policy for evaluating CT application regardless of applicant 19

Rationale: 20

The objective of this sub-indicator is to assure the same criteria is applied to evaluate CT applications 21 from various sources to avoid being biased. 22

Description: 23

The regulation and / or guidelines dictating the criteria applied to evaluate CT applications should be the 24 same regardless of the applicant should be in existence, enacted and implemented. A single set of criteria 25 for the evaluation process should exist, documented and implemented during all CT applications 26 evaluation. The criteria should be supported with a checklist or evaluation form that should be completed 27 during the evaluation process. The assessor should note that in some instance, such as emergencies, the 28 single set of criteria for evaluating CT application may not apply. The assessor should request for and 29 review the documented and implemented procedures and processes that will be used to provide guidance 30 during the review of CT applications in the event of emergencies. 31



1. The regulations and /or guidelines that require that all CT applications are evaluated with the 34 same single set of criteria regardless of the applicant. 35

2. The guidelines and /or SOPs that presents the detailed criteria for evaluating CT applications. 36


3. Whether the assessors are aware of the criteria, how to apply the criteria in their assessment 1 activities, and whether the criteria are documented, published and implemented. 2

Framework: 3

Process 4

Rating Scale: 5

NI: There is no defined policy and criteria or different policies are used for the evaluation of CT 6 applications of the different applicant from different sources (e.g. domestic, foreign, public/private 7 sector). 8

OI: There is a drafted policy or documentation that requires to follow the same criteria for the evaluation 9 of CT applications regardless of the applicant (e.g. domestic, foreign, public/private sector). 10

PI: There are regulations or guidelines that require same criteria are used for the evaluation of CT 11 applications regardless of the applicant (e.g. domestic, foreign, public/private sector) for less than two 12 years or there is no evidence to demonstrate full implementation for all received CT applications. 13

I: The same criteria and policy are used for the evaluation of CT applications regardless of the applicant 14 (e.g. domestic, foreign, public/private sector) for all received and approved CT applications. 15

Limitations and remarks: The assessor should note that in some countries only one source may exist, 16 the assessor can score this sub-indicator as implemented if all regulation and requirements are the same. 17

The assessor should consider there are different requirements based on the nature of each product. 18


References: 20

Indicator: CT05 MECHANISM EXISTS TO PROMOTE 21

TRANSPARENCY, ACCOUNTABILITY AND COMMUNICATION. 22

Rationale: 23

The objective of this indicator is to assure mechanisms are in place to ensure that information on CT 24 applications, including authorized, suspended, rejected and completed CTs are published to promote 25 transparency and information sharing amongst stakeholders and potential stakeholder such as trial 26 subjects. 27

Category: Transparency, accountability and communication 28

Sub-Indicator: CT05.01: THERE IS CLARITY ABOUT THE FUNDING OF THE 29

ETHICS COMMITTEE AND ITS MEMBERS 30

Scope: All 31

Maturity: 4 32

Requirement: 33

Clarity on the source of funding 34

WHO global benchmarking tool rev. VI ver. 1, CT Rationale: 1

The objective of this sub-indicator is to assure there is a dedicated source of funding for the operations of 2 the EC and the source of funding is known, transparent and devoid of any conflict of interest. 3

Description: 4

The assessor should verify that the source of funding for the EC activities is known, documented and seen 5 as appropriate –devoid of any conflict of interest. The source of funding for their activities should be 6 documented and supported by a regulation which should provide clarity on the funding mechanism, 7 disbursement of funds and management of funds. All fee and charges should be legally approved and 8 implemented. The regulation should emphasis clarity on the source of funding and its impact on general 9 conflict of interest. 10



1. The regulation detailing the source of funding made available to the EC to fund its activities. 13

2. Whether the identity of the source may compromise the general policy on conflict of interest. 14

3. Whether the level of transparency regarding the source of funding and application of the funds is 15 sufficient to eliminate doubts on conflict of interest. 16

4. Whether the fees and charges are legally approved. 17

5. Records of funding report. 18

Framework: 19


Rating Scale: 21

NI: NRA does not have information or clarity about the funding of the ethics committee and its members. 22

OI: There are drafted procedures and policy to provide information about the funding process of the ethics 23 committee and its members. 24

PI: There are procedures to provide information about the funding process of the ethics committee and its 25 members, however there is no evidence to demonstrate availability of this information regarding all IECs. 26

I: The NRA has clear information about the funding of the ethics committee and its members supported 27 with documented evidence. 28



• CT04.02 31

• CT01.02 32

• CT04.07 33


References: 1

1. 38-WHO TRS 1004, Annex 9, 2017 2

2. 39- WHO TRS 987, Annex 2, 2014 3

3. 119- WHO TRS 987, Annex 2, 2014 4

Sub-Indicator: CT05.02: THE LIST OF THE CLINICAL TRIAL (APPROVED AND 5

REJECTED APPLICATIONS), INCLUDING SUMMARIZED EVALUATION 6

REPORTS BY THE NRA, ARE PUBLICLY AVAILABLE OR RECORDED IN A 7

DOMESTIC OR INTERNATIONAL DATABASE 8

Scope: All 9

Maturity: 4 10

Requirement: 11

Publication of approved and rejected CT applications as well as CT evaluation reports 12

Rationale: 13

The objective of this sub-indicator is to assure approved and rejected CT applications, as well as 14 summarized CT evaluation reports are listed and published in local and international database. 15

Description: 16

The assessor should verify the regulation and / or guidelines or similar documents that dictate that all CT 17 applications either approved or rejected should be listed together summaries of the evaluation in domestic 18 or international database, and should be publically available should be in existence, enacted and 19 implemented. The regulation should be supported with guidelines that provide guidance on the 20 information to be listed as well as the content, format and information that should go into the summary 21 evaluation report that would be made available to the public. The guidelines should provide guidance on 22 the database to the used (i.e., local, international, type of hosting organization, other) as well as the 23 mechanism for updating the database. 24



1. Regulations and/or guidelines requiring that all approved and rejected CT applications, as well as 27 summary evaluation reports should be listed and available for easy access in local and international 28 database. 29

2. Regulations/ guidelines requiring that the list of all approved and rejected CT applications, as 30 well as summary evaluation reports should be updated periodically. 31

3. The rate (when and how) to update the list. 32

4. The list of approved and rejected CT applications, as well as summary evaluation reports on the 33 local and international database. 34

WHO global benchmarking tool rev. VI ver. 1, CT 5. Guidelines and / or SOPs that provide guidance on the content, format and information that 1 should be uploaded to the database. 2

6. Evidence that stakeholders are aware of the availability of the list, and have clear understanding 3 of where to source the list and the content of the list. 4

Framework: 5

Output 6

Rating Scale: 7

NI: There is no list of clinical trials (approved and rejected applications), including summarized 8 evaluation reports by the NRA, publicly available or recorded in a domestic or international database. 9

OI: There is a draft procedure to publish the list of clinical trials (approved and rejected applications), 10 including summarized evaluation reports by the NRA, however it is not yet published. 11

PI: There is a list of clinical trials (approved and rejected applications), including summarized evaluation 12 reports by the NRA, and it is publicly available or recorded in a domestic or international database; 13 however, it is not updated or it was published less than two years. 14

I: There is an updated list of clinical trials (approved and rejected applications), including summarized 15 evaluation reports by the NRA, publicly available or recorded in a domestic or international database. 16



• CT06.01 19

References: 20

1. 38-WHO TRS 1004, Annex 9, 2017 21

2. 39- WHO TRS 987, Annex 2, 2014 22

3. 119- WHO TRS 987, Annex 2, 2014 23

Indicator: CT06 MECHANISM IN PLACE TO MONITOR 24

REGULATORY PERFORMANCE AND OUTPUT. 25

Rationale: 26

The objective of this sub-indicator is to assure mechanisms are in place to monitor and ensure that all CT 27 activities are subjected to quality controls (QC) and other checks to reduce errors and to rationally ensure 28 that the processes, as well as the results at the various stages of the CT application processing flow are 29 consistent in order to generate an assured output. 30

The activities include: receipt of CT applications, acknowledgement of applications, 31 process/evaluation/assessment of the various parts of the applications, generation of recommendations 32 after evaluation/assessment process, approval/deferral/rejection of applications, issuance of certificates, 33 publication and making publicly available the approved or rejected applications together with summary 34 evaluation reports. 35


This would lead to consistency in the regulatory performance of the CT function as well as reliable 1 outputs. 2

Category: Monitoring progress and assessing outcomes & impact 3

Sub-Indicator: CT06.01: THERE IS AN INTERNAL LIST/DATABASE OF ALL 4

APPROVED AND REJECTED CTS, AND THE NRA MAINTAINS A RECORD OF 5

EACH APPROVED AND REJECTED CT 6

Scope: All 7

Maturity: 3 8

Requirement: 9

Internal list/ database for all CT applications 10

Rationale: 11

The objective of this sub-indicator is to assure an internal list /database is kept for all approved and 12 rejected CT applications and that the NRA / responsible regulatory authority (ies) maintain a record of all 13 approved and rejected CTs. 14

Description: 15

The assessor should note that the register /list/ database where all approved or rejected CT applications 16 are entered should be established and constantly updated and maintained to reflect the current situation. 17 The establishment and maintenance of the register and / or database should be supported by guidelines 18 and /or SOPs. It should also provide guidance on the content, format and type of information to enter and 19 maintain in the database and when and how to update the register or database. In addition, guidance on 20 who should be given access to the stored information should clearly be documented. 21


The assessor should request for and review 23

1. The guidelines requesting the establishment and maintenance of a register/list/ database of 24 approved or rejected CT applications. 25

2. The register/list /database of all CT applications that have been approved or rejected, and the type 26 of information was kept, as well as entered. 27

3. Persons with the authority to access stored information as well as the documentation to complete 28 before access is granted. 29

Framework: 30

Output 31

Rating Scale: 32

NI: There is not an internal list/database of all approved and rejected CTs. 33

OI: There is a drafted procedure to create an internal list/database however the list/ database does not 34 exist. 35

WHO global benchmarking tool rev. VI ver. 1, CT PI: There is an internal list/database of all approved and rejected CTs, and the NRA maintains a record of 1 each approved and rejected CT; however, it is not up to date and all applications are not reflected. 2

I: There is an updated internal list/database of all approved and rejected CTs, and the NRA maintains 3 records of each approved and rejected CT for more than two years. 4



• CT05.02 7

References: 8

1. 38-WHO TRS 1004, Annex 9, 2017 9

2. 39- WHO TRS 987, Annex 2, 2014 10

3. 119- WHO TRS 987, Annex 2, 2014 11

Sub-Indicator: CT06.02: PERFORMANCE INDICATORS FOR THE CLINICAL 12

TRIAL OVERSIGHT ACTIVITIES ARE ESTABLISHED AND IMPLEMENTED 13

Scope: All 14

Maturity: 4 15

Requirement: 16

Performance indicators for CTO activities 17

Rationale: 18

The objective of this sub-indicator is to assure performance indicators are documented and implemented 19 for all activities along the entire CTO chain. 20

Description: 21

The assessor should verify that the system stating performance indicators for CTO activities is established 22 and implemented. It should provide performance indicators along the entire CTO activity chain, and 23 adequately justify each and every indicator. The guidelines should be supported by SOPs/tools that would 24 be used to monitor and evaluate the performance indicators, and provide guidance on when and how to 25 revise /review the indicators. 26



1. The tool/ systems in place to monitor and evaluate the indicator. 29

2. The performance of CTO activities for the last three years, such as the annual inspection plan and 30 the GCP inspections conducted annually. The action taken by the NRA on the report of the GCP 31 inspections. 32

Framework: 33



Rating Scale: 2

NI: There is no defined performance indicators for the clinical trial oversight activities. 3

OI: There is a draft document to define performance indicators for the clinical trial oversight activities but 4 it is not followed. 5

PI: The performance indicators for the clinical trial oversight activities are defined and documented 6 however there is no systematic approach for evaluation and follow up with the result of that. 7

I: The performance indicators for the clinical trial oversight activities are established and implemented 8 and documented and a systematic approach in place to monitor and evaluate the indicator. 9



References: 12

1. 38-WHO TRS 1004, Annex 9, 2017 13

2. 39- WHO TRS 987, Annex 2, 2014 14

3. 119- WHO TRS 987, Annex 2, 2014 15

Sub-Indicator: CT06.03: PROGRESS REPORT FROM SPONSORS OR CLINICAL 16

RESEARCH ORGANIZATIONS (CROs) DURING AND AFTER CLINICAL TRIALS 17

SENT TO AND SHARED BETWEEN NRAs AND ETHICS COMMITTEES. 18

Scope: All 19

Maturity: 3 20

Requirement: 21

Accessibility and availability of feedback from stakeholders 22

Rationale: 23

The objective of this sub-indicator is to assure a progress reporting and documentation system is in place 24 to receive, store and disseminate reports from sponsors or clinical research organizations (CROS). 25

Description: 26

The assessor should verify that the mechanism to receive, store and disseminate information received 27 from stakeholders during and after CTs should be established and implemented. The mechanism should 28 be supported with guideline that states that feedback reports along the entire CT chain should be sent by 29 the sponsor and/or CROs periodically to the NRAs and ECs and documented by the NRAs and ECs. The 30 guidelines should provide guidance on the content and format for preparing the reports, as well as the 31 procedure for submitting the report for storage. In addition, SOPs should provide guidance on the how to 32 review, summarize and store the reports received. The database where reports are kept should be 33 documented. 34

WHO global benchmarking tool rev. VI ver. 1, CT Evidence to review: 1

The assessor should request for and review 2

1. The guidelines that stipulate that feedback reports along the entire CT chain should be sent by the 3 sponsor and/or CROs to the NRAs/ECs periodically and documented by the NRAs/ ECs. 4

2. Guidelines on the content and format for preparing the reports, as well as the procedure for 5 submitting the report. 6

3. Documented list of reports received from sponsors / CROs, as well as the content and format for 7 compliance 8

4. Records of reports from sponsors / CROs. 9

5. The database /data storage facility where the reports are stored. 10

Framework: 11

Process 12

Rating Scale: 13

NI: There is no feedback mechanism and progress report between sponsors or clinical research 14 organizations (CROs) and NRAs/ethics committees during and after clinical trials. 15

OI: There is a draft guideline to define feedback mechanism and send progress reports from sponsors or 16 clinical research organizations (CROs) during and after clinical trials to NRAs/ethics committees; 17 however, it is not followed. 18

PI: There is a feedback mechanism and progress reporting from sponsors or clinical research 19 organizations (CROs) during and after clinical trials to NRAs/ethics committees, however all reports are 20 not available. 21

I: There is a feedback mechanism and progress reporting from sponsors or clinical research organizations 22 (CROs) during and after clinical trials to NRAs/ethics committees established for more than two years 23 and is supported with adequate documentation, guidelines and records. 24



References: 27

1. 38-WHO TRS 1004, Annex 9, 2017 28

2. 39- WHO TRS 987, Annex 2, 2014 29

3. 119- WHO TRS 987, Annex 2, 2014 30

Sub-Indicator: CT06.04: THERE ARE TIMELINES FOR THE ASSESSMENT OF CT 31

APPLICATIONS AND AN INTERNAL TRACKING SYSTEM TO FOLLOW THE 32

TARGETED TIME FRAMES 33

Scope: All 34


Maturity: 3 1

Requirement: 2

Availability of timelines and check to monitor processing of CT applications 3

Rationale: 4

The objective of this sub-indicator is to assure timelines exist for processing CT applications, and there 5 are internal systems or mechanisms to monitor CT applications processing for compliance with the 6 timelines. 7

Description: 8

The assessor should verify that documented timelines and internal timeline tracking systems that guides 9 the CT application processing are established and implemented. It should be supported by guidelines 10 requiring that CT applications should be processed/assessed per a published timelines that should be 11 monitored internally for compliance. The guidelines should be supported with SOPs that provide 12 guidance on how to establish the timelines and how to monitor the established timelines. It should be 13 designed to adapt to the routine and non-routine CT applications (e.g. public health emergencies). In 14 addition, it should be designed to address each stage of the CT application process flow. The timelines 15 should be known by all stakeholders for the purposes of transparency and trust. 16



1. The guidelines that stipulate that CT applications should be processed / assessed per the 19 prescribed timelines. 20

2. Regulations establishing that timelines for CT application assessment should be internally 21 monitored for compliance with published timelines. 22

3. The timelines for CT application assessment, and the internal tracking system for the timelines 23 for effectiveness 24

4. Sample report from the internal tracking system for CT application assessment for content as well 25 as CT application assessment compliance. 26

5. The work schedule /work plan for staff responsible for monitoring timelines. 27

Framework: 28

Process 29

Rating Scale: 30

NI: There is no defined timelines for the assessment of CT applications and an internal tracking system to 31 follow the targeted time frames. 32

OI: There is a drafted timelines and an internal tracking system to follow the targeted time frames for the 33 assessment of CT; however, it is not followed. 34

PI: The timelines for the assessment of CT applications are defined; however, the internal tracking system 35 to follow the targeted time frames has not been fully documented. 36

WHO global benchmarking tool rev. VI ver. 1, CT I: The timelines for the assessment of CT applications and an internal tracking system to follow the 1 targeted time frames is implemented for more than two years. 2



References: 5

1. 38-WHO TRS 1004, Annex 9, 2017 6

2. 39- WHO TRS 987, Annex 2, 2014 7

3. 119- WHO TRS 987, Annex 2, 2014 8

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