Clinical Trials & Regulatory

Transcription

1 Clinical Trials & Regulatory Infrastructures t MENA Raeda Mustafa, B.Sc.Pharm., MBA, CCRA, CCRC/ Molecule CRO Updates to ICH GCP E6 (R2) and BE Studies 3rd MENA Regulatory Conference on Bioequivalence, Biowaivers, Bioanalysis and Dissolution in Amman (Jordan).

2 ICH Formal Process 2

3 BE Studies Each BE Study would be inspected as 4 parts: 1 General Section 2 Clinical Section 3 Bio analytical Section 4 Pk / Statistics and Reporting 3

4 What is ICH GCP E6 Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects 4

5 What ICH GCP E6 is about? 5

6 ICH GCP and BE Studies ICHGCPis applied through: 1 General Section 2 Clinical Section 3 Bio analytical Section 4 Pk / Statistics and Reporting 6

7 ICH GCP Sections ICHGCPis composed of 8 sections: 1 Glossary 2 Principles of GCP 3 IRB 4 Investigator 5 Sponsor 7

8 ICH GCP Sections 6 Protocol & Protocol Amendments 7 IB 8 Essential Documents 8

9 Why updated? Dramatic Changes to Clinical Research environment (Scale, Complexity and Cost). Evolution in Technology. Evolution in RM Processes. Inspections Findings! 9

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11 MHRA GCPInspectionsReport 11

12 EMA GCP Inspections Report 12

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14 Why is it important? 1 Risk Management at the core of Quality. 2 Closing the loop of significant noncompliance. 3 Technology with ihpaper as golden inspiration. i i 4 Oversight by Investigators. 5 Requirement for sponsors to demonstrate oversight ihtof tasks dl delegated tdto CROs

15 What is it? Section 1: Glossary 15

16 What is it? Section 1: Glossary 16

17 Section 2: GCP Principles Sub section # Was Is 2.10 All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification. This principle applies to all records referenced in this guideline, irrespective of the type of media used. 17

18 Section 2: GCP Principles Sub section # Was Is 2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented. Systems with procedures that assure the quality of every aspect of the trial should be implemented. Aspects of the trial that are essential to ensure human subject protection and reliability of trial results should be the focus of such systems. 18

19 Section 3: IRB 19

20 Section 4: Investigator 20

21 Investigator Oversight Enhanced oversight requirements over team and 3 rd Parties. Mi Maintain i quality and Control 21

22 Investigator Oversight Ensuring sufficient PI oversight and involvement in different practice models Establish consistent communications infrastructure Schedule research meetings to be attended by the PI, Sub I and study staff Maintain PI s oversight oesgtand involvement e tby having him/her receive updated and consistent information on the trial and patient status 22

23 Investigator Oversight Have documented SOPs/guidelines to dictate and regulate PI oversight and involvement Require PI to confirm subject eligibility for a trial by signing off on inclusion/exclusion criteria and randomization lists in each subject s s source documents Require PI to sign all lab results and assess AE causality for each study subject. 23

24 Investigator Oversight Further, the PI must ensure any party performing study tasks is qualified and must implement procedures to ensure the integrity of study tasks and data. 24

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26 Section 4: Investigator 26

27 Section 5: Sponsor 27

28 Section 5: Sponsor 28

29 Section 5: Sponsor 29

30 Section 5: Sponsor 30

31 Quality Management Quality Management: QA+QC QA: focused on providing confidence that quality requirements are fulfilled QC: focused on fulfilling quality requirements 31

32 Quality Management Quality Management must be commensurate with the Company business objectives and business model. Top management commitment and active involvement are critical in order to ensure at all times the adequacy, suitability, effectiveness and efficiency of the quality systems. 32

33 TheTwo Two level QualityManagement Organizational level: Organizational structure (management, tasks, responsibilities) Resources, trainings SOPs: Authorities submission, i study planning, investigator assessment, etc Internal audits Host external audits/inspections 33

34 TheTwo Two level QualityManagement Study/Project level: ICH GCP requires study processes/traceability/documentation at different stages: 34

35 TheTwo Two level QualityManagement Such questions should ldbe answered via process and documentation: Study design: Is the trial design appropriate? Can the trial answer the proposed research question or will the data be equivocal, e.g. adequate statistical power? etc. Study performance: Is the trial performed according to approved protocol? Do subjects give informed consent freely? 35

36 Quality by Design (QbD) What needs to change? How do Sponsors need to change? 36

37 Quality by Design (QbD) What needs to change? How do Sponsors / CROS need to change? All quality and compliance efforts are geared at ensuring: 1 Subjects safety & integrity and protection of their rights. 2. Integrity of data collected in a trial to avoid false rejection or acceptance of the study hypothesis 37

38 Quality by Design (QbD) What needs to change? How do Sponsors need to change? 3. Compliance with the laws & Regulations 4. Acceptance of deviations / non conformities that do not impact on the above 3 objectives 5. A strict & predefined planning process followed when developing a protocol and setting up the trial 38

39 Quality by Design (QbD) What needs to change? How do Sponsors need to change? 6. A suite of meaningful and objective KRI and KPI is used to measure quality performance 7. Objective criteria are developed to trigger on site monitoring or audit activities, respectively 39

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41 Section 5: Sponsor Sub section # Was Is Any trial related duty and function that is transferred to and assumed by a CRO should be specified in writing. Any trial related duty and function that is transferred to and assumed by a CRO should be specified in writing. The sponsor should ensure oversight of any trial related duties and functions carried out on its behalf, including trial related duties and functions that are subcontracted to another party by the sponsor s contracted CRO(s). 41

42 Section 5: Sponsor Sub section # Was Is (a) When using electronic trial data handling and/or remote electronic trialdatasystems, the sponsor should: (a) Ensure and document that the electronic data processing system(s) conforms to the sponsor s established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e. validation). The sponsor should base their approach to validation of such systems on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human subject protection and reliability of trial results. 42

43 Section 5: Sponsor Sub section # Was Is (b) When using electronic trial data handling and/or remote electronic trialdata systems, the sponsor should: (b) Maintains SOPs for using these systems. The SOPs should cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use. 43

44 CSV Inventory for all computerized systems with version control. For Each computerized system one or SOP to Cover: System Installation System Operation System Administration [Covering Security and Maintenance] 44

45 CSV Company policy for validation/testing against the above SOPs Company policy for disaster recover and business continuity Company policy for electronic data retention, and backup Backup & Recovery testing. 45

46 GAMP 5 According to Gamp5 maintenance includes: 1 Backup/Recovery 2 Issue Management 3 Service Agreement(s) 4 Training 5 Security & Preventive Maintenance 6 Business Continuity 7 Data Retention 8 Retirement Plan 9 Configuration Management / Change Control 10 Performance Management 46

47 Section 5: Sponsor 47

48 Section 5: Sponsor

49 Section 5: Sponsor

50 Risk Based Monitoring 50

51 Risk Based Monitoring An adaptive approach to clinical trial monitoring that directs monitoring focus and activities to the evolving areas of greatest need which have the most potential to impact subject safety and data quality. 51

52 The Adaptive Design 52

53 Qualityand and Integrity of Data: Factors Well designed protocol DMP study specific Mix of centralized and on site monitoring practices ecrfs or CRFs Study objectives Critical data Patient safety Qualified and trained Investigators, staff, and monitors 53

54 Critical Data and Processes Data supporting primary and secondary objectives Data critical to subject safety: SAEs and events leading to treatment discontinuation Data critical to trial design and statistical endpoints Adherence to eligibility Informed Consent process, prior to any study related procedures Documentation of administration of investigational agent or treatment procedures 54

55 Section 5: Sponsor (e) 55

56 Section 5: Sponsor

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58 Monitoring Plan Monitoring plans should emphasize critical data and processes, giving a rationale for their selection. Applicable policies and procedures are to be referred to in support of the plan. Note: Inadequate justification of monitoring sampling plans has been the recent cause of many inspection findings. 58

59 Section 5: Sponsor Sub section # Was Is Noncompliance with the protocol, SOPs, GCP, and/or applicable regulatory requirement(s) by an investigator/institution, or by member(s) () of the sponsor's staff should lead to prompt action by the sponsor to secure compliance. If noncompliance that significantly affects or has the potential to significantly sg tyaffect human subject protection or reliability of trial results is discovered, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. 59

60 Section 8: Essential Documents 60

61 Requirements of a Certified Copy True copy Paper / Electronic Verified against the original Proof of verification Examples: Stamped (signed and Dated) 61

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