1. The EMA Inspection Process
Procedures, Timelines & Expectations
Presented by
Vaska Toné

2.  TYPES OF INSPECTIONS
 EMA DEFINITIONS & PROCEDURES
 EMA INSPECTION TIMELINES
 EMA INSPECTION PREPARATION
 DOSSIER REQUEST
 SITE SELECTION
 INSPECTION SELECTION
 INSPECTION PROCESSES
GCP Inspections
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3. GCP Inspections
 Systems Inspections
● Look at all relevant SYSTEMS for CTIMPs
o CTIMP = Clinical Trial of Investigational Medicinal Product
● Check that the expected process is used in practice
 Study Specific Inspections
● Carefully review the study data
● Is it real, reliable and trustworthy?
● Reduced reliance on interviews
● But site staff will/may be interviewed
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4. Inspection Reason
Mainly based on questions raised by assessors
reviewing the submitted dossier
But can be caused by intelligence obtained relating to
potential problems within clinical trials
EMA has no inspectors – they “subcontract” inspecting
to the individual member states to perform the inspection
according to the EMA SOPs
Each member state has its own inspectorate and
inspects in its own territory independently
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5. EMA Definitions
 Reporting Inspectorate (RI)
● The inspectorate member state designated by the EMA to
manage the inspection and timelines and writing the Integrated
Inspection Report
 Reporting Inspector
● The Inspector at the RI with responsibility for the inspection
 Lead Inspector (LI)
● The inspector leading the conduct of an inspection and writing
the Inspection Report. The LI is based in the member state
where the inspection is performed
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6. EMA Definitions
 Inspection Report (IR)
● The report produced after each site inspection by the Lead
Inspector. Should responses not be provided in the expected
timeframe this fact is documented in the report by the LI.
 Integrated Inspection Report (IIR)
● Prepared by the RI based on each of the IRs for the whole
inspection. Contains an evaulation of the quality of the data and
GCP compliance. Signed by all LIs who have written IRs for the
overall inspection. Includes recommendations for follow-up and
further inspections
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7. EMA Inspections
 EMA has no inspectors – they “subcontract” inspecting
to the individual EU member states to perform the
inspection according to the EMA SOPs
 Each member state has its own inspectorate and
inspects in its own territory independently
 All EMA procedures are documented and in the public
domain
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8. EMA Procedures
 All EMA procedures are documented and in the public
domain
 Located on the EMA website under:
o EMA Home Regulatory → Human Medicines → Inspections →
GCP Compliance → Inspections Procedure
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulatio
 This documents all the EMA SOPs relating to GCP
inspection processes
 Each SOP can be opened and is readable
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9. EMA Procedures
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10. EMA Procedures
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11. EMA Timelines
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12. Dossier
 Dossier request – usually 30 days prior to inspection
• Can be very helpful to get to know your own company better and for
QA to be “In the Loop”
• Takes a long time to complete with participation of many
departments
• Listing of systems in use for the trials and those outsourced
• List of trials taken place over a period of years
• Plan – inspector prepares with input from the inspectee
• Studies are pre-selected by the inspectors
• Generally more than one study selected
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13. Dossier
 Dossier Details: There are 2 sections that need to be
completed:
• Section 1 has 6 required items to be provided:
• Item 1: Organizational Charts
• Item 2: List of Clinical Trial Processes (SOPs, etc)
• Item 3: Adverse Event Reporting Systems & Procedures
• Item 4: List of Computer Systems & Validation Status
• Item 5: For non-commercial organizations only
• Item 6: List of clinical trials (use the provided spreadsheet)
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14. Dossier
 Section 2 has 3 items:
• Item 1 & 2:
Names and addresses of all facilities involved in the
clinical trials, including:
o Vendors (i.e. labs, drug depots)
o CROs (full scope, niche i.e.: DM, Stats, Safety)
o Support services (readers: ECG, CT/MRI/Bone
Scan imaging, etc)
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15. Dossier
 Section 2 has 3 items:
• Item 3:
Summary information of your organization’s clinical trial
systems (info on 1 side of paper for each department)
1. Contract and Agreement Preparation
2. Quality System (including training)
3. Clinical Quality Assurance
4. Project Management
5. Clinical Trial Monitoring
6. Pharmacovigilance (including medical expertise)
7. Regulatory Affairs
8. Computer Systems
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16. Dossier
 Item 3 continued:
9. Investigational Medicinal Products (IMP)
10. Data Management & Statistics
11. Clinical Trial Reporting
12. Trial Master File
13. Archiving
14. Clinical Facilities
15. Laboratories
16. Equipment Maintenance
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17. Investigator Site Selection
EMA
• Can be selected by the EMA or the assessors of the
data depending on the information and intelligence held
about each investigator site
• The inspectors may add in more or change the
investigator sites after review of the data
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18. Inspection Process
• Usually site inspection AFTER the Sponsor/CRO
inspection but NOT always
• If the Inspection is based on a marketing application,
more emphasis will be placed on data credibility and
assurance that data exists and is true at the site
• Less interview, more data review
• CRA should be present to provide assistance to the
inspectors
• Documents may be requested during the inspection
(requested using a request form)
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19. Inspection Topics
 System inspections
• Look at any issues seen in monitoring visit reports
• Issues with safety, data or site knowledge of GCP or the protocol
• Not always the highest recruiter
 Study Inspections
• Depends on the issues that the assessor has noted within the
submitted dossier
• It may be an issue relating to credibility of site data
• It may be a company data management issue
• The investigator site provides the data so are key inspection
areas for both types of inspection
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20. Inspector Selection
• Two member states present if EMA requested, the host
member state plus one other member state
• The lead inspector will contact the site to arrange the
dates for the inspection
• But the dates need to be acceptable to both member
states attending the inspection
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21. General Inspection Process
• Review of documentation and interview with staff
members
• Interviews can be by video/telecon if necessary
• Documents will be requested using a request form
• Further unannounced studies can be requested
• Review of areas where the research is managed
• Inspectors can go “off-plan” if there is a need
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22. On Site Inspection Conduct
• Inspection hours – from 9am to 5pm but can be longer if
necessary
• Opening meeting – to explain the purpose of the
inspection
• Inspected company provides a SHORT relevant
presentation to the inspectors
• Have ALL requested documentation ready from the
beginning
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23. Expectations & Close Out
• Document review sessions – leave the inspectors alone
unless they request assistance
• Don’t offer more info than necessary – if TMF is paper
leave it at that, if you have online access to it, the inspector
will want the same
• Inspectors closed meeting to collate findings and prepare
for closing
• Closing meeting
o to provide the observations noted and the grading of
those observations
o to inform inspectee of the selected investigator sites
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24. Any Questions?
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25. LaVaPharm Consulting
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Vaska Tone
President & CEO
LaVaPharm Consulting LLC
Email: vaska.tone@lavapharm.com
US Office Phone: +1-951-240-5635
European Office: +389-75-417-417