21
FDA/EMA INSPECTION READINESS ANTICIPATE AND BE READY FOR GROWING REGULATORY EXPECTATIONS IN EARLY PHASE CLINICAL TRIALS ANNICK VAN RIEL

FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

  • Upload
    sgs

  • View
    161

  • Download
    0

Embed Size (px)

Citation preview

Page 1: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

FDA/EMA INSPECTION READINESS ANTICIPATE AND BE READY FOR GROWING

REGULATORY EXPECTATIONS IN EARLY PHASE

CLINICAL TRIALS

ANNICK VAN RIEL

Page 2: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

2 SGS BIOPHARMA DAY – OCTOBER 25, 2016

FDA – EMA GCP INSPECTIONS CHALLENGES

GCP inspection

Clinical inspection of registration trials submitted in support

of marketing application of new drug products, to ensure

data integrity

subject’s safety

Challenges

Globalisation of clinical trials - same trials used to support

• Marketing Authorization Application (MAA) to EMA

• New Drug Application (NDA) and Biologics License Application

(BLA) to FDA

Page 3: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

3 SGS BIOPHARMA DAY – OCTOBER 25, 2016

FDA – EMA GCP INSPECTIONS SIMILARITIES AND DIFFERENCES 1/2

Topic FDA EMA

General BIMO program - since 1977

Routine (80%) ~ NDA

For cause (20%) ~ IND

GCP inspections since 1997

Routine

Triggered

GCP FDA CDER Title 21 CFR parts

11/50/54/58/312/314

Less details vs ICH GCP

ICH Topic E6

Directive 2005/28/EC

Clinical Trial Directive 2001/20/EC

Local requirements

Announcement Announced / unannounced Formal announcement letter

Preparation Inspection plan

documents from application dossier

Central / local inspection plan

Site to provide documents

Conduct Data reliability/subject protection

Systems / processes to obtain data

/ ensure subject protection

Page 4: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

4 SGS BIOPHARMA DAY – OCTOBER 25, 2016

FDA – EMA GCP INSPECTIONS SIMILARITIES AND DIFFERENCES 2/2

Topic FDA EMA

Reporting Closing meeting

Observations in 483

General classification

(NAI – VAI – OAI)

Negative inspection

- rejection of data

- Disqualification of investigator

Closing meeting

no written summary

Grading per finding (critical, major,

minor)

Negative inspection

-Negative opinion

-Rejection of data

-Restrictions on SPC

-Refusal MAA

NAI (No action indicated) – VAI (Voluntary action indicated) – OIA (Official action indicated)

Page 5: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

5 SGS BIOPHARMA DAY – OCTOBER 25, 2016

FDA – EMA GCP INSPECTIONS JOINT INSPECTIONS BECOMING ‘STANDARD’

More ‘joint’ inspections FDA + EMA

Identify gaps in processes

Expand outside US / EU

Focus sponsors and CRO as well as sites

Focus on triggered inspections

More ‘parallel’ inspections with exchange of inspection

reports

* Report on the Pilot EMA-FDA GCP initiative, September 2009 – March 2011 (EXT/INS/GCP/56289/2011)

Page 6: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

6 SGS BIOPHARMA DAY – OCTOBER 25, 2016

ICH E6 (R2) - HOT TOPICS REFLECTING RECENT GCP INSPECTION FINDINGS 1/2

Sponsor Risk Management at the core of Quality

To implement for QMS and Monitoring

To incorporate risk science, ALCOA communication, record

keeping

Risk based monitoring

Closing the loop of significant non-compliance

Identification / Root cause analysis / correction and

prevention

Human Factor Analysis

Oversight by investigators

Delegation oversight

Quality and control at all times of data and documents

provided to sponsor

Page 7: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

7 SGS BIOPHARMA DAY – OCTOBER 25, 2016

ICH E6 (R2) – HOT TOPICS REFLECTING RECENT GCP INSPECTION FINDINGS 2/2

Technology

Paper access control, data perenniality and ALCOA at the

basis

Validity, longevity, fidelity of data

Standard processes to avoid that real-time data influence trial

outcomes early in the process

Control by site of the generated data

Vendor oversight by sponsor

Sponsor oversight of tasks delegated to CROs

CRO to ensure transparency of data and tasks

Final guideline by November 2016

Page 8: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

8 SGS BIOPHARMA DAY – OCTOBER 25, 2016

EU CLINICAL TRIAL REGULATION 563/2014 CLINICAL RESEARCH WITH HIGH PATIENT SAFETY

What’s New?

No more national interpretation of Directive

Single trial application covering all EU countries involved

SUSAR reporting coordinated across EU

Predictable application timelines

Transparent clinical trial reporting

Flexibility in TMF content and monitoring

Trial registration in database

• prior to start (<-> FDA : 21 days after FPFV)

• Phase I registration (<-> FDA : exempted)

• US trials to adhere

Applicable in 2017/2018

Page 9: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

9 SGS BIOPHARMA DAY – OCTOBER 25, 2016

HOW CAN WE BE PREPARED ?

Page 10: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

10 SGS BIOPHARMA DAY – OCTOBER 25, 2016

INSPECTION READINESS A CULTURE OF COMPLIANCE

Inspection readiness as “STATE OF BEING”

not as preparation activity

Management as active participant in a commitment to a

“Culture of Compliance”

Quality Management / Control

Digital solutions for data, document and quality

management

eSource, CTMS, eTMF, QMS…

Routine internal audits

Page 11: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

11 SGS BIOPHARMA DAY – OCTOBER 25, 2016

CASE STUDY CPU QUALITY CONTROL - PURPOSE

Continuous Quality Improvement

Quality Data Collection performed according to

Protocol

ICH-GCP, GDP and local regulations

SOP / WI

Risk assessment

Management enforcement

Page 12: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

12 SGS BIOPHARMA DAY – OCTOBER 25, 2016

CASE STUDY CPU QUALITY CONTROL - APPROACH

Plan

Objectives / processes

Do

Implementation

Check

Monitor / evaluate

testing the results against

objectives

Act

Apply actions necessary for

improvement if the results

require changes

Shewart Cycle (WE Deming)

Page 13: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

13 SGS BIOPHARMA DAY – OCTOBER 25, 2016

CASE STUDY CPU QUALITY CONTROL - PROCESS

A NEW DIRECTION

100% QC defining Critical QC Check Points

“Spot check” activity

Based on Risk Analysis

Against GCP / GDP / protocol

Electronic + manual

Cross – functional

Daily/weekly/Monthly

Protocol Related Guidelines

Ice ECG rechecks Drug screen Centrifuge setting …

GCP

Documentation

Version control signatures corrections empty fields black pen …

GDP

Page 14: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

14 SGS BIOPHARMA DAY – OCTOBER 25, 2016

CASE STUDY CPU QUALITY CONTROL – SPOT CHECKS

IQC SPOT CHECK

TACTILE approach

OFFICE

Set-up IF

Signature process All docs present

FLOOR

Screening, pre-dose – Dosing FU – Samples – Lab –

Pharmacy

Drug screen ECG – ICF

Prescription Log Centrifuge settings…

PROCESS approach

DAY -1 to Day 2 24h post-dose

Predose – Dosing FU – Samples – Lab

Pharmacy

Drug screen ECG – ICF

Prescription Log Centrifuge settings…

Predefined # studies – randomly identified

Page 15: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

15 SGS BIOPHARMA DAY – OCTOBER 25, 2016

CASE STUDY CPU QUALITY CONTROL – ELECTRONIC QC

100% sampling and review

What Why Function Frequency

OOR values GCP PI Weekly

Time between ECG GCP CTN Monthly

Eligibility GCP PI Daily

Events pre-dose GCP PI Weekly

Heights GDP CTN / CLT / TOA Monthly

Lab centrifuge setting GCP CLT Monthly

Lab storage in time GCP CLT Monthly

Rescreening of a volunteer GDP RSO Monthly

Time on paper source same as in eSource GDP CTN / CLT / TOA Monthly

Page 16: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

16 SGS BIOPHARMA DAY – OCTOBER 25, 2016

CASE STUDY CPU QUALITY CONTROL – TRENDING

Page 17: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

17 SGS BIOPHARMA DAY – OCTOBER 25, 2016

CASE STUDY CPU QUALITY CONTROL - REPORTING

Reporting tool

Monthly QC meetings / minutes / actions

Actions ~ Root Cause Analysis / CAPA

Management commitment

Who Responsibility

Team lead GCP related actions / evidence

Management Team GDP related actions / evidence

IQC Collection of EVIDENCE

Senior Management GCP and GDP TRENDING

Outcome: Spot checks linked to risk modus

Page 18: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

18 SGS BIOPHARMA DAY – OCTOBER 25, 2016

CONCLUSION QUALITY COMPLIANCE LEADS TO INSPECTION READINESS

Spot check

Manual QC

Electronic QC

Management

accountability

Trending

CULTURE OF COMPLIANCE

Page 19: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

19 SGS BIOPHARMA DAY – OCTOBER 25, 2016

Life Sciences van Riel Annick

Director CPU Antwerpen

SGS Phone:: + 32 (0) 3 217 25 60

Clinical pharmacology Unit Antwerpen Fax: + 32 (0) 3 217 25 81

Lange Beeldekensstraat 267 E-mail : [email protected]

B 2060 Antwerpen

BELGIUM Web : www.sgs.com/lifescience

THANK YOU FOR YOUR ATTENTION

+ 41 22 739 9548

+ 1 866 SGS 5003

+ 65 637 90 111

+ 33 1 53 78 18 79

+ 1 877 677 2667

+ 33 1 41 24 87 87

Page 20: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

20 SGS BIOPHARMA DAY – OCTOBER 25, 2016

QUESTIONS ?

Page 21: FDA/EMA Inspection - Regulatory Expectations in Early Phase Clinical Trials

21 SGS BIOPHARMA DAY – OCTOBER 25, 2016