Upload
others
View
1
Download
0
Embed Size (px)
Citation preview
“CONFIDENTIAL AND PROPRIETARY Any use of this
material without specific permission of Janssen is strictly
prohibited.”
Considerations for Implementation ofContinuous Manufacturing (CM) in a Legacy Product
Quality Systems Management, General Regulatory Aspects, and Relevant Terminology
FDA/PQRI ConferenceMarch 22, 2017
Gilfredo Navarro – RPh, MSAssociate Director - CMC Regulatory Affairs
Janssen Research and DevelopmentGuaynabo, Puerto Rico
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Presentation Topics
•Quality Systems•QA Organization•Training
Quality Systems Management
•Communications with Regulatory Agencies•Initial/Preliminary Meetings (Agency Facilities)•Courtesy/Pre-Operational Visits (Company Facilities)•Pre-Approval Inspections (PAI)
General Regulatory Aspects
Relevant Terminology
•Definitions & Clarifications
3
Quality Systems Management Quality Systems
•Quality Agreements•Complaints•Change Control (CC)•Annual Product Review (APR)•CAPA
NOT-IMPACTED Quality Systems
•It can be impacted based on batch definition.
Product Disposition / Batch Release
Release Data Strategy
•Data input from CM line to LIMS
•Data Review and Approval (QC)
Batch Record Review
•Batch Record review on a daily basis for GMP Compliance. A concept of Real Time Batch Record Review might be established .
•Expedites the process at the end of the batch since only last day manufacturing is pending for review
Investigation
•More investigational elements to consider (PAT , CM, RTRt, etc.)
Stability Strategy
•Make sure data is obtained with the same methods
•Re-assess methods, if there is a formulation change
Product Specification
•RTR testing (Assay, UDU, ID) + Conventional Testing (Dissolution, Appearance, etc.)
•Conventional Testing (Stability, Investigations, Complaints, Chemometric Models Maintenance)
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
•Material attributes were suitable for CM process without limits modifications
•Raw Materials did not require changes in specifications
NOT-IMPACTED Material Specifications
4
Quality Systems Management Quality Systems
Product Specification Strategy
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Test Batch Process CM Process/PAT
Assay 1 Analytical Test for the Batch 1 NIR/Chemometric Test per QH/Drum (RTRt)
UDU 1 Analytical Test for the Batch: Weight Variation
1 NIR/Chemometric Test per QH/Drum: Content Uniformity (RTRt)
ID 1 Analytical Test for the Batch 1 NIR/Chemometric Test per QH/Drum (RTRt)
Dissolution 1 Analytical Test for the Batch 3 Analytical Tests for the Run: Beginning/Middle/End
Appearance 1 Analytical Test for the Batch 1 Analytical Test for the Batch
CM Process/PAT enables more tests to be performed real-time leading to higher Quality Assurance
RTRt & Conventional Testing Strategy
5
Quality Systems Management Quality Systems
Product Specification Strategy
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Moving to Complete RTRt Strategy
Test Batch Process(No RTRt)
CM Process(RTRt)
Identity Lab: HPLC Line: RTRt (PAT/NIR)
CU Lab: HPLC Line: RTRt (PAT/NIR)
Assay Lab: HPLC Line: RTRt (PAT/NIR)
Dissolution Lab: HPLC Line: RTRt (Surrogate Method)
Appearance Lab: Visual Line: RTRt (Visual)
6
Quality Systems Management QA Organization
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Main Resources
Don’t under estimate QA resources required for CM Implementation
7
Quality Systems Management Training
Training Strategy: Training Matrix
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Audience Content Duration
Technical Operations & QA Auditors
- Project Overview-Detailed PAT, RTRt, CM Concepts
(CBT & Room Training) 3 hrs
Management- Project Overview
-General PAT, RTRt, CM Concepts(CBT & Room Training)
2 hr
Operations(Production)
- Project Overview-Intro PAT, RTRt, CM Concepts
(Room Training, On-the-Job Training)3 hr
Exempt Colleagues (Non Technical Personnel)
- Project Overview-General PAT, RTRt, CM Concepts
(CBT)2 hr
QC - Project Overview
-General PAT, RTRt, CM Concepts(Room Training)
1.5 hr
CM / PAT / RTRt
• SOPs• Forms• Job Aids• Protocols• Batch Records
Operations (Production)
• SOPs• Forms• Protocols• Batch Records
Technical Operations
• SOPs• Forms• Protocols• Batch Records
Quality Assurance
• SOPs• Forms• Protocols• Batch Records
Automation
Functional Areas
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Presentation Topics
•Quality Systems•QA Organization•Training
Quality Systems Management
•Communications with Regulatory Agencies•Initial/Preliminary Meetings (Agency Facilities)•Courtesy/Pre-Operational Visits (Company Facilities)•Pre-Approval Inspections (PAI)
General Regulatory Aspects
Relevant Terminology
•Definitions & Clarifications
9
General Regulatory Aspects Communications
Regulatory Agency
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Communications with Regulatory Agencies are essential to establish a Partnering Relationship
Courtesy Meetings/POV
Submission
PAI
ApprovalPost Approval Feedback Meetings
Initial/Preliminary Meetings
MEETINGS WITH REGULATORY AGENCIES
Key Activities
10
General Regulatory Aspects Meetings/Inspections
Key Points
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Initial-Preliminary / Type C Meetings
• Project Overview• Biowaiver Agreements• Sampling Strategy (Sample Size and Frequency)• Control Strategies
• Provide the Regulatory Agency the opportunity to visit the facilities and see the equipment
• Further expand on control strategy, sampling strategy, and other relevant topics
• Offer the setting for the Regulatory Agency to preliminarily preview the available documentation
Courtesy Meetings/Pre-Operational Visit
11
General Regulatory Aspects Meetings/Inspections
Key Points
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Pre-Approval Inspection
• Demonstrate company competencies on: –Systems/Equipment Qualifications–Process Understanding, Robustness, and Efficiency–Documentation Completeness–People Qualifications–Quality Systems Readiness
• Prove to the Regulatory Agency the suitability of the control strategy, sampling strategy, and other relevant topics
• Provide the Regulatory Agency the opportunity to see the equipment running and processing of a batch
Post Approval Meeting
• Results/Key Points from previous meetings
• Learnings to be applied for the next CM product
• What areas would FDA have liked to spend more time
“CONFIDENTIAL AND PROPRIETARY Any use of this material
without specific permission of Janssen is strictly prohibited.”
Presentation Topics
•Quality Systems•QA Organization•Training
Quality Systems Management
•Communications with Regulatory Agencies•Initial/Preliminary Meetings (Agency Facilities)•Courtesy/Pre-Operational Visits (Company Facilities)•Pre-Approval Inspections (PAI)
General Regulatory Aspects
Relevant Terminology
•Definitions & Clarifications
13
Relevant Terminology
“CONFIDENTIAL AND PROPRIETARY Any use of
this material without specific permission of Janssen
is strictly prohibited.”
Acronyms
RTRt Real Time Release testing
RTBR Real Time Batch Release
RTRR Real Time Record Review
RTNC Real Time Non Conformance
Material is continuously transferred from one operation to the other
Does not mean the batch is run without planned and/or unplanned interruptions
CMProcessing time of the continuous material feeding operation allowing for more accurate material reconciliation (includes startup and state of control)
Does not include equipment pauses when CM line is not processing material
Runtime
RTRt
RTRRRTNC
rTBR can be OK when translating
to OTBR
OTBR On Time Batch Release
rTBR reduced Time Batch Release
15
Q & A
16
Continuous Manufacturing Line Process Overview
“CONFIDENTIAL AND PROPRIETARY Any use of
this material without specific permission of Janssen
is strictly prohibited.”
17
Continuous Manufacturing A Transformation in Manufacturing Capability
Extremely consistent Product Quality Results
Control Strategy: Real Time Release testing – reduces
testing cycle time
More flexible operation: production can be adjusted
based on orders
Cycle Time Reduced from Batch Process Reduction in Footprint
Reduced Development Requirements (no scale-up/scale-down needed)
Continuous Manufacturing Realized Benefits
“CONFIDENTIAL AND PROPRIETARY Any use of
this material without specific permission of Janssen
is strictly prohibited.”