Translating a QbD PFS into Tangible Value for Biopharmaceuticals

A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
Translating a QbD PFS
into
Tangible Value for Biopharmaceuticals
Friedrich Haefele, PhD
VP Biopharma Fill & Finish
Boehringer Ingelheim Pharma GmbH & Co. KG
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Content
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Visual Inspection of Parenterals
Trending VI Results for PFS - Main defects
TCO Approach for PFS
BD NeopakTM Quality Attributes
Summary
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
Visual Inspection of Parenterals
Critical? – Major
Defect
22% of Recalls
Warning letters
Visibility:
50μ/ 100μ/150μ/200μ???
Route of administration
iv/ sc
Continuous Improvement
100% Inspection
Trending
Safety risk?- GMP issue
Process Capability
Pharmaceutical Industry/Component vendors
Alignment of GMP systems
PhEur/USP: Essentially free of particles
USP 790
AQL 0.65%
Extrinsic/Intrinsic/Inherent
Visible/Subvisible
Particles
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PFS- Trending Visual Inspection Results
Main defects (May2011 – July2014)
CAPAs implemented
for HypakTM Dec. 2012
Start
NeopakTM
Implemented CAPAs reduced the particle load of HypakTM syringes significantly
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
PFS- Trending Visual Inspection Results
Main defects
Trend data & investigations indicate that black particles and other defects related to
the barrel manufacturing process contribute to increased reject rates (“main defects”)
Deep scratches
Inner adherence
Particles
Chip / Check
Broken flange
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Post CAPA Lots/Implementation of NeopakTM
Start
NeopakTM
Triggered by defects
type
“stain outside”
0,404% correspond to 283
Syringes (Lot size 70.000)
0,044% correspond to 31 Syringes
(Lot size 70.000)
Hypak process after CAPA implementation:
Neopak process (current available data):
approx. 0,40% are rejected due the “main defects”*)
approx. 0,04% are rejected due the “main defects”
*) assumed that the total reject peak (lot 125 to 129) does not represent the process capability of Hypak TM process (outlier)
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
TCO approach for PFS based on savings
on operational cost and risk management
Indirect Cost Savings of PFS per Unit
Operational Costs Savings
Risk Management Costs Savings
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Reduced Costs of Preventable Waste (breakage &
defects)
-Form (i.e., syringes vs. drug)
-Reason (i.e., cosmetic, breakage, dead-space,…)
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Reduced Costs of Preventable Complaints
- Administrative costs
- Brand / collateral damage
2
Reduced Costs of Preventable Downtime
- Costs of corrective action
- Opportunity costs
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Reduced Cost of Preventable Recalls
- Opportunity costs
- Administrative costs
- Brand / collateral damage
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Reduced Costs of Preventable QA inspection
- Incoming inspection
- Deviation / Manual inspection
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Reduced Costs of Preventable Development Delays
(only for new drugs)
- Opportunity costs
- Reduced development costs
Direct Cost Premium of PFS per Unit
=
Value of PFS per Unit
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Increased Reject rates => increased TCO
Operational Costs
Rejects/batch
Reduction of Scrap rate
Preventable
CAPA Inspection
Failure investigations
HypakTM: average 780;
NeopakTM:
31
96%
max. 3.192
99%
2 x 100% Inspection
Investigation in filling,
visual inspection, logistics
Microscopy/
EDX analysis
Lab investigation/
Incoming inspection
Risk management costs
Intercompany complaints
Root cause investigation
Market complaints
Root cause investigation
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
Value Modelling for BD NeopakTM
Biopharma legacy drug, 25$/filled PFS: 96% less rejects
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Value of BD NeopakTM
Biopharma legacy drug, 75$/filled PFS: 96% less rejects
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
Value of BD NeopakTM
Biopharma pipeline drug 25$/filled PFS: 96% less rejects
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Key TCO Drivers for Biopharmaceuticals
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Costs of the API
Costs related to scrap and reject
Costs related to complaint management
Costs associated with incoming inspections
Potential development delays (legacy or pipeline drug?)
• Assessment of value of intangible factors like avoidance of
manufacturing and commercial risks
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
BD NeopakTM -Quality Attributes
Attribute
BD Hypak™
BD Hypak™ for Biotech
BD Neopak™
Production Model
Process Environment
High unit volume
production equipment
Standard environment
High unit volume production
equipment modified for biotech needs
Standard environment
Minimized glass to glass contact
Line Type
Standard Line
Certificate Type
Specification Approach
Inspection / Controls
Increased Compatibility w/ AI
COC
AQL approach
Standard
Forming to assembly,
indexed transfer
COC
AQL approach
Additional IPCs
Customized production equipment
designed for biotech needs
Controlled environment
No glass-to-glass contact
Nothing in barrel
New fully indexed line
(including washer)
COA
PPM approach
Focus on 100% controls
N/A
IPC
100% controls
Broken flange – AQL 0.15
N/A
≥40 N – AQL 0.010
LUF 74.85 +/- 0.85mm (AQL)
0.4 mg or 0.8 mg
≥50 N – 3.4ppm (dev tgt)
LUF 74.85 +/- 0.85mm (Cpk)
< 0.4 mg
N/A
Low tungsten 500 ppb max.
Low tungsten 500 ppb max.
Ultra-low tungsten option at 50 ppb max.
N/A
Semi-indexed
Indexed
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Glide Force /
Silicone Distribution
Flange Resistance
Injection Depth
Silicone Level
Minimize Protein Interaction
Reduced Tungsten
Reduce Cosmetic Defect Level
Process handling
Pre-inspected glass canes
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BD NeopakTM - Autoinjector Compatibility
Breakage Resistance
Reducing occurrence of defects
Bubbles
Scratches
Crush resistance
Cracks
• Improved glass quality
• No glass to glass contact
• Automated visual controls
Reducing energy applied
Flange Resistance
• Optimized design
• Residual Stress specification
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
BD NeopakTM - Autoinjector Compatibility
Injection Time
Gliding Force
g
Optimized Gliding
b ti
• Optimized silicone distribution
• Optimized silicone layer thickness
State-of-the-art Needle Technology
• Optimized drug flow
• Optimized comfort Manage injection time
(reduce variability)
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BD NeopakTM - Autoinjector Compatibility
Dimensional Precision and Reduced RNS Pull-Off Force
Dimensional Capabilities
• Right injection depth : LUF & LUS
• Optimized assembly : Barrel run-out,RNS concentricity
RNS Removal Force
• Tighter Specification on RNS Pull-off force
• Rubber material, design consideration, silicone
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
Conclusion for Biopharmaceuticals
Why to choose NeopakTM….
Continuous Improvement of our Biotech products
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Re-designed manufacturing process
Focus on 100%-controls
Improved Autoinjector compatibility
Reduced TCO (scrap rate, 2x 100%inspections, failure
investigations, complaints)
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Summary
¾ Persistent Quality Feedback
¾ Multi Company Approach
PDA Task Force
¾ Supplier Regulatory Support
Translate a QbD PFS
into
Tangible Value for
Biopharmaceuticals
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A4: Partnership Approaches Along Drug Life Cycle
to Improve Patient Outcomes
Presented by:
Friedrich Haefele, PhD
Thank you for yor your attention
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