introducing an innovative advanced aseptic filling ... · introducing an innovative, advanced...
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Introducing an Innovative, Advanced Aseptic Filling Technology to a New Manufacturing Facility
PDA Europe Current Trends in Aseptic Fill & Finish of Pre-filled SyringesLindau | 26. - 27. April 2017
Dr. Aidan HarringtonDPS Engineering
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• Introducing New Manufacturing Technologies – Perceived Barriers to Entry
• Current State of Advanced Aseptic Processing
• Our Business Case and Progress to Date
Agenda
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“Large corporations welcome innovation and
individualism in the same way the dinosaurs
welcomed large meteors.”
Scott Adams aka Dilbert
Barriers to Innovation
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‘Despite increasing recalls, contamination events, and
shortages, drug companies continue to rely on outdated
manufacturing plants and processes’
W. Nicholson Price II, Making Do in Making Drugs: Innovation Policy and Pharmaceutical Manufacturing 55 B.C.L. Rev. 491 (2014), http://lawdigitalcommons.bc.edu/bclr/vol55/iss2/5
Current State
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‘Desired State: A maximally efficient, agile, flexible
pharmaceutical sector that reliably produces drug products
without extensive regulatory oversight’
Ashley Boam, FDA Acting Director Office of Policy for Pharmaceutical Quality – FDA/PDA Joint Regulatory Conference, Sept 2015.
Desired State
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Barriers to Innovation
Reluctant
or
Frustrated
Innovators?
Innate Conservatism
Lack of Process Understanding
If it’s not broken….no issues from last audit
Perceived Regulatory Hurdles
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Regulatory Support
FDA Draft
Guidance
for Industry
Advancement of Emerging Technology Applications to
Modernize the Pharmaceutical Manufacturing Base, Dec.
2015
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Advanced Aseptic Processing
‘An Advanced Aseptic Process is one in
which direct intervention with open
product containers or exposed product
contact surfaces by operators wearing
conventional cleanroom garments is not
required and never permitted’
Akers, J, Agalloco, J, Madsen, R. What is Advanced Aseptic Processing? Pharm. Manuf. 2006: 4(2) 25 – 27.
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What are we seeing?
• Isolator technology is almost exclusively the pathway
• RABS becoming limited to debagging and capping operations
• Enhanced sterility assurance thanks to aseptic transfer systems and use of single‐use technologies
Isolators…. Isolators…. Isolators
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Market Projections
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What we are seeing?
Growth in personalized medicines
Lot sizes range from 50 – 500 vials
Need for very rapid turnaround
Micro Lot Sizes
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Reliable Robotics
Minimal Handling, Minimal Damage
Simple to use Components
Gloveless
Flexible
Minimal Environmental Monitoring
Fast Turnaround – high OEE
Supplier CQV that works for all
Where
do we
need to
go?
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Business Case/Drivers for New AP Facility
De‐Risk the Supply Chain
Low Volume, High Value Products
Advanced Aseptic Technology
Flexible, Agile, Reduced Cycle Times – Vials / Cartridges / Syringes
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Vanrx SA25 Aseptic Filling Workcell
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Slide Title
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Technical Due Diligence
Specific Closure
Requirements – Availability
VHP Technology & Robustness
Challenge of operating
without gloves – corrective interventions
Viable and Non – Viable EM
Media Fill Data
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Sterility Assurance with Advancing Technologies
Significantly Increased
Sterility Assurance
• Conventional A/B arrangement
• Isolator with gloves
Contamination Risks
• Restricted Access Barrier •Operator interventions•Glove integrity failure
•Operator interventions •Material transfer
•Operator interventions•Glove integrity failure
Enhanced Sterility
Assurance
•Remove the Operator
•Remove the Gloves
• Isolator with no gloves
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Gloves and Regulations
The transfer of materials into and out of the
unit is one of the greatest
potential sources of contamination
– Annex 1
A program to minimize the risk
of loss of integrity of
gloves, sleeves and suits should be present –
PICS
A faulty glove or sleeve assembly represents a route of
contamination and a critical breach of
isolator integrity ‐ FDA
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Gloves
How Risky are Pinholes in
Gloves?
A Rational Appeal for the
Integrity of Gloves for
Isolators
Gessler, A. ; Stark, A.; Sigwarth, S. & Moirandt, C. PDA J. Pharm Sci and Tech 2011 65: 227‐241
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EM
ProposalOptions:
By removing operator interventions and removing gloves, the biggest risk to sterility failure is removed.
By removing operator interventions and removing gloves, conventional environmental monitoring is not possible.
Re‐engineer the system by additional robotic arms or adding gloves.
Provide an alternative to conventional environmental monitoring which is at least equivalent to the convention
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Regulatory Feedback
While acknowledging the step change in Aseptic Control, a form of EM is warranted during the
Critical operation
EM – New Technologies
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Regulatory Expectation
Article 23
of Directive
2001/83/EC
‘…the authorization holder must, in respect of the
methods of manufacturing and control…take account of
scientific and technical progress’
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Regulatory Feedback
• EM – New Technologies• Not necessarily settle plates
• NVP Monitoring is useful – but viables behave in a completely different way
• Consequence of equipment failure• Ability to clean system prior to VHP
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Conclusion
Successful collaboration between vendor / user / regulatory authorities
This (Advanced)2 Aseptic Processing platform has the potential to deliver to the lean, flexible and agile desired state
Open your mind
We’re almost there !
Dr. Aidan HarringtonSenior Consultant DPS [email protected]
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Acknowledgements