oct 2015 prosys sampling - mmcl · 06/10/2015 20 unit 1 unit 1 ––––sectional plansectional...
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ProSys Containment
ISOLATOR CONTAINMENT TECHNOLOGY FOR THE MANUFACTURE OF
ANTIBODY DRUG CONJUGATES (ADCS)
OCTOBER 2015
Pharmaceutical Market in Transition
Targeted Drug Therapies (Personalised Treatment)
◦ Mabs, (Monoclonal Antibodies)
◦ ADCs, (Antibody Drug Conjugates)
◦ CART (Chimeric Antigen Receptor T) Cell Immunotherapy
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ADC IN ACTION !
� ADC Monoclonal antibody (mAb) + cell-killing cytotoxic drug
� mAb Delivery system which selectively targets the tumour cells
It has high binding specificity for tumour-specific antigens
� Once in the tumour, the ADC releases its cytotoxic payload by chemical or enzymatic processes, eventually leading to the death of the targeted cell
Components of ADC
COURTESY: (GENENTECH INC., 2015)
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Clinical Landscape of ADCs
COURTESY: ROSTAMI, S., I. QAZI, AND R. SIKORSKI, THE CLINICAL LANDSCAPE OF
ANTIBODYDRUG CONJUGATES. ADC REVIEW. AUGUST 1, 2014.
Isolator Definition
A separative device that provides assured protection by using physical
and dynamic barriers to create separation between operation
(product) and operator/exterior environment.
Containment Aseptic
Operator protection Product protection
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Containment Performance Target (CPT) & Occupational Exposure Limit (OEL)
CPT measured in ‘ µg/m³ or ng/m³@’ at 8 hours Time weighted average (TWA)
CPT= Containment capacity in terms of airborne concentration (µg/m3) of the isolator based on the OEL of the compound/API to be handled
OEL = Airborne concentration of a compound/API to which nearly all workers can be repeatedly be exposed 8 hours a day, 40 hours a week, without adverse effects.
ADC projects Customer Location : Cambridge, USATarget CPT : ≤10ng/cubmAchieved CPT: ≤5ng/cubm
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ADC projects Customer Location : California, USATarget CPT : 10 nanogram/cubm
MSB Isolator
Achieved CPT: 8ng/cubm
VSE Isolator
Achieved CPT: 10ng/cubm
CASE STUDYCASE STUDYCASE STUDYCASE STUDYCustomer Location : Dublin, IrelandTarget CPT : 50ng
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Project ObjectiveProject ObjectiveProject ObjectiveProject Objective
To develop a Production Suite for the contained manufacture of HPAI of an ADC
Project Drivers
EHS Achieve appropriate OEB 5 containment levels – less than
50ng/m3
EHS/GMP Prevent escape of airborne material from the suite or ingress
of material to the suite
GMP GMP improvements over existing cleanrooms (class and bio-
burden)
Production Maintain production during project execution
Concept Concept Concept Concept studystudystudystudy
2 processes:
� Lyophilisation of liquid API
� Lyophilisation of API Salt
Review existing process, equipment and SOP’s with production staff –decide what is sacrosanct and what can be changed.
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Process No.1 Process No.1 Process No.1 Process No.1 ----Lyophilisation of liquid API Lyophilisation of liquid API Lyophilisation of liquid API Lyophilisation of liquid API
Lyophilisation of liquid API Lyophilisation of liquid API Lyophilisation of liquid API Lyophilisation of liquid API
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Process No.2 Process No.2 Process No.2 Process No.2 ----Produce API Salt Produce API Salt Produce API Salt Produce API Salt
Produce API salt Produce API salt Produce API salt Produce API salt
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Key success factors for achieving Key success factors for achieving Key success factors for achieving Key success factors for achieving ng ng ng ng containment containment containment containment levelslevelslevelslevels
� Isolation technology
� Transfer technology
� Minimise number of transfers
� Minimise internal dust levels
� Perform transfers after cleaning where possible
� Effective cleaning
Key Equipment requirements to satisfy Key Equipment requirements to satisfy Key Equipment requirements to satisfy Key Equipment requirements to satisfy driversdriversdriversdrivers
� Separate units in independent rooms
� Achieve CPT of 50ng/m3
� Test in accordance with ISPE good practice guide
� Analyse results in accordance to EN 689
� Fit within available footprint (long and thin)
� Adhere to product registration –final package format
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Biggest isolator design challengesBiggest isolator design challengesBiggest isolator design challengesBiggest isolator design challenges
� Parallel development of isolator and process equipment
� Integration of 3rd party equipment (4 suppliers)
� Ergonomics
� Layout to provide logical process flow with minimum footprint
Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) ––––Design considerations Design considerations Design considerations Design considerations ----ergonomicsergonomicsergonomicsergonomics
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Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) ––––Design considerations Design considerations Design considerations Design considerations ----ErgonomicsErgonomicsErgonomicsErgonomics
Conclusion:
Integrate into isolator
base, accessed from
half-suit
Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) ––––design design design design considerations considerations considerations considerations ----ergonomicsergonomicsergonomicsergonomics
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Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) ––––design considerations design considerations design considerations design considerations ---- ergonomicsergonomicsergonomicsergonomics
Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) Isolator (unit 1) –––– design considerations design considerations design considerations design considerations ----ergonomics ergonomics ergonomics ergonomics
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Unit 1 Unit 1 Unit 1 Unit 1 ––––Concept Design LayoutConcept Design LayoutConcept Design LayoutConcept Design Layout
Unit 1 Unit 1 Unit 1 Unit 1 ––––Concept Design LayoutConcept Design LayoutConcept Design LayoutConcept Design Layout
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Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) ––––design considerations design considerations design considerations design considerations ----ergonomicsergonomicsergonomicsergonomics
� Non-hazardous dispensing outside isolator: Solids and liquids in VBE.
� Need Peristaltic Pump connections
Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) ––––design considerations design considerations design considerations design considerations ----ergonomicsergonomicsergonomicsergonomics
50 l vessels
� ergo issues similar to unit 1 mixing vessel
� 2 vessels require agitator and weigh cells
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Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) ––––design considerations design considerations design considerations design considerations ----ergonomicsergonomicsergonomicsergonomics
� Need to be able to inspect internals
� Need to be able to remove basket
� Need a filtrate receiver
Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) ––––design considerations design considerations design considerations design considerations ----ergonomicsergonomicsergonomicsergonomics
Conclusions:
� Access OK for door opening and tray loading
� Access not OK for cleaning and inspection
� Half-suit preferred
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Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) –––– design considerations design considerations design considerations design considerations ---- ergonomics ergonomics ergonomics ergonomics
Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) Isolator (unit 2) ––––design considerations design considerations design considerations design considerations ----ergonomicsergonomicsergonomicsergonomics
Same design as Unit 1
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Unit 2 Unit 2 Unit 2 Unit 2 ––––Concept Design LayoutConcept Design LayoutConcept Design LayoutConcept Design Layout
Unit 2 Unit 2 Unit 2 Unit 2 –––– Concept Design LayoutConcept Design LayoutConcept Design LayoutConcept Design Layout
Vessels Centrifuge
Sieve
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Post Procurement Post Procurement Post Procurement Post Procurement ––––detailed design phasedetailed design phasedetailed design phasedetailed design phase
� Initial GA / P&ID review
� Ergonomic review of physical model
� Design documents review –
◦ Design specification
◦ FDS
◦ Software design and testing
�Testing
P&ID P&ID P&ID P&ID ––––Unit 1Unit 1Unit 1Unit 1
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Ergonomic reviewErgonomic reviewErgonomic reviewErgonomic reviewSuccess factors:
� Involve people with good process knowledge
� Involve people of different heights
� Step through process, cleaning and maintenance
� Simulate activity durations
� Identify control element locations
� Use actual equipment or weights
� Use gloves and half-suits
� Take photos
� Take minutes and agree during review
97 design points minuted for unit 1
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Unit 1 Unit 1 Unit 1 Unit 1 ––––Sectional planSectional planSectional planSectional plan
Unit 1 Unit 1 Unit 1 Unit 1 ––––Sectional elevationSectional elevationSectional elevationSectional elevation
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Unit 2 Unit 2 Unit 2 Unit 2 ––––Sectional planSectional planSectional planSectional plan
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Unit 2 Unit 2 Unit 2 Unit 2 ––––Sectional elevationSectional elevationSectional elevationSectional elevation
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Factory TestingFactory TestingFactory TestingFactory Testing
� Get protocols signed off early
� Pre-FAT recommended
◦ 149 items on unit 1 punch list
� Ensure vendor has completed testing
� Allow time in your schedule
◦ Pre-FAT, FAT, remedial work, Re-FAT -8 wks
◦ Bespoke solutions
Factory Testing Factory Testing Factory Testing Factory Testing ----challengeschallengeschallengeschallenges� Started too early –schedule driven
� Design errors of minor components
◦ bespoke designs
�Leak rate tests
�Cleanroom recovery tests
�Vessel Weigh cells
�Vessel agitators interface
�Peristaltic pump interface
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Layout Layout Layout Layout
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Installation Installation Installation Installation ––––Unit 1Unit 1Unit 1Unit 1
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Installation Installation Installation Installation ––––Unit Unit Unit Unit 2222
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Surrogate Testing
� Conducting air sampling and surface sampling to determine how much dust escapes from the containment.
� The sampling results provide a means of estimating how effectively the equipment will contain the API under similar conditions of use.
�Evaluate containment performance without potential exposures to potent Active Pharmaceutical Ingredients (APIs)
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Surrogate Materials
Containment testing Containment testing Containment testing Containment testing ----SATSATSATSAT
CPT: 50ng/m3
Geometric mean target: <25ng/m3
Equipment accepted.
Further actions: Test during operation
Consider using worker activity multiplier if necessary
Note: Operational results with product may be higher or lower
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ScheduleScheduleScheduleSchedule
High pointsHigh pointsHigh pointsHigh points
� Met the goals
� Successful integration of third party equipment
� Use of 3D to interrogate design
� Ergonomics
� Project on budget and schedule
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Low PointsLow PointsLow PointsLow Points
� Integration of Weighing and pump control system
� FAT time
� SAT time
Thank You
Contact Details
Michael McLoughlin
Managing Director
Email: [email protected]
Tel: +353 (0)21 4853900
Web: www.prosys.ie
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ProSys Containment HQ, Ireland
Our Clients
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Our Vision Our Vision Our Vision Our Vision (purpose)(purpose)(purpose)(purpose)
Our Vision is to be the Preferred Supplier of Custom Containment Equipment to the Global Pharmaceutical Production
Industry
Strategy StatementStrategy StatementStrategy StatementStrategy Statement
To be the Preferred Supplier of Custom Containment Equipment to the Global Pharmaceutical Production Industry
by
Delivering High Quality Engineered Solutions
by
Providing a responsive, can-do service driven by a sense of urgency to exceed customer expectations
by
Leading innovation in Containment Technology
by
Developing lean agile processes across the organization
by
Keeping our Promises
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ProSys Core ValuesProSys Core ValuesProSys Core ValuesProSys Core Values
Customer Orientation
Innovation
Flexibility
Communication - Face to Face Interaction
Co-operation & Knowledge Sharing
Accountability
Cost Conscious