Considerations for Implementation of Continuous Manufacturing (CM) in Legacy Products
Eric J. Sanchez-Rolon, MS Director Advanced Technologies CoE, Janssen Supply Chain “CONFIDENTIAL AND PROPRIETARY Any use of this
material without specific permission of Janssen is strictly
prohibited.”
ConceptualizationJanssen supply chain works with Rutgers and UPRM ERC –SOPS defining the technological framework toward a commercial CM line
DesignLine design, line location and facility preparation at Janssen Supply Chain facility at Gurabo, PR
2010-12 2012-132008-12
Construction and CommissioningFacility construction started, equipment installation and qualification period
OUR Journey to CONTINUOUS MANUFACTURING
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Process Development at RutgersWith ERC SOPS support at Rutgers university and UPRM, Janssen Scientist performed the feasibilities studies that provided the knowledge base for further development activities at Janssen facility
Technology TransferEquipment qualification completed line ready for process development and registration lot manufacture
2014 End of 20142013
Registration Batch ManufacturingJanssen manufactured the registration batch for Prezista 600 mg Tablets at the Continuous Manufacturing Line
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Process Development, Control Strategy and Dossier Filling2015 was a heavy year for us, we were able to complete the Development studies, perform our process confirmation batch, complete the dossier required documentation and submit the sNDA to the FDA
2015
APPROVALOn April 2016 Janssen received approval of the Prezista 600 mg Tablet Continuous Manufacturing Process sNDA for commercial distribution of product manufactured at the CM Line
20162016-2017
and beyond
CM GrowthCommercial production started on Prezista, Second and Third product development and technology transfer started, line full capacity usage by 2018
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BUILDING ON THE CONTINUOUS MANUFACTURING TRANSFORMATION OF LEGACY PRODUCTS
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Operations Driven Research: The Batch to Continuous Transformation Process
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Criticality analysis and
risks evaluation
Process design and Feasibility
Analysis
PAT Development and Process Development
Confirmation and Automation
Process Performance
Qualification and Launch
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Operations Driven Research: Criticality analysis and Risk Evaluation
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PhaseRequirement.
Ref.#CQA CPP/CA HAZARD
Se
ve
rity
Cause of the failure
modeRisk Control mechanisms (RCM's)
ID Number critical aspect
(system code + CA000)
Pro
ba
bilit
y
Detection mechanisms
De
tec
tab
ilit
y
Ris
k P
rio
rity
Nu
mb
er
Acceptance
criteria of critical
aspect to be
confirmed at
Interim Release/
acceptance and
release
action plan comments
CQA impacted
by the hazard
CPP impacted by
the failure mode
Potential source
of harm to
patient or
product quality
How the hazard will occur in the
process step
What can cause the
failure mode
What prevents the failure mode
from occurring
(procedural / documentation
feature to prevent the failure mode
from occurring; ex., SOP,
calibration, training)
ID Number critical aspect
(system code + CA000)
What detects a Failure/Hazard
(Visual Inspection of Components via Operator While
in Production, analytical testing, in-process checks,
alarm or other indication from a monitoring device)
Tableting PPU - 033 AppearancePunches
installation
Incorrect
embossing5 Wrong Punches Installation Operator mistake
Training program
Procedure of UseTabletting - CA001 2
Use SOP and training Verification
Double Check before each manufacturing run1 10 Y - BA
The procedure
must indicate how
to correctly install
the punches.
The procedure
must include a
double check of
the correct
installation of the
punches before
starting the run
Wrong orientation of the
punchesCorrect orientation verification Tabletting - CA002 2
Verification by chiavetta of the correct orientation of the
punches1 10 Y - BA
The system must
not permit to install
punches with a
wrong orientation
Operator mistake IPC Tabletting - CA003 2 IPC - Visual check of the embossing on tablets 1 10 Y - BA
The IPC Visual
Check of the right
embossing must
be in place
Tableting PPU - 034 Appearance
Final
Compression
Force
Tablet visual
defects5 Wrong Final Compression Force
Value not controlled,
displayed
The system visualize and control the
CPPTabletting - CA004 3
The CPP is regulated, continuously adjusted, visualized
and recorded1 15 Y - BA
System must
regulate, adjust
according to actual
value, visualize
and record the
CPP (range and
accuracy to be
defined)
Out of production limits Alarm set on high and low value Tabletting - CA005 3 Alarm (warning and alarm levels) 1 15 Y - BA
Warning and alarm
thresholds should
be foreseen for the
H and L limits of
the CPP.
Out of production limitsReject system for granules if the CPP
out of rangeTabletting - CA006 3 Reject System 1 15 Y - BA
The machine must
reject the tablets if
the CPP is out of
specification
Wrong value measuredCalibration Program
(Control System)Tabletting - CA007 2 Periodical Calibration Checks 1 10 Y - BA
The first calibration
of the CPP control
system must be
done by the vendor
and the certificates
must be available.
The CPP control
system must be
included in the
calibration
program
Failure mode
Ris
k c
on
tro
lle
d t
o
ap
pro
pri
ate
le
ve
l (Y
/N)
CQA: Appearence
Risk Evaluation
FMEA
Criticality Matrix
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Operations Driven Research: Process Design and Feasibility
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this material without specific permission of Janssen
is strictly prohibited.”
9
Operations Driven Research: PAT Development and Process Development
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is strictly prohibited.”
10
Operations Driven Research: Process Confirmation and Automaton
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ProcessWaste
Distributed Control System PCS7 provides tracking system for waste, and good product formation and traceability
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Operations Driven Research: Process Performance Qualification and Launch
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Accepta
nce
Criteria:
RSD of all individuals ≤6.0% (n=60) = actual 0.6 %
Each location mean is within 90.0% - 100.0% of target potency,
and individuals are within 75.0% and 125.0% of target potency. =
actual 99 to 101.7 %
Typical control of Tables Content Uniformity Data for a Continuous Manufacturing Batch
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QUESTIONS?
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