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"PAT" For "SOFT GELATIN CAPSULES" Manufacturing: Designing, In

Line Analyzing & Feedback Controlling © by Dr. Shivang Chaudhary
from QbD-Expert™

Article  in  Pharmaceutical Development and Technology · September 2017

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National Institute of Pharmaceutical Education and Research
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 Definition of

QTPP PAT FOR

SOFTGEL CAPSULE MANUFACTURING

PROCESS ANALYTICAL TECHNOLOGY FOR DESIGNING, ANALYZING & CONTROLLING
Determination of CMAs & CPPs OF SOFTGEL CAPSULE MANUFACTURING LINE
CQAs

Quality Risk
Assessment of
CMAs &
CPPs

DoE
& Development
of Design Space

PAT
&Development Designed & Developed by
of Feedback
Control system
SHIVANG CHAUDHARY
Chief Knowledge Officer (CKO) & Global Head Quality by Design at QbD Expert™
MS (Pharmaceutics), Ph.D. (Pharmaceutical Sciences), LSSMBB, EDMP (PM), PGDPL
Implementatn of www.facebook.com/QbDExpert www.linkedin.com/groups/8264051
Control  +91 -9904474045, +91-8866327899
Strategy  qbdexpert@gmail.com
 www.qbdexpert.com

© Created & Copyrighted by Shivang Chaudhary.

 What is PAT?

Definition of

QTPP

Determination of

CQAs

Process Analytical Technology (PAT)

Quality Risk
Assessment of
A System for-
CMAs & • Designing,
CPPs
• Analysing &
• Controlling Manufacturing
DoE
through Timely Measurements (i.e., during processing) of Critical Quality
& Development
of Design Space and Performance attributes of raw and in-process materials and
processes with the goal of ensuring final product quality.

PAT
&Development
of Feedback Note: Through PAT, Online Feedback Controlling System for each & individual CMAs &/or CPPs will be
Control system
developed through designing of controls by analysis at line/ on line/ in line analyser system

Implementatn of
Control
Strategy

© Created & Copyrighted by Shivang Chaudhary.

 IDENTIFICATION OF DESIGNING ANALYZING CONTROLLING
CRITICAL STEPs PHASE PHASE PHASE

Definition of

QTPP

Determination of

CQAs

Quality Risk
Assessment of
CMAs &
CPPs

DoE
& Development
of Design Space

PAT FILL MASS

PREPARATION
GELL MASS
PREPARATION
ENCAPSULATION OF FILL MASS INTO
FORMED GELATIN MASS
PRIMARY
DRYING
SECONDARY DRYING
&Development
of Feedback
Control system
A B C D E

CRITICAL PROCESSING STEPS

Implementatn of Risk Identification of Critical Material Attributes &/or Critical Processing Parameters
Control with respect to In-Process &/or Finished Product Critical Quality Attributes
Strategy

© Created & Copyrighted by Shivang Chaudhary.

 IDENTIFICATION OF DESIGNING ANALYZING CONTROLLING
CRITICAL STEPs PHASE PHASE PHASE

Definition of

QTPP
API / EXCIPIENT PURITY
analyzed by
At line UV/ HPLC/ GC,
On line LOD/ HMB or W/KF

API / EXCIPIENT PARTICLE

SIZE DISTRIBUTION
Determination of analyzed by At line Malvern TEMPERATURE &
Particle Size Analyzer
CQAs OR On Line
MOISTURE CONTENT of
RELATIVE HUMIDITY
by At Line Thermo-
Sieve Shaker Analysis hygrometer
GEL MASS by At line
HOMOGENEITY off FILL Toluene Distillation
analyzed by At line Method
UV/ HPLC system

SPECIFIC GRAVITY VISCOSITY of GEL MASS

Quality Risk by On line Brookfield
Assessment of Of fill material analyzed by
online Sp. Gravity bottle Viscometer
CMAs &
CPPs

DoE
& Development
of Design Space

RESIDUAL MOISTURE OF
PAT SEAL THICKNESS
by On line Digital Stage
CAPSULE FILL WEIGHT by
On Line Weight Variation &
FILLED CAPSULES
by At line Toluene
&Development Microscopy & Calipers Disintegration Testing
of Feedback Distillation Method
Control system
ONLINE VISUAL INSPECTION
for cleaning, polishing &
sorting of unfilled/ half
filled/ defective capsules

Implementatn of Risk Analysis of CMAs & CPPs with respect to CQAs at Lab Scale Developmental level
Control with IN LINE / ON LINE / AT LINE Analyzers for Prediction of Real Time Data &
Strategy For Designing of Control Strategies for Commercial Scale by DoE-MVDA

© Created & Copyrighted by Shivang Chaudhary.

 IDENTIFICATION OF DESIGNING ANALYZING CONTROLLING
CRITICAL STEPs PHASE PHASE PHASE

Definition of

QTPP
API / EXCIPIENT PURITY
analyzed by
In line Bruker FT-NIR

API / EXCIPIENT PARTICLE

SIZE DISTRIBUTION
analyzed by In line
Determination of TEMPERATURE &
Lasentec Focused Beam
CQAs Reflectance Measurement
(FBRM)
MOISTURE CONTENT of
RELATIVE HUMIDITY
by In Line Thermo-
GEL MASS by Inline Bruker/ hygrometer
MT FT_NIR System
HOMOGENEITY off FILL
analyzed by In Line
Bruketr FT_NIR VISCOSITY of GEL MASS
by In line Viscometer
SPECIFIC GRAVITY
Quality Risk SPECIFIC GRAVITY
Of FILL MATERIAL
Assessment of
analyzed by inline Of GEL MASS analyzed by
CMAs & hydrometer inline hydrometer

CPPs

DoE
& Development
of Design Space

RIBBON THICKNESS
by In line Digital HD
Microscopy & Video
Monitoring

PAT SEAL THICKNESS

by In line Digital HD
CAPSULE FILL WEIGHT
by In line Check Weigher
RESIDUAL MOISTURE OF
FILLED CAPSULES by In line
&Development Microscopy & Video based on Gravimetric
of Feedback Bruker FT-NIR
Monitoring EMFR System
Control system
DIAMETER SORTER for inline
CONTENT UNIFORMITY sorting of under/ overfill capsules
analyzed by In Line Bruker FT-NIR
COLOR SORTER for inline sorting of
defective capsules with air bubbles

Implementatn of Real Time Data Analysis at Scale UP-Exhibit Manufacturing Scale

Control by IN LINE analyzers with auto-sensors & Real time data comparison with Raw scale ON LINE / AT LINE data
Strategy For Finalization of Control Strategies for Commercial Scale

© Created & Copyrighted by Shivang Chaudhary.

 IDENTIFICATION OF DESIGNING ANALYZING CONTROLLING
CRITICAL STEPs PHASE PHASE PHASE

Definition of

QTPP

Determination of Auto-controlling of

CQAs TEMPERATURE &

RELATIVE HUMIDITY
Air Handling Unit
(AHU)

Quality Risk
Assessment of
CMAs &
CPPs

DoE
& Development
of Design Space

Auto Controlling of Auto Controlling of Auto-controlling of Auto-controlling of

PAT HOMOGENEITY off FILL
By adjusting Homogenizer
RIBBON THICKNESS
by adjusting Gap between
FILLED CAPSULE WEIGHT &
by adjusting
RESIDUAL MOISTURE
by adjusting
&Development Mixing Speed & spreader box & rotating Die Roller Speed, Drying Temperature
of Feedback Mixing Time cooling drum Rotating Drum Speed Drying Time
Control system
Auto controlling of
SEAL THICKNESS
by adjusting Gap
between Die Rollers

Implementatn of Application of Auto-controllers at Real Time Manufacturing Scale

Control For Continuously attaining Acceptable ranges of CMAs &/or CPPs to achieve desired CQAs
Strategy

© Created & Copyrighted by Shivang Chaudhary.

 Definition of

QTPP QUALITY MEANS DOING IT RIGHT

WHEN NO ONE IS LOOKING
Determination of

CQAs

Quality Risk
Assessment of
CMAs &
CPPs

DoE
& Development
of Design Space

PAT
&Development Created & Copyrighted by
of Feedback
Control system
SHIVANG CHAUDHARY
Chief Knowledge Officer (CKO) & Global Head Quality by Design at QbD Expert™
MS (Pharmaceutics), Ph.D. (Pharmaceutical Sciences), LSSMBB, EDMP (PM), PGDPL
Implementatn of www.facebook.com/QbDExpert www.linkedin.com/groups/8264051
Control  +91 -9904474045, +91-8866327899
Strategy  qbdexpert@gmail.com
 www.qbdexpert.com

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