Implementatn of

Control Strategy

PAT &Development

of Feedback Control system

DoE & Development of Design Space

Quality Risk Assessment of

CMAs & CPPs

Determination of CQAs

Definition of QTPP

© Created & Copyrighted by Shivang Chaudhary

SOFTGEL CAPSULE MANUFACTURING PROCESS ANALYTICAL TECHNOLOGY FOR DESIGNING, ANALYZING & CONTROLLING

CMAs & CPPs OF SOFTGEL CAPSULE MANUFACTURING LINE

SHIVANG CHAUDHARY

© Copyrighted by Shivang Chaudhary

Formulation Engineer (QbD/PAT System Developer & Implementer) MS (Pharmaceutics)- National Institute of Pharmaceutical Education & Research (NIPER), INDIA

PGD (Patents Law)- National academy of Legal Studies & Research (NALSAR), INDIA

+91 -9904474045, +91-7567297579 shivaniper@gmail.com

https://in.linkedin.com/in/shivangchaudhary

facebook.com/QbD.PAT.Pharmaceutical.Development

Presented by

PAT FOR

© Created & Copyrighted by Shivang Chaudhary

Implementatn of

Control Strategy

PAT &Development

of Feedback Control system

DoE & Development of Design Space

Quality Risk Assessment of

CMAs & CPPs

Determination of CQAs

Definition of QTPP

Process Analytical Technology (PAT) A System for- • Designing, • Analysing & • Controlling Manufacturing through Timely Measurements (i.e., during processing) of Critical Quality and Performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality. Note: Through PAT, Online Feedback Controlling System for each & individual CMAs &/or CPPs will be developed through designing of controls by analysis at line/ on line/ in line analyser system

What is PAT?

Implementatn of

Control Strategy

PAT &Development

of Feedback Control system

DoE & Development of Design Space

Quality Risk Assessment of

CMAs & CPPs

Determination of CQAs

Definition of QTPP

CONTROLLING PHASE

ANALYZING PHASE

DESIGNING PHASE

IDENTIFICATION OF CRITICAL STEPs

© Created & Copyrighted by Shivang Chaudhary

MEDICINE HOPPER

LUBRICATION

ROLLERS

SPREADER

BOX

MEDICINE PUMP

LUBRICATION

ROLLERS

DIE

ROLLER

DIE

ROLLER

INJECTION

WEDGE

SPREADER

BOX

COOLING

DRUM

COOLING

DRUM

CONVEYER ROLL

ME

LT

ING

JA

CK

ET

ME

LT

ING

JA

CK

ET

COOLING

FAN

COOLING

FAN

GELATIN

MIXER /MELTER

GELATIN PREPARATION DRUG MATERIAL

PREPARATION A

D

B

C

E

F

G

CRITICAL PROCESSING STEPS

METERING OF DRUG MATERIAL

RIBBON CUTTING

CAPSULE SEALING

NAPHTHA BATH WASHING

1 ° FLUID BED TUNNEL & 2° TRAY DRYING

SPREADING OF GELATIN

COOILING OF RIBBON

H

I

© Created & Copyrighted by Shivang Chaudhary

Implementatn of

Control Strategy

PAT &Development

of Feedback Control system

DoE & Development of Design Space

Quality Risk Assessment of

CMAs & CPPs

Determination of CQAs

Definition of QTPP

Risk Analysis of CMAs & CPPs with respect to CQAs at Raw Scale Developmental level by ON LINE / AT LINE Analyzers for Prediction of Real Time Data &

Designing of Control Strategies at Commercial Scale

CONTROLLING PHASE

ANALYZING PHASE

IDENTIFICATION OF CRITICAL STEPs

DESIGNING PHASE

MEDICINE HOPPER

LUBRICATION

ROLLERS

SPREADER

BOX

MEDICINE PUMP

LUBRICATION

ROLLERS

DIE

ROLLER

DIE

ROLLER

INJECTION

WEDGE

SPREADER

BOX

COOLING

DRUM

COOLING

DRUM

CONVEYER ROLL

ME

LT

ING

JA

CK

ET

ME

LT

ING

JA

CK

ET

COOLING

FAN

COOLING

FAN

GELATIN

MIXER /MELTER

TEMPERATURE &

RELATIVE HUMIDITY

by At Line Thermo-

hygrometer

API / EXCIPIENT PURITY

analyzed by

At line UV/ HPLC/ GC,

On line LOD/ HMB or W/KF

API / EXCIPIENT PARTICLE

SIZE DISTRIBUTION

analyzed by At line Malvern

Particle Size Analyzer

OR On Line

Sieve Shaker Analysis

HOMOGENEITY off FILL

analyzed by At line

UV/ HPLC system

CAPSULE FILL WEIGHT by

On Line Weight Variation &

Disintegration Testing

ONLINE VISUAL INSPECTION

for cleaning, polishing &

sorting of unfilled/ half

filled/ defective capsules

ONLINE GROUP

WEIGHT

CHECKING of

Filled Capsules

MOISTURE CONTENT of

GEL MASS by At line

Toluene Distillation

Method

RIBBON THICKNESS

by On line Digital Stage

Microscopy & Calipers

SEAL THICKNESS

by On line Digital Stage

Microscopy & Calipers

VISCOSITY of GEL MASS

by On line Brookfield

Viscometer SPECIFIC GRAVITY

Of fill material analyzed by

online Sp. Gravity bottle

RESIDUAL MOISTURE OF

FILLED CAPSULES

by At line Toluene

Distillation Method

© Created & Copyrighted by Shivang Chaudhary

IDENTIFICATION OF CRITICAL STEPs

Implementatn of

Control Strategy

PAT &Development

of Feedback Control system

DoE & Development of Design Space

Quality Risk Assessment of

CMAs & CPPs

Determination of CQAs

Definition of QTPP

Real Time Data Analysis at Scale UP-Exhibit Manufacturing Scale by IN LINE analyzers with auto-sensors & Real time data comparison with Raw scale data

for Finalization of Control Strategies at Commercial Scale

CONTROLLING PHASE

DESIGNING PHASE

ANALYZING PHASE

MEDICINE HOPPER

LUBRICATION

ROLLERS

SPREADER

BOX

MEDICINE PUMP

LUBRICATION

ROLLERS

DIE

ROLLER

DIE

ROLLER

INJECTION

WEDGE

SPREADER

BOX

COOLING

DRUM

COOLING

DRUM

CONVEYER ROLL

ME

LT

ING

JA

CK

ET

ME

LT

ING

JA

CK

ET

COOLING

FAN

COOLING

FAN

GELATIN

MIXER /MELTER

CONTENT UNIFORMITY

analyzed by In Line Bruker FT-NIR

TEMPERATURE &

RELATIVE HUMIDITY

by In Line Thermo-

hygrometer

API / EXCIPIENT PURITY

analyzed by

In line Bruker FT-NIR

API / EXCIPIENT PARTICLE

SIZE DISTRIBUTION

analyzed by In line

Lasentec Focused Beam

Reflectance Measurement

(FBRM)

HOMOGENEITY off FILL

analyzed by In Line

Bruketr FT_NIR

CAPSULE FILL WEIGHT

by In line Check Weigher

based on Gravimetric

EMFR System

DIAMETER SORTER for inline

sorting of under/ overfill capsules

MOISTURE CONTENT of

GEL MASS by Inline Bruker/

MT FT_NIR System

RIBBON THICKNESS

by In line Digital HD

Microscopy & Video

Monitoring

SEAL THICKNESS

by In line Digital HD

Microscopy & Video

Monitoring

VISCOSITY of GEL MASS

by In line Viscometer

SPECIFIC GRAVITY

Of FILL MATERIAL

analyzed by inline

hydrometer

SPECIFIC GRAVITY

Of GEL MASS analyzed by

inline hydrometer

COLOR SORTER for inline sorting of

defective capsules with air bubbles

RESIDUAL MOISTURE OF

FILLED CAPSULES by In line

Bruker FT-NIR

© Created & Copyrighted by Shivang Chaudhary

IDENTIFICATION OF CRITICAL STEPs

DESIGNING PHASE

Implementatn of

Control Strategy

PAT &Development

of Feedback Control system

DoE & Development of Design Space

Quality Risk Assessment of

CMAs & CPPs

Determination of CQAs

Definition of QTPP

Application of Auto-controllers at real time Manufacturing scale For Continuously attaining Acceptable ranges of CMAs & CPPs with respect to desired CQAs

A DEVELOPED PAT SYSTEM FOR CONTINUOS AUTOMATIC ANALYSING & CONTROLLING MANUFACTURING THROUGH TIMELY MEASUREMENTS OF CQA & CPPs WITH THE ULTIMATE GOAL OF CONSISTANTLY ENSURING FINISHED PRODUCT QUALITY AT REAL TIME COMMERCIAL SCALE

ANALYZING PHASE

CONTROLLING PHASE

MEDICINE HOPPER

LUBRICATION

ROLLERS

SPREADER

BOX

MEDICINE PUMP

LUBRICATION

ROLLERS

DIE

ROLLER

DIE

ROLLER

INJECTION

WEDGE

SPREADER

BOX

COOLING

DRUM

COOLING

DRUM

CONVEYER ROLL

ME

LT

ING

JA

CK

ET

ME

LT

ING

JA

CK

ET

COOLING

FAN

COOLING

FAN

GELATIN

MIXER /MELTER

Auto-controlling of

TEMPERATURE &

RELATIVE HUMIDITY

Air Handling Unit

(AHU)

Auto Controlling of

HOMOGENEITY off FILL

By adjusting Homogenizer

Mixing Speed &

Mixing Time

Auto-controlling of

FILLED CAPSULE WEIGHT &

by adjusting

Die Roller Speed,

Rotating Drum Speed

Auto Controlling of

RIBBON THICKNESS

by adjusting Gap between

spreader box & rotating

cooling drum

Auto controlling of

SEAL THICKNESS

by adjusting Gap

between Die Rollers

Auto-controlling of

RESIDUAL MOISTURE

by adjusting

Drying Temperature

Drying Time

Implementatn of

Control Strategy

PAT &Development

of Feedback Control system

DoE & Development of Design Space

Quality Risk Assessment of

CMAs & CPPs

Determination of CQAs

Definition of QTPP

© Created & Copyrighted by Shivang Chaudhary

WHEN NO ONE IS LOOKING

SHIVANG CHAUDHARY

© Copyrighted by Shivang Chaudhary

Formulation Engineer (QbD/PAT System Developer & Implementer) MS (Pharmaceutics)- National Institute of Pharmaceutical Education & Research (NIPER), INDIA

PGD (Patents Law)- National academy of Legal Studies & Research (NALSAR), INDIA

+91 -9904474045, +91-7567297579 shivaniper@gmail.com

https://in.linkedin.com/in/shivangchaudhary

facebook.com/QbD.PAT.Pharmaceutical.Development

Created & Copyrighted by

QUALITY MEANS DOING IT RIGHT