Continuous Manufacturing

Indonesia 2018 by Werner Fromm, Glatt

Germany, Area Sales Manager Asia/South Pacific ,

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 Glatt Group - Past and Present

1954 1971 – 1990

Company foundation Expansion & new technologies
• Initial production of stovepipes • Foundation of several new Glatt companies
and ventilation systems • Development of the first drum coater

1959 1990 – 2000

Introduction of New management & new business areas
fluidized bed technology • Leadership handed over to Werner Glatt´s
-> Transition to pharmaceutical son-in-law, Reiner Nowak
plant engineering • Glatt Ingenieurtechnik in Weimar
Expansion to continuous technologies
• Glatt Systemtechnik in Dresden

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 Glatt Group - Past and Present

2011-2013
New partners & new locations
• Member of the strategic network Excellence United
• Foundation of Glatt Systems Pvt Ltd., India

Today
2000 employees in
14 companies worldwide
• Market leader for granulation and coating
2013 - 2015 technologies in pharmaceutical and related
Recent innovation – highlights:
industries
• 2013 MODCOS (cont. granulation lines)
• Further development and adaption of
• 2014 High Containment Solution: TKS flap
established devices and processes
• 2015 Lab Containment Barrier System
• 2015 New Glatt Tablet Coater: GCC

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 Glatt´s four Areas of Expertise- Global Full Service Provider
> 2000 employees in 14 companies worldwide

Product Development
Contract Manufacturing Offers niche pharmaceutical
for Pharmaceutical Industry Excepients and API´s

Offers contract manufacturing of

innovative granulates and pellets

Process Equipment
Planning & Construction
for the Pharmaceutical Industry
Offers services for automation,
qualification and validation,
calibration, process engineering
and facility planning
Process Equipment Planning &
Construction for the Food, Feed
and Fine Chemical Industry
Technology training center
offers
specialized workshops about
technology expertise for solid
processing disciplines
Designs and implements complete projects.
Expansion or modernization of existing Offers services and
production sites to new construction of entire development
facilities. of new products based on metal,
ceramic powder and contract
manufacturing capacities

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 Traditional Solid dosage process

• Room 1 • Room 2 • Room 3 • Room 4 • Room 5

• Controls System • Controls System • Controls System • Controls System • Controls System
• Data • Data • Data • Data • Data
• Sampling • Sampling • Sampling • Sampling • Sampling

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 Continuous is a well known Technology

Better Process
understanding
& Quality
control

Faster to
market

Variable & more

Better Monitoring > Less
effecient
More Data points No scale up Space
Production
From small to big

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 Continuous manufacturing concepts

Direct Compression
Exibients
API

Roller Compaction
S Coating
Wet granulation / Drying t (Batch)
Dosing Blending Compacting o
r
Wet g Coating
Drying Milling (Batch)
Granulation e

Fluid Bed Granulation

Other processes (extrusion)

Handling & Options

Rotary Waste
Conveying WIP
Valve gate

PAT Technology

Tablet
Moisture Particle Content System Integration
Check-
MW Size NIR
master Overall Controls System ( Track & Trace)
Data Management

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1. Feeding & Dosing
For continuous wet granulation and direct compression

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 Loss in Weight feeding Principle

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Continuous direct compression

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 Coating
Dosing Blending Compacting
Coating Open System

Coating

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 Example of modulized blender

 Modular design of mixing shaft and mixing chamber

 Modular residence time
 Multiple feeding ports with flexible position possible
 Transparent or stainless steel mixing chamber
 Fast change over- Easy cleaning-GMP design
 Integration of PAT feasible
 Different capacities
Type Mixer diameter capacity Length
(mm)
GCG 70 70 mm 2-50 kg/h 250/500
GCG 130 130mm 5-200 kg/h 880
GCG 200 200 mm 5-700 kg/h 1340

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Case study MUPS

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 Case Study Direct Compression of a MUPS

Spezies Pellets Powder Tablet

400mg, 11.2 x 5.6 mm

Concentration/mass 23% 77%
200mg, 11,2 x 5,6 mm
Eudragit L 30 D-55 Avicell 101, Ac-Di-Sol, 23% Pellets,
Composition
Coating, 35% solid coat MgSt 77% Powder

Preblend 10 sec MgSt

Test Installation

• One K-Tron feeder KT 20 for powder premix

• One K-Tron feeder MT 16 for Meto pellets
• Glatt dry mixer, short version
• NIR-Measuring device at mixer outlet, Sentronic
• Tablett press 102i, Fette
• Tablet checkmaster, Fette

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MODCOS
 Flexible Lab Test Installation today

Case Study

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MODCOS
 Results pellet distribution 200 mg tablets

Case Study

Immidiate stady state

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MODCOS
Conti Wet Granulation

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 Wet Coating
Dosing Blending Drying Milling Compacting
Granulation
Coating Open Systems
Equipment:
Container
1

Vakuum conveyer
2
1 2 Docking system
3
2 4 Tablet Checkmaster
4 Dosing feeder,
3

5 High shear granulator

4 4 Conti dryer
8 6
4
7 7 Rotary valve

8 Dry mill

9 Dry blender
9
Binder addition

10 Waste discharge valve

5
11 Tablet press

12 Storage

6 13 Coating / Auto laod /Discharge

10

11

12

7 1 1

Good Waste
Product Product

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MODCOS June 2016
 Twin Screw Granulation ( TSG)

Ratio: 40:1

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 Fluid Bed Machine

GPCG 2  MODCOS s-line for multi application

Conti drying insert

Batch insert

Conti granulation insert

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 Fluid Bed Dryer

• 10 chamber rotating insert

• Very narrow residence time distribution
• No cross mixing during production process
• Controlled drying process

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 3 Sizes capacities available

S-Line 4-15 kg/

XS-Line 0,6-2 kg/h

M Line 10-50 kg

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Traceability / Documentation

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Residence time distribution

time

time

time

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 Residence time distribution

The overall residence time distribution of all process units gets

wider with each single process unit

One process
unit Two process
units Three process
units Four process
units

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 Documentation

How to define a batch? Batch definition does not change

By time or mass
Batch definition (21 CFR 210.3):
A specific quantity of a drug or
other material that is intended to
EA3 EA2 EA1 have uniform character and
quality, within specified limits, …

Definition
W2 W1does not specify the
Continuous mode of manufacture
EB3 EB2 EB1
process
Waste Lots

One process
unit Two process
units Three process
units Four process
API3 API2 API1 units P4 finished-product
P3 P2 P1

Source Lots Target Lots

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 General thoughts

Keep the continuous process as long alive as possible

OOS ( Out of spec) product (waste) discharge late in process chain
OOS product gets a virtual “OOS stamp” and the controls tracks it
through the continuous line until discharge to waste
Every process parameter can be supervised

Stopmax

OOSmax
set point
OOSmin

Stopmin

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 GlattView CONTI
The following events are shown (time stamp):
• Docking at Outlet the Good Lot & Waste Lot (00:02)
In this slide, a graphic-video is shown, • Docking at Feed the API Lot(s) & Excipient Lot(s) (00:06)
• Start process -> Lots move through process units of MODCOS (00:10)
however not available in PDF-format. • Docking of next API & Excipient Lot -> Lots change-over (00:25)
• TSG is out of Spec -> Waste lot appears and move through process units (01:25)
• Waste lot arrive at Milling („Sieve“) --> Ejection (waste gate) opens (01:30)
Visualization in GlattView CONTI: • Lots after Milling („Sieve“) leaves product stream to Waste (01:40)
residence time of source lots within process units • TSG is back in Spec -> Waste lot start to leave the process units (01:43)
• Waste lot leaves Milling („Sieve“) -> Ejection (waste gate) closes (02:17)
• Lots arrive in Tableting (02:22)

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MODCOS January xxxx, 2016 -
GlattView CONTI

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 GlattView CONTI

Reporting
• Source and target lot report to trace all lots from target to source and the other way

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MODCOS January xxxx, 2016 -
Controls Structure with SIPAT

PAT Data Management System

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Please feel free to contact us under:
werner.fromm@glatt.com

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