OSD Forms

Baseline Guide
Prof. Jack C. Chu, PE
Associate Director, Engineering
Merck & Co.
07-Oct-2015

ISPE OSD Baseline Guide

• Professional guidance to global
pharmaceutical industry that provides
acceptable practice guidance tool in
design and developing OSD facilities
• Provides a good guidance as starting
point for industry professionals
• Delivers an acceptable practice for
achieving regulatory
latory compliance

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 Benefit from the
ISPE OSD Baseline Guide
Intended to be used by various industry
professionals for:
• Business Development
• Manufacturing Ops & Quality Management
• Regulatory Agencies, Inspectors & Auditors
• Science, Technology, Arch & Engineering
• Warehousing/Distribution

1st edition 2nd edition 3rd edition

1998 2009 2016

Volume 3 Rewrite - Team

Approximately 75 Professionals
Chair and Co-
Chair
Lead by Steering Committee
Chapter
Authors
2-10
Organized by Chapter people

Reviewers
10-15
people
Overall ISPE Guidance

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 Volume 3 Rewrite - Team

ISPE Tech
Writer

3rd Edition Progressive Outlines

Team Final
Update finalization, Edits/GDC
Proposal & agreement Reviews
Initial Plan and 4Q2015
June 2013 Rewrites (progress)
Nov 2013-
July2014

Officially Industry
Kicked off Review and
Nov 2013 Revisions
Aug 2014- Industry Available
Annual Release
Meeting Jan 2015
1Q2016

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 Content and Revisions New chapter that goes into more
detail on the challenges, issues and
considerations relating to
containment and cross
contamination issues faced by OSD
manufacturers.

Significant expansion of Product and

Processing including the addition of ATEX, a Numerous updates and considerations relating
European directive focused on equipment to modern OSD facilities in the areas of
intended for use in potentially explosive architectural (layout, functional areas, etc.),
situations. process support utilities (approach, critical
systems, and code issues), HVAC (further aligned
with the ISPE HVAC Good Practice Guide),
electrical (classified areas, systems and
preventive maintenance), controls and
instrumentation (PAT, MES, EBR) and other
considerations (non-cGMP risks, exposure,
life/safety, hazardous operations,
environmental, emergency preparedness).
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Content and Revisions

– Revised the structure for better flow and
communication
– Increased coverage of process technologies
– Risk Based Approach
– Incorporate with EU and JP standards and
regulations, e.g. ATEX
– Quality by Design (QdB)
– Product Quality Lifecycle Implementation (PQLI)

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 OSD BG3 - Highlights
x Expanded discussion related to Risk Management (Chapter 3)
with content including the topics of: Principles, Processes and
Applicable Tools.
x Significant expansion of Product and Processing (Chapter 4)
including the addition of “ATmospheric EXplosible (ATEX)”, a
European directive focused on equipment intended for use in
potentially explosive situations.

x New chapter entitled Product Isolation and containment -

Principles of Product, Operator, and environmental Protection.
x Detail on the challenges, and considerations relating to containment and
cross contamination issues inOSD manufacturers
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Quality by Design (QdB)

Aligned with ICH regulatory guideline Q8R2 as:
A systematic approach to development that
begins with predefined objectives and
emphasizes product and process understanding
and process control, based on sound science and
quality risk management

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 Key to Success
Process and Process Development

Protection by Design: Product, Process, Personal and

Environment

Facility Layout, Critical Utility Criteria and Facility

Equipment Configuration

Fit-in-use; Time-valued-Investment; Technological-

Advancement

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Facility Layout Comparison

Conceptual
Future
Continuous
Manufacturing
with Robotic
Warehouse

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 Vertical & Integrated
Process 13

Benefits
Create more capable and capabilities in the global
marketplace:
– Introduction of facility models which are:
– smaller
– more energy efficient
– less wasteful
– Opportunities for increasing productive
– significantly less costly to build and operate
– reduced WIP (Work In Progress) space and material
– Improves the quality control for consistency
– Decrease scale up issues and tech-transfer cycle time
Enable for faster launching of new products
Opportunity for reduction of Full-Time-Equivalents and
increasing of OEE
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 PAT and CMP

The way of our future

Pharmaceutical
Manufacturing
Operations

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Oral Solid Dosage today

Delay
D Delay
D Delay
D Delay
D

Raw Material
1 to 2
months to
release
Granulator

Blender Dryer
Blender Tablet press Coating

High inventory including “work in progress”, long changeovers, disconnected

processes, high process losses, off line analysis, low asset utilization, …

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Granulation Processes Review

Designs compatible with Batch by

Continuous Operations17 Nature

Continuous Processing
In- Line Granulation

Continuity
Moisture

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 Continuous Processing
Fluid Bed Dryer Concepts

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What to Understand: Product CQA

and Process Control Requirements
Raw
Material

Blender Dryer Quality Check Film Coating

Granulator Tablet Press Release

Moisture Content Blend Weight & Digital Imaging

Chemical Properties Concentration &
Homogeneity Hardness Coating Substance
Physical Properties Uniformity

Critical-to-Quality Attributes (CQA)

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 What to Control: PAT Quality Data
Management System

Raw Material

Quality
check

Coating
Blender Dryer

Granulator Tablet press

In/At line check

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PAT? Product &

Process
Design
PAT

(Advanced) Data
Information
Process Collection
Management
Controls Storage &
Tools
Retrieval

?
Document
Control
Data
&
Analysis
Change
Control

௡
௡
݊ ௞ ௡ି௞
‫ݔ‬൅ܽ ൌ෍ ‫ܽ ݔ‬ Process
݇ Analytics
௞ୀ଴

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 PAT in Solid Dosage
Content
Uniformity Bulk Physical
Defects
control
Loss On Drying
Process
control
parameters Particle size Test against
Process control Sampling & specifications
parameters Off-line analysis
Process control
Dispense
Bulk Physical
parameters
Process
& Blend Wet control Defects
parameters
Process control
Granulation
Drying parameters Process control
Blending /
parameters Process
ƒ Api Lubrication parameters
Liquid addition Compression
ƒ Excipients
Coating
Lubricant Packaging
excipient
•
Coating
solution

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PAT in Solid Dosage

Input material
characteristics Content Assay
Uniformity Dissolution/disintegration
(NIR)
control Loss On Drying

Process (NIR)
control Particle size Visual
parameters Weight
(Malvern) Inspection
Process control Hardness
parameters Thickness
Dispense Process control
Coating
parameters
& Blend Process control
Wet thickness
parameters
Process control
Granulation
Drying parameters Process control
Blending /
parameters Process
ƒ Api Lubrication parameters
Liquid addition Compression
ƒ Excipients
Coating
Lubricant Packaging
excipient
•
Coating
solution

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 CQA to CPP – the Specification

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Efficiency
• Processes will require less Foot-Prints, less Initial-
Capital
• Operation could be continuous for 24/7
– Fewer startup/shutdown quality problems
– 100% capacity utilization (OEE)
• Closed Operation with Fully Automated Systems
– Less Human Intervention; Less operator exposure to product
– Less Exposure to Environment; Less Exposure of Cross-Contamination
to Product
• Just-in-time operation minimizes the product
storage and in-process quarantine

Source: Duquesnes University

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 Statistical Data Suggests
– Continuous Manufacturing must be aligned with PAT
– Reduced scrap/rework
– Reduced human errors
– Increased & consistent product quality
– Reduced quality costs
– Reduced regulatory compliance costs
– Faster time to market: scale-up & tech transfer
– Real-time product release

– The future is not a million miles away; it is here, in

Boston Area!

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