PLANNING OF PHARMACEUTICAL FACTORIES

CONCEPT AND IMPLEMENTATION

WORLD CLASS PHARMA FACILITY

PRESENT SCENARIO :
The globalization and open market policies have proved to be a boon for
the industries, but also have generated the need for globally acceptable
manufacturing facilities.

There are many flourishing manufacturing facilities, but not all are in
compliance with the various regulatory standards.

NEED FOR A FACILITY :
Rapid change in manufacturing technology & various regulatory
compliances to upgrade for better solution in line with cGMP.

With globalization, the need for a compliant facility has become a
statutory necessity.





PARTICIPANTS TO THE PLANNING PROCESS
Forecasts for
x years
Objectives
Budget
Company internal approvals
Technology
Logistics
Building services
Building technology
Approvals (pharmaceutical)
Approvals (non-pharmaceutical)





Planning

Execution
Internal Planner Authorities
PLANNING TEAM(S)
SCHEDULE EXAMPLE
Company standards, planning
conditions (quantities, technologies,
products, deadlines, budget ...)
Specific guidelines, (Biosafety,
Fed Std, OSHA)
for conception, planning, operation ...
Norms
ISO, ATEX, etc...
Labour and environmental
requirements...
Pharmaceutical regulations,
EU, FDA, PIC/S, WHO, requirements of
pharmacy inspectors, product registration ...
NORMS, REGULATIONS AND REQUIREMENTS
General laws + regulations
Process / Equipment
GMP and Hygiene Zoning
Quantitative data
Layout

Feasibility
Concept

Basic Design

Detail Design

Execution
Complete detailing for all
disciplines
Layouts 1:20, 1:50
Tendering
Refining of elements
Calculations
Functional tendering
Layouts 1:100
PLANNING STEPS
HOAI

Feasibility
Concept

Basic Design

Detail Design

Execution

Conceptual
design

Basic Design

Detail Design

Execution
CONVENTIONAL MODEL
IMPROVED MODEL
PLANNING MODELS
FEASIBILITY VERSUS CONCEPTUAL STUDY
Static
Dominated by Economical Criteria
No Project Alternatives:
Yes / No only
No Influence on Schedule of
Subsequent Phases




Feasibility
Includes the Feasibility Study
Dynamic / prospective
Dominated by Technical Criteria
Project Alternatives are generated
User oriented
Choices possible
- Costs
- Technology
- Organisation
Reduces Time spent on subsequent
Phases, while increasing
their Precision
Conceptual Study
Strong
Conceptual
design

Basic Design

Detail Design

Execution
PLANNING MODELS
It pays to invest into a strong conceptual design

Low initial costs
Early clarification of main issues
Powerful decision tool
Possibility to develop alternatives
Freewheeling


PLANNING SEQUENCE AND ITERATION PROBLEMS
Planning Task Start
Task Definition
Targets Requirements
Analysis
Conceptional Design
with Alternatives
Basic Design
Execution
easy
difficult
Detail Design
100%
90%
80%
60%
50%
40%
30%
20%
10%
70%
100%
RELATIVE COSTS OF THE DIFFERENT PHASES
The cheapest and most promising Phase is the Conceptual Phase !
Detail Engineering
Factory size
Factory organisation
Technology
GMP concept
Basic Design
Conceptual Design
Execution
Cost saving potentials
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
POSSIBILITIES OF COST MINIMISATION
Basic Design
The best and cheapest chance to minimise cost of
investment and operation is in Phase 1 !
Detail Engineering
Execution
Costs
saving potential
Conceptual Design
Factory size
Factory organization
Technology
GMP
Small teams
Brainstorming
Alternatives
New ideas
Feasibility
Conceptual design
Basic design
Detail design
Execution
Supervision
Documentation
Cost estimation
Cost calculation
Tender documents
Offers
Final quotations
The better the concept,
the higher the precision
DETERMINATION OF COSTS
in relation to the planning stage
PRICE PAID
PRECISION OF COSTS
in relation to the planning stage stage
30%
Cost estimation
Feasibility
Conceptual design
5%
Final Quotations
Execution
Supervision
Documentation
20% Cost calculation
Basic Design
10%
Tender documents
Offers
Detail Design
The better the concept,
the higher the precision
Feasibility
Conceptual design
Basic design
Detail design
Execution
Supervision
Documentation
DETERMINATION OF COSTS
in relation to the planning system
Turnkey price:
poor control
General planner:
good control
- +
The Purpose of the Conceptual Design is to arrive to

Layout
General Factory Organisation Procedures
Hygiene Concept
Technology Concept
Air Handling and Utilities Concepts

which can be successfully presented to Authorities for a
Pre-Approval Design Review
GMP Considerations and Factory Planning go Hand in Hand
PURPOSE OF CONCEPTUAL DESIGN
and to get a high degree of safety about
Investments
Schedule

- Planning of a production plant
future oriented
flexible
economical in investments and operating costs
GMP conform
conform to local / international regulations


- High motivation of staff by high quality of working place
- Efficient planning
- Adequate quality standard (value for money)
- Architecture compatible with local surroundings
TARGETS OF PHARMACEUTICAL FACTORY
PLANNING
HOW TO REACH
A GOOD CONCEPTUAL DESIGN RESULT ?
Right team

Good method

Discipline

Good data

Some fantasy
Right team

Good method

Discipline

Good data

Some fantasy
Right team

Good method

Discipline

Good data

Some fantasy
Right team

Good method

Discipline

Good data

Some fantasy
Right team

Good method

Discipline

Good data

Some fantasy
PEOPLE AND PLANNING
A Quote:

You do not really understand something
unless you can explain it to your grandmother."

Albert Einstein
The idea is to work intensively with a small group of people,
possibly detached from their daily chores.

These people must have the necessary know-how (or back-ups)
and the power of decision
CORE TEAM
Production Manager
Quality Assurance
Integrated Factory
Planning Experts
Process GMP Expert
Controller
AD HOC MEMBERS
Utilities Specialist
Other Specialists
Logistics
Engineering
PEOPLE AND PLANNING
Generalists Specialists
Execution Detail Design Conceptual Design Basic Design
PLANNING
VALIDATION
Generalists Specialists
Number of people
Number of people
PEOPLE AND PLANNING
90%
100%
80%
70%
60%
50%
40%
30%
20%
10%
Individuals
Concept
Team
Large
Organisations

J
u
d
g
e
m
e
n
t

E
r
r
o
r
s

Number of Participants
Role of participants :
To plan AND to decide
JUDGEMENT ERRORS
By Experimenting and Innovating
By Cloning Existing Units
By Adding Individual Functions
By Turnkey Contracting
PLANNING METHODS
There are many
design methods
By Systematic Planning
Masterplan
General organisation factory
Site, Site selection
Departments
Functional groups
Equipment, single units
PLANNING FROM INSIDE TO OUTSIDE
PLANNING FROM MACRO TO MICRO
PLANNING FROM IDEAL TO REAL
OPTIMAL PLANNING METHOD
NEED FOR FOCUSING
Economy of scale
Efficiency / Best practice
Flexibility
Performance
Organisation
Analysis of
Product range
Process
Technologies
Organisation
Conceptional design
Make or buy
Specialisation
Capacity increase
Technology
Standardisation
Regulatory aspects
Results versus costs
Requirements
Vision
of client
PLANNING METHOD
DEVELOPMENT OF IDEAL ORGANISATION
Information Strategy
Identification
key problems
Analysis
Material /
Information
flow
Idenfication
necessary
infrastructure
Analysis
process

START

Definition
Modules
Functional
units
Vertical
Horizontal
Resulting Organisation

END

Verification
process flow,
material flow
Other
requirements,
constraints,
etc.
Calculation
necessary
space
Definition of
constraints,
etc.
Adaptation
Process,
machinery +
equipment
Evaluation
+
Selection





Plant
strategy

+

Process
architecture




Rough layout
development
Layout
alternatives
Combination
material flows
functional
inter-
dependencies
B/W-
Orientation
of factory
Analysis
organisation
Analysis space
situation
Analysis
machinery /
equipment
Analysis of
products
and
production
volumes
Verification
GMP
concept
Morphological Analysis + Search for Solutions Capacity and Rationalisation Analysis
Existing
Technology
GMP-Concept
Technological
Alternatives
Investment /
Budget
Forecasts,
Quantities,
Product Mix
Batch Sizes
Galenical
Properties
Degree of
Automation
Project-
Technology
Degree of
Automation
Batch Sizes
Shifts ?
Product
Seasonality
Campaign Sizes
Cleaning +
Change-over
Times
Foreseen
Equipment
Dimension.
Machines
(Type/
Quantity)
PLANNING METHOD
RATIONALISATION, INNOVATION AND OPTIMISATION
GMP-Concept





Plant
strategy

+

Process
architecture




PLANNING PROCEDURE: CONCEPTUAL DESIGN
Development of the
masterplan
for the design onthe green field
Development of the
integration of the layout into
an existing building structure
Production forecasts / next 6-10 years
Description of process flows
from starting materials until
finished product
Design of the overall flow
diagram indicating all
GMP-classes
Calculation of material flow quantities
Definition of personnel,
shifts, etc.
Design of the ideal layouts
+ modules for each step
Ideal layouts
personnel
areas
Ideal layouts
peripheral
areas
Combination of individual layouts to functional units
--> Granulation, tabletting, preparation of liquids, filling ...
Design of the ideal overall total layout
Definition of
- Process technology
- Machinery + equipment
- Transport systems + containers
PLANNING PROCEDURE: CONCEPTUAL DESIGN
FORECASTS
Product lists, quantities

Sorting by galenical forms

Sorting by types (conventional, toxic, hormones, beta-
lactames, etc.)

Strategy for marginal products (quantities, types, galenical
forms):
Make or buy
ABC ANALYSIS
SELECTION OF TECHNOLOGY AND EQUIPMENT
EXAMPLES OF SELECTION FACTORS
Vision of client
Properties of products to be processed
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment
(standardization)
GMP issues
Safety of operator

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client:
size, degree of sophistication, automated guided vehicles,
architecture, budget, future-oriented or not
Properties of products to be processed
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues
Safety of operator

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed:
eg granulation properties: is direct compression possible or dry
granulation ?
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues
Safety of operator

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed:
type of granulation, aseptic processing or terminal sterilization,
ampoules or syringes
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed
Output requirements
High capacity / one shift, low capacity / 2 or 3 shifts
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues
Safety of operator

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed
Output requirements
Degree of automation, sophistication
fully automated preparation of solutions, with CIP/SIP, equipment for
solids with CIP capability, cartoning, palettisation, etc.
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues
Safety of operator

NUMBER OF
PRODUCTS
Q
U
A
N
T
T
I
T
E
S
AUTOMATION
POSSIBILITIES
SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues
Safety of operator

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Can influence the type or the supplier: eg difference in size between
FBG and one-pot system
Previous experience, available equipment (standardization)
GMP issues
Safety of operator

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues
Safety of operator

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues
Aseptic processing problems: automated loading of freeze-dryer,
increased automation
Safety of operator

SELECTION OF TECHNOLOGY AND EQUIPMENT
Vision of client
Properties of products to be processed
Output requirements
Degree of automation, sophistication
Supplier: price, service and serviceability
Cleanability and maintenance needs
Space constraints
Previous experience, available equipment (standardization)
GMP issues
Safety of operator: containment or PPE ?
In most cases, several factors will play a role simultaneously
ABA ADA ACA
BAA
BAE BAD
BAC BAB
CAA CAB
DAA
DAD
DAC DAB
EAA EAC EAB
FAA
FAE FAD
FAC FAB
GAA GAB
HAA HAC HAB
AAA
BBB
CCC
DDD
EEE
FFF
GGG
HHH
SELECTION OF TECHNOLOGY AND EQUIPMENT
MORPHOLOGICAL ANALYSIS
P
R
O
C
E
S
S

S
T
E
P
S
PROCESS ALTERNATIVES
PLANNING METHOD
PROCESS AND ORGANIZATION FLOW CHARTS
Whereas a process flow chart reflects the process only,
an organization flow chart includes the process, its
organization as well as additional elements such as
quantities, personnel needs, hygiene zoning, equipment
and inter-relationships within the production or between
production and related functions.

The process flowchart must be transformed into an
organisational flow chart

Organization flow charts exist at different levels, micro-
and macro:
Micro: within a department
Macro: within a production unit/plant
PLANNING METHOD
PROCESS FLOWCHART
Granulation
Binder
preparation
Drying
Sieving
Addition
lubricants
Blending
Compression
dit
Granulation
Binder
preparatio
n
Drying
Sieving
Addition
lubricants
Blending
Compression
Weighing
Staging
m
2
?
Staging
m
2
?
Staging
m
2
?
Container
washing
Staging
m
2
?
Granulation
Drying
Sieving
Addition
lubricants
ding
Compression
m
2
?
Binder
preparatio preparat
n
GG
nd dddddder
Blend
r
Stagi
dit
PLANNING METHOD
ORGANIZATION FLOWCHART
PLANNING METHOD
FLOWS PERSONNEL AND MATERIALS
Exterior
Lockers G
G
Lockers D
D
Lockers C
C
A/B
Lockers A/B
Exterior
Lockers G
G
Lockers D
D
Lockers C
C
A/B
Lockers A/B
Selection of alternative important, later changes practically impossible
LOGISTICS
Goods IN handling
Cleaning
Administration
Sampling
Palletisation
Etc
Storage activities
Main storage
Special storages
Goods OUT handling
Picking
Commissioning
Administration
Etc
Production
Exterior
Clients
Logistic centre
LOGISTICS
Raw material
Primary packaging material
Secundary packaging material
Finished products
Receiving
area
P
r
e
p
a
r
a
t
i
o
n

a
r
e
a

f
o
r

r
a
w

-

a
n
d

p
r
i
m
a
r
y

p
a
c
k
a
g
i
n
g

m
a
t
e
r
i
a
l

Sampling
Booth
Shipping
w
e
i
g
h
i
n
g

Production
area
Marshalling
B
u
l
k

s
t
o
r
e

Packaging
lines
pal / h
pal / h
pal / h
pal / h
pal / h
pal / h pal / h
pal / h
pal / h pal / h
pal / h
pal / h
pal / h
pal / h
pal / h

Warehouse
Pharma
Storage
capacity:

pallet
places
Sampling
Quarantine separation
Change of pallets to/from production
Procedures in material air locks
GOOD GMP
Minimized risk of contamination / cross-contamination

Clear material flows (uni-directional whenever possible)

Clear personnel flows (uni-directional whenever possible)

Unambiguous definition of GMP zones

Separation clean dirty (washing areas)
Overkill
Cost issues
Nice to have
GMP is not an attribute, no black and white attitudes
SUMMARY
A good pharmaceutical factory is a factory that is:

Pharmaceutically approved (qualification / validation )
Economical to operate and maintain
Flexible and adaptable quantity-wise and for new technologies

To design such an excellent pharmaceutical plant, an integrated,
multi-disciplinary and experienced team is required.
The objectives, the vision, the method and the involvement of each
member of the team will achieve this goal, and not the principle
function follows adding up individual inputs