Transcript cGMP Biopharmaceutical Facility Basic Construction

cGMP Biopharmaceutical Facility
Basic Construction
cGMP Biopharmaceutical Facility Basic
Construction
Manufacturing Facilities
Different types of facility and factory engineering
Primary business plan
Specification
Systems
Consultants, Audit,
accreditation body
Instrument
suppliers
Project
engineering
Main Utilities
(W,E,G)
Contractor(s)
NEW
PLANT
Location, road
and traffic
connection
Project
Engineering
Raw Materials
Civil
Engineering
Suppliers?
Mechanical
engineering
Contractors
Electrical
Engineering
Legalization
TechnologyProduct(s)
Scheduling and Logistic
Chemical
Engineering
Human Resource
Marketing and client net-work
Types of Biopharmaceutical Facilities
Engineering
• Conventional
• Modular Design
Technology /
application
• Product Based Platform
• Cell Factory Based Platform
Process
Biosafety Class
• Dedicated Facility
• Multi-purpose Facility
• BS1, BS2, BS3
Modular facility is more than prefabricated building!!!
Modular concept in Pharmaceutical
and Biopharmaceutical Facilities
Life-time of Modular
Biopharmaceutical Plant
Conventional vs Modular Design
Conventional
Modular
Time
Speed may governed by
many factors (location
related)
Can cut 6 to 12 months of
the project schedule
Facility final quality
Quality may effected by the
level of skilled worker in the
area, available raw materials
for major construction
Allow design of complex,
high-quality project in are
where is a shortage of
skilled worker
Site disruption
High
Low
Safety during manufacturing
High risk
Low risk
Cost
Usually less than modular by
30% (material, labor cost)
Usually higher than
conventional 30%
Design change
Easier if
Could be done if consider
in the initial Engineering
Value (Company assess)
Less than Modular
High value factory (more
attractive for investors)
Technology Application
Product Platform
Based
Cell Factory Platform
Based
Manufacturing facility is
designed for one product or
certain group of products
Flexible platform structure
Rigid platform structure
Preferable in mid- and small
pharmaceutical company
Example: Insulin Production
in Novo Nordisk and Elli Lilly
Preferable for TollManufacturing facility
Product Based Platform
vs
Cell factory Based Platform
Product Based Platform
Cell factory Based Platform
Less Flexible
More flexible
Dedicated for one product (or branch
of product)
Can produce different types of products
from the same biofactory (without or
with minimal modification)
Limited use as Toll-Manufacturing
Less Expensive
For well-establish products
Low-Value facility (in case of sale)
Easily applied as Toll-Manufacturing
More expensive
For well-establish products and new
products
High-value facility (in case of sale)
Biosafety Level
BSL
AGENTS
PRACTISE
SAFETY
EQUIPMENT
(Primary Barriers)
FACILITIES
(Secondary Barriers)
1
Not known to
consistently cause
disease in healthy
human adults
Standard animal care and
management practice,
including appropriate medical
surveillance programs
As required for normal
care of each species
Standard animal facility
• no recirculation of
exhaust air
• directional air flow
recommended
• Handwashing sink
recommended
2
Associated with human
disease. Hazard:
Precutaneous exposure,
ingestion, mucous
membrane exposure
A BSL-1 practice plus:
• Limited access
• Biohazard warning signs
• Sharps precautions
• Biosafety manual
• decontamination of all
infections wastes and of
animal cages prior to washing
A BSL-1 equipment plus
primary barriers:
containment equipment
appropriate for animal
species, PPEs, laboratory
coats, gloves, face and
respiratory protection as
needed
A BSL-1 facility plus:
• autoclave available
• handwashing sink
available in the animal
room
• mechanical cage washer
used
Biosafety Level (cont.)
BSL
AGENTS
PRACTISE
SAFETY EQUIPMENT
(Primary Barriers)
FACILITIES
(Secondary
Barriers)
3
Indigenous or exotic
agents with potential for
aerosol transmission:
disease may have serious
health effects
A BSL-2 practice plus:
• controlled access
• decontamination of
clothing before laundring
• cages decontaminated
before bedding removed
• disinfected foot bath as
needed
A BSL-2 equipment plus
• Containment equipment for
housing animals and cage
dumping activities
•Class I or II BSCs available for
manipulative procedures
(inoculation, necropsy) that may
create infectious aerosols. PPEs
appropriate respiratory
protection.
A BSL-2 facility plus
• physical
separation from
access corridors
• self-closing,
double door access
• sealed windows
• autoclave
available in facility
4
Dangerous or exotic
agents that pose high risk
of life treating disease;
aerosol transmission, or
isolated agents with
unknown risk of
transmission
A BSL-3 practice plus:
• entrance through change
room where personal
clothing is renoved and
laboratory clothing is put on;
shower on exiting
• all wastes are
decontaminated before
removal from the facility
A BSL-3 equipment plus
• Maximum containment
equipment (i.e. Class III BSC or
xxx containment equipment in
combination with full body, airsupplied positive pressure,
personnel suit) used for all
procedures and activities
A BSL-3 facility plus
• separate building
or isolated zone
• dedicated supply
and exhaust
vacuum and
decontamination
systems
• other
requirement
outlined in the lab
Special Safety Requirement
High Sporulating
fungal cultivation
Pichia pastoris
cultivation
Vaccine
production using
pathogens
Vaccination plan
Air born spore
Controlled access
Using of toxic,
flammable substrate
(methanol)
Spore germinating in
filter system and surface
Special equipment
Design
Special treatment of
biomaterial
HVAC (differential
pressure)
Recommended Facility and Practice for
BSL 2 & 3
BSL
Agents
Practice
Safety Equipments (Primary
Barriers)
Facilities (Secondry
Barriers)
2
Associated with human
disease. Hazard comes
from autoinoculation,
Ingestion, mucous
membrane exposure
Standard Microbiological
Practice plus
• Biohazard sign
• sharps precautions
• Biosafety manual defining
any needed waste
decontamination or
medical surveillance
policies
Primary barriers involving
Class I physical containment
devices used for all
manipulations of agents that
cause splashed or aerosols
of infectious materials;
personnel protection
equipment involving
protective lab, clothing,
gloves, respiratory
protection when required
Open bench top sink
required plus
autoclave available
3
Indigenous or exotic
agents with potential
for aerosol
transmission: disease
may have serious or
lethal consequences
Similar to BSL-2
Similar to BSL-2
BSL-2 plus
• physical separation
from access corridors
• self-closing double
door access
•Exhaust air not
recirculated
•Negative airflow
into laboratory
Primary Business Plant
(Cost Estimation)
Technology
Facility required
(Process availability)
GMP requirement
Technical Decision
Facility Cost
Process Cost
Reviewing by consultation committee
Project Cost (35%)
Let’s Start Our Facility!
Project Concept
Project Objective
(product, market etc)
Project Basic Idea
Technical data, Know-How,
Consultant
Basic design
Develop Options
Change / Revision
Review Options
Complete Concept
Overall Cost Estimation
Project Contractor(s)
Fully Turn-Key approach
(including Technology
Transfer)
• (Build/ Design/ cGMP/ Validation. Etc…)
• Plus (Know-How, trainning, SOP, PV)
Fully Turn-key approach
• (Build/ design/ cGMP/ Validation, etc…)
Major Contractor
Approach
• (Building, electrical, equipment, HVAC)
Fully Client Managed
• all contracts managed by the client
(sometimes, more than 30 contracts!)
What are the cGMP regulation which we
should follow in our new facility?
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you like to
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