Mô tả:
HVAC – GPG
Practical Guidance for GMP Facilities
By: Norman Goldschmidt
VP Genesis Engineers
1
Obj ti
Objectives
• P
Provide
id an overview
i
off th
the new HVAC
GPG
• S
Sett expectations
t ti
on what
h t is
i and
d iisn’t
’t iin th
the
GPG
• Review some key concepts from the guide
• Provide selected examples from the guide.
• Discuss what’s in the 3 day HVAC class
• Bust some Myths
2
Q
Question
ti #1
• Who are you?
• Quality Control / Quality Assurance
• Manufacturing Operations
• Maintenance / Facilities /Utility
Operations
• Commissioning / Qualification/ Validation
• Engineering
• Project Management
3
Q
Question
ti #2
• Why are you here?
•
•
•
•
•
Learn what’s unique to HVAC for GMP’s
Better understand what engineers are doing
Explore new resource for compliance
Looking for sustainability ideas
Boss ordered me to come
4
Q
Question
ti #3
• What do you know about HVAC?
•
•
•
•
H, V… What?
A little exposure, but not much
Familiar, but not expert
Experienced in HVAC, but not for
pharma
• My name is Willis Carrier, I invented
HVAC
5
5
Overview
O
i
off the
th HVAC GPG
What’s In
and
d
What’s Out
6
HVAC – Practical Guidance for GMP
F iliti
Facilities
• What’s in the guide?
•
•
•
•
•
•
•
•
Table of Contents
I t d ti and
Introduction
d Key
K Concepts
C
t
Design process for HVAC
Design Considerations (w/ Airflow Diagrams)
Design Review
Equipment
q p
Spec,
p , Install,, Qualify
y and Operate
p
Documentation Requirements
Appendices
7
Wh t’ in
What’s
i the
th guide?
id ?
• Appendices
A
di
•
•
•
•
•
•
•
Fundamentals of HVAC
HVAC Applications
pp
and Equipment
q p
Psychometrics
Science Based Risk Management
Science and Risk Based Verification
Economics and Sustainability
Medical Devices
• Misc.
8
Wh t’ in
What’s
i the
th guide?
id ?
• Th
The guide
id outlines
tli
structured,
t t d rigorous
i
approach
h
to HVAC at all stages of it’s life
• Key to this approach is Understanding the Product
and Process
• As is stressed in QBD, ICH Q9 and guides for
qualification the HVAC GPG highlights that process
qualification,
knowledge is paramount in cGMP.
• Rules of thumb – are given for conceptual use
• M
May nott produce
d
an effective
ff ti design.
d i
• Will not produce an efficient design
• Are a way of going wrong with confidence
9
Wh t’ NOT in
What’s
i the
th guide
id
•
•
•
•
•
•
•
Equipment Sizing
Load Calculations
Recommended Manufacturers
Detailed Procedures and MOT
Environmental Monitoring
Offices and Vivariums
Your Product Considerations
10
What’s in the guide
S
Summary
off the new G
GPG
G
•
Wh t it is:
What
i
• A guide for pharmaceutical applications of HVAC technology
• A quick reference for HVAC nomenclature
• A guide for understanding HVAC in relation to Process
Development
• A collection of practical tips on Pharma HVAC issues
•
Wh t it is
What
i not:
t
• A detailed reference on HVAC science
• A cookbook
•
What it intends to do:
• The new GPG is intended to establish a common platform for
pharmaceutical professionals of all disciplines to discuss HVAC
11
Key Concepts
12
GMP IIs N
Nott At The
Th T
Top Of A Hierarchy
Hi
h
GMP
Not every decision is
GMP driven
GEP
We don't engineer
g
for the
sake of engineering!
GBP
We are in the pharmaceutical BUSINESS.
We can't deliver products at a loss….
Well not for long.
Well,
long
13
GMP Interacts With Business And Engineering
GOOD BUSINESS
PRACTICE
Marketing
Product Development
Distribution
R&D
Community Relations
Shareholders
GOOD ENGINEERING
PRACTICE
GOOD
MANUFACTURING
PRACTICE
Product
Patient
(SISPQ)
14
Facility
Equipment
Life Cycle Cost
Wh t Is
What
I A Classified
Cl
ifi d Space?
S
?
•
•
•
•
•
•
T, RH,
T
RH airborne
ib
particles
ti l controlled
t ll d b
below
l
specified
ifi d lilimits
it
Bioburden (surface and airborne) under control
Particles and CFU as shown on Table 5-1 of ISPE Sterile
Guide
Applies to parenterals, some inhaled products and
ointments, and most exposed biopharm API
REQUIRES PROCEDURES (people control)
Regulatory Authorities define their own
•
•
•
•
Syste s for
Systems
o classifying
c ass y g ccleanrooms
ea oo s
FS209
ISO
EU
15
ISPE
S
Bridge between Space
S
C
Classifications
f
Air
Classification
FDA CDER Asepetic Guideline 2004
EUROPEAN Annex 1
In Operation
Grade 5
Particle level per Action Level
CFU/cu.m.
cubic meter 0.5
g
(plate))
(p
micron and larger
3520
1
(ISO 5)
(1)
In Operation
At Rest
A
3520
(ISO 5)
3520
(ISO 5)
B
352,000
(ISO 7)
3520
(ISO 5)
C
3,520,000
(ISO 8)
352,000
(ISO 7)
"D"
None
3,520,000
(ISO 8)
Description
CRITICAL AREA
Grade 6
35,200
(ISO 6)
7
(3)
Supporting clean
Grade 7
352,000
(ISO 7)
10
(5)
CONTROLLED
AREA
Grade 8
3,520,000
(ISO 8)
100
(50)
CNC (with local
monitoring)
CNC
Unclassified
NA
NA
NA
NA
Support
100 PCF =100 particles/cu.ft. = 3520 particles/cu.m.
16
CNC = Controlled, Not Classified
Lifted from draft ISPE Sterile Baseline Guide
How Much Air Flow is Enough for a
Cl
Classified
ifi d S
Space?
?
• Enough
g to meet Regulation
g
• >20 air changes per hour (USA)
• 15-20 minute recovery (Europe)
• 10-20
10 20 cfm fresh air/ person (usually no issue)
• Enough to meet cooling load
• Sensible btu = 1.085 x Q in cfm x ∆T in °F
• Enough to offset exhaust + exfiltration
• Enough clean air to offset particle generation
• Dilution
• Displacement
17
Wh t' an Air
What's
Ai Change?
Ch
?
• Air
Ai change
h
= th
the replacement
l
t off one room volume
l
• ACH (air changes per hour) = cubic feet supply
air/hr (CFH or CuM/hr) divided by room volume (in
cu.ft. or CuM)
• Supply air CFH = CFM x 60
Question:
• Do I subtract the volume of fixed items in the
room?
18
Why Air Changes?
Formula for Dilution of Contaminants
Where the ventilation rate has been adjusted by a mixing factor K.
C = concentration of a gas
G = contaminant gas generation rate
V = room volume
Q = Ventilation rate into or out of the room
Q' = adjusted ventilation rate of the volume
19
The Fallacy
y of Air Changes
g
Contaminant Generation
Process
Design
Process
People
Contaminant Ingress
Pressurization
/ Direction of Airflow
Filtration
Risk
Mitigation
Isolation
Contaminant Removal
Containment
Local
Exhaust Ventilation
Room
Performance
System
Performance
Ventilation
Effectiveness
20
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