Pharm Life Sciences

Particle Counting and Environmental Monitoring In
Pharmaceutical / Life Sciences
LIGHTHOUSE WORLDWIDE SOLUTIONS

WWW.GOLIGHTHOUSE.COM
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Introduction
The pharmaceutical and medical device industries are developing new
technologies and new techniques at an ever increasing rate. Regulatory
requirements are being defined, implemented and audited more
frequently.
Certain aspects of manufacturing and R&D require the use of
cleanrooms and controlled environments. In order to comply with the
various cleanroom and regulatory requirements facilities must have
environmental monitoring programs.
This presentation will cover the various cleanroom standards as they
relate to environmental monitoring programs and highlight the use of
particle counters and their use and implementation in the
pharmaceutical industry. Additional information is provided on the use
of FMS system for pharmaceutical monitoring, their validation and
compliance with various regulations.
Outline
cGMPs and Regulations
Cleanroom Standards for Pharmaceutical and Medical
Device Manufacturing and Explanation of Grades
The Purpose of an Environmental Monitoring Program
Regulatory Requirements
Recommendations for Microbial Contamination
What to Monitor
Current Good Manufacturing Practices

Umbrella GMPs, 21 CFR parts 210, 211
Biologics, 21 CFR part 600 series
Devices and Diagnostics, 21 CFR part 800 series
International GMPs
FDA Guidelines for Aseptic Processing
FDA Guidelines for Process Validation
FDAs Points to Consider
NIH Containment Guidelines
ISO 14644-1/FED-STD 209E
Application of Regulations
Pre-clinical Work
Material is Experimental with no GMPs applicable
(Good Documentation Recommended)
Phase I Trails
Acute Toxicity to Animals and Then Very Preliminary
testing of Healthy Volunteers: GMPs Apply for Raw
Material Controls, Documentation, Analytical Methods
etc.
Application of Regulations
Phase II & III
Compliance With Full GMPs and Validation
Production Phase
Compliance With Full GMPs and Validation
What Makes a Cleanroom Work? Conventional Cleanroom
HEPA Filters
Return
in ceiling
Air
Plenum
Grade Level Floor

Return Air Grill
Near Floor
1) Control Of Incoming Air Volume (Dilution)
Return Air Grill

Near Floor
2) Filtration
What Makes a Cleanroom Work? Uni-Directional Cleanroom
HEPA Filters
Return
in ceiling
Return
Air
Air
Plenum
Plenum
Raised Floor
Return Air Plenum
1) Control Of Air Flow and Direction
2) Filtration
Cleanroom Standards
FED-STD 209E
BS 5295
ISO 14644-1
EU GGMP
Fed-Std 209 E
CLASS NAME
0.1M
0.2M
FED-STD 209
0.3M
0.5M
VOLUME UNITS VOLUME UNIT VOLUME UNIT

S.I.
ENGLISH (M )
M1
M1.5
1
M2
M2.5
10
M3
M3.5 100
M4
M4.5 1000
M5
M5.5 10000
M6
M6.5 100000
M7
350
1240
3500
12,400
35,000
VOLUME UNIT
3
(FT ) (M )
(FT ) (M )
(FT )
(M )
9.91
35
99.1
350
991
2.14
7.5
21.4
75
214
750
2,140
0.875
3
8.75
30
87.5
300
875
10
35.3
100
353
1,000
3,530
10,000
35,300
100,000
353,000
1,000,000
3,530,000
10,000,000
75.7
265
757
2,650
7,570
26,500
75,000
30.9
16
309
1,060
3,090
10,600
30,900
5.0M
VOLUME UNIT
3
(FT )
0.283
1
2.83
10
28.3
100
283
1,000
2,830
10,000
28,300
100,000
283,300
(M3)
(FT3)
247
7
618 17.5
2,470 70
6,180 175
24,700 700
61,800 17,500
Fed-Std 209 E
IEST WG 100 has recommended to the GSA (U.S. General Services
Group) that they (GSA) discontinue the use and maintenance of
FED-STD-209. The next step is for GSA to poll the U.S. Federal
Agencies on the proposal that FED-STD-s09 be dropped and that the
Federal Agencies use ISO 14644-1 and 2.
Many organizations refuse to change, stating the cost of document
changes are too expensive to warrant replacement of the standard.
It is commonly accepted still in some facilites in the United States and in
Asia.
BS 5295
Part 1 : 1989 Appendix 3 - Designation of Environmental Cleanliness
Table 2. Requirements for controlled environment installations
Maximum permitted number of particles/m3
Minimum pressure difference*
(equal to, or greater than, started size)
Class of
environmental
cleanliness
C
D
E
F
G
H
J
K
L
M
0.3 m
100
1000
10000
NS
100000
NS
NS
NS
NS
NS
0.5 m
35
350
3500
3500
35000
35000
350000
3500000
NS
NS
5 m
0
0
0
0
200
200
2000
20000
200000
NS
10 m
NS**
NS
NS
NS
0
0
450
4500
45000
450000
25 m
NS
NS
NS
NS
NS
NS
0
500
5000
50000
Maximum
Between
floor area per
classified
sampling
area and
position for unclassified
clean rooms
area
m2
Pa
10
15
10
15
10
15
25
25
25
50
50
50
15
15
15
15
10
10
Between
classified area
and adjacent
area of lower
classification
Pa
10
10
10
10
10
10
10
10
NA***
* This applies only to clean rooms and totally enclosed devices

* NS: no specified limit
*** NA: not applicable as no limit specified
ISO 14644-1
Classification
numbers
numbers (N)
Maximum concentration limits (particles/m of air) for particles equal to and

larger than the considered sizes shown below
0.1m
0.2m
0.3m
0.5m
ISO 1
10
ISO 2
100
ISO 3
1m
5.0m
24
10
1 000
237
102
35
ISO 4
10 000
2 370
1 020
352
83
ISO 5
100 000
23 700
10 200
3 520
832
29
ISO 6
1 000 000
237 000
102 000
35 200
8 320
293
ISO 7
352 000
83 200
2 930
ISO 8
3 520 000
832 000
29 300
ISO 9
35 200 000
8 320 000
293 000
ISO 14644-1
The most international of all cleanroom standards. Has effectively
replaced FED-STD 209E and BS 5295 (in the UK)
Some organizations refuse to change, stating the cost of document
changes are too expensive to warrant replacement of the standard.
EU Guide to Good Manufacturing Practice

Manufacture of Sterile Medicinal Products
3
Maximum permitted number of particles / m equal to or above
at rest
Grade
A
B (a)
C (a)
D (a)
0.5M
3,500
3,500
350,000
3,500,000
in operation
5M
0
0
2,000
20,000
0.5M
3,500
350,000
3,500,000
not definded ( c )
5M
0
2,000
20,000
not definded ( c )
(c) Notes:
(a) In order to reach the B, C and D air grades, the number of air changes should be related to the size of the room and the
equipment and personnel present in the room. The air system should be provided with appropriate filters such as HEPA for grades
A, B and C.
(b) The guidance given for the maximum permitted number of particles in the at rest condition corresponds approximately to the US
Federal Standard 209E and the ISO classifications as follows: grades A and B correspond with class 100, M 3.5, ISO 5; grade C
with class 10 000, M 5.5, ISO 7 and grade D with class 100 000, M 6.5, ISO 8.
(c) The requirement and limit for this area will depend on the nature of the operations carried out.
EU GGMP Explanation of the Grades

For the Manufacture of Sterile Medicinal Products Normally 4 Grades
Can be Distinguished.
Grade A: The Local Zone for High Risk Operations
Filling Zone
Stopper Bowls
Open Ampoules and Vials
Making Aseptic Connections
Normally Such Conditions are Provided by a Laminar Air Flow Work Station.
Laminar Air Flow Systems Should Provide an Homogeneous Air Speed of 0.45
m/s +/- 20% (Guidance Value) at the Working Position.
Grade B: In Case of Aseptic Preparation and Filling

The background environment for grade A zone.
Grades C and D:
Clean areas for carrying out less critical stages in the manufacture of sterile products.
Recommendations for Microbial Contamination

Recommended limits for microbial contamination (a)
air sample
settle
contact plates
glove print. 5
cfu/m3
plates
(diam.55 mm),
fingers.cfu/glove
(diam. 90
cfu/plate
GRADE
mm), cfu/4
hours(b)
A
< 1
< 1
< 1
< 1
B
10
5
5
5
C
100
50
25
D
200
100
50
Notes:
(a)
(b)
(c)
These Are Average Values.

Individual Settle Plates May Be Exposed For Less Than 4 Hours.
Appropriate Alert And Action Limits Should Be Set For The Results Of
Particulate And Microbiological Monitoring. If These Limits Are Exceeded
Operating Procedures Should Prescribe Corrective Action.
Examples of operations to be carried out in the various grades

Grade
Examples of operations for terminally sterilised products. (see par. 11)
Filling Of Products, When Unusually At Risk.
Preparation Of Solutions, When Unusually At Risk. Filling Of Products.
Preparation Of Solutions And Components For Subsequent Filling.
Grade
Examples Of Operations For Aseptic Preparations. (See Par. 12)
Aseptic Preparation And Filling.
Preparation Of Solutions To Be Filtered.
Handling Of Components After Washing.
Order of Risk Based on Route of Administration

Parenteral & Ophthalmic Products
Inhalation Solutions
Aerosol Inhalants
Nasal Sprays
Vaginal And Rectal Suppositories
Topicals
Oral Liquids
Oral Tablets & Capsules
19
The Purpose of an Environmental Monitoring Program

Human Drug cGMP Notes, March, 1999 states that the
purpose is to:
Provides crucial information on the quality of the aseptic
processing environment during manufacturing
Prevents the release of potentially contaminated batch if
appropriate standards are not fulfilled
Prevents future contamination by detecting adverse trends
20
What are the Regulatory Requirements for Microbial Monitoring in
a Pharmaceutical Manufacturing Area?
21
21 CFR 211.42 Design & Construction Features

211.46 Ventilation, Air Filtration, Air Heating & Cooling
211.113 Control of Microbiological Contamination
211.22 Responsibilities of the quality control unit
22
FDA Guideline on Sterile Drug Products Produced by Aseptic
Processing, June 1987
FDA Guide to Inspection of Sterile Drug Substance
Manufacturers, July 1994
EU Guide to Good Manufacturing Practice. Annex on the
Manufacture of Sterile Medicinal Products, June 1997
23
Regulatory Requirements: 21 CFR 211.42

21 CFR 211.42
Design & Construction Features highlights that buildings used
to manufacture pharmaceutical products shall be of suitable
size, construction & location to facilitate cleaning, maintenance
and proper operation.
24

21 CFR 211.42 (Cont)
Aseptic processing requires floors, walls & ceilings of smooth,
hard surfaces that are easily cleaned, temperature & humidity
controls, HEPA-filtered air, systems for environmental
monitoring, cleaning & disinfecting, & maintaining the controlled
environment.
25
21 CFR 211.46
Ventilation, Air Filtration, Air Heating & Cooling (b) requires
equipment for adequate control over microorganisms for the
manufacture, processing, packaging or holding a drug product.
26

21 CFR 211.113
Control of microbiological contamination. Requires that
appropriate written procedures, designed to prevent the
objectionable organisms in non-sterile drug products and
microbiological contamination of sterile drug products, be
established and followed. Such procedures shall include the
validation of any sterilization process.
27
Regulatory Requirements: 21 CFR 211. 22
21 CFR 211. 22
Responsibilities of the Quality control unit.
Requires that the quality control unit monitor & ensure
ongoing control of an aseptic process with the responsibility
of approving or rejecting all drug products manufactured.
28
FDA Guideline on Sterile Drug Products Produced by
Aseptic Processing, June 1987
Guideline suggests that a clean room air quality of not more
than 0.1 colony-forming unit (CFU) per cubic foot in a Class
100 aseptic process area is reasonable.
29
EU Guide to Good Manufacturing Practice. Annex 1 on the

Manufacture of Sterile Medicinal Products, 1997
Recommends limits for environmental monitoring that differ
from the USP
30
Industry Practice
PDA Technical Report No. 13 Fundamentals of a
Microbiological Environmental Monitoring Program
*PhRMA Task Force Report on Environmental Monitoring in
Non-Sterile Manufacturing Areas.
BS 5295 Classification, Design & Commissioning Cleanrooms
US Federal Standard 209E for Cleanrooms
ISO and BS 14644 for Cleanrooms
*Pharmaceutical Research and Manufacturers of America (PhRMA)
31
Difference between US and European Practices - Class 100
US monitors during each operating shift
For Grade A aseptic preparation & filling the EU

recommended limits as average values are:
<1 cfu per m3 of air
<1 cfu per 4 hour on a 90 mm settling plate
<1 cfu per 55 mm contact plate
<1 cfu for a 5 finger glove print
32
Setting Limits and Trend Analysis

Limits Would Be Consistent With Regulatory Guidelines
Alert Limits Should Be Set From Monitoring Histories At The
95% Percentile
With >98% Of The Samples Taken Containing No
Microorganisms, Limit Setting & Trend Analysis Is More Difficult
Reaction Should Be To Consecutive Out-of-limit & Not
Individual Results
33
Timing of Microbial Monitoring
The Air And Surface Monitoring Should

Be Conducted Actively During The Aseptic
Processing Operation With Personnel
Monitoring When The Operator Leaves The
Process Area. An Exception Would Be The
Monitoring Of Product Contact Surfaces
Which Would Be Monitored At The End Of
The Filling Operation.
34
Environmental Monitoring Program

Surface Monitoring
Active Air Monitoring
Passive Air Monitoring
Microbiological Media and Identification
Particle Counting
Surface Monitoring
Testing Various Surfaces for
Microbiological Quality:
Product Contact Surfaces
Floors
Walls
Ceilings
Testing Carries Out By Using:
Contact Plates
Touch Plates
Swabs
Surface Rinse Method
Active Air Monitoring

Method to Determine the
Microbial Quality of the Air
Using Active Devices Such as:
Slit to Agar
Membrane Filtration
Centrifugal Samplers
All Allow a Quantitative Testing of
the Number of Organisms per
Volume of Air Sampled
Passive Air Monitoring (Settling Plates)

Petri Dishes Containing
Nutrient Growth Medium
Exposed to the Environment
Lack Quantitative Value (Only
What Settles On Plate)
Qualitative Value Important As
Can Be Placed In Locations
With The Greatest Risk
Microbiological Media and Identification

Routine Characterization of Recovered Microorganisms
Monitoring of Critical and Surrounding Areas
Monitoring of Personal
Should Require Identification of Species or Genus
The Goal Is To Reproducibly Detect Microorganisms For
The Purpose Of Monitoring Environmental Control
Particle Counting
Useful in detecting significant deviations in air
cleanliness from qualified processing classifications
Immediate understanding of air quality can be realized
Useful as a tool for qualification and monitoring before /
during and after operations
Particle Counter Theory of Operation

There are three basic elements in all particle counting systems:
1) The Sensor
The Sensor Is The Device That Detects Particles Using A Light Scattering
Techniques.
2) The Sample Delivery System
The Air Sample is Delivered the Sensor by Some Method.
3) The Counting Electronics
The Particle Counts Are Processed And Displayed By On Board Circuitry
Or In Software In Facility Monitoring Systems (FMS).
Particle Counter Operation

Reflector
Reflector
Limited
Limited
Beam
Beam
Stop
Stop
Reflector
Reflector
LASER
Source
Collection
Collection
Lenses
Lenses
Photo
Photo
Detector
Detector
For
For
Particle
Particle
Detection
Detection
Photo
PhotoDetector
Detector
For
ForCalibration
Calibration
Voltage
Voltage
Output
Output
Signal
Signal
Sensor View Volume
The View Volume is

The area where the
air stream and the
laser beam intersect.
The View Volume is
the width of the inlet tube
and + 1mm high.
Inlet Tube
Laser beam viewed in cross section
Particle Sizing
Largest
The larger the particle , the

larger the corresponding
output pulse from the
Larger
sensor.
Smaller
Signal To Noise Ration
C
O
U
N
T
S
Noise valley
10
Peak Signal
20
30
40
50.
Milivolts
In accordance with the Japanese Industrial Standard (JIS) the minimum Signal to Noise Ratio is 2 to 1.
50% Counting Efficiency

50% point of a
monodisperse
distribution
C
o
u
n
t
s
Smaller than nominal size
Larger than nominal size
Particle size
Definition: In a monodisperse distribution, the sensor detects all particles at the nominal size and larger.
JIS requires that the counting efficiency of the smallest detectable size of a sensor be between 30 and 70%.
Sensor Resolution
Poor resolution
Good resolution
Perfect resolution
Causes of poor resolution:

Contamination. A buildup of particles in the sensor can disturb the light path.
Misaligned sensor. A misaligned sensor must be returned to the factory for alignment.
Failing laser diode. This sensor must also be returned to the factory for diode replacement.
Why perfect resolution can not be achieved.

Laser beam in cross section
Particle
The above laser beam has uniform light intensity across the entire width.
Wherever a particle enters the beam the output pulse is the same.
This can not be achieved due to slight flaws in the optics and laser diode.
=
In this example a particle has entered the laser beam in an area of lower light intensity.
The resulting output pulse is low.
Note: These examples

assume uniform sized
particles
=
In this example the particle has entered the higher intensity area of the beam and
the output pulse is higher in amplitude.
Coincidence Error
If particle counter is used in environments where the concentrations of particles are too high
more than one particle at a time can enter the view volume. This results in coincidence errors.
=
In this example shows one 0.5 particle in the view volume and its output pulse.
=
This example shows two 0.5 particles in the view volume at the same time. The counter would
report a size larger than 0.5 and only one count.
Effects of Flow on Sizing

The amplitude of the sensor output is a function of the particles residence time in the view volume.
0.5 particle
1.0cfm flow rate
0.5 particle
1.2cfm flow rate
0.5 particle
0.8cfm flow rate
=
=
=
Optimum flow
Flow is too high. The

particle appears smaller than
it actually is
Flow is too low. The

particle appears larger than
it actually is.
Sample Delivery
A vacuum pump is used to pull the sample air through the sensor.
The flow is measured in cubic feet per minute (cfm). The use of
some type of flow control is required to maintain the correct flow.
1.0 cfm pump
0.1 cfm pump
Critical Orifice
In remote counters a critical orifice is used to regulate the flow through the sensor.
A critical orifice is a precision opening that will only allow a certain amount of air flow
once the critical vacuum pressure is applied.
In the case of Lighthouse counters the critical pressure is 18Hg.
Regulated flow
(1.0cfm or 0.1cfm
Depending on the sensor)
Critical
orifice
18Hg vacuum pressure
Counting Electronics
+V
Threshold Circuit
This circuitry is
duplicated from one
channel up to six
channels depending on
the model counter
CH3
+V
CH2
Digital signals to
counting circuitry
Analog Signal in
+V
CH. 3
CH. 2
CH1
CH. 1
Counting Electronics cont.
Threshold Circuit
This circuitry is
duplicated from one
channel up to six
channels depending on
the model counter
+V
CH3
+V
CH2
Digital signals to
counting circuitry
Analog Signal in
+V
CH. 3
CH. 2
CH1
CH. 1
Counting Modes (Cumulative vs. Differential)
Cumulative
Differential
Size 3
Size 2
Size 1
Data Display Modes (Printed vs. Electronic Records)
Remote Communication Modes
Digital
RS232
RS485
Modbus
Computer
Monitoring
System
Analog
4-20mA
PLC
CEMS
Sensor Interface Unit
SIU or SIU Lite
Particle Counting: Manual

Manual Particle Counting
Lowest Cost
Purchase
Service
Calibrate
Routine Tests For Compliance

Finding Contamination Sources
Used To Identify Sensitive
Locations For Continuous
Monitoring
Particle Counting: Extended Sampling

Manual Particle Counting
Program and Forget
Good for Long Term
Testing
Flexible
Better Then Periodic
Testing When Issues
Arise
Portable Particle Counters
Variety of Manufactures
Tethered or Battery Operated Options
Typically Higher Flow Rates (1 CFM)
Built In Printers / Data Storage
Some Units are Manifold Ready
Automated Sequential Particle Counting

A. Automated Tests For Compliance
B. Up to 32 Points / Particle Counter (in sequence)
C. Sensitivity 0.1 micron
D. Time Between Particle Counts (same location) Based Upon The
Number of Points Sampled by the Counter
E. Episodes Of Particle Excursions Can Be Missed
Sequential Particle Counting System Operation: (Manifold or Scanner)
Purge
Sample 1
Sample Time 1 minute
Sample 2
Last
Sample
Purge

Wall Mount
Isokinetic Probes
Purge
Up to 32
Locations
Blower
32 Port Universal
Manifold
Universal Manifold
Controller
SOLAIR
Particle Counter
Sequential Sampling Particle Counting Systems:

Variety of Manufactures
Lower Cost / Point (Higher Sensitivity Possible)
Monitor Up To *32 Points With A Single Counter
Maximum Time To Re-Sample Is Dependant On
Number of Points
Connection To External System Easy
Lower Calibration Cost
* Manufacturer Dependant
Manifold Points vs. Samples / Day

Number of Ports Samples
* Time between Samples at

the same location
* Number of samples per day

at same location
10 Ports
11 Minutes 40 Seconds
123 Samples
12 Ports
14 Minutes
103 Samples
16 Ports
77 Samples
24 Ports
28 Minutes
51 Samples
32 Ports
39 Samples
40 Ports
31 Samples
* Based on 1-minute sample, 10 second purge time
Dedicated Remote Particle Counters

A.
B.
C.
D.
Real-Time Monitoring and Alarming

Sensitivity 0.1 Micron
Catches Every Particle Event
Can Utilize Less Sensitive and Less Expensive
Discrete Counters (0.3m vs. 0.07 m )
Real Time Particle Monitoring

Individual Sensors
Vacuum Source
(Process Vacuum or Separate Vacuum Pump)
Comparison of Counting Techniques (Samples / Day Same Location)

1440
* Real Time 1 Minute Sample
** Real Time 10 min. Avg
144
***Seqential (32 Points)
36
3
**** Manual
0
200 400 600 800 1000 1200 1400 1600
1 Minute Sample Time
**
Based On Continues Counting And Average Data For 10 minutes
*** Using 32 Port Sampling System, 1 Minute Sample / Point, 15 Second Purge Step
**** 1 Sample per Shift
Why Use an FMS System?

REGULATORY COMPLIANCE:
STATUTORY REQUIREMENTS
INDUSTRY STANDARDS
ISO COMPLIANCE
QUALITY CONTROL:
YIELD MANAGEMENT
RELIABILITY GROWTH
PROCESS CONTROL
Benefits of a Cleanroom Facility Monitoring System
Real Time Response The monitoring system provides

early warning when conditions exceed user defined limits.
This minimizes environmentally induced yield losses by
providing the operators and supervisors with the visibility
they need to react to problems in real-time.

Process Improvement By correlating cleanroom or
process modifications against historical data from the
system, better process improvement decisions can be
made.
Yield Improvement Early warning and correlation of
events to yield losses helps in improving the
manufacturing conditions. This correlation ability also
facilitates the analysis of equipment maintenance cycles.
Proactive Contamination Control Using an on-line

system allows you to take a proactive roll in identifying
potentially damaging contamination issues before they
happen.
Customer Confidence An on-line system gives your
customer confidence that you are concerned about their
products.

Data Correlation The data from an on-line system allows
you to correlate various events and tie them back to yield
loss.
Shift change and particle counts
Particle counts and yield loss
Tool operation and particle, TRH and ESD
Differential pressure and particle
Humidity and ESD events
Product transport operations and particle counts
Air Quality in Cleanrooms
Many parameters affect the quality of the air

in a clean room or minienvironment
A. Airborne particle concentration
B. Temperature and relative humidity
C. Room and minienvironment pressurization
D. Air velocity and direction
E. Airborne Molecular Contamination
F. Other Factors
Facility Monitoring System Parameters

Monitor Parameters:
Aerosol Particle Counts
Temperature
Relative Humidity
Differential Pressure
Air Velocity
TC, TOC
Conductivity
Electrostatic Discharge
Viable Particle Monitoring / Control
Liquid Particle Counts
WFI Particle / Conductivity
Considerations in System Design

PURPOSE OF THE SYSTEM
Watch Dog
Evaluation of Cleanroom Conditions
Tool For Facilities
Customer Satisfaction
Marketing Tool
Considerations in System Design

PARAMETERS TO BE MONITORED: Considerations
Sensor Sensitivity
Sensor Scale
Sensor Cost
Sensor
Connectivity
Durability
of Sensors for the Application
Service
and Calibration Schedules of the Sensors
Sensor
Location
Integration
Impact
of Sensors Into the Cleanroom
of Installation on Cleanroom
Factors To Consider When Choosing A System

System Management:
Who Will Be Using The System?
Who Will Be Managing The System?

Data Collection
How Will The System Respond To Catastrophic Events?
How Will The System Generate And Display Alarm Conditions?
Historical Records
How Will The System Record Incoming Information?
Will The System Generate Reports to Compare Different Areas at Different

Times?

Information Management:
How Will The System Record Data From The Installed Sensors?
Will The System Collect Data At A Higher Rate When The Sensor Is In An
Alarm Condition And At A Lesser Rate When The Sensor Is In Normal
Range?
Manipulation and Access

How Will The Interact With The User?
What Type Of Graphical User Interfaces Are Available With The System?
What Operating System Will The System Run On?
How Many Users Will Need To See The Data?

Configuration And Expansion:
What Features Are Available To Assist Users In

Configurations, Expanding and Managing The System?
How Will The System Be Expanded In The Future?
What Options Are Available to Connect Future Sensor

Technology
What to Monitor? Cleanroom:

Cleanroom Conditions (Conditions Related to Cleanroom Operation)
Aerosol Particle Counts

Differential Pressure
Temperature
Relative Humidity
Air Velocity
Air Changes / Per Hour
Air Handlers or Fan Filter Unit Status
Air Plenum Return Pressures
What to Monitor? Process:

Process Related Conditions (As Related To Products Produced)
Airborne Molecular Contamination Levels (AMC)

Electrostatic Charge (Environmental or on Product Surfaces)
Ionization System Status
Ground Status
EMI
SYSTEM DEVELOPMENT LIFE CYCLE GAMP 4 V-MODEL
Electronic Records and Signatures
Audit Trails
Provide activity record as required by 21 CFR Part 11
Entries include
User ID
Date and Time
Type of Action or Event
Previous value
New Value
System can be set to require user to enter password and insert a

comment when
making system changes

acknowledging alarms
Audit trail log can be printed

Logs of Alarm, Event or Audit Activities
each log can be separately printed

User Access Controls
Multi-level permissions
Unique User ID using Passwords
Password Aging
Auto Log out for User Inactivity
Lock Out of User after Failed Log-ins
Administrator can DISABLE access by a user
Separate public NAME used for listing on reports or
comment fields
Hardware Supported
Room-to-room Pressure Differential
Humidity and Temperature
Air Velocity
PLC Inputs and Outputs
Contacts Closures (Doors, events)

Alarm signaling: Light stacks; audible alarms; relays
Analog inputs through PLC (0 to 5 v; 4 to 20 ma)
Liquid Parameters;
Liquid Particle Counts, TOC, Conductivity, pH, DO, and more
Airborne Particle Counters
Individual Counters
Manifold / Scanner Multi-point systems
Remote (Fixed) Counters
any combination of the above
System Configuration Examples

Standalone system (server/client combined)
Standalone System with Network Mirror Site
Simple Networked system
Single server/database with multiple clients
Complex Networked System
Multiple servers and databases, multiple clients
Standalone system (server/client combined)
Server/client
with database
Counter with
manifold
Met One 2315 or
similar Remote
Counters
PLC
Standalone system with Database Mirror
Optional: secondary
database storage on
another computer
Customer's
Network
Server/client
with database
Counter with
manifold
Met One 2315 or
similar Remote
Counters
PLC
Simple Networked System
CLIENT
#1
Room A
CLIENT
#2
Room B
CLIENT
#3
Room C
CLIENT
#4
Room D
Server/client
with
database
Counter with
manifold
Met One 2315 or
similar Remote
Counters
PLC
Complex Networked System
CLIENT# x
CLIENT# y
Counter
with
manifold
CLIENT# z
Met One 2315 or similar
Remote Counters
CLIENT# 1
CLIENT# 2
CLIENT# 3
CLIENT# 4
Server/client
with database
Building #1
Building #2
Met One 2315 or similar

Remote Counters
Counter
with
manifold
PLC
Thank You
Thank You
LIGHTHOUSE WORLDWIDE SOLUTIONS
WWW.GOLIGHTHOUSE.COM

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Particle Counting and Environmental Monitoring In

Pharmaceutical / Life Sciences

LIGHTHOUSE WORLDWIDE SOLUTIONS

Current Good Manufacturing Practices

What Makes a Cleanroom Work? Conventional Cleanroom

Grade Level Floor

Return Air Grill

What Makes a Cleanroom Work? Uni-Directional Cleanroom

VOLUME UNITS VOLUME UNIT VOLUME UNIT

(equal to, or greater than, started size)

* This applies only to clean rooms and totally enclosed devices

Maximum concentration limits (particles/m of air) for particles equal to and

EU Guide to Good Manufacturing Practice

Maximum permitted number of particles / m equal to or above

EU GGMP Explanation of the Grades

Grade B: In Case of Aseptic Preparation and Filling

Recommendations for Microbial Contamination

These Are Average Values.

Examples of operations to be carried out in the various grades

Examples of operations for terminally sterilised products. (see par. 11)

Filling Of Products, When Unusually At Risk.

Preparation Of Solutions, When Unusually At Risk. Filling Of Products.

Preparation Of Solutions And Components For Subsequent Filling.

Examples Of Operations For Aseptic Preparations. (See Par. 12)

Aseptic Preparation And Filling.

Preparation Of Solutions To Be Filtered.

Handling Of Components After Washing.

Order of Risk Based on Route of Administration

The Purpose of an Environmental Monitoring Program

21 CFR 211.42 Design & Construction Features

Regulatory Requirements: 21 CFR 211.42

Regulatory Requirements: 21 CFR 211.42

Regulatory Requirements: 21 CFR 211.46

Regulatory Requirements: 21 CFR 211.113

Regulatory Requirements: 21 CFR 211. 22

EU Guide to Good Manufacturing Practice. Annex 1 on the

Difference between US and European Practices - Class 100

US monitors during each operating shift

For Grade A aseptic preparation & filling the EU

Setting Limits and Trend Analysis

Timing of Microbial Monitoring

The Air And Surface Monitoring Should

Environmental Monitoring Program

Active Air Monitoring

Passive Air Monitoring (Settling Plates)

Microbiological Media and Identification

Particle Counter Theory of Operation

Particle Counter Operation

Sensor View Volume

The View Volume is

Laser beam viewed in cross section

The larger the particle , the

Signal To Noise Ration

50% Counting Efficiency

Smaller than nominal size

Larger than nominal size

Causes of poor resolution:

Why perfect resolution can not be achieved.

Note: These examples