The document provides an overview of cleanroom classifications according to ISO, US Federal Standard 209E, and European standards. It discusses particle sources and control methods like filtration, dilution with higher air changes, and isolation. PIC/S guidelines recommend grade A environments with precise air control for high-risk aseptic operations, and grade B-D cleanrooms for less critical stages. Microbial limits and air monitoring frequencies are specified depending on the cleanroom grade.
This is the 1st part of our "All about cleanrooms". This presentation will take you through the history of cleanrooms, types and applications of cleanrooms.
Contamination Control in Cleanrooms_Dr.A. AmsavelDr. Amsavel A
Basic’s of Contamination
Sources of Contamination
Environment Specification
Elements of Cleanroom Design and Qualification
Definitions
Control of Contaminations
People, Cleaning, Environment & Material
Operation, Monitoring and Control
Documents and Records
This is the 1st part of our "All about cleanrooms". This presentation will take you through the history of cleanrooms, types and applications of cleanrooms.
Contamination Control in Cleanrooms_Dr.A. AmsavelDr. Amsavel A
Basic’s of Contamination
Sources of Contamination
Environment Specification
Elements of Cleanroom Design and Qualification
Definitions
Control of Contaminations
People, Cleaning, Environment & Material
Operation, Monitoring and Control
Documents and Records
To maintain the desired SAL at the plant is task which demands great care and control over Man, Machine & Method. This summarize work will definitely help you as hand note.
Cleaning and Disinfecting the CleanroomPeter Lojac
Cleaning and disinfecting your cleanroom environment is the only way to maintain its efficacy. This presentation explains the cleanroom cleaning methods and types of contaminants.
Source of contamination, Air flow system: conventional, Unidirectional, laminar air flow unit, Air filtration, mechanisms: Fibrous and HEPA filters, Temperature and humidity control, Building design, construction and use, personnel, Protective clothing, cleaning, and disinfecting, commissioning test of clean and aseptic rooms, routine monitoring tests, The operation of clean aseptic room, Key factors in clean room operations.
Includes cleanroom rules, cleanroom techniques, cleanroom behavior, protocol and practices. Movement in cleanroom, handling in the cleanroom, nature of cleanroom personnel and wrong practices in the cleanroom.
What is likely to go into the revised Annex 1, including:
Terminal sterilisation vs aseptic processing
WFI produced by reverse osmosis
Guidance for media simulation trials
This remains speculative
To maintain the desired SAL at the plant is task which demands great care and control over Man, Machine & Method. This summarize work will definitely help you as hand note.
Cleaning and Disinfecting the CleanroomPeter Lojac
Cleaning and disinfecting your cleanroom environment is the only way to maintain its efficacy. This presentation explains the cleanroom cleaning methods and types of contaminants.
Source of contamination, Air flow system: conventional, Unidirectional, laminar air flow unit, Air filtration, mechanisms: Fibrous and HEPA filters, Temperature and humidity control, Building design, construction and use, personnel, Protective clothing, cleaning, and disinfecting, commissioning test of clean and aseptic rooms, routine monitoring tests, The operation of clean aseptic room, Key factors in clean room operations.
Includes cleanroom rules, cleanroom techniques, cleanroom behavior, protocol and practices. Movement in cleanroom, handling in the cleanroom, nature of cleanroom personnel and wrong practices in the cleanroom.
What is likely to go into the revised Annex 1, including:
Terminal sterilisation vs aseptic processing
WFI produced by reverse osmosis
Guidance for media simulation trials
This remains speculative
GMP Requirements for Sterile Products manufacturingsurafel kebede
This training module is prepared based on (Annex 6. TRS 961, 2011) & trainees are highly recommended to read this document together with Annex 6. TRS 961, 2011.
GMP Requirements for Sterile Products manufacturingsurafel kebede
This training module is prepared based on (Annex 6. TRS 961, 2011) & trainees are highly recommended to read this document together with Annex 6. TRS 961, 2011.
TRAINING MODULE FOR IMPLEMENTATION OF GOOD MANUFACTURING PRACTICES FOR STERILE PRODUCT MANUFACTURING.
This training module is prepared based on (Annex 6. TRS 961, 2011) & readers are highly recommended to see this document in conjunction with Annex 6. TRS 961, 2011.
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
4. References
• ISO 14644
• Part 1: Classification of air cleanliness
• Part 2: Continued compliance with
• Part 3: Metrology and test methods
• Part 4: Design, construction and start-up
• WHO Technical Report Series, No. 902, 2002
• Annex 6: Good manufacturing practices for sterile pharmaceutical
products
• WHO Technical Report Series, No. 961, 2011
• Annex 5: WHO guidelines on good manufacturing practices for
heating, ventilation and air-conditioning systems for non-sterile
pharmaceutical dosage forms
• Annex 6: WHO good manufacturing practices for sterile
pharmaceutical products
• PIC/S GMP Guide (Part I: Basic Requirements For Medicinal Products)
• PIC/S Guide To Good Manufacturing Practice For Medicinal Products -
Annexes
1.ISO 14644
2.WHO Technical Report
3.PIC/S
( Pharmaceutical Inspection Co-
operation Scheme )
5. Scope
What will be
covered during
this
presentation
A. A Brief review on cleanroom
classification.
B. Introduction of Design Concepts and
Considerations based on ISO 14644 Series
Standards, PIC/S and WHO Guidelines.
C.Testing Methods and Procedures.
8. Purposes
Cleanrooms provide for
the control of airborne
contamination to levels
appropriate for
accomplishing
contamination-
sensitive activities.
Area Covered :
1. Aerospace,
2. Microelectronics,
3. Pharmaceuticals,
4. Medical devices,
5. Healthcare (Hospitals)
6. Food.
9. Purposes
Three Main
Purposes are :
1. The concentration of airborne
particles is controlled.
2. Constructed and used in a manner to
minimize the introduction,
generation, and retention of particles
inside the room
3. Other parameters (Temperature,
Humidity, and Pressure) are
controlled
10. Classification
Occupancy states:
1. As-built:
Installation is complete, all services functioning,
no production equipment, materials, or
personnel present
2.At-rest:
No personnel present
3. Operational:
The installation is functioning in the specified
manner, specified number of personnel present
and working.
level of airborne particulate
cleanliness,
represents maximum
allowable concentrations
(in particles per cubic
metre of air) for considered
sizes of particles.
11. Classification
The maximum permitted concentration of particles, Cn, for each
considered particle size, D,
where:
Cn represents the maximum permitted concentration ( in
particles/m^3 of air ) of airborne particles that are equal to or
larger than the considered particle size. Cn is rounded to the
nearest whole number.
N is the ISO classification number, which shall not exceed the
value of 9. Intermediate ISO classification numbers may be
specified, with 0.1 the smallest permitted increment of N.
D is the considered particle size in m m.
0.1 is a constant with a dimension of m m.
The particulate cleanliness
of air shall be defined in
one or more of three
occupancy states, viz. “as-
built”, “at-rest”, or
“operational”.
15. Classification
2. US FEDERAL
STANDARD 209E
This standard was first published in
1963 in the USA and titled "Cleanroom
and Work Station Requirements,
Controlled Environments". It was
revised in 1966 (209A), 1973 (209B),
1987 (C), 1988 (D) and 1992 (E)
CLASS LIMITS : 0.5 MICRON
Class CLASS LIMIT
ISO SI ENGLISH CUBIC FOOT
CUBIC
METER
6 M 3.5 100 100 3530
7 M 4.5 1000 1000 35300
8 M 5.5 10000 10000 353000
9 M 6.5 100000 100000 3530000
16. Classification
2. US FEDERAL
STANDARD 209E
CLASS LIMITS : 5 MICRON
Class CLASS LIMIT
ISO SI ENGLISH CUBIC FOOT
CUBIC
METER
6 M 3.5 100
7 M 4.5 1000 7 247
8 M 5.5 10000 70 2470
9 M 6.5 100000 700 24700
17. Classification
3. EUROPEAN ECONOMIC
COMMUNITY
(WHO Technical Report Series,
No. 902, 2002 Annex 6 )
CLASS LIMITS : 0.5 MICRON
Grade MAX. PERMITTED NO OF PARTICLES PER CUBIC
METER EQUAL TO OR ABOVE 0.5 MICRON
At Rest In Operation
A 3520 3520
B 3520 3520 X 100
C 3520 X 100 3520 X 1000
D 3520 X 1000 Not Defined
18. Classification
3. EUROPEAN ECONOMIC
COMMUNITY
CLASS LIMITS : 5 MICRON
Grade MAX. PERMITTED NO OF PARTICLES PER CUBIC
METER EQUAL TO OR ABOVE 0.5 MICRON
At Rest In Operation
A 20 20
B 29 2900
C 2900 29000
D 29000 Not Defined
19. Classification :
Summary
Comparison of Different
Airborne Particulate
Classification System for Clean
Areas.
(This comparison is defined
based on at-rest limitations )
21. Particles
Simply stated, airborne
particles are solids
suspended in the air, falls
within a threshold size in
the range from 0.1 to 5µm.
Since many of these air borne contaminants are
harmful to products and people, their removal is
necessary on medical, legal, social or financial
grounds.
Air, whether it is from outside or re-circulated,
acts as a vehicle for bacterial and gaseous
contaminants brought in by the movement of
people, material, etc.
22. Particles
There are two main
sources of particulates :
1. External Sources and
2. Internal sources.
1. Outside make-up air introduced into the
room: this is typically the largest source of
external particulates
2. Infiltration through doors, windows and
other penetration through the cleanroom
barriers
1. EXTERNAL SOURCES
24. Particles
There are two main
sources of particulates :
1. External Sources and
2. Internal sources.
1. People in the clean area: people are
potentially the largest source of internally
generated particulates
2. Cleanroom surface shedding
3. Process equipment
4. Material ingress
5. Manufacturing processes
2. INTERNAL SOURCES
25. Particles
Control Action
1. Design airflow path to shield humans
from surroundings
2. Use of air showers [to continually wash
occupants with clean air]
3. Using hard-surfaced, non-porous materials
such as polyvinyl panels, epoxy painted walls,
and glass board ceilings
4. Proper gowning procedures, head wear
1. INTERNAL SOURCES
29. Airborne particle
physical control
Calculation of ACH
STEP-1 : Velocity of Air Flow below the HEPA Filter in ft/min.
( V1+V2+V3+V4+V5 )
V =
5
ft/min.
Average Velocity from diffeent Point of HEPA Filter.
STEP-2 : Area of the filter
A = Length X Width ( Sq. Ft )
STEP-3 : Total Air volume Per Minute Supplied in Room.
T = V ( Step-1 ) X A ( Step-2 )
STEP-4 : Total Air in the Room.
Volume = Length X Width X Height ( Cube ft )
STEP-5 : Air han Change Rate per Hour
ACH = T/VOLUME X 60
V1
V
5
V
3
V
2
V
4
31. Selective Area According
to CleanRoom
Classification :
PIC/S
( Pharmaceutical
Inspection Co-
operation Scheme )
• Grade A: The local zone for high risk operations:
• Filling zone, open ampoules and vials, making aseptic
connections.
• Provided by a LAF work station with a homogeneous air speed in
a range of 0.36 – 0.54 m/s (guidance value)
• A unidirectional air flow and lower velocities may be used in
closed isolators and glove boxes.
• Grade B: For aseptic preparation and filling, this is the
background environment for the grade A zone.
• Grade C and D: Clean areas for carrying out less critical
stages in the manufacture of sterile products.
32. PIC/S General
Paragraphs
• Clean Areas:
• Entry through airlocks for personnel and/or for equipment and
materials.
• Supplied with air has passed through filters of an appropriate
efficiency.
• The various operations of component preparation, product
preparation and filling in separate areas within the clean area
• Manufacturing operations:
• Product is terminally sterilized. ( A process whereby a product is
sterilized in its final container or packaging, which permits the
measurement and evaluation of quantifiable microbial lethality. In
principle, the SAL should be less than 10-6.)
• Conducted aseptically at some or all stages.
• In order to meet “in operation” conditions, areas should be
designed to reach certain air-cleanliness levels in the “at rest”
occupancy state.
33. PIC/S General
Paragraphs
• “In operation” classification may be demonstrated
during normal operations, simulated operations or
during media fills (worst-case)
• Clean rooms and clean air devices should be routinely
monitored
• Monitoring locations based on risk analysis and the results
of classification
• Grade A: full duration of critical processing
• Grade A: Such a frequency and sample size that all
interventions, transient events is captured and alarms
triggered
• Grade B: The same as grade A; the sample frequency may
be decreased.
• Grade C and D: in accordance with the principles of
quality risk management.
34. PIC/S General
Paragraphs
• Terminally Sterilized Products
• Preparation of components and most products
should be done in at least a grade D environment
• Where the product is at a high or unusual risk
of microbial contamination Grade C
• Filling of products for terminal sterilization
Grade C
• Where the product is at unusual risk of
contamination from the environment,
filling Grade A with Grade C background.
• Preparation and filling of ointments, creams,
suspensions and emulsions should grade C
before terminal sterilization
35. PIC/S General
Paragraphs
• Aseptic Preparation
• Components after washing Grade D
• Handling of sterile starting materials, unless
subjected to sterilization or filtration Grade A
with Grade B background.
• Otherwise Grade C
• Handling and filling of aseptically prepared products
Grade A
• Transfer of partially closed containers, as used in
freeze drying,
either in a Grade A environment with grade B
background or in sealed transfer trays in a grade B
environment
36. PIC/S Paragraphs
on Premises
• All exposed surfaces should be smooth, impervious
and unbroken
• To reduce accumulation of dust and to facilitate
cleaning there should be no unclean able recesses
and a minimum of projecting ledges, shelves,
cupboards and equipment.
• False ceilings should be sealed.
• Sinks and drains should be prohibited in grade A/B
areas
• Changing rooms should be designed as airlocks, The
final stage of the changing room should, in the at-
rest state, be the same grade as the area into which it
leads.
37. PIC/S Paragraphs
on Premises
• Both airlock doors should not be opened simultaneously;
interlocking system or a visual and/or audible warning
system should be operated.
• A filtered air supply should maintain a positive pressure and
an air flow relative to surrounding areas of a lower grade. a
pressure differential of 10-15 pascals
• It should be demonstrated that air-flow patterns do not
present a contamination risk.
• A warning system should be provided to indicate failure in
the air supply.
38. PIC/S Paragraphs
on Premises
Airlock : Airlock helps to
protect Classified area from
the contamination that may
occurs during entry and exit
of personnel & Materials
.Airlock is called as PAL (
Personnel Airlock ) & MAL
( Material Airlock )
Type :
A. Cascade Airlock : Higher Pressure is one side & Lower pressure is
another side.
Prevent to enter dust & Contaminants from outside
to airlock and from airlock to inner side.
B. Bubble Airlock : Higher pressure inside the Airlock and Lower
Pressure in both out side.
Prevents the flow of air between two areas through
the airlock by creating a pressure barrier.
C. Sink Airlock : Lower Pressure inside the airlock & Higher Pressure
in both the outside.
This airlock Pulls air from both adjacent area by
creating a low pressure barrier.
40. Planning &
Designing
• A project plan shall be developed to define the
requirements of the products, the processes and the scope
of the installation.
• A process equipment list shall be compiled, and shall
include the critical requirements for each piece of process
equipment.
• Diversity factors shall be defined, considering peak and
average demand for each utility and environmental control
system.
• A contamination control concept shall be developed for
each zone of an installation.
41. Design: Control
and segregation
concepts • For economic, technical and operational reasons,
clean zones are often enclosed or surrounded by
further zones of lower cleanliness.
• The zones with the highest cleanliness demands is
reduced to the minimum size.
• Movement of material and personnel between
adjacent clean zones gives rise to the risk of
contamination transfer,
management of material and personnel flow
45. Design: Air Flow Patterns
Air flow patterns:
Clean room airflow patterns can be
categorized as either unidirectional
or non-unidirectional (or mixed).
Unidirectional airflow:
-ISO Class 5 and cleaner
-May be either vertical or horizontal
-Airflow rely upon a final filtered air supply and
-Return inlets are nearly opposite air supplies to
maintain the airstream straight
46. Design: Air Flow Patterns
Air flow patterns:
Clean room airflow patterns
can be categorized as either
unidirectional or non-
unidirectional (or mixed).
48. Design: Air Flow Patterns
- Horizontal Air Flow
- Vertical Air Flow
49. Design: Air Flow Patterns
- Horizontal Air Flow
- Vertical Air Flow
The Position in which the operator stands relative to the
source of Dust liberation and Air flow should be determined
to ensure that the operators is not in the path of an airflow
that could lead to contamination of the product. ( Working
Document QAS/15.639 ).
50. Design: Air Flow Patterns
Situation where an open bin is placed below a
vertical Unidirectional flow distributor. The
downward airflow should be prevented from
entering the bin , and then being forced to rise
again, as this would carry light dust up toward’s the
operators face . So, in this case a partial cover is
need to add over the bin to limit the entry of air .(
Working Document QAS/15.639 ).
- Horizontal Air Flow
- Vertical Air Flow
51. Design: Air Flow Patterns
Air flow patterns:
Cleanroom airflow patterns
can be categorized as either
unidirectional or non-
unidirectional (or mixed).
Non-Unidirectional
airflow:
-Air flow outlets located in
multiple positions. Filter
outlets may be distributed at
equal intervals or grouped over
the core process.
The final filter location may be
remote, (avoid contamination
ingress between filters and
cleanroom)
Return air locations in non-
unidirectional airflows are not
as critical
Distribute the returns to
minimize dead zones within
the cleanroom
52. Design: Air Flow Patterns
Air flow patterns:
Cleanroom airflow patterns can
be categorized as either
unidirectional or non-
unidirectional (or mixed).
56. Design: Segregation
Concepts
1. Displacement concept :
(low pressure differential, high airflow)
-by means of a low turbulent "displacement" airflow, >0,2 m/s.
2. Pressure differential concept :
(high pressure differential, lo.w airflow)
-The pressure differential in the range of
5 - 20 Pa, to allow doors to be opened
and to avoid unintended turbulence.
3. Physical barrier concept
-Use of an impervious barrier to prevent contamination transfer to a clean
zone from a less clean zone.
In order to protect clean
rooms from
contamination from
adjacent less clean
spaces:
57. Design: Layout of an
installation
General
Considerations:
• Size: of cleanroom should be minimum. if a large space
is required, it should be divided, with or without physical
barriers.
• Workstation siting and organization: critical
workstations away from, major traffic pathways.
less clean operations site downstream of cleaner
operations.
• Ancillary areas and adjacent cleanrooms:
• Pressure or flow differentials,
• Access and communication arrangements
(such as airlocks, speech panels and intercoms
cross-contamination from less
clean zones does not compromise
the cleaner zones.
58. Design: Layout of an
installation
General Considerations
( Contd ):
• Utility services and ancillary equipment
• General: Utility services should be designed and installed
such that the cleanroom is not compromised by
contamination.
• exposed piping, tubing and cable runs should be
minimized,
• Vacuum-cleaning equipment
• Sprinkler systems (A fire sprinkler system is an active fire protection method,
consisting of a water supply system, providing adequate pressure and flow rate to a water
distribution piping system, onto which fire sprinklers are connected. )
• Communication systems: to reduce personnel movement
• Glazing: Avoid heat loss and solar gain, non-opening
double glaze
60. Design: Layout of an
installation
General Considerations
( Contd ):
• Access (contd.)
• Changing rooms: Have three functional zones:
• Entry: access from ancillary. appropriate for removal, storage,
disposal and/or redonnning of garments not permitted within
the cleanroom;
• Transition zone: where garments or personal equipment
dedicated to the cleanroom are stored, donned or removed.
• Inspection/access zone: where inspection of the completed
gowning is accomplished and provides access to cleanroom.
• The three functional zones may be separated by a physical
barrier (e.g. a stepover bench or airlock)
62. Design: Layout of an
installation
General Considerations
( Contd ):
• The following requirements should be defined:
• number of people passing through the gowning procedure
• the gowning procedure (i.e. what garments are to be taken off
and put on)
• the frequency of garment replacement.
• Consideration should be given to the following provisions:
• Storage and disposal of garments;
• Storage before use and disposal of consumable items
• Storage of personal items;
• Hand-washing and drying or other decontamination processes;
• Display or posting of gowning sequence, with clear instructions;
• full-length mirrors to check effective fit.
63. Design: Construction and
materials
• The materials used should be selected to meet the
requirements of the installation, and should take
into account the following:
a) the cleanliness class;
b) effects of abrasion and impact;
c) cleaning and disinfection methods and
frequencies;
d) chemical/microbiological attack and corrosion.
• Surface cleanliness and cleanability of materials of
construction
• Fittings in airlocks: Minimum horizontal surfaces
64. Design: Construction and
materials
• Ceilings: Ceilings should be sealed, penetration points should
be kept minimum.
• Walls: Materials and surface finishes should meet all general
requirements.
•Particular considera tión to impact and abrasion. (rubbing strips,
protective bars)
•Cover strips or seals between panels should be smooth, with
rounded edges
•Use double glazing, with airtight seal, which can enable flush
mounting
•Doors should present as few horizontal surfaces as possible,
thresholds avoided.
•Consider use of push plates, automatic openings, or appropriate
door-swing
• Floors: Floors or floor coverings should be non-porous, slip-
resistant, abrasion-resistant, conductive if necessary.
66. Design: Control of air
Cleanliness
1. Air filtration systems
• Air filtration systems including filter elements,
mounting frames, housings, gaskets, sealants and
clamping systems should be selected to suit both the
cleanliness and using condition.
• Three basic stages of air filtration are recommended:
• prefiltering of the outside air to ensure adequate
quality of air supply
• secondary filtering in the air conditioning plant to
protect the final filters;
• final filtering before cleanroom supply.
• “Sacrificial" filters or temporary filters: considered to
protect the air cleanliness of air-handling systems
during construction and commissioning.
71. HVAC Systems
( Diffusers )
Definition & Types
Air diffusers are used in clean rooms and other controlled
areas to distribute the clean air passed through the HEPA
filters. Diffusers are important part of the HVAC system and
play vital role in maintenance of classified area.
Number of diffusers in a room depends upon the volume
of the area, size of diffusers and required air changes par
hour. Diffusers are mounted in the ceiling of the room to
distribute the uniform air in the area and return risers
should not be near the diffusers. Otherwise air pockets will
form that can increase the contamination level in the area.
Place and type of diffusers to be used should be included
in the HVAC system qualification.
Generally two types of air diffusers are used in
pharmaceutical industries.
1. Induction Diffusers
2. Perforated Plate Diffusers
3. Swirl Diffusers
72. HVAC Systems
( Diffusers )
1. Induction Diffuser
Induction diffusers are generally used in offices and
therefore also called office type diffusers.
These diffusers direct the air to flow in different directions.
WHO does not recommend these types of diffusers to use
in pharmaceutical processing areas because these diffusers
mix the fresh air with the contaminated room air (see
figure) and the air should be replaced with the fresh air to
minimize the contamination.
In the areas where dust is liberated it is important to
replace the air containing dust with the fresh air.
73. HVAC Systems
( Diffusers )
2. Perforated Plate Diffusers:
These are the WHO recommended and widely used diffusers
in pharmaceutical industries. They allow the air to flow in
all directions replacing the air containing dust and
contamination with the fresh air from supply.
74. HVAC Systems
( Diffusers )
3. Swirl Diffusers:
These rotating diffusers are also recommended by the WHO
which rotates during the fresh air supply allow distributing
the fresh air throughout the area.
75. Tests Methods
Cleanroom tests:
1.Required Test
2.Optional Test
• Required Tests: An airborne particle count test shall
be carried out in order to classify an installation
• Optional Tests:
• Airborne particle count for ultrafine and/or
Micro-particles
• Airflow test
• Air pressure difference tests
• Installed filter system leakage test
• Air flow direction tests and visualization
• Temperature, Humidity and Electrostatic tests
• Particle deposition tests
• Recovery tests
• Containment leak tests
76. Required Tests
Airborne particle count for
classification and test
measurement:
1.Measurement of airborne particle concentrations with size 0.1
- 5 μm.
2.A discrete-particle-counting, light-scattering instrument is used
to determine the concentration of airborne particles.
3.Prior to testing, verify that all aspects of the cleanroom and
functioning in accordance with specifications.
-Airflow rate or velocity tests;
-Pressure difference test;
-Containment leakage test;
-Filter leakage test.
77. Required Tests
Airborne particle count for
classification and test
measurement:
Sampling
- Minimum number of sampling point locations:
-Sampling locations evenly distributed, at the height of the work activity.
-Sample a sufficient volume of air that a minimum of 20 particles would
be detected if the particle concentration for the largest considered
particle size were at the class limit for the designated ISO class.
-The volume sampled at each location shall be at least 2 litres, with a
minimum sampling time at each location of 1 min.
-Compute the overall mean of the averages, standard deviation, and 95%
upper confidence limit from the average particle concentrations for all
locations.
78. Optional Tests
Airborne particle count for
ultrafine and/or Micro-particles
Airborne particle count for ultrafine particles
-Smaller than 0,1μm
-DPC, with a capability for accurate particle size definition
up to at least 1μm.
-Condensation nucleus counter (CNC)
-Small sampling flow & long sampling tube diffusion
loss.
Airborne particle count for macro-particles
-Larger than 5 μm.
-There are two general categories of macroparticle
measurement methods.
= collection by filtration or inertial effects, followed
by microscopic measurement
= in situ measurement of the concentration and size
of macroparticles with a time-of-flight particle
counter or DPC
79. Optional Tests
Airborne particle count for
ultrafine and/or Micro-particles
Two general categories of macroparticle measurement methods:
A. collection by filtration or inertial effects, followed by microscopic
measurement of the number and size, or measurement of the mass of
collected particles:
-filter collection and microscopic measurement will report
macroparticles using particle size based upon the agreed
diameter;
-cascade impactor collection and microscopic measurement will
report macroparticles using particle size based upon the
microscopist's choice of reported particle diameter;
-cascade impactor collection and weight measurement will
report macroparticles using particle size based upon an
aerodynamic diameter;
B. In situ measurement of the concentration and size of
macroparticles with a time-of-flight particle counter or a DPC:
-DPC measurement of particle size based upon an equivalent
optical diameter;
-Time-of-flight particle size measurement based upon an
aerodynamic diameter.
80. Optional Tests
Airflow Test
Airflow Test
• To measure airflow velocity and uniformity, and supply airflow rate
• Measurement of velocity distribution is necessary in unidirectional
airflow cleanrooms, and supply airflow rate in non-unidirectional
cleanrooms.
• Supply airflow rate (air volume supplied to the clean installation per
unit of time) can also be used to determine the air changes.
• Airflow rate is measured either downstream of final filters or in air
supply ducts; both methods rely upon measurement of velocity of
air passing through a known area.
81. Optional Tests
Airflow Test
Procedure for unidirectional airflow installation test
• Supply airflow velocity
• Measured at approximately 150-300 mm from the filter face.
• Number of measuring points should be the square root of 10
times of area in m2 but no less than 4. At least 1 point for each
filter outlet
• Uniformity of velocity within the cleanroom
• measured at approximately 150-300 mm from the filter face and
the subdivision into grid cells should be defined
• Supply airflow rate measured by filter face velocity
• The results of the airflow velocity test can be used to calculate
the total supply airflow rate.
• Supply airflow rate in air ducts
• by volumetric flowmeters (orifice meters, Venturi meters and
anemometers)
82. Optional Tests
Airflow Test
Procedure for non-unidirectional airflow
installation test
• Air volume supply rate and air-change rate are the
most important parameters.
• Supply airflow rate measured at the inlet
• Because of local turbulence, use of a flowhood that
captures all of the air issuing from each supply
diffuser is recommended.
• Supply airflow rate calculated from filter face
velocity
• Evaluation of the supply airflow rate without a
flowhood may be done with an anemometer
downstream of each final filter. The supply airflow
rate is determined from the airflow velocity multiplied
by the area of exit.
84. Optional Tests
Air Pressure Difference
Test
• Verify the capability of the complete installation to maintain the
specified pressure difference between separate spaces
• With all doors closed, the pressure difference between the
cleanroom and any surrounding should be measured and
recorded.
• The following should be considered:
• installation of permanent measuring points;
• take measurements near the middle of the cleanroom
away from any supply air inlets or return air outlet.
85. Optional Tests
Installed filter system
leakage test
Installed filter system leakage test
• To confirm that the filter system is properly
installed and that leaks have not developed
• Introducing an aerosol challenge upstream of the
filters and scanning immediately downstream of
the filters and support frame or by sampling in a
downstream duct.
• Applied to cleanrooms in “as-built” or in “at-rest”
occupational states, and when commissioning new
cleanrooms, or existing installations require re-
testing, or after the final filters have been replaced
• Detection of leakage by Scanning / Stationary
remeasuring
86. Optional Tests
Apparatus and materials
for installed filter system
leakage tests
-Aerosol photometer
-Discrete-particle counter (DPC)
-Suitable pneumatic or thermal aerosol
generator(s)
-Suitable aerosol dilution system.
-Suitable aerosol source substances
87. Optional Tests
Airflow direction test and
visualization
• To confirm that the airflow direction and its
uniformity conform to the design and performance
specifications
• can be performed by the following four methods:
1. Tracer thread method;
silk threads, single nylon fibers, flags or thin film
tapes and effective lighting
2. Tracer injection method;
tracer particles illuminated by high intensity light
sources (DI Water , alcohol/glycol)
3. Airflow visualization method by image processing
techniques; (Quantitative)
4. Airflow visualization method by the measurement
of velocity distribution.
89. Optional Tests
Temperature Test
• Capability to maintain the air temperature level within
the control
• Measured at a minimum of one location for each
temperature-controlled zone.
• Measurement time should be at least 5 min with one
value recorded at least every minute.
• Comprehensive temperature test:
• At least 1 h after the air-conditioning system has been
operated
• The number of measuring locations should be at least
two.
• Probe should be positioned at work-level height and at
a distance of no less than 300 mm from the ceiling,
walls, or floor of the installation
90. Optional Tests
RH Test
• Capability to maintain the air humidity level
• Expressed as relative humidity or dew point
• The sensor should be located at least at one location
for each humidity control zone, and sufficient time
should be allowed for the sensor to stabilize.
• The measurement time should be at least 5 min.
91. Optional Tests
Particle Deposition Test
• Sizing and counting particles that can be deposited
from the air onto product or work surfaces in the
installation.
• Particles are collected on witness plates with surface
characteristics similar to those of the at-risk surface
• Are sized and counted using optical microscopes,
electron microscopes, or surface scanning apparatus.
• The witness plate should be placed in the same plane
as the at-risk surface. And at the same electrical
potential as the test surface.
Measuring Device :
Witness plate material: micro-porous membrane filters, double-
sided adhesive tape, Petri dishes Petri dishes containing a
contrasting colour (black) polymer, such as polyester resin;
photographic film (sheet), microscope slides (plain or with
evaporated metal film coating), glass or metal mirror plates;
semiconductor wafer blanks; glass photo mask substrates
92. Optional Tests
Recovery Test
• Ability of the installation to eliminate airborne
particles.
• Only important and recommended for non-
unidirectional airflow systems
• This test is not recommended for ISO Classes 8 and
9.
• 100:1 recovery time is defined as the time required
for decreasing the initial concentration by a factor
of 0,01
93. Optional Tests
Containment leak test
• Determine if there is intrusion of contaminated air
into the clean zones from non-controlled areas
• Particle concentration outside should be greater
than the cleanroom concentration by a factor of
103. If the concentration is less, generate an aerosol.
• To check for leakage through construction joints,
cracks or service conduits, scan inside the enclosure
at a distance of not more than 5 cm from the joint,
at a scan rate of approximately 5 cm/s.