This presentation provides information on minimizing contamination from human personnel in cleanrooms. It discusses how human skin naturally hosts many microorganisms and how cleanroom garments and practices aim to contain these microbes. Proper gowning techniques and high-quality, tightly woven fabrics are important to limit contamination from the billions of skin cells shed daily and prevent microbes from reaching sensitive products. Understanding the human microbiome helps improve strategies to exclude microorganisms from all body areas.
Cardiac Output, Venous Return, and Their Regulation
Understanding and Preventing Clean Room Contamination
1. This presentation is compiled by “ Drug Regulations” a
non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
4/1/2016 1
2. This presentation is compiled from freely available resources like
the websites of FDA, EMA ,WHO and research papers published
by experts in this field like
Sandle, T Reinmüller, B , Hyde, W,, Costello, E.K., Lauber, C. L.,
Hamady, M., Fierer, N., Gordon, J.I., Knight, R.
Paper published by T. Sandle on clean room contamination was
referred extensively for this presentation.
“Drug Regulations” is a non profit organization which provides
free online resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest information from
the world of Pharmaceuticals.
4/1/2016 2
Drug Regulations : Online
Resource for Latest Information
4. Staff gowning
Personnel behavior
How to minimize cleanroom risk
Basic training
◦ Cleanroom staff
◦ Cleanroom entry
◦ Gowning practices
4/1/2016 4
Drug Regulations : Online Resource for Latest
Information
5. Cleanroom contamination can arise from a
number of sources.
Type of cleanroom
Its geographic location
The types of products processed
4/1/2016 5
Drug Regulations : Online Resource for Latest
Information
6. Contamination sources can be divided into
following
◦ People
◦ Water
◦ Air and ventilation Surfaces
◦ Transport of items in and out of clean areas
4/1/2016 6
Drug Regulations : Online Resource for Latest
Information
7. Most contamination can be traced to
humans working in cleanrooms.
◦ Conclusion based on organisms associated with
isolates from environmental monitoring in
controlled environments.
These microorganisms are transient or
residential to the human skin.
4/1/2016 7
Drug Regulations : Online Resource for Latest
Information
8. Human personnel shed high numbers
of skin cells mostly as skin flakes.
The cleanroom garments worn by
personnel cannot contain all human
detritus.
4/1/2016 8
Drug Regulations : Online Resource for Latest
Information
9. Trillions of microbial cells across the epithelial surface
and within the mouth and gut.
These microorganisms play a role in human physiology
and organ function including digestion and immunity.
The microorganisms also affect the outside
environment
This is due to shedding from the skin or deposited
through different orifices.
4/1/2016 9
Drug Regulations : Online Resource for Latest
Information
10. This latter issue has important implications for
cleanrooms.
The outer layer of human skin can host up to one
million microorganisms per square centimeter.
The population, as well as the diversity, varies
according to anatomical locale.
4/1/2016 10
Drug Regulations : Online Resource for Latest
Information
11. Microorganisms within Human Body
◦ Scalp: 1 million
◦ Saliva and nasal fluid: 10 million/gram
◦ Back: 100
◦ Groin: 1 – 20 million
◦ Forehead: 100 – 1000
◦ Hand: 10,000 – 100,000
◦ Armpit: 1 – 10 million
◦ Feet: 1 million
4/1/2016 11
Drug Regulations : Online Resource for Latest
Information
12. Research suggests that a typical person sheds
1,000,000,000 skin cells per day of a size 33 μm x 44 μm x 4
μm
This is equivalent to a rate of 30,000 to 40,000 dead skin cells
shed from the surface of the skin every minute.
Of these approximately 10% of particles carry microorganisms.
There are, on average, four microorganisms per skin cell.
A term commonly used to describe skin flakes with adhered
microorganisms is “microbial carrying particles.”
4/1/2016 12
Drug Regulations : Online Resource for Latest
Information
13. People are
A source of contamination,
Agents for transferring contamination possibly to locations
that could pose a product risk.
4/1/2016 13
Drug Regulations : Online Resource for Latest
Information
14. Microorganisms are spread from
◦ Sneezing
◦ Coughing
◦ Touching
Microorganisms suspended in the air are less of a
concern
When such organisms gravitate towards a product
or critical location, they present a significant risk.
4/1/2016 14
Drug Regulations : Online Resource for Latest
Information
16. The Human Microbiome Project (HMP)
◦ United States National Institutes of Health initiative.
◦ The project goal is to identify and characterize the
microorganisms found in association with both healthy and
diseased humans (the human microbiome).
Our understanding of the risk the people pose to
cleanrooms has been advanced
4/1/2016 16
Drug Regulations : Online Resource for Latest
Information
17. The human microbiome describes the aggregate of
microorganisms and their genetic interactions that
reside
◦ On the surface and in deep layers of skin
◦ In the saliva and oral mucosa
◦ In the conjunctiva
◦ In the gastrointestinal tract
4/1/2016 17
Drug Regulations : Online Resource for Latest
Information
18. Skin is a complex ecosystem
Supports a range of microbial communities
These live in distinct niches
These niches are affected by
◦ Available nutrients
◦ Several non-nutritional factors such as pH, humidity, and
temperature.
Epithelial cells are continually being shed,
Many microbial communities on the external surface are
rarely stable.
4/1/2016 18
Drug Regulations : Online Resource for Latest
Information
19. Outer layer of Skin
Has High population
Considerable diversity of microbial species
across
There are approximately 1000 species of
bacteria from 19 phyla on human skin.
4/1/2016 19
Drug Regulations : Online Resource for Latest
Information
20. Of these, most bacteria can be categorized
into following phyla:
◦ Actinobacteria (51.8%).
◦ Actinobacteria are a group of Gram-positive
bacteria with high guanine and cytosine content,
Such as Micrococcus, Corynebacteria and
Propionibacteria.
4/1/2016 20
Drug Regulations : Online Resource for Latest
Information
21. Of these, most bacteria can be categorized
into following phyla:
◦ Firmicutes (24.4%).
◦ This includes the genera Clostridia and Bacillus.
4/1/2016 21
Drug Regulations : Online Resource for Latest
Information
22. Of these, most bacteria can be categorized into
following phyla:
Proteobacteria (16.5%).
◦ This is a major phylum of bacteria
◦ Includes a wide variety of pathogens such as
Escherichia,
Salmonella,
Vibrio,
Helicobacter, and
many other notable genera.
4/1/2016 22
Drug Regulations : Online Resource for Latest
Information
23. Of these, most bacteria can be categorized into
following phyla:
Bacteroidetes (6.3%).
The phylum Bacteroidetes is composed of three
large classes of
◦ Gram-negative
◦ Nonspore-forming
◦ Anaerobic
◦ Rod-shaped bacteria
4/1/2016 23
Drug Regulations : Online Resource for Latest
Information
24. Reasons for the topographical variations relate
to the physicochemical properties of the skin.
This is especially so for
◦ Temperature
◦ pH
◦ Amounts of oil
◦ Moisture
4/1/2016 24
Drug Regulations : Online Resource for Latest
Information
25. From this, there are three main
ecological areas of the skin:
◦ Sebaceous
◦ Moist
◦ Dry
4/1/2016 25
Drug Regulations : Online Resource for Latest
Information
26. Examples of microbial divergence include
◦ Propionibacteria and Staphylococci species dominating the Dry, calloused areas
(arms and legs)
◦ Gram-positive cocci (primarily the Micrococcaceae) are found on the arms and
legs
◦ Gram-positive rods are found in high numbers on the torso.
◦ Staphylococci and Corynebacteria are found together with some Gram-negative
bacteria in moist areas.
These types of microorganisms generally reflect the types recovered
from cleanrooms
4/1/2016 26
Drug Regulations : Online Resource for Latest
Information
27. Gram-positive bacteria predominate across the
skin as
◦ The skin is generally a dry environment
◦ Any fluids present on the surface generally have a high osmotic
pressure
Thus Gram-positive bacteria are better adapted for
such environments, not least to being resistant to
desiccation.
◦ (especially the Staphylococci and Micrococci)
4/1/2016 27
Drug Regulations : Online Resource for Latest
Information
28. Where other species occur this is due to
◦ Variations in temperature and
◦ With areas of higher sweat production
For example, this can lead to higher levels of fungi
on the feet
In relation to pharmaceutical manufacturing, the
presence of any such organisms remains
problematic.
4/1/2016 28
Drug Regulations : Online Resource for Latest
Information
29. The ratio of the microorganisms recovered from
the skin is relatively evenly divided between the
aerobic and the anaerobic.
The aerobic microorganisms tend to live on the
outermost layers of the skin
The anaerobic microorganisms live in the deeper
layers of the skin and hair follicles
4/1/2016 29
Drug Regulations : Online Resource for Latest
Information
30. The information from HMP introduces several
implications for cleanroom environmental monitoring.
◦ Whether gowning practices are adequate to exclude all
microorganisms from the richest areas of the skin microbiome.
Most bacteria free-floating in cleanroom air current are
not free-living
They are instead the result of
◦ Direct particle shedding of desquamated skin cells and
◦ Subsequent re-suspension of skin detritus in the air stream.
4/1/2016 30
Drug Regulations : Online Resource for Latest
Information
31. The answer to earlier question should lead to a
consideration of:
◦ The types of cleanroom undergarments used
◦ An examination as to whether these provide an effective
barrier, especially for the more moist parts of the body.
◦ The importance of the outer gown covering all parts of the
body, including the forehead.
◦ The quality of cleanroom certified undergarments.
4/1/2016 31
Drug Regulations : Online Resource for Latest
Information
32. The answer to earlier question should lead to a
consideration of:
◦ The level of training required for operators in relation to
gowning and the way that gowning qualification was
conducted.
◦ How long a cleanroom suit should be worn for in relation to
material integrity against operator perspiration.
◦ The environment in which gowns are donned, where higher
air-change rates might prove effective.
4/1/2016 32
Drug Regulations : Online Resource for Latest
Information
33. The answer to earlier question should lead to a
consideration of:
◦ How often gowns should be recycled which involves
washing and irradiation.
◦ What types of testing is conducted on recycled gowns
◦ What the procedures are for rejecting gowns where a
loss of integrity is detected.
4/1/2016 33
Drug Regulations : Online Resource for Latest
Information
34. Cleanroom microbiologists may wish to consider how
concerned they are with each of the items listed in
excluding microorganisms found on all regions of the
skin.
There must be good understanding of the environmental
monitoring methods used to assess cleanrooms.
These may not show how good or bad gown changing and
gown wearing is.
These concerns are best addressed through good gowning
practices
4/1/2016 34
Drug Regulations : Online Resource for Latest
Information
36. Despite some advances with automation and robotics, in
most situations people cannot be eliminated from
cleanrooms.
Control of contamination from people in cleanrooms is
achieved by application of two principles:
◦ We “wrap” the people to minimize the amount of “shedding” of
microorganisms.
◦ We put localized protection around the product to minimize the amount of
contact with the people.
4/1/2016 36
Drug Regulations : Online Resource for Latest
Information
37. The localized protection is achieved through local air
protection, such as
◦ Unidirectional airflow cabinets and
◦ Isolators.
With clothing, personnel working in cleanrooms are required
to wear special clothing designed for the clean environments.
Such clothing is necessary because the human body creates
its own microenvironment of potentially damaging particulate
contamination.
4/1/2016 37
Drug Regulations : Online Resource for Latest
Information
38. To be effective, cleanroom clothing must:
◦ Form a particulate barrier for the human micro-
environment.
◦ Allow freedom of movement and be comfortable.
◦ Address any specialist requirement,
e.g. static dissipation.
Avoid being a significant particulate contributor in itself.
◦ Cleanroom garments must meet specific protection criteria.
4/1/2016 38
Drug Regulations : Online Resource for Latest
Information
39. Not all cleanroom garments are of the same quality.
This involves manufacturing the garments from special
materials, following particular construction methods, and
then tailored for individual styling.
The gowns must be comfortable, easy to apply and practical
in use.
Some gowns are disposable and others are made to be re-
laundered and sterilized depending on the cleanroom grade.
4/1/2016 39
Drug Regulations : Online Resource for Latest
Information
41. Fabrics used in the manufacture of cleanroom garments must
have the following features:
◦ Be low in particulate shedding.
◦ Permit the body to breathe while trapping particles within the garment.
◦ The contaminant should be retained within the garment and not released
into the surrounding atmosphere.
◦ Be flexible enough for comfortable wearing.
◦ Withstand repeated cleaning and sterilization cycles.
◦ Meet any specific requirements such as control of static.
◦ Meet opacity requirements.
◦ Look and feel as good as possible. Be cost-effective.
4/1/2016 41
Drug Regulations : Online Resource for Latest
Information
42. There are three broad categories of fabric used in the
construction of cleanroom garments:
4/1/2016 42
Drug Regulations : Online Resource for Latest
Information
43. Woven fabrics.
◦ Woven or re-usable fabrics are the most commonly used fabrics in
cleanroom environments.
◦ Such garments are woven on sophisticated looms from yarns of
continuous filaments of polyester.
◦ The thickness of the yarn and filaments is important –
the finer the yarn, the tighter the weave can be made, and the better the filtration.
◦ The pattern and tightness of the weave is important to reduce the pore
size to a minimum.
◦ The use of continuous filament polyester means that there are few loose
ends from which particles may be shed.
4/1/2016 43
Drug Regulations : Online Resource for Latest
Information
44. Laminated or membrane fabrics.
◦ Laminated fabrics are favored for some high-
grade microelectronic environments.
◦ These types of garments are not commonly used
in the pharmaceutical sector.
4/1/2016 44
Drug Regulations : Online Resource for Latest
Information
45. Disposable or limited life materials.
◦ The most common of these non-woven fabrics are from spun
bonded olefin and polypropylene.
◦ Comprising a densely interlinked matt of fibers, these fabrics can
provide good results for a limited period.
◦ Garments from such materials need to be processed and
decontaminated before use in the cleanroom.
◦ Disposable or limited use garments are mainly used in those
environments where protection of the wearer against potentially
hazardous products is required.
4/1/2016 45
Drug Regulations : Online Resource for Latest
Information
47. Garments are designed to provide protection for the head, body,
hands and feet.
In establishing a system for garment selection, it is important to
consider the broader aspects of cleanroom use:
◦ Suitability of fabric,
◦ Garment style,
◦ Layers,
◦ The nature of the tasks involved,
◦ Costs,
◦ Regulatory requirements, and
◦ Any specific customer requirements.
4/1/2016 47
Drug Regulations : Online Resource for Latest
Information
48. The classification of the cleanroom will inevitably be the
major factor in determining the degree of personnel
protection required and the fundamental choice of garments.
One important issue with gowns is the maximum length of
time that a gown can be worn.
As people perspire, the integrity of the gown will weaken.
4/1/2016 48
Drug Regulations : Online Resource for Latest
Information
49. Complicating factors are the temperature and humidity
of the cleanroom and the variations between people.
The length of time will also depend upon the grade of
the cleanroom.
In aseptic areas, such as ISO 14644 class 7 / EU GMP
Grade B areas, gowns are typically worn only for the
length of the shift
◦ (normally four hour periods to enable operators to take breaks).
4/1/2016 49
Drug Regulations : Online Resource for Latest
Information
50. In lower grade cleanrooms, a gown might be worn
for several sessions during the course of the
working day.
Other factors affecting the lifespan of the gowns
that are subject to recycling are repairs and the
number of permitted washing cycles.
With repairs, it is prudent to have a repair policy.
4/1/2016 50
Drug Regulations : Online Resource for Latest
Information
51. This will vary across facilities, and again, it will be affected by
the cleanroom class.
With aseptic areas, if a gown becomes torn it is normally
discarded.
In other grades of cleanroom, a gown can be repaired
depending upon the size of the hole and the impact on the
material.
Some organizations set a maximum size for any hole or tear
and for the number of times a gown can be repaired.
Gowns that are recycled are subject to laundering.
4/1/2016 51
Drug Regulations : Online Resource for Latest
Information
52. Gowns are washed by special washing machines with suitable
detergents,
They are then dried, folded, and then wrapped in cleanroom packaging.
For gowns that are to be used in aseptic areas, such gowns are
irradiated.
A policy should be in place outlining how often a gown can be processed
-- typical times range between 20 and 40 times.
To make the tracking task easier, many gowns sterilized by irradiation or
gassing are fitted with barcodes and scanned.
It is further important to establish the extent that the sterilization
process affects the integrity of the gown material.
4/1/2016 52
Drug Regulations : Online Resource for Latest
Information
53. In order to assess the contamination risks from re-
laundering, gowns are subject to particle counting.
There are different ways to do this
Most common means is the Helmke Drum particle
emission test.
With this, the test method simulates particle
shedding of clothing under movement.
4/1/2016 53
Drug Regulations : Online Resource for Latest
Information
54. The garment under test is tumbled in a rotating drum
(approximately 10 revolutions per minute)
This releases particles from the surface of the
cleanroom garment in a controlled manner.
An automatic particle counter is used to sample the air
within the drum
Determination of the average particle concentration of
the air during the initial ten minutes of the test is
performed.
4/1/2016 54
Drug Regulations : Online Resource for Latest
Information
55. The common standard is the IEST "Recommended Practice RP-CC003.3:
Garment System Considerations for Cleanrooms and Other Controlled
Environments".
An alternative measure is the Body Box test.
This method simulates particle filtration and release under real wear
conditions.
As a consequence it measures the contamination of the cleanroom by
the clothing/wearer.
For this, particle counters determine the quantity of particles generated
by the wearer/garment that are emitted into the chamber.
4/1/2016 55
Drug Regulations : Online Resource for Latest
Information
57. Cosmetics, such as powder, rouge, eye liner, mascara, and lipstick
must be banned in cleanroom environments.
Jewelry, such as rings, watches, necklaces, bracelets, earrings and
other items, together with all forms of visible piercing, are
commonly not allowed in cleanrooms.
The best method of changing into cleanroom garments is one that
minimizes contamination getting onto the outside of the garments.
Change areas can vary in design, but it is common to find them
divided into three zones:
4/1/2016 57
Drug Regulations : Online Resource for Latest
Information
58. Pre-change zone.
Outside of changing rooms 'tacky mats' or polymeric flooring can be
positioned to help reduce the level of particles carried on footwear.
4/1/2016 58
Drug Regulations : Online Resource for Latest
Information
59. Changing zone.
The changing room design contributes to the assurance of
appropriate personnel access and microbial contamination control.
The changing room should be provided with filtered air.
Intermediate (bag) filters will typically be suitable for this purpose,
though High Efficiency Particulate Air (HEPA) filtration may be used.
The air pressure should be negative with regards to the
manufacturing area corridor, but positive relative to external
adjacent areas.
4/1/2016 59
Drug Regulations : Online Resource for Latest
Information
60. Cleanroom entrance zone.
This must be of the same grade or class as the main cleanroom into
which the area leads.
Ideally there should be separate routes through airlocks for material
required in cleanrooms.
Taking items through personnel change areas should be
discouraged.
4/1/2016 60
Drug Regulations : Online Resource for Latest
Information
62. Personnel training in gowning is an important function.
Gowning practices must be assessed periodically and monitored
frequently.
Training programs should ideally include visual assessment and
microbiological assessment.
The microbiological assessment varies, but can include
◦ The exposure of settle plates during the change process and
◦ The assessment of gown cleanliness through post-use suit contact plates.
The results of the cleanroom sampling should not exceed those of the
room class.
If results are exceeded, the individual may be an unusually high shedder
of skin particles.
4/1/2016 62
Drug Regulations : Online Resource for Latest
Information
63. Training required for staff who work in cleanrooms should
include:
◦ Introduction to micro-organisms and microbiological contamination
control.
◦ Entry and exit of production facilities (including gowning)
◦ Personal hygiene training
◦ Microbiological risks associated with specific production tasks.
◦ Training must be documented and regularly reviewed. Training must be
effective.
◦ Actual performance of personnel competency in gowning should be
demonstrated on a regular basis.
4/1/2016 63
Drug Regulations : Online Resource for Latest
Information
65. Working in clean environments demands
Knowledge,
Discipline,
Motivation as well as
A thorough understanding of contamination risks among all
personnel involved.
Each individual cleanroom should have its own documented rules
and procedures.
4/1/2016 65
Drug Regulations : Online Resource for Latest
Information
66. Training includes reminding personnel that they must not be
allowed to touch critical products and equipment with their naked
hands.
All critical work must be undertaken wearing gloves.
Critical activities requiring personnel contact such as aseptic
processing or sampling must be done through the use of clean
utensils such as tweezers, forceps, and the equivalent.
All devices and gloves used must fully comply with the cleanliness
demands of the cleanroom and work undertaken in the cleanroom.
They must be cleaned, disinfected, or sterilized as appropriate for
the criticality or activity and risk of contamination.
4/1/2016 66
Drug Regulations : Online Resource for Latest
Information
67. Another aspect of best practice is in instructing personnel in the
appropriate behaviors within the cleanroom.
The generation of contamination is proportional to activity
conducted.
A person with head, arms, and body moving can generate about
1,000,000 particles ≥ 0.5 μm/min.
A person who is walking can generate about 5,000,000 particles ≥
0.5 μm/min.
4/1/2016 67
Drug Regulations : Online Resource for Latest
Information
68. However a person in motionless position can generate only
100,000 particles ≥ 0.5 μm/min.
In addition, personnel should reduce activities like talking,
singing, whistling, coughing, sneezing etc., especially when
being close to the handled products and production
equipment.
4/1/2016 68
Drug Regulations : Online Resource for Latest
Information
69. People working in cleanrooms and other forms of controlled
environments must be physically healthy.
Diseases in the upper respiratory tract as well as stomach disorders can
create problem in hygienic applications.
Another factor that can impact upon the environment is the number of
people in the cleanroom.
Only necessary and limited number of persons should be allowed in a
cleanroom at the same time.
The more persons simultaneously present in a cleanroom, then the
higher the contamination level will be,
◦ i.e., the higher concentration of particles in the air
This is particularly important in relation to changing rooms.
4/1/2016 69
Drug Regulations : Online Resource for Latest
Information
71. Good personal hygiene is a requirement of all
pharmaceutical cleanroom activities.
However, studies show poor compliance is
common in relation to basic hand washing
technique.
Hand hygiene and glove hygiene are important
given the high numbers of microorganisms found
on the human body
They also pose risk of contamination by transfer
4/1/2016 71
Drug Regulations : Online Resource for Latest
Information
72. Microorganisms associated with hands are found mainly
on the surface of the skin and under the superficial cells
of the stratum corneum.
The dominant species is Staphylococcus epidermidis
This is found on almost every hand, together with other
species of Staphylococcus and species of the genera
Micrococcus.
Hands must be washed with soap and water prior to
entry to the cleanroom.
4/1/2016 72
Drug Regulations : Online Resource for Latest
Information
73. Hand washing facilities should not be located in an
actual cleanroom, but rather in an area leading to
the cleanroom changing room.
As an alternative, a hygienic handrub can be used.
Where gloves are required these should be put on
using a method designed to prevent the ungloved
hand from touching the clean or sterile outer part
of the glove.
4/1/2016 73
Drug Regulations : Online Resource for Latest
Information
74. Once in the cleanroom, gloved hands should be
subject to periodic hand sanitization
When decontaminating hands with an alcohol-
based antiseptic hand rub,
◦ Apply product to palm of one hand and rub hands together,
◦ Covering all surfaces of hands, fingers and wrists,
◦ Until hands are dry
(alcohol-based hand rubs are not to be used with water).
4/1/2016 74
Drug Regulations : Online Resource for Latest
Information
75. The process typically takes between thirty seconds
and one minute.
Follow the manufacturer’s recommendations
regarding the volume of product to use.
The technique for applying alcohol to gloved hands
is similar to applying a handrub to skin.
It is important to ensure that all surfaces are
covered.
4/1/2016 75
Drug Regulations : Online Resource for Latest
Information
76. With glove sanitization, there are two alcohols of
choice:
Ethyl alcohol (ethanol) and isopropyl alcohol (IPA)
Other alcohols, such as methyl alcohol (methanol)
are unsuitable.
4/1/2016 76
Drug Regulations : Online Resource for Latest
Information
77. IPA is slightly more bactericidal than ethanol
Ethanol has better viricidal properties
Another factor is application to the skin;
IPA can be quite harsh.
Thus, ethanol is more often applied to bare skin
(often in a denatured form)
Whereas IPA is more often applied to gloves.
4/1/2016 77
Drug Regulations : Online Resource for Latest
Information
78. These sanitizers have bactericidal action against vegetative
cells but not spores.
The concentration of alcohol to water varies, although the
optimal range is 60 to 90% (volume/volume).
Below 60%, bactericidal action drops,
Above 90% there is insufficient water for the bacterial cell to
absorb water.
The alcohol does not enter the cell and is unable to denature
the bacterial proteins.
Most preparatory concentrations are 70%.
4/1/2016 78
Drug Regulations : Online Resource for Latest
Information
79. While most bacteria are killed after ten seconds of
contact with alcohol contact times in practice are
longer due to the variability of hand rubbing.
Typical contact times are thirty seconds.
It is important that the selection of a hand sanitizer
is qualified.
4/1/2016 79
Drug Regulations : Online Resource for Latest
Information
80. There are different approaches that can be taken
for qualification.
Most of these require
◦ Individuals to wear gloves
◦ Place their hands into broth containing a high concentration
of a non-pathogenic microorganism.
◦ Disinfectant is then applied
◦ Bacterial reduction is assessed through placing the treated
hands into broth and performing dilutions
4/1/2016 80
Drug Regulations : Online Resource for Latest
Information
82. Assess the risk of personnel to the process by taking suit
contact plates of the gown as worn by the person as they
leave the aseptic area.
The gown must be discarded after the plates have been taken
This is due to the potential effect on the gown integrity when
an agar plate contacts the gown.
It is good practice to begin suit sampling with a higher
number of samples.
These can then be reduced over time.
4/1/2016 82
Drug Regulations : Online Resource for Latest
Information
83. Some facilities perform more samples from the
gown during gowning test qualifications compared
with routine sampling.
Sites considered for selection include
◦ The top of the head
◦ The facemask
◦ Both arms
◦ Middle torso
◦ Both legs
4/1/2016 83
Drug Regulations : Online Resource for Latest
Information
84. In terms of limits, for EU GMP Grade B/ISO class 7 areas, the aim is
often to adopt the same limits as per the limits applied to
fingerplates.
The action level for gowns is ordinarily 5 CU/25cm
Experience has shown that higher counts are obtained from the top
of the head,
This is perhaps because this is the warmest region of the body.
Care must be undertaken when sampling as so not to break the
integrity of the gown.
4/1/2016 84
Drug Regulations : Online Resource for Latest
Information
85. In addition to gowning control, a procedure should be in
place for the notification of health conditions by staff.
Staff who are ill (coughs, colds, and so on) should not enter
cleanrooms.
This is because the illness may affect product quality.
It is important to control the potential risks from personnel
carrying Infectious disease.
Open lesions on any exposed part of body.
4/1/2016 85
Drug Regulations : Online Resource for Latest
Information
86. Shedding skin conditions, such as eczema or psoriasis,
dermatitis, and dandruff
◦ (skin scales may harbor objectionable micro-organisms that may impact
pharmaceutical products and patients).
Gastric upsets.
Personnel with any of the above conditions must be excluded
from working within cleanrooms for the duration of their
illness.
4/1/2016 86
Drug Regulations : Online Resource for Latest
Information
87. This presentation is compiled from freely available resources like
the websites of FDA, EMA ,WHO and research papers published
by experts in this field like
Sandle, T Reinmüller, B , Hyde, W,, Costello, E.K., Lauber, C. L.,
Hamady, M., Fierer, N., Gordon, J.I., Knight, R.
Paper published by T. Sandle on clean room contamination was
referred extensively for this presentation.
“Drug Regulations” is a non profit organization which provides
free online resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest information from
the world of Pharmaceuticals.
4/1/2016 87
Drug Regulations : Online
Resource for Latest Information