organization facility- genial para espina de pescado
TRANSCRIPT
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Amjad Ganma
M. Sc Pharmaceutical Validation (London)
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1. Organization Set-up
Design Criteria The Facility should be designed to help to protect the
product.
One of the Process and Operational critical requirement is
the role in how a facility is organized to preventcontamination and mix of products.
Considerations of potential product hazards and
containment requirements.
Fitting or integrating the process or operationalrequirements into a project site is considered essential for a
successful project. The main goal is to protect the product.
The implementation of the facility design to achieve this is
facility modeling.
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1. Organization Set-up
Design Criteria
Site and Building Considerations in the aspect of
Sanitization :
Environmental Protection is essential Operator protection is essential
Product
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1. Organization Set-up
Layout Consideration
The main goal is to protect the product from contamination.
Layout and facility design should achieve the ways for facilitymodeling.
The process specialist, architect, layout engineer, HVAC engineerand QA should collaborate for successful integration design.
Product and Process requirements and information.
Conceptual layout should be enhanced and refined to produce anequipment and facility layout.
The layout should determine equipment relationship andintegrate equipment needs as well access and movementrequirements for people, components etc.. To permitdevelopment of an efficient layout.
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1. Organization Set-up
Room Function/Finishes Room for aseptic processing for product or components.
Room/area immediately adjacent to the above,comprised of material/personnel airlocks.
Preparation room closely related to aseptic processingroom.
Room/area immediately adjacent to preparation room,comprising material airlocks, personnel clean change,secondary packaging and other associated areas.
Room for ancillary/support functions includes: Warehousing Office
Plant utilities
Circulation area
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1. Organization Set-up
Surface Finishes and Materials of Construction Finish materials should be non-shedding, non-porous and
resistant to sustaining microbial growth.
Surfaces should be smooth and easy to clean with
minimal ledges Joints
No corners (that are difficult to access)
Importantly near the product and process equipment.
Finishes should be able to withstand repeated Cleaning Sanitization with various chemicals
Resist surface oxidation.
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1. Organization Set-up
Surface Finishes and Materials of Construction
Doors hardware should be carefully considered
Easy Cleaning
Hands Off proximity sensors and openers wherever
necessary.
Door swings should be opposite direction of airflow to
assist in maintaining the differential pressure. 10. ISO_Controlled Environment Design.pdf
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1. Organization Set-up
GMP Requirement for Electrical Systems GMP considerations when designing, selecting and installing
electrical equipment within aseptic processing areas are limitedto ensuring that equipment is cleanable, ledge and crevice free,non-shedding and sealed.
The criteria for equipment appear to be identical from Grade 5to Grade 8 environments, the degree of these aspects maydiffer (e.g. equipment in grade 5 environment will require ahigh standard). Recessed electrical devices will help achieve thestandard required in each of these areas.
Sealed components are specified, no only to alleviate the risk of
contamination, but also to cope with the different pressureregimes of adjacent rooms. In Grade 5 environment, the termsealed refers to being hermetically sealed, whereas in Grade8 environments, the term sealed to a high degree ofprotection against the ingress of water and dust.
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1. Organization Set-up
GMP Requirement for Electrical Systems Sealing properties of the fixtures should withstand water jet
pressures in wash down areas.
Stainless steel or aluminum fixtures, because they are non-
shedding and resistive to corrosive environments, may
considered appropriate. Materials should be compatible with
room cleaning agents, which may be corrosive.
Wiring and wiring accessories should be hidden within the:
Building fabric to improve cleanliness.
Particularly in higher classification areas.
The number of penetrating through walls, ceiling, or floors for
services to equipment should be minimized.
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1. Organization Set-up
Electrical System
Room Classification
Pharmaceutical Grade 8 EnvironmentGrade 5 and Grade 7
Environment
Power distribution Non, Outside Area None, Outside Area None, Outside Area
LightingCleanable, ideally non-
shedding
Cleanable and sanitizable,
minimum ledges, non-
shedding, sealed, crevice free.
Cleanable and sanitizable,
minimum ledges, non-
shedding, sealed, crevice
free.
Outlets and
miscellaneous
Equipment
Cleanable, ideally non-
shedding
Cleanable and sanitizable,
minimum ledges, non-
shedding, sealed, crevice free.
Cleanable and sanitizable,
minimum ledges, non-
shedding, sealed, crevice
free.
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2. Basic Training
Microbiology for Non-Microbiologist:
The FDA Requirement
Control of microbiological contamination . 21 CFR
211.113.
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2. Basic Training
Microbiology for Non-Microbiologist: The Characteristics of Microorganisms
Fungi: molds, yeasts, mushrooms, rusts, and smuts. Parasites ordecomposers. Fungi contain no chlorophyll and cannot synthesize food.Instead they secrete enzymes that digest food material outside theorganisms.
Bacteria: Bacteria are tiny single-cell microorganisms, usually a fewmicrometers in length that normally exist together in millions. A gram ofsoil typically contains about 40 million bacterial cells. A milliliter of freshwater usually holds about one million bacterial cells. Bacteria come inthree main shapes:
- Spherical (like a ball) : These are usually the simplest ones. Bacteria
shaped like this are calledcocci(singularcoccus).- Rod shaped: These are known asbacilli(singularbacillus). Some of
the rod-shaped bacteria are curved; these are known asvibrio.
- Spiral: These known are asspirilla (singularspirillus). If their coil isvery tight they are known asspirochetes.
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2. Basic Training Microbiology for Non-Microbiologist:
Mycoplasma species are often found in research laboratories ascontaminants in cell culture. Mycoplasma cell culturecontamination occurs due to contamination from individuals orcontaminated cell culture medium ingredients. The acceptedname was chosen because Mycoplasma were observed to have afungi-like structure - hence "Myco," and it also had a flowing
plasma-like structure without a cell wall - hence "plasma." The Characteristics of Microorganisms
Mycoplasma: Mycoplasma is the smallest known cell and is about0.1 micron (m) in diameter.
Virus
Viruses are too small to be seen directly with a light microscope.Viruses infect all types of organisms, from animals and plants tobacteria and archaea. although there are millions of different types.Viruses are found in almost every ecosystem on Earth and theseminute structures are the most abundant type of biological entity.The study of viruses is known as virology, a sub-specialty ofmicrobiology.
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2. Basic Training
Microbiology for Non-Microbiologist:
What is Microbe?
Bacteria are named with two names.
The first name is the Genus and is always capitalized.
The second name is the species and is never capitalized.
The names of bacteria are always written in italics, or underlined.(example: Escherichia coli or Escherichia coli).
Microbes are Bacteria, Fungi, Yeast, Algae and Virus.
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2. Basic Training
Microbiology for Non-Microbiologist: Microbes in Facility
Bacteria can double themselves by splitting in half. This doubling time
varies with the type of bacteria.
E. coli has a doubling or generation time for 20 minutes.
With this generation speed, a single E. coli bacterial cell can grow as
indicated in this table.
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Endotoxins- gram negatives we are always
looking to prevent in products. Cause
serious adverse events in patients, such as,
fevers, shock and even death. Endospores- Spore forming bacteria, they
can survive heat, UV. If spores survive the
Aseptic Process they can germinate andgrow in favorable conditions
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2. Basic Training
Microbiology for Non-Microbiologist: Pyrogens:
When bacteria are killed using an autoclave, their
skeletal remains are still present on the item thatwas sterilized.
These are known as pyrogens.
When injected into the body, pyrogens will cause
the patient to have a fever.
A dry heat oven /Tunnel is used to eliminate
pyrogens.
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2. Basic Training
Microbiology for Non-Microbiologist Sources of Bacteria
Humans
1 gram of fecal matter container 109 bacteria.
40% of fecal matter is microbial matter.
Our body has 1kg of bacteria at any one time.
These are reasons we humans are the greatest contributor to
contamination in the clean room. We can slough off bacteria from
our skin, and we can carry soil in with us.
Other sources of Bacteria:
Bio-burden is the bacteria in the environment.
- These comes from water, air, personnel, raw material, working
surfaces and the manufacturing area.
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2. Basic Training
Gowning Training: Good personnel hygiene including the following:
Bathing or showering routinely.
Washing the hair.
Trimming facial hair
Cleaning the fingernails.
Wearing clean clothing and shoes.
Clean room personnel must believe in and practicethese basic steps in good hygiene practices.
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2. Basic Training
Gowning Training: Five criteria must be met for a fabric to be used as a clean
room garment:
Comfortable to wear.
Function design to contain contaminating
particles and bacteria shed from the skin and
clothing of personnel.
Posses antistatic characteristics. Ability to withstand sterilization.
Durability.
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2. Basic Training
Gowning Training: Pre-Gowning Procedure:
Remove all street garments that are not required for warmthand or modesty.
Bouffant/Hair net (Make sure to contain all hair)
Shoe covers: Contain all laces and lassels.
Wash hand: Using bactericidal soap and dry thoroughly.
First sterile gloves: Follow aseptic technique by touching onlythe inside of gloves. Sanitize.
Sanitize gloves after donning each articles, if required. Mask: Adjust for a snug facial fit.
Hood: Ensure snug fit and proper neck seal.
ENTER THE CHANGE AREA WALKING ACROSS THE TACKY MAT.
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2. Basic Training
Gowning Training: Gowning Procedure: Maintain Proper Gown Control Prior to
and throughout aseptic operations, an operator should notengage in any activity that poses an unreasonablecontamination risk to the gown.
See the Sterile Gowning Procedure in the picture...\sterile_gowning_procedure.pdf
Personnel Process:
Bathing will remove microorganisms, but will increase thenumber of particles emitted from the body.
The mechanical process of washing will remove bacteria frommicrocolonies accumulated on the skin, bacterial cells will bespread over the entire surface of the body, particularly nearthe perineum and on the face
http://localhost/var/www/apps/conversion/tmp/scratch_2/sterile_gowning_procedure.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_2/sterile_gowning_procedure.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_2/sterile_gowning_procedure.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_2/sterile_gowning_procedure.pdf -
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2. Basic Training
Gowning Procedure: The washing process will remove the outer oily sebum layer
of the skin, causing skin scales to dry, curl up, and peel off
the body.
This causes an increase in particulate dispersion ratesimmediately after showering.
Within two hours after bathing the surface of the skin will
resume its original pattern of microcolonies.
Therefore, employees working in clean rooms should batheat least two hours before they enter the clean room
environment to minimize the extent of the skin particulate
shedding due to the bathing process
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2. Basic Training
* 100.000 Particles (Contaminant emission =
dust skin particles, hair, germs, viruses,
smoke etc)
Size: 0.001 micron to 10 micron 1 micron =
1/1.000mm
Cleanroom Behavior: Emission of Particles
1 x 5 x* 10 x* 25 x*
50 x* 100 x* 150x/300x*
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2. Basic Training
Cleanroom Behavior:
Movements no faster than air
flow.
Controlled, not abrupt,movements.
Never taking objects against
the air flow.
Protective clothing always
sealed.
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2. Basic Training
Fast walking causes
turbulences due to low
pressure points
Cleanroom Behavior: Inappropriate behavior
Seizing something quickly from
above creates turbulences and
contamination outbursts.
If installations and appliances are
set horizontally to the air current,
turbulence is created on the
underside.
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2. Basic Training Cleanroom Behavior: Dos Behavior in the Cleanroom
Training: All staff working at a Clean Workplace must be trainedrepeatedly in all aspects which are relevant to the work in question.
Staff: At the clean workplace only the required amount of staff shouldbe present.
Checks: As far as possible, all monitoring and inspections should be
carried out from outside. Visitors: If inspections, service staff or visitors enter the Clean Work-
place, the same rules of behavior apply as for permanent workers in thearea.
Moving about: The movement of people between the clean workplaceand the surrounding areas should be kept to a minimum.
Private items: It is not permitted to take food, cigarettes, jewelry andother personal items to the clean workplace.
Materials: Apart from the materials directly needed or the productiongoods to be processed immediately, no objects or materials may bestored in the vicinity of the Clean Workplace.
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2. Basic Training Cleanroom Behavior: Dos Behavior in the Cleanroom
Movements: At the clean workplace, the staff must move in a controlledand considered manner. Since the emission of particles and germs isrelated to the workers activity and the type of movement, quick and abruptmovements might cause a strong current and thus are to be avoided at alltimes.
Working Clothes: Care must be taken that the prescribed working clothes
are worn in the cleanroom in the correct way at all times. Contacts: In order to avoid contaminating the gloves unnecessarily (dust,
fats, salts, gems), nothing may be touched at the workplace apart from theappropriate equipment and tools. (Do not fold arms, do not scratch, do nottouch door handles or telephone receivers).
Communication: Speaking, coughing and sneezing may never take place inthe direction of the critical working area.
Jobs: When temporarily not working or merely observing at the cleanworkplace, the staff must move as far away as possible from the criticalarea.
Handling: Interventions in the critical work area must take place in such away that neither the hand nor the arm of the staff comes between theHEPA filter and the object.
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2. Basic Training
Understanding Disinfection: Sterilization and Disinfection is afundamental tool of infection control. A large number of equipments andinstruments are designed for reuse, they also can transmit pathogens if anyof the steps involved in reprocessing, cleaning, disinfection, or sterilizationare inadequate.
Sterilization: The complete removal or destruction of allforms of microbial life (Bacteria, Viruses, Fungi, Spores)
Probabilistic Notion:
No absolute assurance that there is 0 microorganisms.
Sterility Assurance Level (SAL) used as measure of sterility.
SAL: Probability of survival of microorganisms after sterilizationprocess.
Expressed as log 10 (Probability of survival)
SAL of 6:
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2. Basic Training
Understanding Disinfection: Cleaning: The removal of adherent visible soil (blood, protein
substance and debris), dust or other foreign material by manual
or chemical process.
Sanitizing: Process that reduces microbial population on object
to a safe level e.g 70% IPA
Decontamination: Process that removes pathogenic
microorganisms from an object to make it safe to handle.
Antiseptics: Chemicals to prevent growth or destroy.
Used on living tissues.
Disinfectants: Chemicals used for disinfection.
Used for objects& Destroys Pathogens
Sterilizing: Absence of Microorganisms
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2. Basic Training Understanding Disinfection
Cleaning agents and Disinfectants:
should be handled with care ,as they are potent and often hazardous.
should not be mixed which can result in drastic reduction in antimicrobial activity.
Care should be taken to ensure that the disinfectant does not causecorrosion or discoloration of paint work or flooring.
Two or more disinfectants are used at regular intervals to obviate theproliferation of resistant strains of micro organisms and for thatdisinfectants used should be of different chemical type and withdifferent spectrum of anti microbial activity.
Disinfectants and cleaning agents should not be stored more than 24 hrsas organisms can grow on storage.
Disinfectants are available as concentrated solutions and hence theyshould be diluted. Dilutions should be made with freshly collecteddistilled water. Used solutions of cleaning agents and disinfectants mustbe discarded and the empty containers must be washed at the end ofthe day.
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2. Basic Training
Understanding Disinfection
Reasons For Using A Disinfectant
Destroy or remove microorganisms that are present
Prevent entry of microorganisms into a manufacturingfacility
Prevent dissemination of microorganisms throughout amanufacturing facility
Eliminate and prevent buildup of pyrogens
A properly designed and maintained disinfection program that provides thepharmaceutical manufacturing areas with an environment relatively freefrom microorganisms on a consistent basis is an expectation of mostregulatory agencies worldwide.
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2. Basic Training
Sources of Contamination Percentage distribution of the sources of
contamination.
Process : 30 40 %
People : 30 40 %
Equipment : 20 30 %
Process Media : 5 10 %
Air : 5 10 %
It is important to take the contamination from people into
account , which contributes considerable 30% of the total
contamination in the cleanroom.
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2. Basic Training
Source of Contamination.
Example "Fishbone" diagram for contaminated
product in next slide is illustrated to simplify the
Cause & Effect Diagram for Potential Causes of
Contaminated Product
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2. Basic Training
Sources of Contamination:
External Impurities Internal Impurities
Introduction of contaminated outside
air or circulating air *Staff
Staff Process
Impure process media or raw materialProduction equipment, machines, tools
etc.
Inadequately cleaned materials, tools
etc.
Unsuitable building materials, work
materials
Mechanical abrasion in the cleanroom
* poor filter quality, not airtight filter seal surfaces, leakage in the ducting
system, abrasion in air recirculation equipment and in the ducting system
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2. Basic Training:
Microbiological Controlled Environment Recommended limits for Microbiological monitoring of clean areas
during operation:
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2. Basic Training
Microbiological Controlled Environment
Parameters that need to be controlled are: air flow
filtration, room pressurizations, air velocities,
temperature, relative humidity
Clean room location must designed that in and out air
locks, gowning and de-gowning, door interlocks,
visibility, personnel flow, material flow, the
introduction of components, location of utilities,
location of the equipment inside the clean room.
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2. Basic Training Microbiological Controlled Environment
Particles in Outdoor Air: Number of Particles / m on
Outdoor Air
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2. Basic Training
Microbiological Controlled Environment Elements of Microbial Monitoring
Sampling Methods
Media & Incubation Conditions
Sampling Locations
Frequency of Sampling
Alert & Action Limits
Trend Analysis
Out of Limits Investigations
Corrective Action
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2. Basic Training
Microbiological Controlled Environments Microbial Monitoring Frequency
Air, Surfaces and Personnel Monitoring Should be doneFrequently During Aseptic Operation.
Product Contact Surfaces Should be Monitored at the Endof the Aseptic Operation.
Monitoring Sites
Air monitoring should be done adjacent to the fillinglocation.
Product contact surfaces areas, non contact areas, openvials, stopper track, etc.
Personnel monitoring should be done at the sleeves andgloves.
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3. Process Flow
Classification of Clearnroom Classification for airborne environmental cleanliness
requirement 0.5 5 Class 100,000 ISO 8 3,520,000 29300
Class 10,000 ISO 7 352,000 2930 Class 1,000 ISO 6 35,200 293
Class 100 ISO 5 3520 29
Micro Settling Plates Action Levels (diam. 90mm; cfu/4hours)
Class 100- 1 CFU however samples from class 100 (ISO 5)
environments should normally yield no microbialcontaminants.
Class 1,000- 3 CFU / 4 hours
Class 10,000- 5 CFU/ 4 hours
Class 100,000- 50 CFU/ 4 hours
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3. Process Flow
Material Movement
Material/Personnel Flow, in order to produce an acceptable sterile
product, the design of personnel and material flows should
minimize or prevent the introduction of contamination to the
clean area. 04. Aseptic Processing Area.pdf
One-way personnel flow is preferred, providing physically separate entry
and exit routes or the separation can be achieved by ? ISO 14644-4
Process or operation waste should be removed from the aseptic area
without contaminating the product either by direct contact or passing
through areas.
Due to the problems in maintaining the Differential pressure , the airlock to
be used between rooms or areas of different air quality classification
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3. Process Flow
Contact sterile materials only with sterile instruments: Sterile instruments should always be used in handling of sterilized materials.
Between uses, sterile instruments should be held under class 100 (ISO 5) conditionsand maintained in a manner that prevents contamination. Instruments should bereplaced as necessary throughout an operation.
Move slowly and deliberately: Rapid movements can create unacceptable turbulence in a critical area. Such
movements disrupt the unidirectional airflow, presenting a challenge beyondintended cleanroom design and control parameters. The principle of slow, carefulmovement should be followed throughout the cleanroom.
Keep the entire body out of the path of unidirectional airflow: Unidirectional airflow design is used to protect sterile equipment surfaces, container-
closures, and product.
Multiple filling rooms: Aseptic filling validation should be performed on all filling lines within a facility on a
rotating basis. Also, the differences in air flow and turbulence can have a directimpact on the performance of the room
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4. Sanitization
Selection of disinfectant: The selection of suitable disinfectants and theverification of their effectiveness in surface challenge testing is critical in thedevelopment of a cleaning and sanitization program :
a) The number and types of microorganisms to be controlled
b) the nature of the surface material being disinfected and its compatibility withthe disinfectant /corrosiveness of the disinfectant to equipment with repeated
applicationc) the concentration, application method, and contact time of the disinfectant
d) the amount of organic compounds on the surface that may inactivate adisinfectant
e) the safety considerations for operators applying the disinfectant
f) the compatibility of the disinfectant with cleaning agents and other disinfectants
g) the planned disinfectant rotationh) the spectrum of activity of commercially available disinfectants
i) Thee steps that need to be taken to avoid the contamination of pharmaceuticalproducts by a disinfectant.
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4. Sanitization:
The cGMP 21 CFR 211.67, Equipment Cleaning and Maintenancerequirements for written procedures for cleaning, maintenance, andsanitization of pharmaceutical manufacturing equipment
a) the assignment of responsibility,
b) establishment of schedules,
c) details of cleaning operations,
d) protection of clean equipment prior to use, e) inspection for cleanliness immediately prior to use,
f) maintenance of cleaning and sanitization records
g) Staff involved in disinfection require training in microbiology, industrypractices for cleaning and sanitization, safe handling of concentrateddisinfectants, the preparation and disposal of disinfectants, and
appropriate application methods Dilutions:
It should be emphasized that the preparation of the correct dilutions iscritical because many disinfectant failures can be attributed to use ofdisinfectant solutions that are too dilute
4 S i i i
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4. Sanitization : Concentration Exponents of
Common Antiseptics, Disinfectants, and Sterilants
DisinfectantConcentration
Exponents
Red. in disinf.activity for 3 folddilution
Hydrogen peroxide 0.5 1.7
Sodium hypochlorite 0.5 1.7
Mercuric chloride 1 3
Chlorhexidine 2 9
Formaldehyde 1 3
Alcohol 9 19683
Phenol 6 729
Quaternary ammonium compounds 0.8 to 2.5 2.4-15.6
Aliphatic alcohols 6.0 to 12.7 729-1146673
Phenolic compounds 4 to 9.9 81-52905
4 S i i i I i
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4. Sanitization: Important issue
need to be taken in consideration MICROBIAL RESISTANCE TO DISINFECTANTS: periodically subjected to
use-dilution testing with the agents used in the disinfection program
The rotation of an effective disinfectant with a sporicide is encouraged
The daily application of sporicidal agents is not generally favoredbecause of their tendency to corrode equipment and because of thepotential safety issues with chronic operator exposure
Disinfectants applied on potential product contact surfaces aretypically removed with 70% alcohol wipes
handling of concentrated disinfectants and the mixing of incompatibledisinfectants. For example, concentrated sodium hypochloritesolutions (at a concentration of more than 5%) are strong oxidants
and will decompose on heating, on contact with acids, and under theinfluence of light, producing toxic and corrosive gases includingchlorine.
4 S iti ti I t t i
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4. Sanitization: Important issue
need to be taken in consideration Material Safety Data Sheets for all the disinfectants used in a
manufacturing area should be available to personnel handlingthese agents
Endotoxins are not appreciably retention by 0.2m sterilizingfilter, so any potential endotoxins contamination to the productfrom compounding and sterile filtrate receiving tank should be
preclude by developing reliable reproducible cleaningprocedures for these vessels
Its good practice to place the equipment in a service area andnot in aseptic area, and to place the outlet of any drain in aservice area due to high moisture level of potential airbornecontamination
Steam traps and other component should be located ourtsidethe clean room to preclude any stagnant condensate/water inthe clean room
4 S iti ti
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4. Sanitization: CLASSIFICATION OF
DISINFECTANTS
Chemical Entity Classification Example
Aldehydes Sporicidal agent 2% Glutaraldehyde
AlcoholsGeneral purpose disinfectant,
antiseptic, antiviral agent70% Isopropyl alcohol, 70% alcohol
Chlorine and sodium hypochlorite Sporicidal agent 0.5% Sodium hypochlorite
Phenolics General purpose disinfectant 500 g per g Chlorocresol, 500 g perg chloroxylenol
Ozone Sporicidal agent 8% Gas by weight
Hydrogen peroxideVapor phase sterilant, liquid
sporicidal agent, antiseptic4 g per g H2O2 vapor, 10%25%
solution, 3% solution
Substituted diguanides Antiseptic agent 0.5% Chlorhexidine gluconate
Peracetic acid Liquid sterilant, vapor phase sterilant
0.2% Peracetic acid, 1 g per g
peracetic acid
Ethylene oxide Vapor-phase sterilant 600 g per g Ethylene oxide
Quaternary ammonium compoundsGeneral purpose disinfectant,
antiseptic
Concentration dependent onapplication, Benzalkonium
chloride
-Propiolactone Sporicidal agent 100 g per g
-Propiolactone
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4. Sanitization
It must be assured that no humidity remain after cleaning ( e.g film or liquidunder equipment)
Cleaning solution must be freshly prepared from contaminant free detergentwith sterile WFI f its not sterilized by filtration. There must be strict limitationfor the time of use for these solution as number of microorganism mayrapidly increased given sufficient time for exponential groth
Its not acceptable to leave wipes or cleaning tools exposed to theenvironment for drying after cleaning process
Wipes for cleaning and disinfectant should be sterile and disposable orsterilized between each use
Its not acceptable to have cleaning solution ready to use during the dayunless it kept well protected in closed container
The area that can be cleaned with a single wipe or portion of cleaningsolution dispensed in a bucket should be limited in order to preventuncontrolled spreading of an eventual contamination over a large area
For cleaning of the rooms, formal validation studies are not required why !!!
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4. Sanitization
For product contact part .disinfection of critical surface with 70%IPA,even its not sporicidal procedure, since there is no concern forspore based on the environmental monitoring data.
In clean room, cleaning fluid are the only source of water available tosupport microbial growth, so the water sources from controlled loophave less than 10cfu\100ml, this mean 10 liters of buckets have 1000
cfu without consideration the organism that were introduced withthe detergent. These organism that would be introduced on the floorwhich is not a problem if the disinfection program is effective.
Alcohol are not sporicidal, but spores cant germinate and proliferatein alcohol , so this spres can be removed by !!
Its impossible to allow sufficient time for disinfectant to be fullyactive as specified by disinfectant supplier, since its understood that adisinfectant agent after entering the microbial cell during the wetperiod,may continue to act intracellularely even after drying of thesurface
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4. Sanitization
Automatic cleaning systemAdvantage
a) No critical intervention in the filling system is needed during setup ofthe equipment
b) Higher security of cleaning and sterilization of pipes and tubes that may
be difficult to sterilize in an autoclavec) Configure both CIP system and the component for cleaning, execute
the cycle and return the component to service or subsequentsterilization
d) Highly reliable and achieve a reproducible process
e) Repeatable temperature, time and reagent concentration control
f) Reduce the number of aseptic connection points to a minimum,therefore, reduce the brisk of microbial contamination at such point
g) Higher capacity and control of process parameters
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4. Sanitization
Antiseptic An agent that inhibits or destroys microorganisms on livingtissue including skin, oral cavities, and open wounds
Disinfectant A chemical or physical agent that destroys or removes
vegetative forms of harmful microorganisms when applied to a surface
pH of the disinfectant.Many disinfectants are more active in the ionized form, while others
are more active in the nonionized form. The degree of ionization
will depend on the pKa of the agent and the pH of the
disinfection environment. For example, phenol, with a pKa of 10,
will be more effective at a pH below 7 where it is nonionized
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4. Sanitization MECHANISM OF DISINFECTANT ACTIVITY
TargetDisinfectant
Cell wall Formaldehyde, hypochlorite, and glutaraldehyde
Cytoplasmic membrane, action on membranepotential
Anilides and hexachlorophene
Membrane enzymes, action on electron-transport chain
Hexachlorophene
Action on ATP Chlorhexidine and ethylene oxide
Action on enzymes with Ethylene oxide, glutaraldehyde, hydrogen peroxide, hypochlorite, andiodine
Action on general membrane permeability Alcohols, chlorhexidine, and quaternary ammonium compounds
Cell contents, general coagulation Chlorhexidine, aldehydes, and quaternary ammonium compounds
Ribosomes Hydrogen peroxide
Nucleic acids Hypochlorites
Thiol groups Ethylene oxide, glutaraldehyde, hydrogen peroxide, and hypochlorite
Amino groups Ethylene oxide, glutaraldehyde, and hypochlorite
General oxidation Hypochlorite
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4. Sanitization: Facility Sanitization
Two Bucket
Fill water in the two suitable different color
bucket (Example: Yellow and Blue) Soak the MOP in the Yellow color bucket
and wring the same in yellow bucket .
Soak the MOP in the blue color bucket andlet the water drip but wring into Yellowbucket .
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4. Sanitization
AFTER FILLING
PHENOLICS ARE USED IMMEDIATELY AFTER BATCH
OPERATIONS
70% IPA IS USED IMMEDIATELY BEFORE BATCH
OPERATIONS
AFTER MAJOR CONTAMINATION EVENTS:
FACILITY: 1 X with 0.5% HYPOCHLORITE
EQUIPMENT: 1 X with 0.5% HYPOCHLORITE AND 2 X
PHENOLICS
FACILITY: TWO PASSES WITH PHENOLICS
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4. Sanitization
DAILY: If NO batch operations were conducted in the
room:
FLOOR ONLY with PHENOLIC
MAJOR CONTAMINATION OR HEPA SHUTDOWN: FULL FACILITY
WITH
0.5% SODIUM HYPOCHLORITE FOLLOWED BY TWO FULL
FACILITY DISINFECTIONS WITH PHENOLICS
WEEKLY: (or after each batch operation):
WALLS, FLOOR AND FIXTURES with PHENOLIC
MONTHLY: FULL FACILITY (CEILING, WALLS, FLOOR)
DISINFECTION with 0.5% SODIUM HYPOCHLORITE
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4. Sanitization:
Material Handing
Step One: Wash the parts by filtered water (WFI)
Step Two: Disinfect on Entry Side of Cleanroom Step Three: Disinfect on Clean side of the cleanroom
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4. Sanitization:
PROCESS FLOW
USE STERILE POLYPROPYLENE WASTE BAGS
DISCARD AND REPLENISH DISINFECTOR AFTER EVERY
ROOM. DISINFECT THE CLASS 100 ROOMS FIRSTWORK
FROM
CLEANER TO DIRTIER ROOMS
WASH THE MOP AND BUCKET HARDWARE BEFORE
AUTOCLAVING FOR THE NEXT USE
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4. Sanitization:
DISINFECTING THE FLOORS
REPLENISH THE MOP
START FROM THE BACK OF THE ROOM AND
MOP TOWARDS THE BACK WALL REVERSE MOP
Repeat
DOUBLE BUCKET
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4. Sanitization:
DISINFECTION OF WALLS
START AT THE WALL FURTHEST FROM THE DOOR
USE THE DOUBLE BUCKET METHOD
MOVE THE MOP IN ONE DIRECTION ONLY RINSE AND REPLENISH USING THE DOUBLE
BUCKET METHOD AFTER EVERY ROW
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Example for the type of Organism
Types of Microorganisms Found in
Cleanrooms: Cleaning and Disinfection in
Cleanrooms.pdf
http://localhost/var/www/apps/conversion/tmp/scratch_2/Cleaning%20and%20Disinfection%20in%20Cleanrooms.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_2/Cleaning%20and%20Disinfection%20in%20Cleanrooms.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_2/Cleaning%20and%20Disinfection%20in%20Cleanrooms.pdfhttp://localhost/var/www/apps/conversion/tmp/scratch_2/Cleaning%20and%20Disinfection%20in%20Cleanrooms.pdf -
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The End
Amjad Ganma, M.Sc (London)
Quality Unit ManagerTabuk Pharmaceutical Manufacturing Co.,
Tabuk, Saudi Arabia
Per. Email: [email protected]
Off Email : amjad@tpmc com sa