organization facility- genial para espina de pescado

7/25/2019 Organization Facility- Genial Para Espina de Pescado

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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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Design Criteria

Site and Building Considerations in the aspect of

Sanitization :

Environmental Protection is essential Operator protection is essential

Product


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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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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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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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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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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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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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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.



shedding, sealed, crevice

free.

Outlets and

miscellaneous

Equipment

Cleanable, ideally non-

shedding



shedding, sealed, crevice free.



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.
http://en.wikipedia.org/wiki/Micronhttp://en.wikipedia.org/wiki/Micronhttp://en.wikipedia.org/wiki/Micron


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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
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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

organization facility- genial para espina de pescado

Documents