PRESENTATION ON CLEAN ROOM AND ITS PROTOCOLS

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KIRAN DESAI

CLEAN ROOM
QUERRIES?

WHAT IS CLEAN ROOM? WHO ARE THE USERS OF CLEAN ROOM? WHY CLEAN ROOMS ARE REQUIRED IN THE PHARMACEUTICAL INDUSTRIES? WHAT IS THE DESIGN OF CLEAN ROOM HOW THE CLEAN ROOMS ARE MAINTAINED?

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CLEAN ROOM
WHAT ARE THE PROTOCOLS TO ENTER IN TO CLEAN ROOM? HOW THE CLEAN ROOMS ARE MAINTAINED? WHAT QUALITY OF AIR TO BE USED IN CLEAN ROOM? WHAT QUALITY OF WATER TO BE USED IN CLEAN ROOM?

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CLEAN ROOM
WHAT IS CLEAN ROOM
DEFINITION: Federal Standard 209 Defines a Clean Room A Clean Room is an enclosed area employing control over the particulate matter in air with temperature, humidity and pressure control as required. To meet the requirements of a 'Clean Room' as defined by this standard, all Clean Rooms must not exceed a particulate count as specified in the air cleanliness class." This standard, first issued in 1963, has been used in the current version 209B amendment 1 since 1976. It is shortly to be re-issued, entitled "Airborne Particulate Cleanliness Classes for Clean Rooms and Clean Zones".

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CLEAN ROOM
WHAT IS CLEAN ROOM
DEFINITION: BS 5295 Definition "A Clean Room is a room with environmental control of particulate contamination, temperature and humidity, constructed and used in such a way as to minimize the introduction, generation and retention of particles inside the room."

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APPLICATIONS

Industry
ELECTRONICS SEMICONDUCTORS MICROMECHANICS OPTICS BIOTECHNOLOGY PHARMACY MEDICAL DEVICES FOOD AND DRINK HOSPITALS Integrated Circuits

Applications
Computers, TV-tubes, Magnetic Tapes

Compact Disc Players, Miniature Bearings, Gyroscopes Lenses, Photographic Film, Laser Equipment Antibiotics, Generic Engineering Sterile Pharmaceuticals, Sterile Disposable Heart Valves, Cardiac by-pass Systems Brewery Production, Unsterilized Food and Drinks Immunodeficiency Therapy, Isolation of Contagious Patients, Operating Rooms

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CLEAN ROOM
WHY CLEAN ROOMS ARE REQUIRED IN PHARMACEUTICAL INDUSTRIES ? CLEAN ROMS ARE REQUIRED TO AVOID THE SOURCE OF CONTAMINATIONS. TYPES OF CONTAMINATIONS 1. Particulate: dust, makeup, skin, hair,

2. Chemical: oil, grease, perfume, 3. Biological: bacteria, fungi, 4. Radiation (ultraviolet light, )
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SOURCES OF CONTAMINATIONS People (~ 75%) Ventilation (~ 15%) Room structure (~ 5%) Equipment (~ 5%)

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HOW TO CONTROL CONTAMINATIONS?

PERSONNEL CONTROL * DRESS CODES * Personal Hygiene * GARMENTS/GOWNING

Hair cover , Hood , Shoe covers , Coverall, Gloves Face mask , Safety Glasses

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CONTINUED... ENVIRONMENTAL CONTROL * ENTERENCE AND EXIT CONTROL--Access Cards Air shower while entering

* SUPPLY OF MATERIAL AND TOOLS CONTROL (Through Pass Box) * ROUTINE CLEAN ROOM CLEANING AND MAINTENANCE

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GENERAL FEATURES OF CLEAN ROOM Protocol for clean room provides general guidance and basic awareness Successful clean room maintenance really relies on individual users understanding, participation and self discipline. Everyone, whether faculty member, student user or staff engineer, is equally important to the success of the protocol. Trust, understanding and shared responsibility among all users ensures the success of every user.
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PRINCIPLES OF CLEAN ROOM Air is highly (HEPA) filtered (99.97% @ 0.3m) Layout should minimize particle sources in filtered air stream Air flow should remove most particles generated by process

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TYPES OF FILTERS
HEPA HIGH EFFICIENCY PARTICULATE AIR FILTER ULTRA LOW PENETRATION AIR.

ULPA Filters-

EFFECT OF EFFICIENCY: ULPA is more efficient than HEPA. HEPA ULPA 99.97% (To remove 0.3 micron particles) 99.99% (To remove 0.1 micron particles)

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HOW TO TEST THE EFFECIENCY?

DOP TEST (PENETRATION TEST) DOP ADVANTAGE Di-octyl-pthalate

TO DETERMINE % OF PARTICLE PASSING THROUGH FILTERS WHY IS THIS TEST PREFERRED? DOP PARTICLE SIZE IS 0.2 MICRON CONSISTANTLY.

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HOW SHOULD BE THE LAYOUT ..?

Production Plant
Change Room

Toilets

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BUILDING FINISHES Not Acceptable PVA Paint Window sills Exposed pipes Horizontal pipes & services Open floor drains Floor cracks, flaking floor surfaces Ceiling cracks & joints Exposed, open light fittings
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Acceptable Epoxy or Enamel paint Window view panels Smooth surfaces (Electro polished) Concealed services Hygienic drains Homogonous sealed floors epoxy finish or welded vinyl Smooth sealed ceilings Flush light fittings S/Steel mirror finished or Melamine furniture KIRAN DESAI
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Wooden furniture

FLOOR FINISHING

Tiled Floor

Epoxy Floor

NOT ACCEPTABLE

RECCOMMENDED

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Poor Window

Good Windows

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NOT ACCEPTABLE

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RECCOMMENDED

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SERVICE DISTRIBUTION

Cleaning is easier Accessibility for cleaning is not there

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Where ever it is possible possible services should be located behind wall panels. Exposed services & pipes are very difficult to clean, sometimes impossible to clean. &

Equipment such as Film Coaters should be enclosed so that only the front face is in the GMP area. This makes cleaning much easier. Make use of service corridors behind equipment (but must be under negative pressure) Insulation of all the utility lines should be GI coated and enamel painted.

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ALWAYS ROOM SHOULD BE WITH POSITIVE PRESSURES. THE INTERNAL PARTICULATE GENERARTION TO BE CONTROLLED BY EPOXY FLOORING HARD SURFACED NON PORUS MATERIAL (PVC PANELS) EPOXY PAINTED WALLS GLASS BOARD CEILINGS PROPER HVAC (HEATING VENTILLATION AIR CONDITIONING) PROPER DOOR CLOSURES

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Continued BOTTOM CLOSURES COVING ON WALLS AND FLOORS TO AVOID ACCUMALATION OF DUST. ENTRY FOR SPECIFIED PERSON WITH ACCESS CARDS ALL THE ROOMS SHOULD HAVE FIRE ALARM SYSTEMS CLEAN ROOM SHOULD HAVE TEMPERATURE AND HUMIDITY CONTROLLER SYSTEMS. AIR LOCK SHOULD BE ROOMS. PROVIDED FOR ACCESSING TWO

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AIR FLOW

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TYPES OF AIR FLOW

1. LAMINAR AIRFLOW 2. TURBULENT AIRFLOW

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LAMINAR AIR FLOW CLEAN ROOM Laminar air flow is used when low airborne concentrations of particles or bacteria are required. This air flow pattern is in one direction, usually horizontal or vertical at a uniform speed of between 60 to 90 ft/min. and throughout the entire space. The air velocity is sufficient to remove relatively large particles before they settle onto surfaces. Any contaminant released into the air can therefore be immediately removed by this laminar flow of air, whereas the turbulent air flow ventilated system relies on mixing and dilution to remove contamination.

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LAMINAR AIR FLOW CLEAN ROOM

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Any obstructions will cause the laminar air flow to be turned into turbulent air flow around the obstructions. Higher contamination concentrations will be established in the turbulent areas. Air changes per unit of time are related to the volume of the room and are many times greater than those supplied to a turbulent air flow Clean room.

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TURBULENT AIR FLOW The general method of ventilation used in turbulent air flow clean rooms is similar to that found in buildings such as offices, schools, malls, manufacturing plants, auditoriums, shops, etc. The air is supplied by an air conditioning system through diffusers in the ceiling. However, a clean room differs from an ordinary ventilated room in three ways. These are increased air supply, the use of high efficiency filters and room pressurization. The increased air supply is an important aspect of particle control. A typical turbulent air flow clean room would have at least 10 air changes per hour and likely to have between 20 and 60.

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TURBULANT AIR FLOW CLEAN ROOM

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TURBULANT AIR FLOW CLEAN ROOM

This additional air supply is mainly provided to dilute to an acceptable concentration the contamination produced in the room. High efficiency filters are used to filter the supply air into a clean room to ensure the removal of small particles. The high efficiency filters used in clean rooms are installed at the point of air discharge into the room. Room pressurization is mainly provided to ensure that untreated air does not pass from dirtier adjacent areas into the clean room. The clean room is positively pressurized with respect to these dirtier areas. This is done by extracting less air from the room than is supplied to it.

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APPLICATIONS
LAMINAR AIR FLOW FORMULATION STERILE PLANTS

TURBULENT AIR FLOW NON STERILE PLANTS

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PARTICLE CHARACTERISTICS OF CLEAN ROOM 50 micron particles are visible Average human hair is about 100 microns Time to fall 1 meter in still air 33 seconds for 10 micron particle 48 minutes for 1 micron particle Humans generate >1x105 particles per minute when motionless (fully gowned) Humans can generate >1x106 particles when walking in the clean room
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GUIDELINES AND DESIGN PARAMETERS OF CLEAN ROOM

FUNDAMENTAL OF CLEAN ROOM DESIGN IS TO CONTROL THE CONCENTRATION OF AIRBORNE PARTICLES. A PROPER HVAC SYSTEM IS CRITICAL PART OF CLEAN ROOM DESIGN. PARTICULATE MATTER CAN BE CONTROLLED BY HEPA FILTERS WITH MIN EFFECIENCY OF 99.97% TESTED ON 0.3 MICRON NUMBER OF AIR CHANGES PER HOUR SHOULD BE IN THE RAGE OF 10 TO 20.

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CLASSIFICATIONS OF CLEAN ROOM HOW ARE CLEAN ROOMS CLASSIFIED? CLEAN ROOMS ARE CLASSIFIED BASED ON CLEANLINESS OF AIR. STANDARDS OF CLEAN ROOM Federal Standard 209D Class Limits Federal Standard 209E Airborne Particulate Cleanliness Classes British Standard 5295:1989 BR 525 Environmental Cleanliness Classes BS EN ISO Standard

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Federal Standard 209D Class Limits

MEASURED PARTICLE SIZE (MICROMETERS) 0.1 1 10 100 1,000 10,000 100,000 35 350 NA NA NA NA 0.2 7.5 75 750 NA NA NA 0.3 3 30 300 NA NA NA 0.5 1 10 100 1,000 10,000 100,000 5 NA NA NA 7 70 700

CLASS

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Federal Standard 209E Airborne Particulate Cleanliness Classes

Class Name 0.1m m Volume Units SI M1 M 1.5 M2 M 2.5 M3 M 3.5 M4 M 4.5 M5 M 5.5 M6 M 6.5 M7 100 000 10 000 1 000 100 10 1 English (m^3) 350 1 240 3 500 12 400 35 000 --------(ft^3) 9.91 35 99.1 350 991 --------0.2m m Volume Units (m^3) 75.7 265 757 2 650 7 570 26 500 75 700 ------(ft^3) 2.14 7.5 21.4 75 214 750 2 140 ------Class Limits 0.3m m Volume Units (m^3) 30.9 106 309 1 060 3 090 10 600 30 900 ------(ft^3) 0.875 3 8.75 30 87.5 300 875 ------0.5m m Volume Units (m^3) 10 35.3 100 353 1 000 3 530 10 000 35 300 100 000 353 000 1 000 000 3 350 000 10 000 000 (ft^3) 0.283 1 2.83 10 28.3 100 283 1 000 2 830 10 000 28 300 100 000 283 000 5m m Volume Units (m^3) -------247 618 2 470 6 180 24 700 61 800 (ft^3) -------7 17.5 70 175 700 1 750

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BS 5295 ENVIRONMENTAL CLEANLINESS CLASSES

Maximum permitted number of particles per m^3 (equal to, or greater than, stated size) Maximum floor area per sampling position for clean rooms (m^2) Minimum pressure difference*

Class of environment al cleanliness

0.3 m m

0.5 m m

5mm

10 m m

25 m m

Between classified areas and unclassifie d areas (Pa) 10 10 10 25 25 25 25 50 50 50 15 15 15 15 15 15 15 15 10 10

Between classified area and adjacent areas of lower classification (Pa) 10 10 10 10 10 10 10 10 10 NA 37

C D E F G H J K L

100 1 000 10 000 NS 100 000 NS NS NS NS

35 350 3 500 3 500 35 000 35 000 350 000 3 500 000 NS NS

0 0 0 0 200 200 2 000 20 000 200 000 NS

NS NS NS NS 0 0 450 4 500 45 00

NS NS NS NS NS NS 0 500 5 000

M NS 11/21/2008

450 000 50 000 KIRAN DESAI

ISO 209 airborne particulate cleanliness classes for clean rooms and clean zones.
Numbers (N) Maximum concentration limits (particles/m^3 of air) for particles equal to and larger than the considered sizes shown below 0.1m m* ISO 1 ISO 2 ISO 3 ISO 4 ISO 5 ISO 6 ISO 7 ISO 8 ISO 9 10 100 1 000 10 000 100 000 1 000 000 0.2m m 2 24 237 2 370 23 700 237 000 10 102 1 020 10 200 102 000 4 35 352 3 520 35 200 352 000 3 520 000 35 200 000 8 83 832 8 320 83 200 832 000 8 320 000 29 293 2 930 29 300 293 000 0.3m m 0.5m m 1m m 5.0m m

* m m Micro Meter
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GRAPHICAL REPRESENTATION OF AIRBORNE PARTICLES

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GENERAL CLEAN ROOM REGULATIONS

Below is a list of general regulations recommended as a minimum for the successful operation of a clean room. All professional cleaning personnel should be aware and follow these regulations at all times. All personal items such as keys, watches, rings, matches, lighters and cigarettes should be stored in the personal locker outside the gowning room. Valuable personal Items such as wallets may be permitted in the clean room provided they are NEVER removed from beneath the clean room garments.

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CONTINUED
NO eating, smoking or gum chewing allowed inside the clean room. Only garments approved for the clean room should be worn when entering. NO cosmetics shall be worn in the clean rooms. This includes: rouge, lipstick, eye shadow, eyebrow pencil, mascara, eyeliner, false eye lashes, fingernail polish, hair spray, mousse, or the heavy use of aerosols, after shaves and perfumes. Only approved clean room paper shall be allowed in the clean room. Approved ball point pens shall be the only writing tool used.
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CONTINUED

Use of paper or fabric towels are prohibited. Use of hand dryers equipped with HEPA filters are suggested. Gloves or finger coats should not be allowed to touch any item or surface that has not been thoroughly cleaned. Only approved gloves, finger cots (powder-free), pliers, tweezers should be used to handle product. Finger prints can be a major source of contamination on some products. Solvent contact with the bare skin should be avoided. They can remove skin oils and increase skin flaking.

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CONTINUED.

Approved skin lotions or lanolin based soaps are sometimes allowed. These can reduce skin flaking. All tools, containers and fixtures used in the cleaning process should be cleaned to the same degree as the clean room surfaces. All of these items are a source of contamination. NO tool should be allowed to rest on the surface of a bench or table. It should be place on a clean room wiper.

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CONTINUED. Only clean room approved wipers are allowed to be used. The wipers must be approved for the Class of clean room being cleaned. ALL equipment, materials and containers introduced into a sterile facility must be subjected to stringent sterilization prior to entrance. NO ONE who is physically ill, especially with respiratory or stomach disorders, may enter a sterile room. This is a good practice in any clean room environment.

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HVAC DESAIGN CONSIDERATIONS 1. Temperature and Humidity 2. Pressurization 3. Ventilation and Make Up Air

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Temperature and Humidity Most clean room require year-round cooling as a result of the fan energy associated with high clean room airflow as well as the heat generated by the process, people, and lighting within the facility. Temperature control is required to provide stable conditions for materials, instruments, and personnel comfort. Human comfort requirements typically call for temperatures in the range of 72F to 75 F, since workers frequently wear clean room garments over street clothes. Humidity control is necessary to prevent corrosion, condensation on work surfaces, eliminate static electricity, and provide personnel comfort. The human comfort zone is generally in the range of 30% to 70% relative humidity
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Pressurization

A clean room facility may consist of multiple rooms with different requirements for contamination control. Rooms in a clean facility should be maintained at static pressures higher than atmospheric to prevent infiltration by wind. Positive differential pressures should be maintained between the rooms to ensure air flows from the cleanest space to the least clean space. The only exception to using a positive differential pressure is when dealing with specific hazardous materials where governmental agencies require the room to be at a negative pressure.

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HOW IS AIR PRESSURE MEASURED? The pressure differential over the doorway is measured with a portable magnahelic gauge or micro manometer

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Ventilation and Make Up Air

Ventilation and makeup air volumes are dictated by the amount required to maintain indoor air quality, replace process exhaust and for building pressurization. This provides assurance that carbon dioxide and oxygen remain in balance, that formaldehyde and other vapors given off by building materials and furniture are diluted, and that air changes occur with sufficient frequency to minimize the chance for high concentration of airborne pollutants within the building.

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HOUSE KEEPING
Every user is responsible for keeping the clean rooms clean. Always clean your workspace before leaving. Dont leave or store items on or in equipment. Do not set liquids on any equipment. Properly store all materials before leaving the clean room Last one out should make sure the room is in a safe idle mode.

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CHEMICAL HANDLING IN CLEAN ROOMS

Chemical waste should be properly disposed of as outlined by EHS systems. No chemicals may be poured down the drains Waste containers should be properly marked as such and have a pink Hazardous Waste tag tied to them at all times. If you have questions about disposal contact a staff member.

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VOILATION OF RULES
First time Warning Report to Advisor Suspension of access Report to Advisor Retraining may be required Suspension of access Report to Advisor Access will not be renewed until an acceptable resolution is reached between Advisor and Clean room Manager
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Second time

Third Offense

Clean room Protocol re-training will be required.

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HVAC SUPPLY CLEAN ROOM DOORS FLUSHED WINDOWS FLUSHED LIGHTING FALSE CEILING

EPOXY FLOORING

COVING
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