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(Table 1). Notice the number oparticles produced per minuteduring these activities.

Cleanroom ClassicationsCleanroom Classications as

specied by dierent standardsare shown in Table 2. Non-sterileproducts are typically produced inan ISO 8 or EU Class D environ-ment. Sterile products are required

to be lled and stoppered in anISO 5 or EU Class A environment.

Cleanroom CleaningAs an example, here are some

recommended procedures orcleaning a Class C or ISO 7 Areacleanroom. These procedures aresimply guidelines, not standardsor rules. It is important to reviewall cleaning procedures to be usedin a cleanroom with responsiblemanagement. A detailed cleaningschedule should be prepared orevery cleanroom.

Procedure

Good housekeeping and main-tenance o the cleanroom and theassociated restricted areas are es-sential to assure quality. Cleaningo an active cleanroom should beperormed daily. However, i theroom is not used daily, a dierentschedule may be implemented,but it should be cleaned aterevery use. Improper cleaning othe cleanroom can lead to con-tamination and compromise prod-

uct quality. Proper selection oequipment, cleaning agents andcleaning materials is importantor proper cleaning. Only prod-ucts that have proven cleanroomperormance records should beconsidered or use. These prod-ucts should be listed in appropri-ate policies or procedures and allvendors should be inormed aboutthe strict policies o how prod-ucts are qualied. All proceduresshould be strictly enorced. Beloware some examples o how to or-

ganize cleanroom cleaning. Theseare guidelines or preparing workprocedures and schedules. Localrequirements must be included inany cleaning program.

Equipment and Supplies all sup-plies must meet the Class C or ISO7 Area minimum requirements

Cleaning and disinectingsolutions

Cleanroom mops

Cleanroom vacuum cleaner(i allowed)

Cleanroom wipers

Cleanroom mop bucket andwringer

Cleaning Tasks requency mayvary depending upon local require-ments Cleaning o all work suraces in

the controlled environment Vacuuming (i allowed) o the

foors and work suraces

Emptying o appropriate trashand waste receptacles

Cleaning o the doors, doorrames and lockers in the pre-staging area and gowning areasusing the approved cleaningsolution

Mop gowning area and cleanroomfoors

General Cleanroom Requirements

Here is a list o general require-ments recommended as a mini-mum or the successul operationo a cleanroom. All cleanroom per-sonnel should be aware and ollowthese requirements at all times.

All personal items such as keys,watches, rings, matches, lightersand cigarettes should be storedin the personal locker outside thegowning room.

Valuable personal Items suchas wallets may be permitted in

the cleanroom provided they arenever removed rom beneath thecleanroom garments.

No eating, smoking or gumchewing is allowed inside thecleanroom.

Only garments approved orthe cleanroom should be wornwhen entering.

No cosmetics shall be worn inthe cleanrooms. This includes:rouge, lipstick, eye shadow,eyebrow pencil, mascara, eyeliner, alse eye lashes, ngernailpolish, hair spray, mousse, orthe heavy use o aerosols, atershaves and perumes.

Only approved cleanroompaper shall be allowed in thecleanroom.

Gloves should not be allowedto touch any item or suracethat has not been thoroughlycleaned.

Only approved gloves, pliers,tweezers should be used tohandle product.

All tools, containers and xturesused in the cleaning processshould be cleaned to the

same degree as the cleanroomsuraces.

No tool should be allowed torest on the surace o a benchor table. It should be placed ona cleanroom wiper.

Only cleanroom approvedwipers are allowed to be used.The wipers must be approvedor the class o cleanroom beingcleaned.

All equipment, materials andcontainers introduced into a

sterile acility must be subjectedto stringent sterilization prior toentrance.

No one who is physically ill,especially with respiratory orstomach disorders, may enter asterile room.

Denitions

HEPA Filter - High EciencyParticulate Air Filter

Viable - a particle capable oliving, developing, or germinatingunder avorable conditions, i.e.,bacteria.

Non-viable - typically dust or liquidparticles

Airborne - carried by or through the

airCleanrooms for Handling PotentCompounds

For handling potent compounds,i.e., toxic materials, in addition tothe requirements described or acleanroom, precautions need tobe taken to avoid spreading thetoxic material to adjacent areas.This may be achieved by main-taining a negative pressure di-erential between the cleanroomand adjacent area so any hazard-ous powder or aerosol is contained

within the cleanroom, i.e., P3 ~P2 > P1 (Figure 1). This is ac-complished by designing the a-cility with HEPA ltered incomingair and providing HEPA ltrationat the exhaust. Also providing ahigher fow through the exhaustlters to assure proper fow, pres-sure dierential and sucientair changes in order to meet therequired room classication; thissetup does not allow air rom thecleanroom to enter into adjacentareas. Additionally, by providing

localized exhaust or incorporat-ing isolators onto manuacturingequipment, the control o aerosolsand dust rom handling powdersis increased. Note that personnelenter the cleanroom through thegowning area whereas equipmentand materials are brought throughthe air lock.

References

1. ISO EN 14644-1, -2, -5, -9International Standards Organiza-tion Cleanroom Standards

2. FDA Guidance or Industry Sterile Drug Products produced byAseptic Processing CGMP Sep-tember 2004

3. EU GMP Annex 1- Manuac-ture o Sterile Medicinal Products

4. ISPE International Societyor Pharmaceutical Engineers

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NEGATIVE PRESSURE CLEANROOM FORHANDLING POTENT COMPOUNDS

Figure 1

= Air Flow

Z = HEPA

Filtered Air

Z = P1

Z = P2

Cleanroom

Gowning Area

Particle Sciences

Air Lock

Z=P3