EHS-045 Building Cleaning Procedure

5.1 Contamination Control Measures used in GMP

The following combination of measures have been introduced to minimise the possibility of product cross contamination between production rooms and adjoining areas.

5.1.1 Building Measures

5.1.1.1 Maintenance of a differential air pressure between rooms and adjoining corridors or service areas

5.1.1.2 Air locks between functional areas of the building.

5.1.1.3 Colour coded cleaning equipment for specific areas of the building.

5.1.1.5 Use of the security system to deny access to manufacturing blending rooms to untrained and / or unauthorised staff where the OH&S risk from the raw materials is high.

5.1.1.6 Modified procedures for “wet” cleaning operations (safety reasons), i.e. use of shoe covers or laying down of towelling (to capture any water) at the entry to the room, while wet cleaning takes place inside the room.

5.1.1.7 Any clothing soiled during cleaning operations is to be changed before the next cleaning task.

5.1.2 Cleaning Measures

 5.1.2.1 All equipment used to clean any product, chemical or soil from a room, product spill or general cleaning must not be reused for any other purpose or cleaning activity until the equipment has been thoroughly re-cleaned and sanitized.

5.1.2.2 After sanitising, equipment must be allowed to air dry before reuse to enable the sanitising agent to effectively kill bacteria.

5.1.2.3 All equipment used is to be stored in clean conditions and maintained in a visibly clean and good condition.

5.1.2.4 Clean mop heads must be stored in labelled, sealed clean and sanitised containers and stored in a separate area from dirty or used equipment awaiting cleaning.

5.2 Areas and Responsibilities

5.2.1 Contract Cleaners

The contract cleaners are responsible for maintaining adequate cleaning and sanitation to the following areas:

Manufacturing Area – excepting Granulation and Blending rooms

Pharmacy and Quarantine sampling booths (Daily)

Pharmacy and Quarantine storage areas

Blister Rooms and Packaging Area

Wash bays and equipment storage rooms

Laboratory (both levels)

All office areas

Packaging, Semi-Finished Goods and Finished Goods Warehouse

Building Amenities and Waste disposal area

5.2.2 Production Operators

Granulation and Blending areas are maintained by operators due to the safety risks associated with the active ingredients used in the blends. Core Area operators have the appropriate training and safety equipment to clean these rooms.

All machinery and equipment used in both Manufacturing and Packaging areas is again maintained and cleaned by production operators.

5.2.3 Workshops and Plant Rooms

Receiving, Engineering workshops and plant rooms areas are maintained under the general housekeeping procedures with assistance from the cleaners for hard floor sealing and roof and wall cleaning (i.e. no equipment or bench cleaning).

5.3 Type of Cleans

Four types of cleans are used for the West Ryde Facility.  They are:

5.3.1 “Full” Clean or “Changeover” Clean

Full Cleans are performed between Product changeovers.  They involve the cleaning of all surfaces in the room.

5.3.2 “Part” Clean or “Interval” Clean

Part Cleans are performed during campaign runs on request of the operator.  Part Cleans normally involve removing mobile equipment to clean and sanitise the floor plus cleaning wiping over the fixtures to sanitize hand contact areas.

5.3.3 “Construction” Clean

Construction Cleans are only performed after new building or building modifications.

5.3.4 “Blending Room” Clean Blending Room Cleans are performed by Production operators. Details and specifics of each clean is contained within SOPs for manufacturing operations.

5.4 Frequency of Cleaning

The frequency of cleaning is documented in the cleaning roster. Common use areas are continually monitored and cleaned at least daily or as required; e.g. change rooms and airlocks may be cleaned up to three times a day depending on traffic flow.

Production rooms are cleaned on request from production Team Leaders.

Areas where production equipment is cleaned (wash bays) or where cleaner’s equipment is sanitised (cleaner’s rooms) as well as sampling booths, airlocks and change rooms are cleaned and sanitised at least once per day by the cleaners.

Production room cleaning generally occurs but is not restricted too, between product changeovers or between batches during campaigns or after maintenance / adjustment to production machinery, but at all times is initiated and remains at the discretion of the operator. The Building Services Coordinator maintains a log recording the frequency of production room cleans.

The Packaging and Finished Goods warehouses are cleaned during the evening shift when forklift activity is significantly reduced.

5.5 Cleaning Verification

Cleaning verification / facility pre-use inspections are performed by trained Quality and Production Team Leaders / Managers and/or their designates and performed after cleaning or maintenance operations.

Cleaning verification / facility pre-use inspections are recorded in the Equipment and Module Logbooks.

5.6 Cleaning Equipment

A colour-coded system is employed for cleaning equipment to minimise the risk of contamination from using non-GMP equipment in GMP areas.  The system applies to the mops, mop buckets, brooms dust pans, etc., used by the cleaning and operator teams. Therefore, only the appropriate colour coded equipment is permitted to be taken into and used in the respective areas.

In descending order of priority, the areas and colours are:

5.6.1 Core Area Clean Zone (All rooms) use RED ONLY equipment.

5.6.2 Packaging Hall (Vinyl floor area) use BLUE ONLY equipment.

5.6.3 Laboratory (Both levels) use YELLOW equipment.

5.6.4 General use (All other areas) use GREEN equipment.

 Additional measures introduced include:

5.6.5 Core and Packaging area equipment is washed, sanitised and stored, off the floor, in dedicated cleaners wash / store rooms (i.e. equipment stays inside the clean zone).

5.6.6 Mop heads for the Core and Packaging Areas are both stored and washed separately from all other mops used anywhere in the factory.

All cleaning equipment is supplied by and remains the property of the Contract Cleaning Company.  Equipment is to be well maintained and replaced as required.

Any equipment borrowed from the cleaners must NOT be placed back in storage after use until it has been cleaned and re-sanitised by the cleaners. Equipment MUST also be suitable for the specific area in which the equipment is to be used and returned to the relevant wash bay.

5.7 Cleaning and Disinfectant Agents

5.7.1 Only approved chemical agents can be used inside the manufacturing building.

5.7.2 All containers of approved cleaning agents inside the building must be stored separately from product and have a green “Released” sticker attached.

5.7.3 A list of approved chemicals can be found in the Approved List for Lubricants, Cleaning Agents, Oils and Miscellaneous Materials.

5.7.4 Copies of current MSDSs for all cleaning agents used must be displayed in all cleaner’s rooms for quick and easy access in the event of a spill.

Note: MSDSs are current for 5 years.

5.7.5 New chemicals or new formulations of existing chemicals cannot be used until approval and acceptance is granted in accordance with the procedure for Change Management System.

5.7.6 Any chemicals received, which are not on the approved list should be immediately quarantined in the Engineering building and not used until the Change Request has been approved for the new chemical.

5.7.7 All chemical containers must be clearly labelled and hazard information displayed if appropriate for the chemical.

5.7.8 Chemical dilution ratios must be clearly displayed and measuring equipment available in each cleaner’s room.

5.8 Cleaner Accreditation and Training

The contract cleaners who are permanently appointed to the site can work with the Production teams on a daily basis. Only qualified GMP trained cleaners are permitted to clean Production modules or rooms unsupervised and to sign the production module GMP logbooks.

To qualify cleaners need to complete the following training programs:

5.8.1 Contractor General Cleaning Training Modules.

5.8.2 Contractor GMP Training Modules

5.8.3 A period of practical training.

5.8.4 Site Induction and GMP training sessions plus the Site SOPs.

5.9 Cleaning Documentation

The contractor should provide a detailed site roster which include all areas cleaned under the current cleaning contract. The Roster / SOP contains steps detailing the cleaning, mixing of cleaning and sanitising agents and frequency of cleaning as well as provision for the cleaner to initial each task when completed for each day of the week. Thus, providing a record of the cleaning activities performed. The roster is used daily. Each step of the procedure signed off as the cleaners progress through their daily routines.

The Building Services Coordinator issues the weekly roster, collates and checks the returned roster at the end of each week to monitor the frequency of the rooms cleaned.

Deviations from the roster are reviewed by the Building Services Coordinator and brought to the attention of the Contractor.

A master copy of the roster is endorsed by Quality Compliance and reviewed every two years.  Any amendment to a contractor document must be recorded on the revision sheet and acknowledged by both Quality and Engineering.

Other Documentation Includes:

5.9.1 A contractor Training Summary for each cleaner working on site.

5.9.2 A Signature Register to record sample signatures for documentation compliance when using module logbooks and cleaning records.

5.9.3 An Equipment Register sheet.

5.9.4 Sample copies of the Contractor Training Modules.

5.9.5 Production rooms ‘No. of Cleans’ record.

5.9.6 Module / Room logbooks.

5.10 Cleaning and Building Audits

Regular monthly cleaning audits are performed to monitor the quality of the cleaning services provided and also to identify any building maintenance issues found during the inspection.  Action items and the actions taken are recorded.

5.11 Raw Materials Sampling and Pharmacy Booths

The raw materials and pharmacy HEPA filtered down-flow booths are fully cleaned and sanitised once per day by the cleaning team. Additional cleaning is performed after each batch or sample lot is processed by the operators and before the next batch or new sample is introduced to the booths.

5.12 Cleaning of Air Intake Grills in the Manufacturing Rooms

The return air grills at the rear of the Compression, Encapsulation and Tote bin rooms have a washable mesh fabric filter applied as a precautionary measure to prevent any contamination of the return air ductwork from dust generated during tableting operations, etc.  In conjunction with the operators these grills are to be opened and the grill assembly and filter fabric cleaned as part of the room cleaning procedure and documented by the cleaners on the roster for the room.

The filters may contain product residue (power) which may exceed the allowable exposure limits.  Protective equipment (dust mask and gloves) must be worn while cleaning both the filter and around the grill frames.

Grills and filters in blending rooms are cleaned by operators due to the heavier concentration of product residue in these rooms.

5.13 Cleaning and Sanitisation of Drains in Wash Bays

The following special procedure should be used for the cleaning of all drains:

5.13.1 Using a scrubbing bush dipped in “Target” solution clean the cover, strainer and drain.  (Do NOT dip the brush into the water inside the drain.)

5.13.2 Rinse off with RO water or clean “Target solution”.

5.13.3 Wipe off excess water with a clean dry cloth or towelling.

5.13.4 Spray drain with 70% Alcohol and allow to AIR DRY (i.e. Do NOT wipe 70% Alcohol dry).

5.13.5 Place “Wet Floor” sign on floor.

5.14 Waste Removal

There are several waste and recycling collection points at various locations around the building.  Cleaners are responsible for transporting the collected waste material from these collection points to various waste streams.

The cleaners also remove non-inventory production waste for shredding and / or incineration. Waste collection and storage areas are to be maintained in a clean condition at all times.

Note: There is no food or waste in the GMP building.

5.15 Cleaning of Pallet Trucks

Cleaning staff assist Production staff by cleaning the hand pallet trucks used in the Production areas as an additional contamination preventive measure.

5.16 Cleaning of Non Production Areas

Non-production areas such as the Laboratory, Office and Amenities areas are also serviced by the contract cleaners to maintain general cleanliness and personal hygiene to an appropriate standard and meet customer expectations for the work areas concerned.  Non-GMP cleaners normally perform these tasks.

5.17 Special Precautions / Cleaning Needs – After Building or Construction Work

Special precautions / additional cleaning measures are required for any works involving new or modified walls and / or door frames.

The following special measures must be implemented for any construction or modification works carried out to rooms in the GMP areas.  The measures are designed to reduce the risk of contamination or product quality being compromised:

5.17.1 Fixtures, (immovable machinery) and epoxy floors are to be covered in plastic or protective sheeting prior to the commencement of any building work.

5.17.2 When transiting GMP areas building materials, equipment and tools as well as waste are to be bagged in plastic for transportation both to and from the work area.

5.17.3 Maintenance contractors are to comply with GMP garment requirements while transiting too and from the work areas.

5.17.4 Micro testing is to be performed prior to the hand over of the room to production staff.

N.B: A separate logbook entry is required for each clean and should be recorded in the room logbook with time, date and signature recorded for each clean.

Micro testing is performed after the second and third cleans to verify the cleaning of the new area.

5.18 GMP Building Structure (General Notes)

The production areas of the building are maintained in a sanitised condition and, where possible, constructed of non-fibre shedding materials (i.e. panel walls, aluminium, glass and epoxy floors).

Older areas, such as the Three Storey Module, the walls are sealed with acrylic paint to seal the surfaces every six to 12 months.  Production area floors are either sealed vinyl or urethane over epoxy surfaces.

Filtered air handling units supply all air to all GMP production areas. Production area corridors and clean storage rooms are operated with pressurised air to create a positive differential between corridors and production rooms.

Sampling booths in Pharmacy and Quarantine areas have dedicated down flow air handling units with HEPA filtration.

Wash bays are located at opposing ends of the production areas and used as stale air sinks.  (Wash bays operate at low positive air pressure to seal against external conditions.)  All exhaust air from the wash bays is discharged to atmosphere.  (Not recycled back into the plant.)