Planning Phase

Because of the cost, duration, and complexity of a cleanroom construction project, some form of project management is typically used. The planning phase for a cleanroom construction project should include definition of costs, timelines and deliverables, and identification of constraints and risks. Careful attention should be taken in the planning phase, as effective planning can make the difference between a project that is delivered on time and on budget and meeting strict quality standards compared to one that is late, over budget, and fails to meet quality standards.

Involving all involved disciplines, including manufacturing, engineering, quality, validation, environmental monitoring, cleaning, sterilization, etc., will make it more likely that the critical requirements are captured in the planning stage, reducing additions to the cleanroom design that increase the cost and duration of the project.

Design Phase

The first phase covered in this flow chart is the design phase, which begins with the preparation of formal process and product requirements. These requirements should answer the following questions:

• Will the facility be dedicated to a single product or will it be a multiproduct facility?
• Will the product(s) include any lyophilized products, any moisture-sensitive products, or any oxygen sensitive or light sensitive products?
• Are any of the products temperature-sensitive?
• Do any of the products have special containment requirements, such as cytoxic products?
• How will the product(s) be presented to the consumer (e.g., vials, syringes, ampoules, cartridges, etc.)? Are any devices included in the presentations that will require additional equipment in the cleanroom?
• Can the products be terminally sterilized or must they be aseptically filled?
• Do the processes require dedicated or disposable equipment, or can equipment be shared between some products with appropriate precautions? Consideration should be given to whether the product dosage is low enough to cause concern with cleaning validation.

Construction Phase

Once the detailed design reviews are complete the project moves to the construction phase, in which the facilities, utilities, and equipment are built. This phase uses standard construction management techniques for the facilities, utilities, and equipment. Special attention should be given to items such as welded piping such as water for-injection (WFI) piping, and cleanroom construction during this phase. The construction phase concludes when the equipment, facilities, and equipment are constructed and installed. Equipment typically undergoes a factory acceptance test (FAT) before it is shipped. An FAT is intended to verify that the equipment meets its approved design specifications and functional specifications before it ships.

The contract with the vendor typically specifies that successful completion of an FAT is required before the equipment may ship. An FAT is typically executed using an FAT protocol that is approved by representatives from the vendor and customer. Once the FAT is approved, the equipment may ship and may be installed at the customer site. A site acceptance test (SAT) may be performed once the equipment is installed in the cleanroom to ensure that
the equipment has been installed properly.

Commissioning Phase

Once the construction phase is complete, the project moves into the commissioning phase. In this phase, the equipment, utilities, and facility are tested to ensure they meet design specifications, functional specifications, and user requirements. The commissioning phase differs from the subsequent qualification phase in that a less formal change management system is typically in place during commissioning, allowing changes to be made and documented with lower levels of approval than would be necessary during the qualification phase. Typical activities that occur during the commissioning phase may include the following:

• Redlining of equipment, facility, and utility drawings to ensure they reflect the actual systems as installed
• Verification of field interconnects, if not performed as part of a site acceptance test
• Verification that equipment and utilities operate as designed
• Verification of materials of construction for equipment, utilities, and cleanrooms, if not verified during the construction phase
• Cycle development for various component, equipment, and material preparation processes such as steam sterilization processes, clean-in-place and steam-in-place, closure washing, siliconization (if necessary) and sterilization processes, dehydrogenation processes, sterile filtration, etc.
• Preparation of forms and procedures for equipment, facilities, and utilities, and many other activities
• Air balancing of the facility to ensure proper air flows and pressure cascades. This is typically done by professional air balancing firms that are certified by the National Environmental Balancing Bureau (NEBB).

The commissioning phase is typically closed out by a formal commissioning report, which evaluates whether the equipment, utilities, and facilities are properly installed and properly operating, and whether or not the equipment, facilities, or utilities are ready for qualification.

Qualification Phase

The qualification phase begins with completion of commissioning of the equipment, facilities, and utilities and continues through aseptic process simulations (media fills) and process validation (conformance) runs. Some installation qualification (IQ) activities, such as verification of piping, wiring, or materials of construction, may begin in the commissioning phase or even in the construction phase, continuing into the qualification phase. Operational qualification (OQ) and performance qualification (PQ) activities are almost totally contained in the qualification phase, although some OQ activities
may be performed during commissioning if no changes are made to the equipment subsequent to the OQ activities.

It is in the qualification phase that cleanroom certification activities are typically performed.

Submission Phase

The submission phase consists of the preparation of regulatory submissions once qualification activities are completed. These submissions are sent for approval to one or more regulatory agencies. Any product manufactured during the submission phase is held pending approval of the submission.

Operational Phase

Once approval is received, the cleanroom can be considered to be operational. Product being held pending submission may be released, assuming it meets its predetermined specifications.