PROJECT TURNOVER AND INSTALLATION QUALIFICATION

The installation qualification (IQ) of a facility is the verifica-tion that all the components within a facility that have

‘‘direct product impact’’ are installed correctly and in accor-dance with the design specifications. There must be support-ing documentation that all components have been installed and that all instruments have been properly calibrated.

The validation plan defines the methodology for preparing and executing the IQ. It also provides guidance with respect to IQ acceptance criteria, the use of support documentation, and responsibilities. The construction and validation team should perform a walk down of the completed system. The walk down is a review of the completed installation of the con-struction against the design documents. Usually, a redlined approved for construction (AFC) P&ID will be generated and used as documentation of the completeness of the installation.

The walk down should also yield a final punch list of incom-plete items.

An example of typical items that would be verified in the IQ phase of validation and in the commissioning of the remaining facility:

verify that the installation of the equipment complies with the design specifications;

verify that all required equipment, piping, electrical and instruments are installed;

redlined AFC P&IDs are completed;

vendor documentation is available for all equipment;

full loop checks are completed;

all necessary utilities are connected and ready for operation.

Any changes from the original P&IDs that are noted dur-ing the redlindur-ing function of IQ must be documented through a change control procedure, which is detailed in the validation plan. These changes, if approved and accepted, must then be incorporated into the final ‘‘as-builts’’ of the facility. It is cri-tical that the start-up team, maintenance, and the operations have complete accurate documentation of the final as-built configuration of the facility and the process. At the completion of the construction, the construction team for maintenance and operations, and the start-up team must assemble a ‘‘turn-over package’’. This package will have at a minimum:

as-builts drawings of the entire facility;

preventive maintenance information and require-ments on all equipment;

suggested spare parts for all equipment, including delivery time and pricing;

vendor manuals on all installed equipment.

The start-up of an API facility is a complex operation that requires early planning and a complete understanding of all the components of the facility. An operations manual with spare part and regular maintenance procedures must be in place on site for every component in the facility. A list of spare parts required for start up should also be assembled and these materials stored on site for use as required during

the start up of the facility. The most critical step in developing a complete start-up plan is to develop standard operating pro-cedures for the facility (SOPs). A complex API process facility will require SOPs be developed on every aspect of the opera-tion and including the maintenance procedures for the facility. The SOPs are ultimately the responsibility of the operations team for the facility, but may be developed by an engineering firm or consultant who is initially more familiar with the specific details of the facility and the equipment.

An important SOP at this phase of the project is the procedure for the start-up and methodology for shut down procedures of the process. These procedures must show the order in which the equipment should be started and stopped, the setting of valve dampers, instruments and controllers to avoid damage to any equipment. For the initial start-up, which is normally done with ‘‘water batching,’’ it may be necessary to compen-sate for the difference in the specific gravity of water to the process when the facility is in full operation.

XVIII. CONCLUSIONS

The chapter outlines the steps required to design and construct a new API facility

The business case

Process development

Design

Execution strategy and planning

Procurement strategies

Construction management

validation, start-up, and project turnover

In the review of the API facilities, distinct differences between the requirements and those of a fine chemical facility exist. The product is manufactured under cGMP guidelines.

There are validation requirements for the facility, which document how the facility was constructed, how the facility and process will be operated, and how the facility will be maintained. In most new product introductions, the primary driver for API projects is the speed to market. The products

have critical marketing considerations and schedule is of paramount importance, consequently at the risk of higher cost to construct. Because of the differences in the require-ments for API facilities vs. fine chemical facilities, both in the construction and final operation, the initial planning strategy for the project is critical to the success of the project.

The design and construction professionals must be knowledgeable in the specific cGMP requirements for API facilities. The construction personnel must plan for the proper documentation of the facility throughout the construction process so that the final facility can be validated and ulti-mately certified to manufacture product. The design and con-struction of an API manufacturing facility is a large investment of time, resources, and capital. The proper plan-ning up front and the diligent effort to evaluate the economic options and interface these options with an overall project schedule will produce a facility that operates as intended and returns the predicted profit on the investment.

REFERENCES

1. ICH Q7A, International Conference on Harmonization. Good Manufacturing Guide for Active Pharmaceutical Ingredients.

Recommended for Adoption at Step 4 of the ICH Process on November 10, 2000.

2. United States Pharmacopoeia (USP) 23 General Information.

Water for Pharmaceutical Purposes. Chapter 1231. Rockville, MD: US Pharmacopoeia Convention, 1995.

3. 21 Code of Federal Regulations (CFR). Current Good Manufac-turing Practices for Finished Pharmaceuticals. Part 211.

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