When designing, constructing, or validating a pharmaceutical facility, it is important that the designers and engineers have an in depth knowledge of all aspects of the regulations of medicinal product, and also recognize that many of these regulations impose additional requirements that must be considered during all activities.
1- General GMP requirements: When first embarking on a new pharmaceutical facility, consideration will need to be made as to what cGMP requirements will apply to the overall project and the specific products that are to be manufactured in that facility. These requirements may vary in different countries but there are general requirements that cover all the cGMPs worldwide. Common elements include guidelines regarding establishment of an effective quality system, ensuring that personnel are suitably trained and supervised, ensuring that facilities and equipment are located, designed, installed, operated and maintained to suit intended operations, and that standard operating procedures are in place to prevent contamination in the premises and cross contamination between products and even batches.
2- GMP design requirements: Based on an assessment of the regulatory requirements for the products to be manufactured, the engineering group at the onset must define the GMP requirements for a facility’s design and construction. Generally,areas to be considered during facilities design will include considerations for process issues such as level of required volumes or batch to batch integrity and productsegregation, layout issues such as site location and facility layout, automation and technology strategy, people, material and equipment flow issues, regulatory considerations, and overall validation strategy. Based on these considerations, basic requirements can then be developed for the various aspects of the project to allow the facility to be adequately and efficiently engineered.
3- Facilities and environment: These include buildings, rooms, and environment that contain the production, testing and storage activities. Therefore, general considerations for the entire facility must take account of local environmental considerations and requirements, suitability and acceptability of physical segregation of processes for manufacturing and storage of products, overall layout of the facility and general layout of production areas. Also, special attention must be paid to eacharea to include considerations for available space for operators, equipment, materials and products in addition to the design and construction of surfaces of walls, floors and ceilings.
In general, the layout of areas must minimize the possibility of product mix-ups. The adequacy of the working and in-process storage space must also permit the orderly and logical positioning and separation of equipment and materials so as to minimize the risk of confusion between different medicinal products or their components. The layout must also establish elements to avoid cross-contamination and to minimize the risk of omission or wrong application of any of the manufacturing or control steps.
In every pharmaceutical facility, the type of product dictates the utilities requirements such as air and steam quality, required electrical loads, and type of water to be used. These elements must be considered well in advance during facility design to ensure that all necessary support systems are included in the project scope.
In addition, since in pharmaceutical manufacturing, the environment is of prime concern wherever product components may be exposed, assessment of environmental classification of the various areas against the level of quality required by the product, airflow regimes and types of processing, air pressure differentials between areas, air change rates per hour, humidity requirements, and methods of monitoring, recording and controlling the environment are usually of utmost concern and require special awareness.
4- Services and utilities: Services and utilities that come into direct product contact are of particular concern when designing and constructing a new facility. Some typical and commonly used critical utilities include de-ionized water and water for injection, clean steam systems, and clean air or filtered gases. For all of these services, materials of construction, system design and sizing, cleaning and sanitation methods, and control of critical process parameters are considerations that must be made to ensure compliant products can be produced in the facility in a cost efficient manner during commercial production.
5- Personnel flows: personnel working in the manufacturing facility have direct influence on product quality. Not only personnel will come in direct contact with the product or its components, but also the number of personnel at a given time in a certain area, personnel movement, and operations techniques could potentially result in microbial or particulate contamination in the facility. Typical criteria affecting personnel flows to consider include gowning stages and changing regimes, location, size, and type of changing facilities , security and access control, occupancy levels, potential points of cross-contamination between personnel, and activity levels.
The use of airlocks also should be considered as part of any manufacturing facility design. Airlocks are one means to control containment necessary due to process or product requirements. Personnel airlocks may be necessary for connection of areas where dust generating processes are performed or certain active substances are handled. Such airlocks should be provided with cleaning facilities as needed and they must have a system in place to prevent the opening of entry and exit doors at the same time.
6- Material flows: In order to avoid cross contamination between different raw materials or finished products, when designing a new pharmaceutical facility, the type and amount of materials that are to be delivered to the manufacturing area must be one of the main considerations during design of the facilities. This includes all the movement of materials, the routes they enter the facilities or exit, and their storage or sampling areas. Typical design elements include general flow of materials through the area, methods of handling and prevention of cross-contamination, possible points of cross-contamination between materials, identification and segregation of materials, and storage conditions.
7- Equipment flows: It is important to consider that not all equipment may be fixed permanently in one position; they may either be moved routinely as part of the production process or be capable of relocation for cleaning and sanitation or plant maintenance. Typical criteria include methods of handling and prevention of cross-contamination, frequency of movements and available space, physical size and weight of equipment against facility construction and load bearing, possible points of cross-contamination between equipment, identification and segregation of mobile equipment, and storage conditions.
8- Validation master planning: Validation Master Plan is a formal document that clearly describes the general philosophy, expectations, intentions and methods to be used for the validation of a facility and its equipment and processes. The purpose of a validation master plan is to establish management commitment, provide management with purpose, resources, and timelines for validation activities, outline overall policy and general SOPs to be used for all validation activities, and define general acceptance criteria. It would also assign responsibility for activities, establish priorities and schedules, and track status and progress of activities.
Validation master plan usually covers process, equipment, cleaning, analytical, and computer systems validation in addition to facilities and equipment qualification and calibration.
Design, construction, and commercialization of a pharmaceutical facility is an expensive and lengthy undertaking that requires detailed planning and assignment of significant resources. It also dictates the quality and compliance of products that are to be manufactured and their profitability over the long run. Therefore, these activities must be planned in detail with the end in mind including the regulatory requirements for the types of products according to intended commercial markets in addition to the facility’s country of location. After all, it would just be too cumbersome and expensive to make any significant changes to the facility design or construction after it is completed and has become operational if errors are found or worse, regulatory agencies deny its approval for manufacturing.