Dietary Supplements manufacturers have to be in compliance with the cGMP regulations specified in the Dietary Supplements Health and Education Act that became law in 2007. These regulations extend to the design, location and operation of the manufacturing facility. Many dietary supplement companies were is business before the regulations came into full effect, but that does not allow them any flexibility to “grandfather in” their existing facility design.
Why it’s important:
There are several things to consider when designing the premises. The land and buildings where the manufacturing operations are located must contribute towards the quality of the products. The design and the construction must avoid the risks of contamination, permitting effective cleaning and maintenance, minimizing the build-up of dirt and dust and preventing quality defects. If the facility design contributes to the adulteration of a product, FDA inspectors can issue 483 citations and warning letters that might lead to closing down operations until compliance is completed.
How to improve:
Location: The geography of the chosen location can have a considerable impact upon the design of facilities. For example, if the location is subject to environmental hazards such as flooding or there are problems with continuity of supply or services, another location may be a better option.
The neighborhood is also important. If the company is to be located next to a mill then the design precautions that it will have to take, and the level of maintenance that it will have to undertake, will be very different than if it is in a rural setting. If the neighbors change, the company will need to take appropriate measures to handle the situation correctly.
Layout: The land and buildings where the manufacturing operations are located must contribute towards the quality of the products. They do this by avoiding the risks of contamination, permitting effective cleaning and maintenance, minimizing the build-up of dirt and dust and preventing quality defects.
Facility Flow: Process flow design considerations take into account the sequence of events so that processes do not contribute to the potential for mix ups or cross-contamination. For example, dusty milling operations should be segregated from final product operations. Material flow is the routing of materials throughout the facility. It is important to show the status of the materials such as indicating whether they are quarantined, approved or rejected. There should be no cross-flow of materials.
People flow: A plan of the factory showing the routing taken by people when they enter the factory, when they move around in the factory from one department to another, and when they leave the factory. People should be limited to those areas where they have their activities. Production areas should not be used as passages or corridors for non-essential personnel movement.
This plan below shows the flow of material and personnel in a small scale GMP manufacturing facility. The arrows indicate the material flow, and show materials that are brought in each room through the corridor zone. The storage areas are separated from the production areas and packaging areas so there few opportunities for mix ups or cross contamination.
Building Materials: Construction should be of suitable materials to ensure proper cleaning, no cracks, and that the building can withstand pressures, vibrations and other effects. The electrical supply is required for consistent performance of equipment and instruments. Where there is not a constant supply of electricity, power generators may have to be considered. Temperature and relative humidity control should be provided where necessary. In many cases, materials and products have to be stored or processed under controlled conditions. The temperature and RH should be controlled, monitored in accordance with an SOP, and the results recorded. Appropriate and effective ventilation should be provided. These may affect products during manufacture or storage as well as functioning of equipment. Walls, floors, ceilings should be smooth and easy to clean. There should be no ledges or areas where dust can accumulate. Overall, the design should prevent build-up of dirt and dust to avoid unnecessary risks of contamination.
Ventilation and Airlocks: An important measure against cross-contamination is the design of the ventilation system. All incoming air should be filtered to an appropriate standard to achieve the grades of cleanliness specified for the room being supplied. The use of appropriate pressure differentials and air extraction, together with airlocks, is one of the main ways of achieving control over cross-contamination. The re-circulation of air must be carefully evaluated. If a ventilation system supplies 100% fresh air, then different rooms can be used for different products at the same time. However, if a system includes re-circulation, then all rooms supplied by that system must be processing the same product, or the air must be filtered to an appropriate standard. If no filters are installed, then all duct work will have to be cleaned during product changeover.
InstantGMP™ is a manufacturing execution system that provides a log where information about each of the rooms in a facility can be kept up to date. The room log can track all activities that are conducted in each room and keep a record of the batches that were produced in that room. The room log can also record the activities conducted in the room, the cleaning agent used, the batch number of the product produced there, the temperature and humidity readings and any comments or observations. This history will be particularly useful if Quality has to do an investigation or evaluate a quality issue involving product made in this room.