One of the most common failures cited by FDA inspectors in Warning Letters is the…
When the Dietary Supplements Health and Education Act that came law in 2007 and was fully implemented in 2010, it mandated that all dietary supplements manufacturers in compliance with the current Good Manufacturing Practices (cGMP) regulations in the act. These regulations extend to the layout, location and operation of the various areas in each manufacturing facility. While many dietary supplement companies were is business before the regulations came into full effect, they were not held accountable for complying with cGMPs. When FDA inspectors arrived to evaluate the compliance standards in these facilities, they found significant violations in ½ of the plants and issued warning letters to ¼ of them. 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.
Why it’s important:
The location and control of the areas where the manufacturing and storage operations are done must contribute to the quality of the products. The selection of the areas and their positions must avoid the risks of contamination while permitting effective cleaning and maintenance.
How to improve:
Once a facility is properly located, the design phase begins. One the important aspects of design is giving thought to the various separate areas that will be needed for each of the major functions in the facility. These areas might include:
- Storage Areas
- Packaging/printed material
- Ancillary areas
Receiving/Shipping: The receiving and shipping areas are usually together near the loading dock or outside entrance to the plant. Since this area often has a large garage type door that opens to the outside, this area should be kept separated from the production and storage areas. It also needs the most attention to keeping out insects, rodents and other pests. When containers come in the receiving area, you should use various means to clean incoming containers. The procedure should eliminate any source of contamination that might be brought in on the containers. Clean with a vacuum cleaner then finish with a cloth or duster. The cleaning should be done in an area separate from the loading dock or done in an air curtain if no separate area is available.
Warehousing: InstantGMP™ MES is a manufacturing execution system with electronic batch records that provides a warehouse receiving function that allows operators to record incoming materials. They can record what received, how much and the vendor information. This data is automatically updated in the inventory control module so everyone can see what is in the warehouse at any time.
Storage Areas: It is recommended that there should be separate areas for the orderly storage of various categories of materials and products. There should also be storage areas of sufficient capacity to ensure proper segregation and separation, easy cleaning of areas. Separate and segregated areas for different materials are recommended including: Starting materials, packaging materials, intermediates, bulk, finished products, quarantined, released, rejected, returned and recalled products and materials.
Packaging/printed material: In some countries, more than half of all product failures occur through problems with printed materials which often result in a product recall. Security of storage, issue and receipt of printed materials is absolutely essential. Quality control procedures for printed components must be very rigorous. This is particularly important if the factory is dealing with export orders requiring foreign language labelling. It’s important to ensure compliance with specifications to prevent mix-ups which then lead to recalls.
Weighing: The design, operation, control systems, recording and cleaning of the dispensing department must all be aimed at ensuring that there is no risk of cross-contamination. The environmental controls should ensure that the powders are kept contained within the area. The air handling, pressure differentials, airflow patterns and dust extraction systems need to be designed carefully to provide good separation from the main warehouse area.
Production: Accommodations must be provided for operators and all visitors to change their clothes and footwear before entering the production area. Storage will be needed for outdoor clothing and a system provided to assist correct entry to the manufacturing areas. Some change rooms have a climb over bench that is used to separate the area for changing clothes from the production area.
Air locks make it easy to provide entry to manufacturing areas as a one-way system so all personnel entering a manufacturing area must pass the changing area in one direction. People exit the factory and gain access to their outdoor clothes from another entrance to prevent any possibility of cross-contamination.
The layout of the production areas should follow the sequence of production to avoid mix-ups and cross-contamination. There should be areas for work and for in-process storage. Orderly and logical positioning of equipment will help minimize the risk of contamination, mix-ups and the missing of production steps.
Ancillary areas: You may need other areas for rest and refreshment for your staff. These should be located apart from manufacturing, packaging, storage and quality control areas. Toilet and other wash facilities should not be directly accessible from manufacturing, storage or quality control areas. Maintenance workshops should be separated from production areas. If tools are to be kept in a manufacturing area, then they should be placed in a container or cupboard specific for that purpose.
A well planned manufacturing design will provide specialized areas for warehousing, storage, production and other purposes. The key is to design storage areas and ancillary areas that are separated from the production areas and packaging areas so there few opportunities for mix ups or cross contamination.