GMP Compliance Series – Part 10: Maintaining Equipment

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GMP Compliance Series – Part 10: Maintaining Equipment

GMP Problems:

Dietary Supplements have to be manufactured under the cGMP regulations specified in the Dietary Supplements Health and Education Act that became law in 2007. Many manufacturers or distributors of dietary supplements have been inspected by the FDA since 2010 and at least 50% get citations for failing to be in compliance with GMP requirements by 2010. About half of the manufacturers who received citations have received Warning Letters that threaten injunctions to stop their manufacturing if their compliance issues are not overcome. One of the issues that confront all manufacturers is how to keep their production equipment in compliance.

Why it’s important:

If equipment used in production are not located, maintained and operated properly, there is a possibility that cross-contamination and mix-ups of products and materials could occur. If that happens, the FDA will consider the products affected to be adulterated and will expect these materials to be rejected. If the products make it to the market place, it could result in a recall which will have undesirable impacts on a company’s reputation and economic health.

How to improve:

Equipment Design: The design of equipment can assist in easy cleaning and maintenance and proper design can prevent operation errors. An example of this is the way in which batch numbers can be changed in the machine. If the labeling machine has a solid block which has to be removed to enable a new batch number to be set up – then physical checks can be done. However, new devices are available that permit changes of batch numbers using a keyboard. In this case there needs to be some form of safeguard to prevent inadvertent batch number changes.

Equipment should be constructed of materials that suit the operation and use of the equipment for the range of products manufactured and tested on site. The construction materials should not corrode or deteriorate and thus influence the manufacturing or testing procedure.

Equipment Layout: The layout and location of equipment should minimize any possible cross-contamination of products. Complex equipment should be positioned to facilitate maintenance, to permit effective cleaning, and to avoid the potential for dust or dirt build up.

Equipment Maintenance: Equipment must be maintained to ensure that it is ready to perform the way it is supposed to. Maintenance schedules should be in place for major pieces of equipment. Logbooks record the use of the equipment, planned preventative maintenance and that regular maintenance had been performed. Keep aware that the older equipment might lead to adverse quality problems. For example, old tablet presses are a common source of problems. As the tablet machine starts to speed up or slow down the tablet weight changes. They can easily produce out-of-specification tablets during start-up or shut-down.

Production Equipment: Equipment must be made of materials that will not react with the product to be made. That often means very high quality stainless steel or other suitable material. The construction materials should not present any hazard to the product being manufactured such as reacting with the materials or product, or absorbing any substance from the product. Some materials and products react or are absorbed by plastic, and some plastic contains plasticizers that may leach into products.

Equipment Cleaning: Production equipment must be designed to be cleaned easily even if it is dedicated to one product. This is even more important if the equipment is to be used on a number of different products. This means that the equipment should be easy to take apart. It should have all crevices designed out to enable easy cleaning and make visual inspection simple.

If the equipment is used to produce a variety of products, a specific written cleaning procedure will be needed. Separate cleaning procedures may be needed for products requiring different cleaning processes. Verification of compliance with the SOP by reviewing the schedule for cleaning and records of cleaning is very important during the inspection. All equipment should be cleaned from time to time, even if it is dedicated to one product.

Cleaning methods chosen should be validated for effectiveness and described in written procedures to ensure that the cleaning methods are practical and include all the steps required for ensuring that cleaning has been correctly completed. There could be problem associated with cleaning when using compressed air, brushes or brooms. The use of compressed air is common for moving dust and dirt from inaccessible places on machines. Unfortunately it can then settle in an uncontrolled way on all the equipment and processes in the vicinity. The same is true of the use of brushes and brooms for cleaning.

Each time a piece of equipment is cleaned, it should be recorded in a log. If the cleaning is done as part of production, the batch number of the material to be produced on that equipment should be recorded.

InstantGMP™ MES has logs for equipment that allow anyone to see if any equipment has been correctly cleaned and maintained, and whether it is ready for use with the next batch or a new product. The logs provide a convenient way to record other activities associated with the equipment such as preventative or routine maintenance. Keeping a good record provides a history that Quality can use when they are investigating deviations or diagnosing quality issues.