In 1962, Congress instructed the FDA to require that all drugs be produced according to Good Manufacturing Practice (GMP), which must be compliant with FDA 21 CFR Part 210 and 211. The move was in response to concerns about substandard drug manufacturing practices.
The first set of GMP regulations were published in 1963, and were meant to guide companies in the production of safe and effective drugs. The regulations outlined in the GMPs continue to be the minimum requirements necessary to ensure safe and effective products.
GMP, with regards to manufacturing, processing, packing or holding drugs, can be broken down into six critical areas. Although they are listed separately for the purpose of discussion in this article, these areas are not siloed. They overlap and relate intimately to each other, creating a comprehensive quality management system.
Understanding the Six Areas of a Pharmaceutical Quality Management System
The quality system is at the center of pharmaceutical manufacturing, providing the foundation for the five manufacturing areas listed below and helping the manufacturer maintain attain compliance. Each area has an impact on the others and they all must work together to consistently produce a quality product.
Production systems relate to the actual processes by which a product is made. The requirement is to have proper batch records in place. It’s helpful to consider a batch record to be a recipe. That recipe has to be followed exactly as specified to ensure that the final product is consistent from batch to batch. The batch record also ensures that the production process is repeatable throughout the life cycle of the production of the drug. Further, as the recipe is what was filed with the FDA, it is what was approved. Not following allows the production of an unapproved drug, which is illegal.
As an example, the production system includes the equipment with which the drug is made. It’s the producer’s responsibility to make sure that the data is in place to show that the equipment has been properly maintained and is functioning correctly according to set parameters.
Facilities & Equipment System
Closely related to the production systems component, the facilities and equipment systems refer to such things as HVAC, electrical, water systems, blenders, and fillers, etc.. The overarching purpose of this critical area is to ensure, per the CFR, that:
- “Any building used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction and location to facilitate cleaning, maintenance, and proper operations.”
- “Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements.”
Laboratory Control System
Once again, it is difficult to discuss the laboratory control systems component separately because it heavily overlaps with the facilities and equipment component as well as all of the other components. The point to make here is that it is critical that the laboratory as a whole is consistently maintained according to subpart I of 21 CFR 211.
The material systems component ensures that the materials used in the packaging of the drug meet established quality standards. Materials systems do not only apply to warehouse personnel. The material system includes the warehouse personnel who receive, store, and handle components and raw materials and distribute final products; purchasers who buy components from qualified vendors; operations personnel who request and receive components and transfer final finished goods to the warehouse; the quality assurance personnel responsible for component and lot release, and the quality control employees who sample and test components and products.
Packaging & Labeling System
This component concerns the packaging and labeling of the drug; it relies upon all of the other components to be in place. All of the production systems must be functioning in line with set parameters. The facilities and equipment systems must be operating properly, and the laboratory must be properly maintained. In addition, it is critical that the material systems are functioning properly at this point as well. Only when everything else is operating as it should can the packaging and labeling component function according to established parameters.
What Makes a Quality Management System Successful?
The Human Factor: Proper Training
No system will function unless the people charged with doing the work know what they have to do. This is perhaps the most important component of any quality management system. Without properly trained personnel, the systems are meaningless.
A laboratory can have all of the critical components in place, but if the people aren’t properly trained to ensure that the processes flow properly, then the end result could lead to non-compliance, which could affect the safety, identity, strength, quality, or purity of the drug product.
Consequently, continuous training and auditing is critical to any quality management system. As a part of their training, it is important that the people working within the organization understand what they are doing as well as why they are doing it. They must remember that they are making a product that could ultimately be used or administered to a patient, and that patient could be one of their loved ones. As such, they must always do their absolute best each and every day.
At the end of the day, it’s all about building a culture of doing things right.
Audits are another critical component of any quality management system. Internal audits provide a sort of self-inspection and allow for improvement. It can be a daily review of practices just to make sure that people are following procedures on a day to day basis. This type of audit is effective at ensuring that the facility and its personnel are in a state of readiness when the FDA audits the facility, ensuring that there are no surprises with any of the six critical components discussed above.
Even though the facility passes internal audits, it is also helpful to conduct external third-party audits. Sometimes internal auditors are too close to the situation and may not see the same things that a third party would. That’s why it’s good to have a fresh set of eyes looking at the quality systems from a different, independent perspective.