Validation is still the most important aspect of pharmaceutical quality control
Pharmaceutical manufacturers have always ensured precise dose uniformity and repeatability. In order to accurately regulate this uniformity, certain procedures and processes have been developed and put into place. Quality control measures and checks need to be implemented at each stage of the drug development and production process, from lead discovery through preclinical and clinical research to production and distribution. Assessing the quality of the drug at each step of the development procedure ensures not only that high quality pharmaceuticals are produced but also that each piece of equipment is functioning to a high level of accuracy. Testing only the final product to ensure quality is a destructive process that does not guarantee that all pieces of equipment used throughout the drug development process are operating effectively.
Every piece of laboratory equipment used in the drug discovery and development process, from refrigerators and freezers to incubators and centrifuges, must be fully validated. The validation process can occur in house or be outsourced; either way, it must be accurately documented. This requirement stems from regulatory bodies like the U.S. Food and Drug Administration (FDA) that specify compliance with a quality control program for the design, manufacture, packaging, labeling, and storage of any pharmaceutical designed for human or animal use. Therefore, related equipment must be validated before use. This rigorous testing regime can demonstrate the effectiveness and reproducibility of both the workflow and the final drug product.
This means that validation is a necessary part of all environments regulated by current good manufacturing practices (cGMP) or current good laboratory practices (cGLP), as well as industries that are required to qualify laboratory equipment in accordance to FDA guidelines. cGMP and cGLP (collectively referred to as cGXP) guidelines are applied on a global basis for the quality control of items such as food products, pharmaceutical products, and medical devices. In essence, they ensure that goods are consistently produced and controlled to the quality standards of their intended use and are safe, pure, and effective.
Failure to comply with cGXP regulations can have serious consequences, including the implementation of regulatory restrictions that prevent the manufactured product from being available to the public, either by prescription or over the counter. Ultimately, compliance with these regulations through the use of validation services improves laboratory procedures as well as product quality, leading to a more efficient and cost-effective working environment.
Quality Control and Repeatability
In order to guarantee high levels of reproducibility, rigorous quality control of laboratory equipment used throughout the drug research and development process is of paramount importance.
All instruments operating within a regulated environment must comply with cGXP requirements to ensure quality of the drug products. This effectively means that all equipment must produce and show repeatable results. One of the most efficient ways to control and maintain the quality of a pharmaceutical is to successfully manage the instruments used in the production and quality assurance analysis processes. With this goal in mind, all laboratory equipment and instruments must be qualified individually before use to ensure that specified standards imposed by the end user or drug manufacturer are met.
Furthermore, ongoing quality control measures must be a part of the entire drug discovery and development process. Preventative maintenance and requalification procedures are required to ensure that every piece of equipment is maintained to a high standard and produces repeatable results throughout its life span, as well as to identify faulty equipment and rectify problems as quickly as possible. In this way, all resulting pharmaceuticals are produced with strict quality control measures, and all data are fully reproducible.
Time, Multiple Equipment Purchases
Time is critical for larger projects with multiple units, in which equipment down time must be kept minimal. Validation can occur in a timely manner, with the standard processes of installation, operation, and performance qualification (IQ, OQ, PQ) occurring simultaneously. This process speeds up equipment commissioning by allowing customers to review protocols and schedule validation before the equipment arrives in the lab. As a result, researchers can be more productive, using their equipment shortly after qualification efforts are complete.
Although IQ, OQ, and PQ are often time-consuming processes, they are still a vital part of the quality procedure. IQ pertains not only to the verification of new equipment but also to the verification of existing equipment that has been moved to a new location. Movement of qualified equipment triggers an internal assessment for requalification to ensure that correct equipment operation is maintained. If the internal assessment deems requalification is necessary, then a full IQ, OQ, and PQ will result. The OQ includes a number of testing procedures to ensure efficient and proper operation. Alarms and safety features are all tested to make sure that the equipment has no faults in any part of its operation.
The PQ typically involves documented verification, ensuring that equipment and experimental methods are appropriate and effective by providing accurate resulting data for its routine use. For example, an incubator or refrigerator would require a temperature uniformity test. This test is performed to verify potential warm and cold spots within the equipment chamber.
Highly accurate temperature sensors from a regulatory-compliant recording device are placed on upper- and lower-most shelves for 24 hours. The temperature results are then compared to pre-determined acceptance criteria (defined by internal quality assurance) for pass/fail analysis. This testing process ensures that all equipment is maintained in a validated state. Periodic preventative maintenance, single point calibration, and requalifications all contribute to maintaining accurate laboratory equipment that is in compliance with regulatory guidelines.
The need to comply with strict standards can be both time-consuming and costly, especially if multiple pieces of laboratory equipment are purchased or introduced to the laboratory at the same time. Working with qualified personnel who have both equipment and cGXP experience can be extremely beneficial. Their expertise can further reduce associated expenses by eliminating the down time associated with costly errors. Completing all processes quickly and efficiently to a high standard will also help to minimize laboratory down time, potentially decreasing time to market by enabling the resulting end product to be released sooner rather than later.
Meeting Differing Requirements
Because all laboratories working within a regulated environment must comply with cGXP guidelines, a variety of different situations require validation services. Some laboratories have their own internal validation processes, which, although effective, can be limited. The number of in-house personnel qualified to undertake these processes may be small, for example, and a large workload can result in a time delay. Outsourcing this need, especially for time-critical projects, can speed up the entire process to minimize equipment down time and maximize productivity.
For example, an upstart pharmaceutical company is keen to release its products to the market but may have limited resources and cost restrictions. In this case, fast and efficient validation of all laboratory equipment is essential, and outsourcing may be more time effective. The pressure on in-house staff is lessened, and all initial validation processes are performed by experienced personnel to ensure that equipment is fully compliant, with comprehensive documentation.
As laboratories expand and evolve, internal structures naturally change, altering, in turn, the availability of qualified staff to undertake complex tasks. In a company that is downsizing, for instance, resources become limited. The validation process can be outsourced, not only to facilitate the quick initial use of new equipment but also to alleviate some of the pressure and time constraints placed on existing staff. Outsourcing eliminates both the down time used to train staff and any concern over the high cost of noncompliance.
As the use of automation within research and development rapidly increases, laboratories must validate a broader range of technologies and equipment. These changes have placed a number of researchers in unfamiliar territory, where they are required to perform qualifications with little or no equipment expertise. As the researchers decide whether or not to provide these services in house, an outsourcing service can be used, as required, whether it is only in the interim or continually. While such decisions are undertaken, time-consuming validation processes can be removed from the laboratory. Outsourcing can provide laboratories with the expertise needed to ensure that all manufacturing and quality assurance equipment and instruments are in full compliance with the specified regulations of a controlled environment.
Conclusion
As a pivotal step in ensuring the quality of pharmaceuticals, the validation of laboratory equipment must be carefully executed and fully documented with detail and care. Equipment must be built and maintained to suit the operation being carried out and to meet the high standards required for ongoing research or production. As more industry processes require stricter quality control, validation becomes more and more applicable. The pharmaceutical industry is regulated to maintain the highest level of compliance through drug discovery, development, and production. The high cost of noncompliance, which could impact product licensing for release, means that laboratories have to validate their equipment accordingly. Furthermore, effective pharmaceutical manufacturing requires accurately performed preventative maintenance—including re-qualification as well as ongoing calibrations for peak performance.
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