The environment in which the scale is used also impacts the uncertainty of the weighing system. The environment is unique to every scale installation and cannot be calculated at the time the scale is manufactured. Significant impacts from the environment on weighing uncertainty can be attributed to wind, dirt or dust; temperature fluctuations; vibrations; and operator errors, among other factors. The only way to calculate the measurement uncertainty associated with the environment is to test the scale installed in the environment using the appropriate tools and methods.
ELIMINATING USER ERROR
Operating errors are a main reason for out-of-specification batches and product recalls due to quality issues. Obviously, the risk of human mistakes in a manufacturing process can be significantly reduced by automating the entire process. In line with QbD principles, such an approach would provide a fully monitored and controlled process, ensuring consistent product quality. However, in pharmaceutical manufacturing, relevant process steps, such as the weighing of formulation components, involve manual tasks that cannot easily be automated. The challenge in ensuring process safety and product quality is to eliminate the risk of operating errors during manual weighing processes as far as possible. Both the usability of the weighing equipment as well as user guidance contributes to secure handling of the weighing process by operating personnel. For example, weighing results that exceed or fall below defined limits can be immediately shown to the operator in distinct colors, helping prevent incorrect weighing. The system can even be set up to only allow the next process step and log the component weight if the actual weight is within defined tolerances. A number of advanced features can help improve usability of the weighing equipment for the operator.
In addition, it is possible to automatically document all batch-relevant information to prevent possible errors during manual or paper-based documentation. All process steps can be filed in detail in the database, and electronic signatures can be given if required to comply with regulations such as FDA’s Good Manufacturing Practice (GMP) regulation 21 CFR Part 11.
Getting the design and operational specifications right and selecting the proper equipment for the specified process are essential steps to achieve quality results. But quality also depends on precise installation, setup, calibration and maintenance of the weighing equipment. According to the FDA’s GMP regulation 21 CFR Part 211, “automatic, mechanical or electronic equipment … shall be routinely calibrated, inspected or checked according to a written program designed to assure proper performance. Written records of those inspections shall be maintained.” In essence, this means that evidence that the weighing instrument works correctly needs to be provided, and it needs to be demonstrated that the manufacturer understands what is measured.
High risk and a narrow process tolerance may call for frequent instrument accuracy verification. Even under a more frequent testing schedule, regulators determine an instrument’s uncertainty principle based on an assumption that proper installation and calibration actions have been performed.
Calibration of the weighing equipment must be conducted according to globally recognized standards, such as OIML and EA 10/18, and need to account for metrology as well as equipment construction. During calibration, eccentricity, linearity and repeatability of the device need to be tested in order to evaluate if the device performs within the range of allowable errors. Finally, validation methods and protocols are required to ensure process reproducibility and safe data management when it comes to software, such as formulation or batching applications. Competent suppliers of weighing equipment not only help specify the right equipment for the intended purpose, but also have knowledgeable service professionals to confirm satisfactory installation of new weighing systems and conduct initial commissioning, set up and testing.
At the end of the day, it is essential operationally to manage the entire lifecycle of weighing equipment. After all, when this equipment is not working up to its optimum potential, or if it needs repair or recalibration, it can produce bad batches that will not only cost companies in financial terms, but cost them in terms of reputational damage, as well as the very real threat of human costs associated with health risks from quality compromised products.