In the pharmaceutical industry, bad batches equal wasted production time, resources, labor and money. But most importantly, bad batches may pose a risk to human health. By avoiding bad batches in the first place, businesses can ensure product safety and protect their profits and reputation; QbD principles can help businesses accomplish this.
BUILDING PROCESS QUALITY
Quality by Design (QbD) is a risk-based approach that identifies potential process errors early so that proactive steps can be taken to ensure safety and efficacy of medications and certain food products. A key aspect of the QbD framework is the assessment of risks and monitoring of process parameters and material attributes that influence finished product quality. In a nutshell, QbD builds quality into each step of the manufacturing process and prevents bad batches in the first place. Quality by Design has been increasingly implemented in pharmaceutical manufacturing, as the stakes are high when there is a chance products of poor quality might get into consumers’ hands. It is strongly supported by regulatory authorities, including the U.S. Food and Drug Administration (FDA), because it focuses the manufacturing process on consumer safety — from the beginning. Some food manufacturers are taking a cue from the pharmaceutical industry and are implementing QbD in their processes as well. We are seeing this with food companies that manufacture particularly sensitive products, including baby formula, dairy products and additives.
A comprehensive QbD framework needs to consider the risks that an inadequate weighing process may pose to final product quality. Depending on the application, different aspects of weighing can play an important role in maintaining an accurate and reliable process. Weighing processes, such as batching, formulating and filling, can critically influence product quality and should be considered in a comprehensive QbD concept. Inaccurate weighments can negatively impact the consistency of the blend of ingredients or the correct potency of the final product.
THE RIGHT STUFF
Choosing the right equipment is an important first step in designing a weighing process according to QbD principles. Depending on the application, different aspects of weighing can play an important role in maintaining an accurate and reliable process and ensuring consistent product quality.
In batching and filling, the accurate and fast transfer of results to controller and I/O devices is essential. In formulation, it is critical to prevent the use of wrong amounts of material or even wrong materials to guarantee accurate formulations. Checkweighing, X-ray and metal detection systems as well as in-process control solutions help fulfill regulatory requirements and ensure consistent product quality. Weighing solutions can provide comprehensive monitoring and control of the manufacturing process, enabling real-time corrections of manufacturing tolerance deviations and fulfilling required regulatory requirements.
It is also important to note that the benchmarks depend on each product’s tolerance and a risk analysis defined in the manufacturing process. The narrower the process tolerance, the higher the requirements for a qualified weighing instrument, which will drive the selection of the scale. Furthermore, a calibration program and a selection of test standards are required to ensure compliance to process tolerances over time.
In addition to the accuracy and reliability of the actual weighing equipment, factors such as the speed and precision of data transfer, can significantly influence the accuracy of the measured result. Other aspects, such as data integration and storage, are required to enable continuous monitoring of the manufacturing process and real-time adjustments. Furthermore, weighing stations are important material ID points. Apart from the weight value, a broad range of information such as raw materials, batch number, responsible operator, and much more can be captured and tracked.
EQUIPMENT ACCURACY AND RELIABILITY
Readability (or display resolution) of a balance or scale is often mistaken for accuracy. In fact, readability is just one contributor to the measurement uncertainty, which is the scientific expression of an instrument’s accuracy. Any measuring device, whether it is a ruler, a speedometer or a scale, is associated with some measurement uncertainty. Uncertainty means that no measurement is perfect; it is always distorted by random, environmental and unknown systematic errors.
For example, suppose one has a scale that is accurate to plus or minus 1 gram. At 10,000 grams (10 kilograms), this uncertainty represents one hundredth of one percent (0.01%) of the weight. In many situations, that uncertainty is small enough that it won’t affect quality. Now suppose someone is weighing a 10-gram sample on this scale with an uncertainty ± 1 gram. Now the uncertainty represents a full 10% of the reported weight. The actual sample may be 10% larger or 10% smaller than what this scale is reporting just due to the uncertainty.
The measurement uncertainty of a weighing system is a combination of many factors. The readability, sensitivity, repeatability, non-linearity and eccentricity of the scale are all factors affecting measurement uncertainty and are associated with the scale design. The scale manufacturer can calculate the uncertainty of the weighing system associated with these factors.