Process engineers in the pharmaceutical manufacturing industry are constantly seeking ways to achieve more precise control over the manufacturing process. With incredibly high quality control standards resulting from the important role that pharmaceuticals play in public health, extreme measures are often taken to ensure that products are of the highest quality and consistency possible. In contrast to traditional methods of costly and time-consuming sample monitoring, a new technology from Prozess Technologie provides closed-loop spectroscopy, which is able to provide real-time measurement on the manufacturing line itself without stopping the production process. When applied correctly, this technology yields much greater process control than previously possible while delivering the twin benefits of reduced cost and time associated with quality control testing.
HOW IT WORKS
Commonly regarded as the world’s most precise molecular measurement technique, spectroscopy is the study of the unique interactions between matter and radiated energy. These interactions can be used to derive chemical information about a sample of material. For process measurement purposes, frequencies along the electromagnetic spectrum ranging from ultraviolet to infrared are pointed toward a sample, and the resulting reflection or absorption of the light is analyzed to extract valuable information about the sample. The data gained in this process can be used to precisely determine chemical and physical information about a sample, such as the concentration of a target compound or active pharmaceutical ingredient (API).
Perhaps more important than the precise measurement of samples using spectroscopy is the fact that the technology has recently become available for in-situ, closed-loop manufacturing-line applications. Previously, spectroscopy-based process measurement was costly and complex, requiring extensive user experience to extract, analyze and process the results. With this newly developed technology from Prozess Technologie, however, spectroscopy-based process measurement devices can deliver real-time measurement data that anyone can implement, utilize and understand. Spectroscopy-enabled measurement devices are able to be controlled remotely, store detailed activity logs and transmit data anywhere it is needed. Prozess Technologie’s process measurement platform can be specifically tailored to suit specific applications and reduce costs associated with spectroscopy-based measurement.
By using the remote monitoring of real-time data immediately available from these new spectroscopy-based measurement systems, Pharma process engineers have been able to significantly improve the efficiency of manufacturing processes. Previous methods of sending a sample to a lab for analysis would require the entire manufacturing line to be shut down or paused for the period of time that the sample was being tested. This was not ideal for substances that were blended, mixed or dried, for example, because by the time the quality of the sample was verified, the substance may have become over-worked or too dry. In a drastic improvement to these methods, these new spectroscopy-based measurement systems allow process engineers to instantly view a detailed breakdown of the components of a substance without any kind of disruption to the manufacturing process.
The unique benefits of this new method of real-time measurement are numerous. First, real-time measurement allows process engineers to know down to the 30-100 millisecond range what is happening in each step of the process they are monitoring. This information is useful for determining sources of inconsistencies or negative trends in the process. Additionally, the closed-loop feedback available from systems like the one Prozess Technologie offers gives engineers the ability to remotely alter or modify process conditions to get a different or better result, instantaneously. The system is also able to monitor process trends and detect when a variable is out of spec or, even more importantly, detect when a variable is trending toward going out of spec. This functionality delivers an unprecedented level of control by enabling potential errors to be corrected before they even happen, saving pharmaceutical manufacturers the cost of wasting product due to incorrect process conditions.
VERIFYING RESIDUAL APIs
One way in which spectroscopy-based measurement has been used to improve process efficiency is in verifying that residual APIs have been completely rinsed from the vessels in which they were previously contained. After each batch is made, the vessels involved in the process need to be cleaned and sterilized of the APIs to ensure future batches are not contaminated. Without a proper way to verify that the vessels were completely sterilized, companies would previously allot a period of time — often as much as 48 hours — to repeatedly rinse the vessels until the chances of contamination were very low.
The phrase associated with this practice, “dilution is the solution,” illustrates the concept that the more a substance is diluted, the less likely it is to contaminate future batches. By using a spectroscopic process analyzer, one can monitor the vessels and piping to determine exactly when any residual APIs, solvents or solutions had dissipated. One pharma company was able to reduce its rinsing time from 48 to 8 hours, instantly gaining about 40 hours of additional manufacturing time per batch. Besides the obvious cost/time savings, this is extremely valuable for water conservation efforts in the midst of the serious water crisis currently being faced by the United States and other parts of the world.
In another unique application of spectroscopy-based measurement, fluid drying bins were able to be monitored for precise moisture content by a leading pharmaceutical manufacturer. Normally, large bins are used to dry fluids into powders over a specified period of time. However, other variables affect the drying process and prevent the use of an exact formula in terms of drying time. Achieving precise moisture content is critical for quality control in pharmaceutical products. If powders are too dry, the resulting pills can crumble; and if powders are too moist, the substance becomes doughy and difficult to work with later in the process. By using a spectroscopy system to monitor the exact, real-time moisture level of drying powders, the manufacturer was able to eliminate all time and product previously wasted by over or under drying.
Another use of spectroscopy systems on pharmaceutical manufacturing lines is the verification of blend uniformity. Blend uniformity, while undoubtedly one of the most critical aspects of pharmaceutical manufacturing, is difficult to achieve due to the fact that certain ingredients are harmful, reactive or even toxic prior to or during the blending process. In the past, operators would need to open a vessel during the blending process to ensure that the substance had achieved the correct uniformity, exposing themselves to the harmful chemicals and creating a potentially dangerous situation. However, with a spectroscopy-based measurement system wirelessly attached directly to the blender continually monitoring the process, the danger of human interaction with the substance is completely eliminated. Manufacturers also are able to benefit from real-time updates on blend uniformity, significantly improving their production and reducing possible waste material.
These are just a few examples of the seemingly endless possibilities available using spectroscopy-based measurement systems on manufacturing lines. One could say that the goal of all process engineers is to achieve consistently excellent results and to know what is happening inside the manufacturing line at all times.