In the bioprocess industry, it is essential to establish and maintain control over the manufacturing process to ensure product quality and consistency.
The Normal Operating Range (NOR) and Proven Acceptable Range (PAR) are two tools that bioprocess engineers use to ensure consistency in their manufacturing processes.
The NOR and PAR are complementary concepts that serve different purposes in the manufacturing process.
The NOR provides a target range for routine manufacturing operations, while the PAR establishes the acceptable range of process parameters that can be used to maintain consistent product quality.
Together, they allow manufacturers to achieve and maintain control over their manufacturing processes, ensuring product quality and consistency.
Index
Using the NOR and PAR to Ensure Consistent Product Quality and Yield
> NOR
The NOR is a range of process parameter values that contains common operational variability that cannot always be controlled.
It is established for several process parameters of the same process step and is not intended to introduce flexibility in the conditions for manufacturing. The NOR is presented in marketing authorizations as what is practically achievable.
The NOR is defined based on the optimal operating conditions that result in the desired product quality, yield, and process efficiency.
> PAR
The PAR, on the other hand, is the range of process parameter values that have been scientifically demonstrated to consistently produce a product that meets the specified quality attributes.
The PAR is determined through robustness studies in which the process is deliberately subjected to variations in the input parameters to determine the effect on product quality.
The PAR is often wider than the NOR, as it accounts for potential process variability and allows for flexibility in manufacturing operations.
> Importance of maintaining a desired process into a range
The importance of consistent product quality and yield in bioprocessing cannot be overstated. Inconsistent product quality and yield can lead to batch failures, product recalls, and other issues that can impact patient safety and a company’s reputation.
Bioprocess engineers can use NOR and PAR parameters to maintain consistency in their manufacturing processes by keeping process parameters within a specified range.
By doing so, they can ensure that product quality and yield remain within the desired range.
Examples of NOR and PAR parameters in bioprocessing include temperature, pH, and agitation rate. For example, if the target temperature for a bioreactor is 37 °C, the NOR for temperature may be ±2 °C, which means that the temperature can vary between 35 °C and 39 °C without affecting the product quality or yield. The PAR for temperature, on the other hand, may be ±3 °C.
The Benefits of Implementing NOR and PAR Parameters in Bioprocessing Operations
Implementing NOR and PAR parameters in bioprocessing operations has numerous benefits.
Firstly, it helps ensure consistent product quality and yield. By establishing NOR and PAR ranges for critical process parameters, bioprocess engineers can design processes that consistently produce products with desired quality attributes. NOR and PAR parameters act as guardrails, preventing process deviations that could negatively impact product quality.
Secondly, implementing NOR and PAR parameters helps reduce process variability. By establishing tight ranges for critical process parameters, bioprocess engineers can minimize the impact of process variability on product quality and yield. This not only results in more consistent product quality, but also reduces the risk of batch failure due to process deviations.
Thirdly, NOR and PAR parameters can be used to optimize manufacturing conditions. By identifying critical process parameters and establishing their optimal ranges, bioprocess engineers can design processes that maximize product yield and quality. This can result in significant cost savings and increased productivity.
Fourthly, NOR and PAR parameters are critical for robustness studies. By establishing NOR and PAR ranges for critical process parameters, bioprocess engineers can evaluate the impact of process deviations on product quality and yield. This can help identify process parameters that are most sensitive to variation, allowing engineers to focus on improving the robustness of those parameters.
Applying NOR and PAR Parameters to Bioprocessing Robustness Studies
Bioprocess engineers can use NOR and PAR parameters to conduct robustness studies, which are designed to assess how much process parameters can be changed before the product quality or yield is impacted.
These studies can help bioprocess engineers identify the most critical process parameters and establish the range of acceptable variation for each parameter.
One of the key benefits of utilizing NOR and PAR parameters in robustness studies is the ability to identify and mitigate potential process failures before they occur.
By understanding the impact of process parameter variations on product quality and yield, bioprocess engineers can establish process control strategies that ensure the process remains robust and capable of consistently producing high-quality products.
In addition, the use of NOR and PAR parameters in robustness studies can also help reduce the overall number of experiments required to evaluate process robustness.
Instead of testing a wide range of parameter values, robustness studies can be designed to focus on the critical parameters while keeping other parameters constant within their respective NOR or PAR ranges.
This not only saves time and resources but also reduces the risk of testing extreme parameter values that may negatively impact product quality.
Utilizing NOR and PAR Parameters in Design of Experiments (DoE) Studies for Bioprocessing
Design of Experiments (DoE) is a powerful tool used to systematically evaluate the impact of process parameters on product quality attributes (PQAs) in bioprocessing.
By using statistical models, DoE can identify optimal ranges of process parameters that achieve desired PQAs while minimizing process variability.
NOR and PAR parameters are critical in DoE studies as they provide a framework for identifying which process parameters are most critical to maintaining consistent product quality and yield.
By establishing NOR and PAR ranges, DoE studies can be designed to focus on the critical parameters while keeping other parameters constant within their respective NOR or PAR ranges.
Furthermore, the use of NOR and PAR parameters in DoE studies can help reduce the overall number of experiments required to identify optimal process conditions.
Instead of testing a wide range of parameter values, DoE studies can be designed to test a smaller subset of values that fall within the established NOR and PAR ranges. This not only saves time and resources but also reduces the risk of testing extreme parameter values that may negatively impact product quality.
In addition, DoE studies can also be used to validate established NOR and PAR ranges by testing the impact of process parameter variations within their respective ranges. This provides additional assurance that the established NOR and PAR ranges are appropriate for maintaining consistent product quality and yield.
Overall, utilizing NOR and PAR parameters in DoE studies can help bioprocess engineers identify optimal process conditions that result in consistent product quality and yield, while also minimizing process variability and reducing the overall number of experiments required.
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