Dataset Information

Integrated Process Modeling-A Process Validation Life Cycle Companion.

ABSTRACT: During the regulatory requested process validation of pharmaceutical manufacturing processes, companies aim to identify, control, and continuously monitor process variation and its impact on critical quality attributes (CQAs) of the final product. It is difficult to directly connect the impact of single process parameters (PPs) to final product CQAs, especially in biopharmaceutical process development and production, where multiple unit operations are stacked together and interact with each other. Therefore, we want to present the application of Monte Carlo (MC) simulation using an integrated process model (IPM) that enables estimation of process capability even in early stages of process validation. Once the IPM is established, its capability in risk and criticality assessment is furthermore demonstrated. IPMs can be used to enable holistic production control strategies that take interactions of process parameters of multiple unit operations into account. Moreover, IPMs can be trained with development data, refined with qualification runs, and maintained with routine manufacturing data which underlines the lifecycle concept. These applications will be shown by means of a process characterization study recently conducted at a world-leading contract manufacturing organization (CMO). The new IPM methodology therefore allows anticipation of out of specification (OOS) events, identify critical process parameters, and take risk-based decisions on counteractions that increase process robustness and decrease the likelihood of OOS events.

SUBMITTER: Zahel T

PROVIDER: S-EPMC5746753 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrated Process Modeling-A Process Validation Life Cycle Companion.

Zahel Thomas T Hauer Stefan S Mueller Eric M EM Murphy Patrick P Abad Sandra S Vasilieva Elena E Maurer Daniel D Brocard Cécile C Reinisch Daniela D Sagmeister Patrick P Herwig Christoph C

Bioengineering (Basel, Switzerland) 20171017 4

During the regulatory requested process validation of pharmaceutical manufacturing processes, companies aim to identify, control, and continuously monitor process variation and its impact on critical quality attributes (CQAs) of the final product. It is difficult to directly connect the impact of single process parameters (PPs) to final product CQAs, especially in biopharmaceutical process development and production, where multiple unit operations are stacked together and interact with each othe ...[more]

PMID: 29039771

Similar Datasets

Project description:PurposePrior versions of the Tool for Reduction and Assessment of Chemical and other environmental Impacts (TRACI) have recognized the need for spatial variability when characterizing eutrophication. However, the method's underlying environmental models had not been updated to reflect the latest science. This new research provides the ability to differentiate locations with a high level of detail within the USA and provides global values at the country level.MethodsIn previous research (Morelli et al. 2018), the authors reviewed a broad range of domain-specific models and life cycle assessment methods for characterization of eutrophication and ranked these by levels of importance to the field and readiness for further development. The current research is rooted in the decision outcome of Morelli et al. (2018) to separate freshwater and marine eutrophication to allow for the most tailored characterization of each category individually. The current research also assumes that freshwater systems are limited by phosphorus and marine systems are limited by nitrogen. Using a combination of spatial modeling methods for soil, air, and water, we calculate midpoint characterization factors for freshwater and marine eutrophication categories and evaluate the results through a US-based case application.Results and discussionMaps of the nutrient inventories, characterization factors, and overall impacts of the case application illustrate the spatial variation and patterns in the results. The importance of variation in geographic location is demonstrated using nutrient-based activity likelihood categories of agricultural (rural fertilizer), non-agricultural (urban fertilizer), and general (human waste processing). Proximity to large bodies of water, as well as individual hydraulic residence times, was shown to affect the comparative values of characterization factors across the USA.ConclusionsIn this paper, we have calculated and applied finely resolved freshwater and marine eutrophication characterization factors for the USA and country-level factors for the rest of the globe. Additional research is needed to provide similarly resolved characterization factors for the entire globe, which would require expansion of publicly available data and further development of applicable fate and transport models. Further scientific advances may also be considered as computing capabilities become more sophisticated and widely accessible.

Dataset Information

Integrated Process Modeling-A Process Validation Life Cycle Companion.

Publications

Integrated Process Modeling-A Process Validation Life Cycle Companion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets