Although regulated life sciences companies involved in manufacturing have successfully been able to leverage advances in computer technology to manage their many aspects of their Quality process, validation has remained a largely paper based, manual process. Until recently, the FDA has remained silent on the issue of adapting electronic systems to manage the validation process. However, with the emergence of the FDA's latest draft guidance for process validation, it is implied that electronic systems are required in order to effectively meet the new requirements. The FDA’s new guidance for Process Validation is a big step forward in process-centric product development that will result in building quality into the process.
The draft guidance places tremendous emphasis on continuous monitoring of critical quality parameters. This suggests that real time access to critical streams of data is mandatory, in order to perform analysis effectively and in a timely manner. The updated guidelines define process validation as “the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products.” Now, on-demand access to the right data in the right context for analysis becomes central to Performance Qualification.
The new guidance is significant in that it attempts to divide the validation step into three discrete phases, integrating a characterization phase as a precursor to the demonstration and monitoring phases. The draft guidance recommends that manufacturers:
- Understand the sources of variation.
- Detect the presence and degree of variation.
- Understand the impact of variation on the process and ultimately on product attributes.
- Control the variation in a manner commensurate with the risk it represents to the process and product.
The FDA describes in the latest draft guidance that, “In all stages of the product lifecycle, good project management and good archiving that capture scientific knowledge will make the process validation program more effective and efficient. These practices should ensure uniform collection and assessment of information about the process, reduce the chance for redundant information gathering and analysis, and enhance the accessibility of such information later in the product lifecycle.” It is almost impossible to achieve this requirement without using a software platform in order to access information quickly throughout the product lifecycle.
“ It is absolutely required to have a software system in place to manage the new process validation approach”To effectively implement the FDA’s current thinking in process development and manufacturing, regulated manufacturing companies need the right technology tools to be successful. Even though PAT implementations have been encouraged by the FDA for years—especially in the agency’s risk-based approach initiative—this is probably the most important published guidance that ties technology to process validation practices in a way that spans process development, quality and manufacturing.
ValGenesis provides the following integrated functional modules to manage the entire process validation process electronic.
To create, review and approve Validation Plan and Projects Specifying the company policy on process validation related to equipment, including ancillary
To create, review, approve and manage requirements/critical quality attributes/ process parameters with risk levels and traceability matrices with risk assessment (Author, review and approve)
To create, review, approve and manage risk assessment, following Failure Modes Effects Analysis (FMEA).
To author, review and approve acceptance criteria protocols (Author, review and approve)
To perform electronic (paperless) or Manual execution of acceptance criteria protocols and summary report. Review and approve the executed protocols acceptance criteria protocols and summary report. Management of Execution Deviations or OSS (out-of-specification) (Initiate, assess, review and approve)
To create, review and approve periodic review schedules.
Understanding the Sources of Variation
Risk associated with each of the critical quality and process parameters will be assessed in ValGenesis through the Failure Modes Effects Analysis process in ValGenesis. Within the system, users are able to define different risk levels for each of the key factors; severity, likelihood of occurrence, and detectability. Users also define the risk class and risk priority. When conducting risk assessment following FMEA principles, users will assign a risk level to each of the risk factors, for each of the critical quality parameters. The system will automatically calculate the risk class and risk level. Based on the risk, users can effectively build appropriate testing to test the degree of variation to mitigate those risks.
Detect the Presence and Degree of Variation
Test cases can be authored and approved in ValGenesis to test the degree of variations for each critical quality and process parameters. The approved test cases for each critical quality and process parameter will be verified and tested in ValGenesis. ValGenesis quantifies the test results with screen shots, additional supporting evidence in the form of an attachment, and test results.
Authoring documents in ValGenesis is a simplified process where users are able to leverage existing MS Word and Excel in order to effectively build testing and requirement documentation. The system is equipped with a controlled workflow for routing documents from inception to completion to ensure consistency in the authoring process.
Executable documents, those documents that can be executed, are similarly authored in ValGenesis by leveraging existing MS Word and Excel. Executable documents can be easily executed in the system and screenshots and file attachments can be easily associated with any test, in order to provide the required supporting evidence. Any failures that occur during the execution process can be managed through the system’s built-in exception management process where failures are assessed, managed electronically in the system, and routed through review and approval for closure.
Understand the impact of variation on the process and ultimately on product attributes
ValGenesis dynamically generates traceability between the critical quality and process parameters and test cases. When there is a failure during an execution, the system will update the traceability matrix and indicate which critical quality and process parameter has been impacted. Based on the risk class and risk priority, users can make educated decisions with regards to how to handle the failure. The system provides a simplified mechanism to ensure that impacted critical quality and process parameters are handled appropriately.
Control the variation in a manner commensurate with the risk it represents to the process and product
Failures that occur in ValGenesis can be bundled together to create exceptions to be handled electronically in the system. When an exception is routed to a subject matter expert (SME) for analysis and assessment, the SME is able to choose one of the many standard decisions. Each of the decisions available will have separate workflows that follow a controlled process. Through the standardization of the exception management approach in ValGenesis, consistency and control over the process is simplified.
Real time Process validation data
It is necessary that Validation Lifecycle Management systems are utilized in order to access, aggregate, analyze, and understand the data generated. ValGenesis meets and exceeds these requirements and provides report data, on-demand and in a meaningful context, such as a report that allows correlation of upstream parameters with downstream process outcomes (automatically accounting tor batch genealogy) during both process design and commercial operations.The FDA is pointing manufacturers to practices that can continuously improve their process understanding and, therefore, make the process validation program more effective and meaningful. Like many of its regulatory efforts and mandates, what is good for the FDA and consumers is also beneficial for manufacturers. In this case, leveraging data in the right way can enable greater Process Intelligence, which assists with control variability and quality improvements and results in higher yields and accelerates the time to market.