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Validation. This one word can invoke a series of feelings in any lab. It might invoke a feeling of fear or uneasiness because the process can be time-consuming and overwhelming. Or it can invoke a feeling of excitement because there is a new instrument coming into the lab. Whatever the feeling is, validating a new platform can be a daunting task.
There are several guidelines, principles, and documentation that must be completed and followed precisely to ensure a successful validation. Instrument qualification is a frequently cited deviation in regulatory audits, making the potential of warning letters even more intimidating while going through the validation process. If the deviation is critical enough, it could shut down production, turning into a costly and timely error.
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What does validation require today?
Validation of a new bacterial endotoxin testing (BET) platform can involve following good automated manufacturing practice (GAMP) principles, guidance from USP general chapter <1058> “Analytical Instrumentation Qualification,” as well as documents for design qualification (DQ), installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ). While DQ is usually completed by the manufacturer, some laboratories may find the need to complete this qualification for instruments designed in house.
In order to ensure the entire platform is properly validated, GAMP principles, together with ALCOA+ and 21 CFR Part 11 guidelines, are used to supplement USP <1058> and help address any gaps related to software validation. One of the most common reasons for noncompliance comes from the fact that instrument qualification followed by software validation can have unclear guidelines and terminology. Despite using current resources and guidelines, a lab that wants to implement a new or alternative analytical method entirely may also need to complete additional testing outlined in USP <1225> “Validation of Compendial Methods” or ICH Q2(R1) “Validation of Analytical Procedures.”
Many manufacturers will provide the documentation to complete IQ, OQ, and PQ testing of new instrumentation and software. This is a welcome relief to some, while others see it as yet another hurdle, should the vendor-provided documentation not meet the requirements outlined in their organization’s Quality Management System. The sheer scope of work required to complete a full IQ/OQ/ PQ, especially related to more complex instrumentation, can result in some users delaying the implementation of the new platform until there is enough time to complete it without interruption. Lab teams rarely have enough time to complete system validations themselves, so unless someone is specifically designated to manage this process, several months can go by with the new platform and qualification documents sitting unused.
Once validation of the platform has been completed, standard operating procedures (SOPs) will likely need to be created or updated. This additional step is required before the platform can be integrated into the lab for routine use.
Validation Challenges
When it comes to endotoxin testing, there is a variety of instrumentation available. Each platform can present unique challenges when it comes to validation. Some platforms with pre- deposited endotoxin and LAL can deviate from the manufacturer’s instructions for use (IFU), as the time required to analyze all samples with some robotic platforms would require consumable and sample hold-time studies to be incorporated into the validation process. This would require additional resources and add several days to an already time-consuming process.
Newer platforms that bring automation into play are welcomed from the perspective of efficiency gains in the quality control lab, however these technologies must be validated in a timely manner in order to realize the true benefits of automation. Some labs may question the time needed to validate the complex actions of robotic technologies, or they may need a dedicated, highly skilled engineer to spend a significant amount of time validating and maintaining the instrument. Additional test cases may also be required to challenge and verify software scripts and functionality.
Other complexities can be seen during additional robustness testing. Not all platforms can handle difficult substances, making it hard to demonstrate robustness. This could force a lab to have multiple platforms in order to meet the demand for all products and water testing. More platforms means more validation testing, not to mention more training, more consumables, and more equipment to maintain.
Testing beyond the validation process may also be required in some labs, should there be additional questions around the analytical method itself. That testing would follow the guidelines outlined in USP <1225> and ICH Q2(R1) for accuracy, precision, specificity, limit of detection, quantitation limit, linearity, range, and robustness and can add multiple days onto any validation.
Ideal Validation Testing
While validation of a platform can be arduous, there are options available that improve upon the typical process and keep a lab functioning at the capacity needed, without disrupting or re- assigning analysts. Simplifying the process allows the quality control lab to complete validation in house, or with the help of the manufacturer.
With IQ/OQ/PQ documentation that is clear, easy to follow, and comprehensive, an ideal platform can be fully validated by almost anyone in the lab within days. Users will have confidence knowing that the instrument and software are fully qualified and validated per the regulations. Such robust qualification ensures that the instrument and software will function as designed, even at full capacity.
Alternatively, a qualified and certified manufacturer’s representative can perform the validation on site. This option lets the lab analysts and managers stay focused on other projects with minimal down time. Once validation is complete, a lab manager or validation engineer can simply review the documented results and sign off to support cGMP release of the equipment. The manufacturer’s representative can then help to integrate the platform into the lab by configuring the software, training analysts how to use the platform, and pointing out helpful features and shortcuts, such as setting up assay templates, product libraries, validated products and user permissions. With this amount of support, a lab can immediately start leveraging the advantages of an exciting new platform.
Conclusion
Overall, validation doesn’t have to be a daunting task. There are options available to the end user to speed up and simplify the process. When investing in a new BET platform, the validation process should be considered. Who needs to be involved? How long does it typically take? Are there options for more support? The last thing a lab wants is to have a new BET platform sitting idle because the time and complexity of validation might overpower the available resources to move the platform into routine use.
Today, pharmaceutical labs can achieve the ideal validation scenario with the Sievers Eclipse BET Platform. The platform can be validated in just a few days, analysts can be fully trained during that time, and the system validation is supported by the manufacturer’s fully documented results for all seven guidelines outlined in USP <1225> and ICH Q2(R1). Quality control labs will immediately see its benefits, even without having run a routine assay yet. Combined with the advantages of micro uidic automation technology, users will realize that straightforward validation, streamlined analyst quali cation, and fast assay setup are only the beginning!
Author Biography
Sydney Jannetta is a Life Sciences Product Application Specialist for the Sievers line of analytical instruments at SUEZ – Water Technologies & Solutions, specializing in endotoxin testing and ultrapure water monitoring. Sydney has supported Sievers instrument customers for the last five years with expertise in TOC and endotoxin applications. She has provided method development services and feasibility testing to pharmaceutical manufacturers and has presented at over 20 national conferences. Sydney holds a Bachelor of Science degree in Chemistry from the University of Northern Colorado.