Case Study: Comprehensive Input Field Validation Study Using Mathematical Equations for Spectroscopy Software

Case Study: Comprehensive Input Field Validation Study Using Mathematical Equations for Spectroscopy Software for a global Contract Research, Development and Manufacturing Organization (CRDMO) offering end-to-end solutions that enable partners to discover, develop and manufacture biologics

Introduction:

Alpha Life Sciences Ltd. upholds its commitment to rigorous Computerized System Validation (CSV) in accordance with the electronic data integrity mandates of 21 CFR Part 11. In this case study, we detail a case study approach to validating input field behaviors within Spectroscopy Software at a greenfield project where we were retained for subcontracting services. This approach was utilized to augment the GAMP lifecycle approach and employs our in-house mathematical equations to symbolize and validate the software's capacity to ensure precise data entry, aligning seamlessly with standard validation approaches regulatory standards.

Scenario: Experiment Setup Parameters in Spectroscopy Software:

The core objective of this validation scenario is to demonstrate that the Spectroscopy Software impeccably detects errors and validates experiment setup parameters. We focus on specific fields: Collect exposure time, Sample Exposures, Review exposure Time, Maximum Calibration Age, Background Exposures, and Maximum age for background (minutes).

Mathematical Equations and Symbolism:

Utilizing mathematical equations, we symbolize the transitions between different states of input fields:

• E signifies "Empty"
• V signifies "Valid"
• I signifies "Invalid"

Validation Steps:

1. Field Verification:

This initial phase involves systematically inputting values into each field and observing the corresponding system response.

During the Field Verification step, Alpha Life Sciences conducted a series of systematic actions to study each input field's behavior within the Spectroscopy Software. This process involved deliberate interactions with the software's user interface and careful observation of the system's responses.

• Collect exposure time (CE):
• The validation team accessed the Spectroscopy Software experiment setup interface.
• They input various values for the "Collect exposure time" field, including values below 0.1, within the range of 0.1 to 999, and values exceeding 999.
• The team closely observed the software's reaction to each input, taking note of any system messages, prompts, or changes in field appearance.
• Sample Exposures (SE):
• Similar to the previous step, the team navigated to the input field for "Sample Exposures."
• Various values were input, including those less than or equal to 2, within the range of 2 to 999, and values exceeding 999.
• Responses from the software were observed and recorded, paying attention to any indication of invalid entries or successful validations.
• Review exposure Time (RE):
• For the "Review exposure Time" field, the Alpha Life Sciences Ltd. team performed a similar set of actions.
• Different values were input to assess the software's handling of values below 1, within the range of 1 to 999, and values exceeding 999.
• Responses from the software were monitored to verify compliance with the defined behavior.
• Maximum Calibration Age (MC):
• In this case, the Alpha Life Sciences Ltd. team focused on testing various values for the "Maximum Calibration Age" field.
• Inputs below 1, within the range of 1 to 999, and values exceeding 999 were used to gauge the system's validation capabilities.
• Software responses were meticulously noted to ensure alignment with the expected behaviors.
• Background Exposures (BE):
• The validation team repeated the process for the "Background Exposures" field, testing entries below 0.1, within the range of 0.1 to 999, and values beyond 999.
• Responses from the software were documented to confirm if they matched the predicted outcomes.
• Maximum age for background (MA):
• Similarly, the "Maximum age for background" field was subjected to a range of inputs.
• The Alpha Life Sciences Ltd. team entered values below 0.1, within the range of 0.1 to 999, and values exceeding 999 to assess the software's behavior.
• Responses from the software were captured to ensure they aligned with the mathematical equations.

By meticulously studying each input field in this manner, Alpha Life Sciences Ltd. ensured that the Spectroscopy Software adhered to the defined behaviors as represented by the mathematical equations. Any discrepancies or deviations from the expected behaviors were documented for further analysis and study, CSV IOQ test script improvements and potential corrective actions. This comprehensive field verification process formed the foundation for subsequent steps in the validation process, including the mathematical checks and range/format testing as described in the case study.

2. Mathematical Checks:

1. By comparing the system's response to the outcomes predicted by the mathematical equations, we ascertain successful validation when the actual response aligns with the expected outcome (E, V, or I) based on the equations.
2. In the case of the Collect exposure time field, for example:
3. Equation for Collect exposure time (CE):
4. CE = { E, if time < 0.1 || time > 999; V, if 0.1 ≤ time ≤ 999; I, otherwise }
5. In this equation, the predicted behaviors are as follows:

• If the time entered is less than 0.1 or greater than 999, the system should respond with "Empty" (E).
• If the time entered falls within the range of 0.1 to 999, the system should respond with "Valid" (V).
• If the time entered does not fall into either of these ranges, the system should respond with "Invalid" (I).

These behaviors are predetermined by the mathematical equations, and during the validation process, the actual system responses are compared to these predicted behaviors to determine whether the system is functioning as expected.

3. Range and Format Testing:

Further validation studies ensued by evaluating the system's behavior when input values fall within or outside the valid range/format. The equations guide and anticipate the system's responses.

During the Range and Format Testing phase, Alpha Life Sciences conducted a series of controlled studies to assess how the Spectroscopy Software behaved when users input values within and outside the valid range/format for each specific input field.

• Collect exposure time (CE):The validation team accessed the Spectroscopy Software's experiment setup interface.
• They began by inputting values within the valid range (0.1 to 999) for the "Collect exposure time" field.
• The system's response was observed to ensure that the software allowed the input and progressed to the next step.
• Next, values below 0.1 and values above 999 were entered to verify that the software correctly rejected entries outside the valid range.
• The system's response, whether it displayed an error message or prevented progression, was meticulously recorded.
• Sample Exposures (SE): Similar to the previous step, the Alpha Life Sciences Ltd. team navigated to the "Sample Exposures" field.
• They entered values within the valid range (2 to 999) to assess the system's acceptance of valid inputs.
• Values less than or equal to 2 and values exceeding 999 were then input to ensure that the software correctly enforced range restrictions.
• The software's responses were noted to confirm compliance with the predefined behavior.
• Review exposure Time (RE):For the "Review exposure Time" field, the process was repeated.
• Values within the valid range (1 to 999) were entered to confirm the software's expected behavior.
• Inputs below 1 and values exceeding 999 were used to test the system's response to invalid entries.
• The software's reaction was documented to ensure that it aligned with the defined behaviors.
• Maximum Calibration Age (MC):In this case, the Alpha Life Sciences Ltd. team focused on inputting values within the valid range (1 to 999) for the "Maximum Calibration Age" field.
• This was followed by entering values less than 1 and values exceeding 999 to evaluate the software's range enforcement.
• The system's responses were carefully recorded to verify compliance with the expected behavior.
• Background Exposures (BE):The validation team repeated the process for the "Background Exposures" field.
• They input values within the valid range (0.1 to 999) to assess the software's acceptance of valid inputs.
• Entries below 0.1 and values exceeding 999 were used to evaluate the system's handling of invalid inputs.
• The software's responses were meticulously documented to ensure they aligned with the predefined behavior.
• Maximum age for background (MA): Similarly, the "Maximum age for background" field underwent testing for input values within the valid range (0.1 to 999).
• Inputs below 0.1 and values exceeding 999 were entered to assess the software's behavior in response to invalid inputs.
• The software's reactions were captured to confirm alignment with the mathematical equations and expected behaviors.

By executing this thorough range and format study for each input field, Alpha Life Sciences ensured that the Spectroscopy Software enforced appropriate range restrictions and validated data format for user inputs. Any inconsistencies between the software's responses and the expected behaviors were documented and analyzed, allowing for corrective actions where necessary. This process further fortified the validation process and ensured regulatory compliance.

4. Mandatory Field Check:

This step verifies whether the system prevents progression or completion when mandatory fields are left empty—an imperative element in maintaining regulatory compliance.

The Mandatory Field Check phase involved meticulous testing to validate that the Spectroscopy Software adhered to regulatory requirements by preventing progression or completion when mandatory fields were left empty. This step was crucial to ensure that users could not proceed without providing essential data.

• Field Identification: The validation team identified the mandatory fields within the Spectroscopy Software experiment setup interface. These fields included "Collect exposure time," "Sample Exposures," "Review exposure Time," "Maximum Calibration Age," "Background Exposures," and "Maximum age for background (minutes)."
• Empty Field Testing:The Alpha Life Sciences Ltd. team initiated the validation process by leaving each mandatory field empty.
• They attempted to progress to the next step or complete the experiment record creation process without providing the required data.
• The software's response was carefully observed, noting whether the system prevented or allowed progression.
• Observation and Documentation: For each mandatory field, the system's reaction to empty entries was meticulously recorded. If the system successfully prevented progression and provided appropriate error messages, it indicated compliance with regulatory standards.
• In case the software allowed progression despite empty mandatory fields or displayed inadequate error messages, these inconsistencies were documented as potential deviations or additional controls put in place.
• Confirmation of Compliance: To confirm regulatory compliance, the validation team repeated the process using valid data entries in the mandatory fields. The software should have allowed progression and completion without any hindrance in this scenario.
• Feedback and Analysis: Any discrepancies observed during the mandatory field check were subjected to analysis. The validation team collaborated with relevant stakeholders to assess the severity of the deviations and determine necessary corrective actions.
• Corrective Measures (if applicable): If deviations were identified, the validation team worked with software developers to rectify or assess the issues. This involved implementing appropriate error messages, preventing progression, and ensuring that users couldn't complete the process without entering mandatory data.

By conducting this thorough mandatory field check, Alpha Life Sciences confirmed that the Spectroscopy Software enforced regulatory requirements related to mandatory data entry. The process ensured that users were unable to progress or complete actions without providing essential information. Any identified deviations were addressed, contributing to the software's overall compliance and data integrity. This comprehensive validation step played a critical role in maintaining regulatory adherence and user data accuracy.

5. Progression Check:

Verification is conducted to ensure that the system permits progress or completion when accurate data is entered. Mathematical equations anticipate such behavior.

6. Progression Check:

The Progression Check phase aimed to validate that the Spectroscopy Software for the Spectroscopy Software allowed users to progress or complete the experiment record creation process when accurate and valid data was entered into the fields. This step was crucial to ensure that users could seamlessly move forward in the software's workflow.

• Field Identification:The validation team identified the fields involved in the experiment record creation process. These fields included "Collect exposure time," "Sample Exposures," "Review exposure Time," "Maximum Calibration Age," "Background Exposures," and "Maximum age for background (minutes)."
• Valid Data Entry:For each field, the Alpha Life Sciences Ltd. team entered accurate and valid data within the specified ranges and formats as defined in the mathematical equations.
• They recorded the data entries and the corresponding system responses, noting whether the software allowed progression.
• Observation and Documentation:The Alpha Life Sciences Ltd. team meticulously documented the software's response to valid data entries. If the system allowed seamless progression to the next steps or completion of the experiment record, it indicated that the software was functioning as intended.
• Data Entry Error Testing (if applicable):To comprehensively validate the system's behavior, the validation team also deliberately entered data outside the valid ranges or formats for certain fields. They assessed how the software responded in such scenarios.
• Validation Through Equations:The mathematical equations formulated earlier were consulted to predict the software's expected responses to valid data entries. The equations served as a reference to confirm that the system's behavior aligned with the anticipated outcomes.
• Analysis and Collaboration: Any discrepancies between the actual system responses and the expected outcomes based on the equations were analyzed. The validation team collaborated with relevant stakeholders to determine the root causes of inconsistencies.
• Documentation and Reporting: The findings of the Progression Check, along with any identified deviations and corrective actions, were documented in detail. This comprehensive documentation provided a transparent account of the software's behavior during the validation process.
• Validation Closure (if applicable): If all software behaviors aligned with expectations and no deviations were identified, the Progression Check was successfully concluded.

By rigorously conducting the Progression Check, Alpha Life Sciences ensured that the Spectroscopy Software provided a user-friendly and intuitive experience. The validation step confirmed that users could progress through the experiment record creation process without hindrance when entering valid and accurate data. Any identified deviations were addressed, contributing to the software's overall reliability and compliance with regulatory requirements. This comprehensive validation phase played a pivotal role in ensuring that the software met its intended purpose effectively.

Integration with CSV Lifecycle:

1. Requirements Analysis:

During the Requirements Analysis phase, symbolic equations are formulated, ensuring alignment with user requirements for precise input field validation criteria.

1. Test Protocol Creation:

The equations guide Test Protocol creation during the Installation Qualification (IQ) and Operational Qualification (OQ) phases. This meticulous approach ensures the creation of rigorous tests that validate input field behavior with precision.

1. Validation Documentation:

The equations and their application results fed into the Validation Documentation, offering transparency into the validation process and how input field validation is executed.

Alignment with Regulatory Standards:

The adoption of mathematical equations for input field validation directly aligns with the electronic data integrity stipulations of 21 CFR Part 11.

The mathematical approach underscores a commitment to systematic and transparent compliance, essential for maintaining high regulatory standards.

Collaboration and Iteration:

1. Collaborative Refinement:

Collaboration among CSV teams refines equations, ensuring their accuracy in representing real-world usage scenarios and complexities.

1. Iterative Validation Cycles:

Equations undergo iterative validation cycles, enhancing their accuracy and practical application. Each cycle validates their suitability in capturing diverse input scenarios.

Conclusion:

This case study aptly demonstrates how Alpha Life Sciences meticulously validates input field scenarios in Spectroscopy Software through mathematical equations. This approach fortifies error detection, range/format validation, and compliance with 21 CFR Part 11 requirements. By seamlessly integrating mathematical rigor with the CSV lifecycle, Alpha Life Sciences reiterates its commitment to precision, quality, and regulatory excellence.