These may involve data security, availability, and compliance aspects.

Engage multidisciplinary teams: Involve IT, QA, continuous manufacturing, and regulatory affairs to formulate comprehensive URS and risk profiles.

This step culminates in a URS document supported by a comprehensive risk assessment, serving as the touchstone for subsequent validation activities.

Step 2: Protocol Design for Qualification

After establishing the URS and assessing risks, the next crucial step involves the design of validation protocols that can adequately evaluate the hybrid cloud model’s functionalities. Protocols should detail acceptance criteria, test methodologies, and documentation requirements in accordance with regulatory expectations.

At this stage, the focus is on developing protocols for three key qualification phases: Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ).

• Installation Qualification (IQ): This phase verifies that all system components have been installed correctly. It should confirm compliance with manufacturer specifications and include relevant documentation such as hardware and software version numbers in the digital infrastructure.
• Operational Qualification (OQ): OQ is designed to verify that the system operates as intended under normal operating conditions. For hybrid cloud applications, this means testing various scenarios across different geographies, especially given the dynamic nature of cloud resources.
• Performance Qualification (PQ): This phase assesses whether the system can deliver consistent results over time. For medical device validation, PQ must meet strict standards to ensure patient safety and product quality.

Particular attention should be given to evaluating cloud vendor controls and Service Level Agreements (SLAs) that govern performance metrics, as these will impact the validation and ongoing compliance.

Step 3: Performing Process Validation Studies

Once the protocols are designed and approved, the next step involves executing validation studies in accordance with your established protocols. The execution process should focus on data gathering, result analysis, and comprehensive documentation. Process validation is a critical aspect in pharmaceutical settings to ensure that products are consistently produced meeting predetermined specifications.

In hybrid cloud settings, data generated during validation studies must be managed with rigour, adhering to the principles outlined in ICH Q8, Q9 and Q10. The validation study is typically divided into three runs, each designed to verify the system’s ability to produce a consistent output within specified limits.

• First Run: Often referred to as the “Installation Batch,” this run helps to determine the suitability of the system settings.
• Second Run: This should focus on troubleshooting and ensuring that performance during peer review meets established performance standards.
• Third Run: The final run should confirm all previous findings and demonstrate the system’s consistency in producing acceptable results.

Documenting each aspect of the validation study is vital for regulatory submissions and inspections. A well-structured validation report, summarizing methodologies, findings, deviations, and conclusions, will offer transparency and ensure compliance.

Step 4: Continued Process Verification (CPV)

Post-validation, it is crucial to implement a system for Continued Process Verification (CPV). CPV is a proactive approach to monitoring ongoing operations and is essential for maintaining compliance with regulatory expectations. This also ties back to concepts outlined in ICH Q10 on Pharmaceutical Quality Systems, ensuring a lifecycle approach to product quality.

CPV entails continuously evaluating process performance and product quality throughout the lifecycle. Regular monitoring of critical quality attributes and process parameters identifies any drift from the established baseline. Data collected through CPV should be carefully analyzed and trends documented.

• Establish Key Performance Indicators (KPIs): Define KPIs relevant to drug quality, production efficacy, and compliance adherence.
• Utilize proper statistical methods: Employ methods like Statistical Process Control (SPC) to analyze performance data effectively.
• Engage cross-functional teams: Involve QA, QC, and production staff to interpret data and review findings regularly.

Conversely, external factors, such as changes in regulations or manufacturing procedures, should always be considered during CPV planning. A robust CPV system can help detect deviations early, reducing the risk of non-compliance with regulatory requirements.

Step 5: Revalidation and Change Management

The final step in the validation lifecycle is understanding when and how to conduct revalidation. Regulatory bodies such as the FDA and EMA emphasize that validation is not a one-time event; rather, it is an ongoing process that must adapt to changes in procedures, equipment, or regulatory mandates.

Due to the flexibility and dynamic nature of hybrid cloud solutions, certain events may trigger the need for revalidation:

• Changes in cloud service providers: Transitioning to a new vendor may necessitate a re-evaluation of all validation activities.
• Upgrades or updates to hardware/software: Any significant modifications to the cloud infrastructure must prompt a re-assessment of the validation protocols to ensure continued compliance.
• Periodic review and updates: A systematic review of validation status should occur at regular intervals. This approach aligns with best practices recommended by GAMP 5 and other industry standards.

Establishing a robust change control process is essential to facilitate timely and accurate revalidation. Documentation generated from change assessments must reflect the rationale for revalidation, actions taken, and the outcome of the assessments. This documentation is important to demonstrate compliance and ensure product safety and efficacy.