New Guide Aims To Build Robust Framework For Digital Validation Tools

A conversation with Mark Drinan, Takeda Pharmaceuticals International AG

The International Society for Pharmaceutical Engineering (ISPE) released the ISPE Good Practice Guide: Digital Validation earlier this year. It comes as the industry seeks more ways to reduce reliance on paper methods for commissioning and qualification.

The guide offers a framework for adopting digital validation tool systems (DVTs), which we wanted to explore in more detail.

Mark Drinan, who is a commissioning, qualification, and validation expert at Takeda, worked on the guide as co-lead and offered to answer questions about the framework.

For the uninformed, can you start by describing digital validation tools? What is their primary purpose? Why are they better than traditional methods?

Digital validation tools are a range of software applications (one or more integrated) designed for managing and overseeing digital assets essential for the qualification, verification, validation, and assurance of compliance in various life sciences domains.

The primary purpose is qualification/validation, including all associated activities such as document routing, document analysis, document review and approval, test execution, task notification, requirements management, evidence attachment management, and deviation handling.

The use cases in the scope of qualification/validation for a DVT are:

• Process validation (including cleaning and sterilization validation/process performance qualification (PPQ))
• Computerized system validation and computer software assurance
• Facilities, utilities, equipment, and systems commissioning and qualification
• Analytical equipment/instrumentation qualification
• Validation of test methods according to regulations
• Packaging validation
• Transport/shipping validation
• Periodic review, requalification, and validation planning
• Change management

Unlike pure paper processes and hybrid paper-document management systems, DVTs support digital execution that meets data integrity standards and allows the management and sharing of validation data.

What gaps in existing regulatory frameworks or guidance is the ISPE trying to close with this latest ISPE Good Practice Guide?

There is no one guidance that specifically mentions digital validation tools or mentions the use of digital validation tools.  Currently, requirements and guidance are provided indirectly through various sources such as:

• FDA CDRH Draft Guidance for Industry: Computer Software Assurance for Production and Quality System Software
• 21 CFR Part 11 and EU GMP Annex 11 and Annex 15
• Case for Quality (MDIC) initiatives
• FDA Discussion Paper, Artificial Intelligence in Drug Manufacturing
• FDA, Good Machine Learning Practice for Medical Device Development: Guiding Principles
• ICH Q9 Quality Risk Management Q9(R1)
• ISPE GAMP Good Practice Guide: Enabling Innovation
• ISPE GAMP 5: A Risk-Based Approach to Compliant GxP Computerized Systems (Second Edition)

Because of the lack of direct guidance on the use of DVTs, the guide aims to present a compliant approach based on current technologies and industry use cases. It also anticipates the future integration of these digital technologies with other systems and their potential applications.

Can you talk about the advantages and disadvantages of transitioning from paper-based to digital validation?

The Advantages:

Reduction in Data Integrity Risks

Data integrity is paramount in the pharmaceutical industry, as a compromise can result in severe regulatory consequences. Traditional paper-based processes are inherently susceptible to data integrity risks, including human errors and document tampering. A DVT mitigates these risks by providing robust data security and audit trails. Electronic records are less prone to manipulation, and access control measures ensure data integrity is maintained throughout the validation process.

Streamlined Audits

Audits play a vital role in pharmaceutical manufacturing. A DVT streamlines the audit process by granting auditors access to electronic records. This expedites audit requests, as electronic documents are easily searchable and retrievable.

Consistent Standardization

Consistency and standardization are essential aspects of compliance in pharmaceutical manufacturing. Regulatory agencies require organizations to maintain standardized processes and documentation. A DVT enforces consistency and standardization by design, ensuring that all validation processes adhere to predefined standards. This reduces the risk of compliance issues and minimizes the likelihood of audit findings.

Historical Data

Pharmaceutical companies often struggle with the lack of historical data in paper-based systems, which can hinder decision-making and risk assessment. A DVT addresses this gap by providing easy access to historical data. Having this information readily available enhances the ability to make informed decisions and enables a thorough assessment of the organization’s compliance history.  

Additional advantages around efficiency and cost saving are:

• Efficiency Gains for Manufacturing Systems – reduced qualification/validation cycle times
• Data Reusability - access to previously developed documents such as specifications, assessments, or testing protocols
• Paper Reduction – no printing, no on-site or off-site paper storage

The Disadvantages:

While I think there are no major disadvantages to deploying a digital validation tool, choosing the correct tool for your needs is important. In addition, if you do not well understand and address your company’s digital maturity, the scale of the rollout, proper governance, and your ability to enable the culture of change required, this may lead to negative opinions about DVTs and the thinking that the tool is a disadvantage.

How do DVTs address data integrity challenges?

A DVT provides opportunities to enhance data integrity in validation documentation. Ensuring data integrity throughout the data life cycle is essential. Data integrity controls should ensure that data and records remain attributable, legible, contemporaneous, original, and accurate (ALCOA). Furthermore, data and records should also be complete, consistent, enduring, and available (ALCOA+).

Any digital validation tool needs to have data integrity at its core; there is no compromise on this. Ensuring that the validation/qualification data is secure and all actions and manipulations are clearly visible via audit trails assures the robustness of the data and compliance with ALCOA+ principles.

The data integrity foundations for a digital validation tool and the data life cycle can be found in the ISPE GAMP Guide: Records and Data Integrity and also one of the core companion guides to ISPE Good Practice Guide: Digital Validation.

Do companies need to be intentional when implementing DVTs to avoid the "paper-on-glass" outcome?

The adoption of DVTs within the pharmaceutical industry necessitates a cultural shift within organizations. Qualification/validation activities using paper often occur in silos due to the nature of the tasks. For example, document review and approval that requires the physical copy of the document must be conducted on an individual basis, as each reviewer/approver must have a physical copy. Similarly, the execution of paper-based test documents must follow this approach, as altering or splitting the documents in any way could lead to missing pages or data. These paper-based processes present significant roadblocks and delays.

With a DVT, the organization must deliberately attempt to move away from these concepts. Post-execution reviews of executed documents should be encouraged to be more collaborative, reviews can happen in parallel and improve communication, and reviews can be more visible between the different functions, leading to improved execution outcomes in terms of delivering on compliance and function.

The role of the reviewer using a DVT changes. Rather than focusing on GxP compliance of tests and attachments, reviewers can concentrate on data analysis to ensure scientific accuracy of the data in relation to the acceptance criteria.

Embracing DVT use to avoid a paper-on-glass approach may require a step-wise approach to achieve fully digital, and users should be encouraged to think of how existing paper aspects may be better designed or even removed when digital. Examples of this include signature logs no longer being required since the user information is already integral to the tool, attachment logs no longer being required as any evidence required to be attached is inline with the applicable test, and the secure, traceable attachment will not require any form of stamping or initials and date as it impossible to lose one page in the sequence, which can happen with paper

The transition from paper-based systems to DVTs requires not just technological adjustments but also a significant cultural shift within the organization.

How does the new guide fit into the ecosystem of digital system frameworks?

Traditionally, all major organizations would have a number of electronic/digital systems to manage the different aspects, such as quality change control, deviation and CAPA management, material resource planning, document management, and computerized maintenance management systems.

Many of these are quite advanced in their development, having been commercially available for a number of years. The area of qualification/validation has been deficient in this area both in terms of solutions available and development.

Publication of this guide has created a new (and very necessary) digital/electronic pillar for organizations and the journey of development and innovation can continue.

About The Expert:

Mark Drinan is the operational technology (OT) compliance lead at Takeda. Previously, he held the role of small molecule and biologics operational unit lead of commissioning, qualification, and validation also at Takeda. He is a member of the International Society of Pharmaceutical Engineering’s (ISPE) Commissioning and Qualification Community of Practice, and the co-lead of the Digital Validation subcommittee. Previously, he was a CVQ lead at CSL Behring, and before that, he worked at Exyte, GSK, and Novartis.