The key to achieving data integrity in pharmaceutical manufacturing

Peter Zipfell, product marketing manager at Thermo Fisher Scientific explains how better software can help pharmaceutical manufacturers keep their data accurate.

Every day in pharmaceutical manufacturing, countless decisions are made which have the potential to directly impact public health. At the core of these decisions lies the constant monitoring of carefully selected parameters with known or potential consequences on product safety or efficacy. The degree to which data is complete, consistent, and accurate across its entire lifecycle is referred to as ‘data integrity’ and is monitored by regulatory agencies. While adherence to data integrity guidelines indicate good practices, incomplete or inaccurate records can reflect poor data management systems, human error, or intentional data falsification. 

As failure to ensure data integrity contributes to compromised product quality, pharmaceutical manufacturers are required to keep an audit trail; a secure electronic system that maintains an accurate record of events to enable a historical reconstruction of the data. However, audit trails are challenging; maintaining a meticulous record of complex processes across multiple sources can be difficult for manufacturers, while audit trail assessments represent an onerous and multifaceted task for reviewers.

Having appropriate software is, therefore, essential for implementing practices necessary for compliance and easing the burden for both parties. The functionality of this software should not only support audit trail maintenance and review; streamlined systems are also critical to enhancing productivity.

Trends shaping audit requirements

In recent years, the focus around data integrity has continued to intensify, following an increasing number of warning letters, notices of concern and statements of non-compliance. Authorities are now striving to reduce incidents of poor data integrity by encouraging transparency and updating regulatory guidelines related to pharmaceutical manufacturing and global clinical trials. As part of the shift towards greater transparency, electronic data systems are now encouraged over paper, making data increasingly searchable, accurate, and difficult to falsify.

The enforcement of ever-evolving audit trail regulations is driven by one underlying factor: the demand for high-quality products. To this end, the US Food and Drug Administration (FDA) is considering novel strategies for incentivising mature quality management systems, especially after the findings from a 2019 report on drug shortages. Of 163 drug shortages in the US between 2013 and 2017, 62% of supply disruptions were associated with manufacturing or product quality problems. Consequently, the FDA has suggested introducing a rating system, whereby pharmaceutical companies could disclose a rating indicative of their commitment to establishing quality management systems that help anticipate problems before they arise. Such a move would provide companies that demonstrate strong quality management maturity with a competitive advantage, potentially enabling them to grow their market share.

In this context, robust audit trails are not just tools for achieving data integrity, compliance and product quality; when used to their fullest, they can become a competitive advantage under greater demands for transparency. The report also recognised that simple adherence to cGMP standards doesn’t necessarily mean a company is investing in improvements; manufacturers are now expected to take greater responsibility and demonstrate quality maturity.

The challenges of creating and reviewing an audit trail

Not only are audit trails a record of the “date and time of operator entries and actions that create, modify or delete electronic records”; manufacturers are also required to “track actions at the record or system level” – as written in the FDA’s Data Integrity and Compliance with cGMP Guidance for Industry. Specifically, any attempt to access the system, or rename or delete a file, must be recorded. Without the right software systems in place, it is impossible to track these actions.

Audit trail reviews are laborious and multifaceted; experienced users must be able to review available data to determine whether the recorded actions can be justified based on the ‘who, what, when, where and why’. Without appropriate filtering and grouping features, it is difficult for the reviewer to quickly identify relevant information among the hundreds of potential entries. In addition, the global nature of pharmaceutical manufacturing and increasing uptake of continuous manufacturing only adds to the challenge of maintaining comprehensive and easily accessible audit trails. Overall, there is a growing need for secure and streamlined software reporting tools.

Forward-thinking chromatography data system (CDS) software provides an invaluable service

A software that affords full traceability is a strong deterrent to malicious intent, so it is imperative that a CDS captures all actions in the audit trail. With Thermo Scientific Chromeleon 7.3 CDS software, for example, the ability to change specific settings or perform certain actions can be restricted to select users. If these settings were changed, the changes would remain visible to all. Every deleted, modified and added event is documented electronically, thereby addressing any concerns around traceability. Even failures and errors that may cause a run to abort are recorded as a significant system event with an accurate date and time stamp.

Throughout the workflow, a number of features are being added to CDS software to simplify compliance and audit trail reviews, for example:

• Single user identity and password authentication for maximal traceability.
• A clear record of activity allows regulators to easily view any changes.
• A highly searchable interface that enables reviewers to query events and extract more information from the data.
• Use of ‘standard comments’ to assist with action verification or reasoning, i.e. a predefined list of the most commonly accepted answers for routine actions or amendments.
• Sequence-centred storage of all associated components related to the dataset, keeping everything in one place for completeness.
• A self-notification system where the software alerts the reviewer to specific high-risk audit trail events, e.g. a manual change to a chromatogram.

Compliance and workflows made easy with advanced CDS software 

The pharmaceutical industry is experiencing significant pressure to demonstrate greater transparency and data integrity to ensure a reliable supply of high-quality pharmaceutical products. Meticulous and evolving audit trail regulations reflect the need to safeguard public health and represent a major challenge for manufacturers. To remain compliant, manufacturers require software systems capable of handling larger and more complex datasets without compromising on productivity. Ultimately, implementing a more modern and advanced CDS platform is an opportunity to achieve compliance, simplify audit trail reviews and enhance workflows.