Data integrity compliance for chromatography methods

The ability to track and trace information from one laboratory to another across the globe is challenging but doable, as Patrick Kenny, Chromatography Software specialist at Thermo Fisher Scientific, explains

The manufacture of pharmaceutical products is becoming increasingly complex in terms of development and production processes, the large amount of data generated and the diverse locations of laboratories and equipment suppliers. Although these advancements enable pharmaceutical products to be made more efficiently, the ability to track and trace information from one laboratory to another across the globe is challenging.

During the last decade, the United States Food and Drug Administration (FDA) highlighted several problems with data integrity during drug production that resulted from the ineffective application of data management systems. Responding to these challenges, in December 2018, the FDA published guidance titled “Data Integrity and Compliance with Drug cGMP (Current Good Manufacturing Practice): Questions and Answers.”1

One of the focus areas is monitoring data throughout a product’s lifecycle. To comply with these more stringent regulatory guidelines, companies have created innovative and robust centralised data management systems that enable comprehensive data tracking and auditing.

Software that can fully integrate a range of analytical instruments, standardise protocols and automate data collection and analysis provides significant advantages

Most laboratories involved in drug manufacturing employ a chromatography data system (CDS) to capture and manage data. However, typically, some parts of the process are still manually operated and involve standalone systems, challenging the availability of complete audit trails and, as such, data integrity.

Software that can fully integrate a range of analytical instruments, standardise protocols and automate data collection and analysis provides significant advantages when compared with many of the existing solutions currently being used within the industry.

This article describes the challenges associated with tracking and tracing data in the drug manufacturing process and how implementing an integrated CDS can overcome many of these limitations. An example of a pharmaceutical service provider that has improved data integrity and tracking through implementing a single CDS is highlighted.

From instrument control to data analysis

Although chromatography methods have been used in drug manufacturing for decades, the latest technologies are generating larger quantities of complex data, which must be collated, analysed and stored for recall. This substantial increase in data means that using manual systems to compile, store and perform analysis — such as using paper files and offline spreadsheets — is no longer sufficient to provide robust and high-quality information for real-time decision making.

In addition to being time-consuming, the manual reprocessing of chromatography data can lead to inefficient visualisation and is prone to error. It can also require repeated batch processing of the entire sequence to view the effects of parameter changes. Even the use of more advanced software can be problematic if used offline or in isolation, as it can be difficult to provide a complete audit trail of events.

As pharmaceutical companies have expanded into multiple geographic regions, the manufacturing process has become more dispersed, making the harmonisation of procedures more difficult and, in some instances, creating a silo effect.

Even the use of more advanced software can be problematic if used offline or in isolation

Without standardised processes and equipment settings that can be translated between laboratories across different facilities and geographies, data can be subject to operator control. This can introduce variability that could put the quality, efficacy and safety of any therapeutic product at risk.

The stricter FDA guidelines recommend that pharmaceutical companies use integrated and automated systems to ensure data integrity at every stage of the manufacturing pipeline.

Developing a fully integrated and compliant chromatography data system

Historically, CDS software could not be used to control and manage instrumentation and could only record analogue data from a single channel, which was then converted into a digital signal. Further developments to CDS software have enabled the control of multiple instruments from different vendors and improved networking capabilities — ensuring the connectivity of all instruments to a single data management solution.

Patrick Kenny

These systems ensure that any changes made are instantly reflected in the data and results, saving valuable processing time, increasing productivity and ensuring compliance across multiple laboratories, buildings and sites.

The manual integration of chromatography peaks is a procedure that has been routinely employed by many laboratories in numerous industries. However, the trend in regulated laboratories has been to minimise its manual use with recent FDA guidelines stating the need for automating these integration methods to provide a more robust data management strategy.

This was in part because of the interpretive nature of manual integration and the potential to introduce non-compliant behaviour.

Regulatory guidelines also stipulate the monitoring of instrument performance through a centralised system to ensure that it’s calibrated and the subsequent data are precise. This has been built into the latest, fully integrated platforms to automate quality control (QC) procedures for both the instruments and software.

The continued execution of this functionality reduces the costs associated with executing multiple manual procedures to track instrument performance and eliminates any user error generated during the process.

Ultimately, the ability of a CDS to track all aspects of product data throughout manufacturing from a single location makes it a worthwhile investment. Streamlined through cloud connectivity, the sharing of information is easy and secure, supporting faster decision making and the delivery of drugs to the clinic in a reduced timeframe.

Implementing a centralised CDS to track and trace data

Many organisations serve the healthcare and pharmaceutical industries, providing a range of specialist services, including analytical expertise, QC testing and scientific and regulatory consultation. Having a centralised data management system for these services would be a significant advantage to these companies, when efficiency and compliance are essential.

Here, we describe how Broughton Laboratories, a company that delivers analytical, scientific and regulatory services to pharmaceutical companies, has successfully implemented a centralised CDS to ensure data can be tracked and traced, independent of equipment vendors, throughout a project.

With increasing sample numbers to analyse, resulting in a greater quantity of data to manage, Broughton was seeking a solution that could be used to manage all of their instruments, workflows and data to improve efficiency while complying with the latest regulatory guidance.

To achieve this, the company upgraded to Thermo Scientific Chromeleon CDS software — providing the ability to bring all their instruments, regardless of vendor, into a single, connected system.

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Within a matter of weeks, Broughton Laboratories doubled their data processing capabilities. The ability to track and trace data throughout this process was also improved and simplified, reducing the administrative burden. To ensure regulatory compliance, Broughton used the CDS’s in-depth audit trails to streamline the review process and answer the questions of who, what, when and why more easily.

Chris Allen, cofounder and Managing Director of Broughton Laboratories, remarked that “the key benefit of Chromeleon was that it didn’t tie us to a single instrument vendor. We could implement a single, networked software platform that was flexible and scalable enough to grow with us.”

Broughton’s regulatory compliance was further strengthened through the ability to standardise chromatography sequences to their internal procedures across all of their instruments and laboratories using a single, centralised system. Previously, the majority of Broughton’s chromatography sequences were created manually, leaving them open to error.

Through eWorkflow templates and the ability to apply standard operating procedure (SOP) rules to sequence creation — and store them in a centralised point that each instrument has access to — the company was able to standardise processes across the entirety of its organisation, reducing errors, increasing the reliability of its results and make further efficiency gains.

Conclusion

As technologies in manufacturing drug products advance, larger quantities of more complex data are generated. This has led to regulatory bodies introducing more stringent regulations to ensure product data can be tracked and traced throughout the manufacturing process.

This can be challenging for pharmaceutical companies that generate a large amount of data in diverse locations; but, a well-executed data management system can provide the necessary management tools to achieve data integrity and regulatory compliance.

The case study presented in this article demonstrates how moving from manually operated procedures to a fully integrated CDS not only enhanced accountability and regulatory compliance, but also increased productivity.

With the globalisation of the pharmaceutical industry continuing, other regulatory agencies have revised their guidelines in line with the FDA, which has created close partnerships and similar governance throughout the world. In the near future, an automated, centralised CDS will be a prerequisite to the successful production of high-quality and safe therapeutic products.

Reference

  1. US Food and Drug Administration (FDA), “Data Integrity and Compliance with Drug cGMP Questions and Answers, Guidance for Industry,” www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers-guidance-industry (December 2018).

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