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Pharmaceutical laboratories must keep lab data integrity practices in mind in order to properly handle the effects of the COVID-19 pandemic.
Taking the time to comply with lab data integrity practices during the COVID-19 pandemic in a resourceful and operative manner is crucial for pharmaceutical laboratories. Pharmaceutical Technology spoke with Bob Voelkner, vice president of Sales and Marketing at LabVantage Solutions; Charles Fracchia, CEO of BioBright and vice president of Data, Dotmatics; John Maier, director of labs data management at PPD Laboratories; and Kimberly Remillard, senior manager of Regulatory Affairs for Digital Science at Thermo Fisher Scientific about the best practices for lab data integrity during the COVID-19 pandemic.
PharmTech: Are there any new regulations regarding lab data integrity? How do current and/or new regulations apply to research going on for COVID-19 therapies?
Voelkner (LabVantage): The most recent regulations or standards for data integrity came in 2018, when FDA published updated guidance for industry on ensuring data integrity and compliance with CGMP [current good manufacturing practice] (1). At the same time, the World Health Organization and [the United Kingdom’s] MHRA issued guidance on data integrity, which is largely in line with FDA’s (2, 3). Today, the need for organizations dealing with COVID-19 to comply and adhere to the FDA guidance is no different than any other organization developing and manufacturing new drug products. The goal of data integrity is to assure the safety of, and therefore increase the confidence in, all pharma products being created and produced. Data integrity takes on heightened importance, as new COVID therapies and vaccines are on the fast track to market and prospective patients want assurances of the integrity of the drugs being offered to them. Operating a compliant lab in this environment, with data integrity at its foundation, is vital.
Maier (PPD): FDA’s industry guidance document, Data Integrity and Compliance With CGMP (1), defines data integrity as ‘the completeness, consistency, and accuracy of data.’ While there haven’t been any new regulations regarding lab data integrity, the good clinical practice (GCP) principle that requires data to be attributable, legible, contemporaneous, original, accurate, and complete (ALCOAC) applies to all clinical trials including ongoing research for COVID-19 therapies. In order to meet the accelerated timelines of COVID-19 trials, study setup timelines have been minimized while maintaining data integrity by employing innovative technologies and processes such as:
Remillard (Thermo Fisher): In response to COVID-19, researchers and regulators have found it necessary to adjust priorities and protocols to meet new restrictions and practices for researchers, patients, and healthcare workers. Several guidance documents have been published to provide direction on how to adjust to the new conditions while maintaining data integrity and patient safety. The guidance documents make it clear that the same ALCOA+ data integrity principles apply in addition to ensuring patient safety, protection of personal data, and data validity for any trial interruptions or protocol changes. With interruptions in protocols and new remote methods of monitoring being utilized, data integrity is becoming even more critical to ensure research data maintains its validity.
Specific documentation is required to detail why protocol changes, deviations, or alternative processes are implemented, including why protocol-specified data may be missing. All alternative approaches must maintain trial participant safety and trial data quality and integrity, while minimizing missing data.
In addition to changes needed in the clinical trial and research space, fast track Emergency Use Authorizations allow for exemptions from certain GMP controls in the manufacturing area. Data integrity is critical to help reduce risk with the use of these GMP exemptions. For example, data integrity to show traceability and adequate control of source materials, data around batch records, and testing must be in place. Validation to support the consistency of the manufacturing process, including computerized systems validation, is also critical to ensure data integrity can be maintained.
Applying data integrity principles during the research and development of COVID-19 therapies to ensure the data complete, accurate, consistent, trustworthy, and reliable will support regulatory submission efforts and contribute to patient safety. Digitalization of the laboratory with integrated technologies such as a laboratory information management system (LIMS) to manage the workflow of data can add efficiency and traceability and help to ensure data integrity principles are met.
PharmTech: How challenging or difficult is it to comply with lab data integrity regulations during the COVID-19 pandemic?
Maier (PPD): Accelerated startup and overall timelines of COVID-19 trials have presented a significant challenge to ensuring compliance with lab data integrity regulations. We have been able to significantly reduce our setup timelines by utilizing specialized global rapid implementation teams along with the innovative technologies and processes previously mentioned.
During study execution, the sheer volume of subject and sample data collected within the condensed timelines has made real-time data monitoring and reconciliation critically important to the success of COVID-19 trials. To facilitate this, we have implemented innovative analytical tools that proactively monitor study data integrity and notify lab and clinical teams of investigator and procedural non-compliance before it impacts timelines.
Remillard (Thermo Fisher): During the COVID-19 pandemic, new protocols and methods for monitoring are often necessary and need to be implemented quickly. More remote data collection and management activities are occurring in the effort to minimize risk of COVID-19 for researchers, trial participants, and manufacturers alike. Due to this, it is critical that data integrity is maintained to ensure the validity of the study data as well as the protection of the patient information. Digitalization of the laboratory workflow using validated systems can reduce the risk of data integrity issues. Permission controlled systems with controlled workflows, integration to reduce potential points of human error, access across sites, and enhanced security features can all work together to support the data integrity and validity of research data. Use of secure cloud-based LIMS systems can help to connect not only the instrument data within your lab, but also allow for connectivity between sites.
Voelkner (LabVantage): I would argue it’s really only challenging or difficult for those labs that aren’t equipped with the right tools and solutions. Lab-dedicated software, like an LIMS, is designed to ensure the integrity of all the data gathered by the system. This includes dynamic auditing, so even data in temporary memory is audited prior to being committed to permanent/durable memory. These automated, connected LIMS eliminate manual data entry and risks of transcription errors or purposeful manipulation of data.
Fracchia (BioBright, Dotmatics): Largely speaking, because the regulations haven’t changed, the compliance hasn’t changed either. There are COVID-19 specific challenges that have arisen, largely due to the fact that fewer people are working on site, personnel density restrictions, access to certain facilities (in particular manufacturing) has been heterogeneous from company to company, and even between sites of the same company. Challenges of this kind have affected our industry particularly hard due to the acute need for the work itself. It is certain that the importance of having a safe and efficacious vaccine, alongside the politicization of the vaccine availability, have negative effects on the environment surrounding the development. Even before the pandemic hit, there have been reports of data integrity bypasses and fraud. Pressure due to the pandemic has only increased existing trends in this environment and combined with a generalized lowering of the public’s trust in any vaccine, this makes data integrity and compliance a crucial aspect of the response.
PharmTech: How do you suggest other organizations improve/enhance their lab data integrity activities (specifically, workflow, day-to-day operations, etc.), and how can this particularly help companies that are trying to develop a COVID-19 therapeutic?
Remillard (Thermo Fisher): Data integrity relies on a combination of people, technology, and processes. Robust processes are necessary to ensure consistency and quality assurance. A good culture of quality will help to ensure the human resources involved in the laboratory will execute the processes in the correct way. And the right technology to meet the needs of the laboratory and regulations such as 21 CFR [Code of Federal Regulations] Part 11 can help to reduce the risk of human error and process deviations.
Whenever possible, integrating the laboratory with validated digital systems to meet your workflow needs will help to reduce the risk of data integrity issues. The same principles will apply whether digitalized or not; however, more checks and monitoring may be required for systems which are not digitally controlled. Ensuring all data specific and attributable, including clearly and specifically documenting any changes or missing data, is key to be able to show the integrity and validity of your data.
Fracchia (BioBright, Dotmatics): In order to improve lab data integrity activities, companies must review their existing practices and replace wherever possible error-prone, manual steps in the reporting of results and tracing of individual steps. With a robust, automated, informatics system taking care of recording and tracking vital laboratory or manufacturing information, a company can reduce the chances of having data integrity issues. Crucially, companies must also assess their systems’ cybersecurity posture, because with increased automation and informatics also comes a potential for external manipulation. Unfortunately, the vast majority of bioinformatics or laboratory informatics tools have very poor cybersecurity practices and hygiene and create a large opportunity for third parties to steal and modify data in said systems, and understanding the weaknesses and avenues that could cause deviations or data manipulations are absolutely key for companies. This is particularly true if —as the FBI has warned (4)—the company has publicly announced efforts in search of a COVID-19 therapeutic. Finally, we strongly recommend that companies set up a process to review new data and results that are being put into the record. This practice, common in clinical environments, needs to be performed by a person who is not familiar with the specific experiment, ideally even a disinterested third party. This will create human oversight and catch errors such as missing data, ambiguous results, unsupported conclusions, and more. Enacting this practice will ultimately give the executives, the company’s team, and even the public a level of safety in trust in the result that is sorely needed in this moment.
Maier (PPD): Organizations can improve lab data integrity by implementing systems and processes that reduce the level of effort to set up and validate the lab database by utilizing a single global database; limit the amount of data captured to only those elements required for analysis; employ robust quality controls that QC [quality control] data on entry, when modification are made and prior to reporting; and provide innovative web-based tools that facilitate electronic data capture (electronic lab requisitions) and real-time data access to investigators and clinical team members for continuous data review and reconciliation.
Voelkner (LabVantage): One critical way to ensure product quality is to prevent data integrity lapses at the outset, so proper lab automation is key. For companies that have abandoned traditional, paper-based record-keeping practices or deficient legacy IT systems, in favor of preconfigured and prevalidated LIMS built specifically for today’s regulated labs, they’re already on the right track. Such a LIMS enables automated connection to lab instruments so that results can be directly recorded into the LIMS, not only speeding the process, but increasing data integrity.
It’s worth noting that modern LIMS, which should be 100% browser-based, can help lab directors and managers to physically distance laboratorians who can work with tablets or other mobile devices.
PharmTech: What trends are driving the need for data integrity in the laboratory setting?
Fracchia (BioBright, Dotmatics): Besides the politicization and fraught recent history of data integrity that was discussed above, the next most important trend affecting data integrity is the deluge of data that is now commonplace in our industry. In processes where thousands of data points per day was the norm, we now routinely see workflows that generate millions of data points per day, both qualitative ones (such as images) and quantitative ones (e.g., assays). This dramatic uptick in data volume is a blessing for data-driven research, but it is also an unprecedented challenge to verify, validate, and commit [these] data to record. The need for automated tools is now clear, and such tools must be aware of automation capabilities and be hardened against cyber manipulations or we risk the robustness and trust of the whole system in this transition.
Maier (PPD): The continuous push to bring therapeutics to market quicker and more cost effectively will continue to drive innovation and system integration throughout all phases of the clinical trial life cycle and in the laboratory setting, to ensure data integrity is maintained. We will continue to develop improved analytical tools and are beginning to explore artificial intelligence predictive models to improve subject, site, sponsor, and lab compliance, which in turn will help enhance data integrity, reduce study timelines, and ultimately drive down costs.
1. FDA, Data Integrity and Compliance with Drug CGMP, www.fda.gov, accessed Nov. 9, 2020.
2. MHRA, ‘GXP’ Data Integrity Guidance and Definitions, www.gov.uk, accessed Nov. 9, 2020.
3. WHO, Guideline on Data Integrity, www.who.int, accessed Nov. 9, 2020.
4. CISA, “FBI and CISA Warn Against Chinese Targeting of Covid-19 Research Organizations,” Press Release, May 13, 2020.
Lauren Lavelle is the assistant editor for Pharmaceutical Technology.
Vol. 44, No. 12
When referring to this article, please cite it as L. Lavelle, “Complying with Lab Data Integrity Practices During COVID-19,” Pharmaceutical Technology 44 (12) 2020.