Effective today (September 9th), the European Medicines Agency (EMA) Guideline on Computerised Systems and Electronic Data in Clinical Trials comes into force with a new set of standards for computerised systems and electronic data in clinical trials. Outsourcing-Pharma checked in on ICON’s perspective about its purpose, scope and any key considerations that have come into light since the guideline was published in March 2023. Hereby we are sharing insights provided by Vesta Marciulioniene, Director Global Regulatory Clinical Services at ICON Biotech.
OSP: Can you share a brief overview of the EMA guideline on computerised systems and electronic data in clinical trials?
VM: The new guideline consolidates expectations on the use of computerised systems, the collection and use of electronic data, and provides a framework to be upheld by sponsors, investigators and their service providers. Any sponsor planning to apply for medicinal product marketing authorisation in the European Union (EU) will need to adhere to the requirements of this new EMA guideline.
OSP: What’s different about these guidelines from previous iterations? Or has anything like this not previously existed?
VM: Some regulatory guidance touched upon some of the topics, but challenge has been how to contemporaneously define the requirements for the ever-evolving technology in clinical research and in what scope.
The need for modernisation of regulatory guidance started in 1990s with a pharma industry request to define the standards of electronic records and signatures. Over the years, the FDA published and further modernised the 21 CFR Part 11 and released the FDA Guidance for Industry on Computerised Systems Used in Clinical Investigations as well as Question-and-Answer type documents targeting specific areas, e.g, electronic informed consents. Recently the FDA has been further working on a draft FDA Guidance for Industry on Electronic systems, electronic records and electronic signatures in clinical investigations, yet to be released.
Meanwhile to address the gap in this space in the EU, the EMA has been building upon the now superseded 'Reflection paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials ', and this is how this new EMA guideline has evolved.
Why this new EMA guideline is unique? Unlike many other guidance documents narrower in scope released over the years, it attempts to be a comprehensive guide for the use of any type of computerised system in clinical trials. It is unique in its broadness and in its forward-thinking mindset directed to address the fast paced digital evolution.
OSP: What are the key considerations for the new EMA guideline?
VM: The two key considerations for me are, simply, understanding who is impacted and how.
Who is impacted? Besides Investigators and Sponsors being the two key stakeholders accountable for the proper use of computerised systems and management of electronic data in clinical research, it is critical to underline this guideline impacts any sponsor and investigator service providers, irrespective of the service provided, and any other parties involved in clinical trial.
Secondly, to answer ‘how you are impacted’, we need to carefully interpret the concepts and scope defined within the guideline. So far, I have faced two most frequent misconceptions in this space. One misconception is that electronic clinical data is limited to the data originated from clinical trial participants – which is wrong. In the context of this EMA guideline the clinical data should be considered as both “data derived from a trial participant and any other trial related data handled in e-systems for the purposes of conducting and reporting a clinical trial, and relevant for the clinical trial”, as explained by EMA in clarification to ICON. Another misconception is an assumption that the guideline applies purely to technical, information technology (IT) related aspects. In contrast, there is a much broader context to consider:
- Processes: Do standard operating procedures (SOPs) and other controlled documents embed and comply to the requirements of this guideline? Do they allow and guide the relevant process roles to make appropriate assessment on the systems and electronic data or guide them on relevant procedures to be used for electronic data access and use?
- People: Do the impacted roles who need to have a specific level of awareness of this guideline, its requirements? How it impacts their roles? What level of training and change management is needed?
- Clinical trial project delivery: How does the guideline impact delivery in ongoing or new clinical trials? What considerations should apply for any investigational product targeting a marketing authorisation in EU?
- Vendors: Do vendors comply with the requirements of this guideline and how that compliance is ensured and overseen?
- Budgets and other financial implications: Does the adherence to this guideline impact costs on clinical research projects or require investments in technology and system updates, process updates, people training?
- Investigators: How are investigators qualified, ensuring appropriate electronic system suitability, access and use? How is source data defined in agreements and access to source data and EMR source data at investigative sites?
OSP: What are the key implications for the use of computerised systems and digital technologies in clinical trials?
VM: The guideline expands on multiple computerised system and digital technology solutions: electronic medical records, eCoAs, eCRFs, eTMFs, eConsents, Sponsor-to-Investigator systems, IMP related systems and tools, automatic data capture tools, remote auditing and monitoring systems, and finally, any other systems holding, managing, analysing, reporting data, such as Clinical Trial Management Systems (CTMS), document management systems, safety systems, etc.
The EMA guidelines implies there should always be consideration of electronic data in an all-encompassing holistic view from its generation in one computerised system and its movement throughout data lifecycle into next system, its transformation, format change, modification, updating and archival. The guideline reinforces the need for data governance, quality and risk management of systems, data integrity, reliability and protection, defined responsibilities and access control, ALCOA++ principles and many more. Besides of some of the already widely established IT features such as system validation and security, it drives new perspectives on electronic signatures, certification of copies, vendor system oversight, live in-system audit trails.
OSP: How can sponsors and investigators prepare to comply?
VM: The clinical research industry has had line of sight on the guideline and its implications since the first draft was released in September 2021, however it has been significantly modified since and release in March gave the industry only six months preparation time. Achieving readiness to comply with an adequate assessment and mitigation of the ultimate impacts of this guidance has been a significant undertaking given the complexity and multilayer nature of clinical research industry. ICON recommends clients, investigators and other stakeholders to conduct assessments of their clinical trial computerised systems and electronic data use, access and management, and advocates for raising the awareness of this new guideline globally. Compliance to the guideline might be in progress by some when it comes into effect.
OSP: What are the wider implications for the role of technology in clinical research?
VM: The complexity of the computerised systems and electronic data in clinical research has evolved significantly over the years. As technology continues to be on a pathway of fast-paced evolution not only in clinical research but also in standard health care, the drug development industry will need to continue to embrace the digital technologies further developed, and adherence to this guidance will be instrumental to ensure regulatory compliance in this space and ensure data quality, integrity, and patient safety.