Better Solutions for the Life Sciences Industry: Agile Development in GxP Digital Systems
Agile product development in FDA regulated digital systems is a pervasive trend in the life sciences industry today as companies look for more efficient approaches for the development of their digital systems. When we look at other industries, those within the software and digital product space have long recognized agile development as the gold standard to efficiently develop quality products, while life sciences companies have been slower to adapt, preferring their traditional waterfall methods.
First, let’s take a step back to define some key concepts within life sciences:
What is validation? When dealing with data that impacts how a drug or device is evaluated by a regulatory agency, and ultimately its safety in patients, it is critical that the data be accurate and unbiased. Validation is a process that guarantees data integrity by ensuring the data is secure and its sources are transparent. System changes have an audit trail, users are held accountable for changes made, and staff are adequately trained for the tasks they perform. Without documentation or validation controls in place, companies could “cherry-pick” data that supports their product while hiding negative results, undermining data integrity.
What is GxP? Validation is related to, but not synonymous with “GxP”. GxP is a generalized acronym for “Good <X> Practices”, the “X” can stand for Clinical, Manufacturing, Laboratory, or Documentation. “GCP” then, is Good Clinical Practices. The common thread is that good practices adhere to documented processes (digital or otherwise) that ensure the integrity of the resulting data, whether it is from a lab, clinic, manufacturing site, or data system. The validation referenced here applies to regulated data of any type.
What regulations govern drug and medical devices? The US FDA and the European Medicines Agency (EMA) are the governing regulatory bodies for drugs and medical devices. The FDA publishes the Code of Federal Regulations Title 21 (CFR 21), with Part 11 pertaining to electronic records. The EMA equivalently publishes EudraLex Volume 4, annex 11 (“Annex 11”). While similar in intent, CFR 21 part 11 is a brief document describing the requirements of a validated system, while Annex 11 also includes guidance on how to meet those requirements. An international trade group (the ISPE) publishes “Good Automated Manufacturing Practice V.5” or “GAMP-5” an extensive document that provides guidance for CFR 21 part 11 and aligns it with Annex 11.
For many decades, life sciences companies validated pre-clinical, clinical, and manufacturing data around CFR 21, but the guidance for digital systems is relatively recent and adoption gradual. For example, as of 2008, some phase 3-stage (late clinical trials) pharma companies were still printing hard copy quality records and manually verifying them. While changing the processes and ways of working is relatively straight-forward, changing people’s minds is not.
A side effect of the parallel evolution of digital technologies and regulations was that early digital systems were driven by industry lab and manufacturing quality people, not by professional software developers. As a result, early solutions came with a strong lab/research bias. Iteration cycles for a drug or device are very long, dependent on years of clinical data and lab research, thus necessitating a waterfall process. With the same people and systems managing digital validation, those processes adopted the same mindset.
Objectively, modern digital life sciences solutions are software products and should be governed by sound agile development principles but transitioning an entire industry mindset is a slow process. Agile methodology, therefore, has not been as widely adopted in life sciences software solutions because of history, not technical or process barriers.
Agile software development applies to regulated digital environments.
Software development best practices apply to the Life Sciences industry just as well as any other. There is one key difference between validated and non-validated systems. While agile aims to release frequent iterations of functional software, in a GxP environment that software must be both functional and validated. However, software can be released frequently and in a fully functional state to a pre-production environment, with a validation process then performed in a parallel work flow (Figure 1). In this model, the releases are tested and working before validation starts so the validation step need only re-run existing tests in a controlled environment and be properly documented. Deviations (i.e. testing failures during validation) contribute to major inefficiencies but should be rare in this model because functional bugs have already been resolved.
Advantages of agile GxP development include:
- A repeatable release cycle featuring continuous parallel development, requirements gathering, testing, and validation
- Flexibility when requirements change, bringing high priority requirements to release in 1–2 sprints
- Metrics to plan staffing needs and better predict timelines
- Enablement of testing automation into iterative delivery
- Fostering an iterative relationship between dev and test to quickly resolve bugs before they become costly deviations
It’s more about people than process.
While there are other ways to implement agile development into digital validation, the hard part is helping life sciences companies entrenched in waterfall practices transition to an agile mindset. There are two reasons for this. First, the client contact is likely to be a quality expert with a clinical or manufacturing background, not a software engineer. Second, and more importantly, processes that involve regulatory submissions are high leverage points for a life science company, resulting in a conservative mindset; the perceived risk of any change is very unappealing.
How to start?
Adoption of agile PEM in validated digital systems has been slow in the life sciences industry. One reason is the way FDA/EU regulatory validation has evolved from decades of pre-digital data handling, and perception of risk has limited process improvements. However, there are no technical barriers to applying agile development principles to validated systems, creating an opportunity for life science companies to improve the quality and efficiency of their validated digital systems.
Companies can start taking advantage of these opportunities by taking three steps.
- First, put the right people in place at high leverage positions that understand both software development and quality validation in life sciences. Software validation is a software development task, but it needs the GxP context.
- Second, promote a change in mindset to regard digital validation as another step in the software development process, rather than an extension of legacy quality processes. One way to do this might be to embed digital validation within a company’s IT department.
- Finally, generate real data to support a change in mindset with a small, experienced pilot team. The demonstration of a positive outcome can be very convincing, and the pilot program is the scaffold to build upon. With these three steps, life sciences companies can reap significant benefits applying agile methodologies to GxP regulated digital systems.
Meet the Author:
Jeff Wellhausen, PhD, MBA is a Consultant in Slalom’s Life Science practice in Seattle. Over the past 25 years, he’s driven process improvements in R&D, quality, global health, medical devices, business development, market research, and IT. Find him here on LinkedIn.
Slalom is a modern consulting firm focused on strategy, technology and business transformation. Our healthcare and life sciences industry teams partner with healthcare, biotech and pharmaceutical leaders to strengthen their organizations, improve their systems, and help with some of their most strategic business challenges. Find out more about our people, our company and what we do.
