The Challenge

In recent years, there has been a rise in orphan drug applications as pharmaceutical companies have increased their investment in rare disease indications. In 2023, 51% of new drugs approved by FDA were orphan indications1. For rare disease populations, there are often challenges with diagnosis, prognosis, and monitoring of progression and thus a need to optimize the care paradigm.

Taking a patient-centric approach across the development lifecycle helps industry providers of health and wellness innovations understand the needs of the patients, their caregivers, their Health Care Providers (HCPs) and other stakeholders. Empathy, compassion, curiosity, and methodical data gathering practices reveal insights and gaps in care that can be addressed, in some instances, through innovative software as a medical device software (SaMD) solutions.

Doctor examining images of a human body

Our challenge was to learn, through insight gathering methods, about the unmet needs of a specific rare disease population, identify sources of curated data to see if we could design new product offerings that augment the health management tool kit and enhance health and wellbeing. We conducted a biomarker exploration program and leveraged data from the clinical trials, real-world data and other sources to address unmet needs that had been discovered during insight gathering. The team was labeled a Bridge Team which stood for Biomarker Research Initiatives for Disease Management, Guidance & E-tools.​ We left no data unturned and explored medical history, clinical, radiomics, genomics, metabolomics, digital biomarkers data and more.

What We Did

  • Established and led a cross functional biomarker exploration team to identify markers of progression that would distinguish between different groups of patients with this rare disease
  • Contextualized an SaMD and data product to collect patient data, characterize organ morphology, and use machine learning to estimate progression of the rare disease
  • Led design and development activities for the SaMD:
    • Conducted stakeholder analyses to define use environment, user roles, and user requirements
    • Researched and defined user workflow
    • Wrote FDA pre-submission and provided regulatory support to devise regulatory strategy
    • Defined and documented user needs and technical requirements
    • Provided technical project leadership to oversee software and algorithm development with key focus on cross functional areas of:
      • Quality Management and Compliance (e.g. 21 CFR 820, ISO 13485, IEC 62304, IEC 62366, ISO 14971, etc.)
      • Cybersecurity
      • Usability (e.g., IEC 62366)
      • Privacy
      • Multi-region scalability
  • Led efforts to define cybersecurity risk management program
  • Developed labeling for the software application and Instructions for Use
  • Drove documentation efforts to populate Design History File
  • Defined the precision of the SaMD’s automated organ morphology calculation by evaluating the measurement precision under the same set of conditions over a short period of time (repeatability) and under a different set of conditions (reproducibility)
  • Determined the accuracy of the SaMD’s automated organ morphology calculation by comparing against the gold standard
  • Planned and conducted 4 Human Factors studies to evaluate perceived ease-of-use and user satisfaction
  • Clinically validated the accuracy of the predictive algorithm that predicted the progression of the disease based on intended use and intended users
  • Wrote De Novo submission for the innovative SaMD

Results Delivered

  • Custom designed, robust, validated SaMD
  • Cybersecurity compliance to FDA 2022 Guidance
  • Provided Human Factors Engineering (HFE) Summary Report
  • Complete Design History File and De Novo submission

Key Outcomes

  • Established clinical association between the SaMD output and target clinical condition
  • Algorithm for progression of disease developed and validated through precision, accuracy, and clinical validation studies
  • Developed SaMD that complies with: ISO 13485, FDA regulations, software development (IEC 62304), risk management (ISO 14971), privacy and security standards, quality assurance, and human factors engineering and usability standards (IEC 62366)
  • Demonstrated the impact of iterative improvements in the design and usability of the software
  • Developed Design History File (DHF) and De Novo submission for SaMD to support client

Reference:

  1. https://www.fda.gov/news-events/fda-voices/fda-approves-many-new-drugs-2023-will-benefit-patients-and-consumers#:~:text=More%20than%20half%20(28%20of,received%20an%20orphan%2Ddrug%20designation.