Gene Therapy Potency Assay Release Test

Impact of Software-as-a-Service on Process Analytical Development


This case study describes the use of the CellPort Software-as-a-Service (SaaS) platform in the Process Analytical Development (PAD) stage for development and transition into a fully compliant GMP potency assay release test for a commercially approved gene therapy product and the positive impact that the platform had on improving the secure and compliant transfer of the technology and protocols to a GMP setting.

Process Analytical Development to GMP Assay

Spark Therapeutics collaborated with Absorption Systems, a Pharmaron Company, in the development of a novel in vitro potency assay for the LUXTURNA gene therapy product that treats an inherited retinal disease. The disease is caused by mutations in both copies of the RPE65 gene passed from parents on to their affected child. [1] Symptoms of patients with RPE65 mutations include night blindness (nyctalopia), loss of light sensitivity, loss of sharpness or clarity of vision, impaired dark adaptation, and repetitive uncontrolled movements of the eye (nystagmus).

The story of LUXTURNA began with a visionary quest at the Children’s Hospital of Philadelphia to use gene therapy to treat children suffering from a rare form of RPE65-related blindness. [2] The resulting gene therapy product, LUXTURNA, works by delivering the missing gene to the retinal cells of a patient. Once incorporated into the DNA of those cells, the RPE65 protein is produced and reverses the symptoms caused by the protein’s absence, there by treating the various forms of blindness with which the people carrying the RPE65 mutation were affected.

The relative potency assay collaborative work was presented as a poster [3,4] at the Annual Meeting of the Association for Research in Vision and Ophthalmology and uses a human, cell-based model to predict relative potency of the product in humans. The prospect of a gene therapy product that cures blindness was inspiring and compelling, however, the inherent complexity of developing a GMP potency assay presented a challenge in making this goal a reality. CellPort Software became the solution to this challenge in the PAD phase of the potency assay development, collecting and tracing all components of the assay in a 21CFR Part 11-compliant manner while the PAD process was underway. Once the assay was fully defined and locked down, the CellPort Software platform, which supports research, GLP, and GMP environments, made the digital transfer of the methodology and protocols effortless to a GMP setting.

LUXTURNA was approved by the FDA in December 2017. [5]

LUXTURNA Gene Therapy Product

1. Deliver RPE65 gene to retinal cells.
2. RPE65 protein is expressed in retinal cells.
3. Visual impairment is alleviated.

Flexibility in an
Inflexible Environment

The case study on the impact of the CellPort SaaS platform on a GMP gene therapy potency assay underscores the importance of flexibility in an inflexible environment. Submissions to the FDA require extreme rigor, and the software systems in which the related data are stored must be fully validated—a most inflexible environment. By contrast, the rapid and iterative nature of Process Analytical Development demands flexibility. In a regulated environment, software has historically been rigid, and compliance and flexibility have not gone hand-in-hand. The CellPort Software platform successfully bridges this gap through the creation of a system that allows easy adaptation of the flow, the look and feel, and the data models for specific customers and situations, all without changing any source code.

The no-code SaaS platform adapts to individual customer and situational needs through transparent configuration without the need to revalidate the core platform.

The FDA’s Technology Modernization Action Plan (TMAP) stresses “communication and collaboration with stake­holders to drive technological progress that is interoperable across the system and delivers value to consumers and patients. The TMAP provides a sturdy technological foundation for development of FDA’s ongoing strategy around data itself—a strategy for the stewardship, security, quality control, analysis, and real-time use of data—that will accelerate the path to better therapeutic and diagnostic options for patients and clinical care providers, and better tools to enhance and promote public health.” [6] In the world of cell culture, cell manufacturing, and cell banking and all the downstream products that are touched by cells, an integrated cloud-based platform like CellPort Software represents a critical leap towards the FDA’s plan to drive technological change across the biomedical ecosystem that is not only interoperable, but is also transparent, traceable, and transferable.


In complex assays submitted to the FDA for gene therapy product approvals, CellPort Software provides traceability, transparency, and transferability to the cell manufacturing process that supported these regulatory submissions and was shown to have a major impact on the speed and outcome of the routine FDA audits that were a part of the process. The CellPort Software no-code SaaS platform provided a flexible and extensible framework that spanned research, GLP, and GMP settings, and allowed rapid adaptation of workflows in the Process Development phase with secure and compliant transfer of the technology and protocols to a GMP setting.