Omar Serang, Chief Cloud Officer
The increasing complexity of regulations and contracts coupled with the lack of supportive infrastructure make it all the more difficult to conduct successful clinical trials. When high throughput genomic data is built in to clinical trial design as a key component of patient stratification and readout of therapeutic response, the challenges become even greater. Clinical trial Electronic Data Capture systems (EDC) are not built to store and analyze large volumes of high-throughput molecular data, for example, NGS assays that capture the genomic sequence variants of study participants. Here, DNAnexus steps in with its ability to store and analyze high-throughput molecular data using its cloud-based genomic analysis and data management platform. DNAnexus formalized security and compliance controls enable incorporation of genomics and other high-throughput molecular data into clinical trials.
“Computer systems used in clinical trials capture and analyze data which affect either the course of trials or the course of treatment, making computer system validation essential,” explains Omar Serang, Chief Cloud Officer of DNAnexus. These systems require effective tracking of quality, reliability, and reproducibility—a traceability matrix tracking features from specification to production deployment is required to satisfy regulatory requirements for Computer System Validation (CSV). “A formalized process comprising CSV, and installation quality, operational quality, and performance quality testing (IQ/OQ/ PQ) is applied to demonstrate the fitness of software deployed into clinical environments for trials,” says Serang. The DNAnexus system becomes a formal validated system integrating with the clinical systems of record which in turn refer to the high throughput molecular data managed by DNAnexus.
DNAnexus, which complies with HIPAA, FedRAMP, and Quality Management standards, increases the efficiency of companies or contract research organizations (CRO) with its clinical trial platform. DNAnexus interfaces with Medidata, which develops SaaS solutions for clinical trials, through its API, extending the validated clinical trial environment to incorporate the high-throughput molecular data. DNAnexus, which has operational compliance and certification—ISO 27001 for information security and ISO 9001 for quality management—is using cloud computing and storage from Amazon and Azure.
When software is deployed into clinical environments for trials, a formalized qualification and validation process is applied to demonstrate the system’s fitness
In an implementation highlight, a global pharmaceutical company conducted clinical trials to treat inflammatory bowel disease using a live biotherapeutic—a cocktail of 17 microbes. Live biotherapeutic manufacture needs next-generation sequencing (NGS) analytics to assess the assay not only during the clinical trial but also during the manufacture of the drug. When the pharma customer sought to conduct trials and eventually deliver the biotherapeutic in diagnostic settings to review patient impact, DNAnexus came to the rescue. This was done by deploying a quality management system (QMS) and working closely with the pharma customer to validate their VE202 pipeline and convert it into a wholly reproducible hardened production pipeline. The DNAnexus Platform thus enabled the implementation of standards and technologies in a pipeline that could be used in multiple contexts: early research, clinical development and clinical diagnostic testing, improving the efficiency of the drug development and diagnostic process.
“If you have a molecular biomarker heading into a trial, you are a lot closer to a drug or treatment by a long shot,” says Serang. Utilizing genomic data in early phases to discover biomarkers useful in participant stratification and inclusion/ exclusion criteria can increase the efficacy of the treatment and open up opportunities for development of companion diagnostics in the near future. Whole exome sequencing is increasingly being incorporated into trial designs for cancer, immune, inflammatory, cardiovascular, and metabolomic diseases, and understanding participants metagenomics is continuing to gain significance. DNAnexus is expanding its translational informatics capability within a clinical context to enable clinical trial investigators, collaborators, and sponsors to gain insight from this data early in the drug discovery process through combined analysis of patients’ real-world evidence, genomic data, and aggregate data from other studies and programs. Integrated management and analysis of the clinical and genomic data enables understanding of the relationship between the participant’s genomic makeup and their response to therapy.
Serang draws attention to DNAnexus’ work powering precision FDA, a cloud-based platform used by the FDA to advance regulatory standards for NGS-based drugs and devices.