Successfully reverse-engineered an off-the-shelf consumer product for medical device
reduction in time to source bill of materials
to test, refine product specifications, and retest
The Human Microbiome
Discoveries made over the past decade—catalyzed by major investments in the Human Microbiome Project, the Metagenomics Project of the Human Intestinal Tract, and other research efforts—have rapidly advanced the understanding of the role that the human microbiome plays in modulating human health.
Once seen only in adversarial terms, today the trillions of bacteria that inhabit or live on our bodies are known to play important, beneficial roles in a wide range of biological processes, including resistance to pathogens, regulation of immune function, and energy metabolism.
Seres Therapeutics Platform
Seres Therapeutics has built a proprietary discovery and design platform that enables the Company to understand the dysbiosis associated with specific diseases, and to rationally design tailored therapies to establish a healthy microbiome.
They draw upon the disciplines of systems biology and comparative genomics—as well as expertise in isolating and characterizing microbes that have been historically difficult to cultivate—to create a new class of therapies aimed at establishing a healthy microbiome. They compare a vast trove of human data from relevant disease states with that from healthy individuals and characterize specific microbiome functions that are disrupted in states of dysbiosis.
Seres has a deep understanding of the biology of specific microbes and the composition of the microbiome in healthy and diseased individuals which allows the Company to identify “keystone” organisms and functional pathways whose absence or over-abundance may be driving a particular form of dysbiosis.
The raw material used for this effort is a proprietary library of thousands of characterized microbial strain isolates derived from healthy human donors, which provides the building blocks of Ecobiotic® drugs. Ecobiotic® drugs are compositions of commensal microbes that are designed to catalyze the transition to a healthy ecology of the microbiome and treat serious human conditions including inflammatory, metabolic, and infectious diseases.
Seres Therapeutics drug discovery process interrogates how diverse microorganisms work together to form “functional ecological networks” that perform specific biological functions, and how the diversity of microbes present in the gut can have a significant impact on the healthy function of the human gastrointestinal tract ecosystem. The Company defines how alterations in a state of health impact disease and design Ecobiotic® drugs tailored to help establish healthy microbial communities that can confront a wide range of diseases.
The Supply Chain Challenge
As the Company began clinical trials for SER-109, its lead development candidate, it identified critical supply chain challenges that it would need to solve to gain FDA approval. Initially, the development work began by using off the shelf products for storage, processing, and filtration of its microbes.
While this is common for early, proof-of-concept work, this presented clear challenges for the Company in the long term because they would need to establish the necessary controls for a commercial pharmaceutical supply chain. In particular, the Company needed to identify the material composition of all materials that came in contact with the product and establish appropriate change controls down to tertiary suppliers.
Building the Solution
Our first task at hand was to perform Fourier Transform Infrared spectroscopy (FTIR) and chemical composition tests on all of the materials. Separately, we also needed to classify the filtration functionality of one of the raw materials, which acts as a filter mesh in the final product solution. To do this, we conducted an analysis of the particle size and distribution from the mesh. Following the testing and analysis, we were able to accurately identify the component materials and construct a bill of materials for the component device.
Having identified the raw materials required, the next step was to engage our commercial supply chain partners. In this circumstance, we needed suppliers who had appropriate change controls in place, could support smaller volumes before commercial scale-up and were equipped to handle the quality and regulatory requirements for pharmaceuticals. Working within our network of flexible materials manufacturers, we partnered with suppliers who could create custom materials while still meeting the rigorous standards required of a pharmaceutical supply chain for the bioprocessing device.
With our commercial supply chain partners identified, we then assembled a proof of concept that could be tested and compared to the off-the-shelf product. To do this, we needed to produce several units via benchtop trial equipment. This equipment lends flexibly to iterative feasibility trials where the design of tooling and the specifications of the parts are subject to changes.
Using in-house testing equipment, we were able to take critical measurements that test various aspects of the part functionality. From that feedback, we optimized the manufacturing process and refined the specification. Testing in-house allowed us to optimize adjustments and condensed the timing of the feedback loop from 8-10 days to a 2-day cycle. This approach gave us the flexibility to test several process settings quickly and cost-effectively, systematically eliminating non-optimal parameters and thereby reducing the cost and time-consuming steps in the development feedback loop. Our engineering development team then moved the product from testing, through process validation, to release the product to production in an ISO Class 7 cleanroom. Ultimately, this allowed Seres Therapeutics to move SER-109 into phase II clinical trials.