Pharmaceuticals in general, and biopharmaceuticals specifically, often are best formulated as crystals. The crystalline state is the most stable of matter, allows a high-concentration, low-viscosity parenteral formulation, and facilitates alternate routes of administration. There is a requirement that the crystals be small, below 100 or 50 micrometers, and uniform (the same size within a few percent). The problem: most recombinant protein biopharmaceuticals do not crystallize uniformly. A solution to this problem has been discovered in on-orbit experiments, which produced size coefficients of variation below ~8%. Manufacturers are creating demand for on-orbit testing of uniform crystallization protocols, but suitable hardware and ISS research opportunities are inadequate.
Techshot proposes a business plan utilizing its versatile fleet of flight hardware, and flexible flight opportunities. These will be made available to industrial and institutional customers seeking improvements/refinements in product purification, formulation and/or delivery. Hardware and flight plans will be offered in which factorial and/or real-time photography experiments can be performed. In the Phase I Techshot (1) adapted four different existing hardware modules for this application, (2) tested them in model protein crystallization experiments in the lab, and (3) performed mathematical modeling for a ground-based crystallization reactor with adjustable parameters for approximating the relevant low-gravity physics. In Phase II, Techshot will (a) define and document an experiment design for a flight demonstration, (b) design and integrate hardware for flight readiness, (c) prepare and execute an ISS use plan, (d) and design and construct a flight-like EDU for an innovative dynamic microscope cassette. The intended outcome is a business paradigm for hastening the availability of stable biopharmaceuticals with favorable options for delivery.
NASA has solicited research topics in the area of pharmaceutical production on spacecraft making deep space voyages to solve problems of availability and stowage. Such projects include short-cut production of biopharmaceuticals by stored microbial cells but also need to include short-cut purification schemes. A clever crystallization plan, Techshot’s proposed innovation, could eliminate several traditional (chromatography, extraction, etc.) downstream steps toward such on-orbit formulation.
Companies that succeed in producing a crystalline product will save enormously due to longer ambient stability, lower delivery volume and novel routes of administration, whether it is an approved pharmaceutical or an emerging therapeutic. Patients and insurers likewise benefit. Therefore, Techshot intends to offer for hire a variety of crystallization capabilities in Earth and space-based labs.