XstalBio, a Scottish company which spun out from Strathclyde and Glasgow Universities, has adopted a new approach for the formulation of proteins, nucleic acids and vaccines using protein-coated microcrystals (PCMC) - a particle engineering approach that intrigued Boehringer Ingelheim.
Apart from the potential to improve therapeutic value, Boehringer Ingelheim's interest in the PCMC technology is fueled by its desire to strengthen patent cover for new biological entities and extend product life-cycles.
According to XstalBio, the PCMC technology offers stability, excellent levels of bioactivity and very low levels of aggregation under temperature and humidity stress conditions.
The platform can be used to prepare dry powders for re-constitution or as high concentration suspensions, and make free-flowing powders for pulmonary drug delivery.
XstalBio claims their production is easily scaleable with low-capital costs compared to freeze-drying and spray-drying technologies, an assertion that will now be put to the test as the two companies jointly develop and scale up the PCMC technology for good manufacturing practice (GMP) production at pilot scale.
"Currently, with a simple lab-based continuous precipitation system, we are producing 50 g per hour, and we are looking to produce 0.5 kg per dayshift with the scaled system," XstalBio CEO Marie-Claire Parker told In-PharmaTechnologist.com.
"We don't anticipate scale-up being costly, as the PCMC process combines fluid mixing to form the PCMC particles with particle drying, and these processes are well understood by chemical engineers and widely applied in the pharma industry."
As part of the agreement, whose details were not disclosed, XstalBio will receive milestone payments and manufacturing rights to the jointly developed manufacturing process.
Making the microcystals involves the dissolution of the appropriate crystal-forming carrier together with the given biomolecule in aqueous solution.
Rapid dehydration of the two components is facilitated by addition to a water miscible organic solvent, such as ethanol, leading to the immediate formation of the PCMC, and the particles can then be dried via filtration.
Thus, PCMC are water-soluble micron-sized particles that typically consist of a core crystalline material, such as an amino acid, sugar or salt on which the therapeutic biomolecule is coated.
XstalBio says the technology is ideally suited to the delivery of proteins via the pulmonary route since it features very low water sorption and no change to particle morphology upon hydration.
Biomolecule payload is flexible and can be tuned depending on the drug potency and dosing regime required.
PCMC are therefore suitable for the delivery of both high and low potency biomolecules, and can be administered as an inhaleable dry powder or for injectables, either as a suspension or redissolution of the dry powder.