Drop-on-Demand Pharmaceutical Manufacturing Improves Drug Dosage
Researchers at the NSF-funded Engineering Research Center (ERC) for Structured Organic Particulate Systems (C-SOPS) based at Rutgers University, in partnership with New Jersey Institute of Technology, Purdue University, and the University of Puerto Rico-Mayaguez, have established a Drop on Demand Pharmaceutical Manufacturing platform that exploits liquid phase processing for custom drug dosage production.
Drop on demand pharmaceutical manufacturing enables the production of highly active, low-dose drug products whose manufacture using conventional powder-based processes is very challenging. When further combined with predictive analytics, drop on demand manufacturing has the potential to dramatically improve drug treatments for patients. The technology provides a platform for early clinical trial dosage manufacture as well as for individualized medicine applications. An automated bench-top version of the C-SOPS platform further facilitates point-of-use delivery of drug dosages that may support a paradigm shift in the pharmaceutical product supply chain away from distribution-based models to custom production on demand.
There are many drug products, especially in oncology, which exhibit high inter-patient therapeutic variability; the dosage regimens of these drug products need to be tuned carefully to the individual patient. This is generally true for geriatric and pediatric patients and particularly for drugs with narrow therapeutic windows. But the tuning of drug administration has until now been performed only empirically: the doctor prescribes the recommended baseline dosage regimen and then adjusts it higher or lower over the next two to six months based on tradeoffs between therapeutic benefit and side effects. With this approach, the most beneficial therapeutic range of the drug treatment takes some time to achieve for the individual patient and can be problematic, especially for cancer patients for whom quality of life is important during the patient’s remaining lifespan.
Members of the Purdue team and C-SOPS are researching the use of patient-specific data combined with population-based pharmacometric models to rapidly optimize individual patient dosing regimens. A doctor can use this methodology to determine and prescribe customized dosage regimens in an evidence-based manner to arrive at optimized treatment much sooner. A key missing piece has been the ability to readily and conveniently make such customized drug products for individual patients on demand.
The Drop on Demand Pharmaceutical Manufacturing platform established by C-SOPS exploits liquid phase processing as a means of avoiding the complexities associated with the powder and granule handling operations conventionally used to manufacture solid oral products. The process accommodates a variety of fluid phase formulations as well as alternative substrates onto which the drop is deposited. This mode makes it possible to transition away from the manufacture of large quantities of identical product to the manufacture of small lots of product with more flexible drug substance loading. One version of the platform has also been configured as a compact, self-contained, automated bench-top unit suitable for deployment directly in hospital dispensaries, clinics, and compounding pharmacies for point-of-use delivery of dosages. The role of the pharmaceutical manufacturer with this system would shift to providing a formulation intermediate, packaged in pouch or cassette form, which would serve as the “ready made” input to the Drop on Demand unit.
The C-SOPS Drop on Demand platform has received attention and support from several sources, including a two-year grant from the Indiana Next Generation Manufacturing Competitiveness (IN MaC) program, a state-funded initiative led by Purdue University. PhD student support has also been obtained under a recent multi-year Department of Education, Graduate Assistance in Areas of National Needs Grant. The drop on demand facility is part of a recently awarded Defense Advanced Research Projects Agency (DARPA) project, “Analytic-directed Multi-scale synthesis system” for a flexible and small scale, end-to-end small molecule manufacturing platform. Targeted projects are under negotiation with two commercial companies.
