SBIR-STTR Award

In the medical device industry, silicone oil is a ubiquitous lubricant - used in the manufacture and assembly of components and also as the terminal lubricant for proper device operation. For prefilled syringes, the problem arises when micro-droplets of silicone oil migrate into the drug medium and act as a contaminant and possible reactant for the packaged drug. In the case of biological drugs, such silicone oil contamination has been implicated in protein conformational changes and aggregation. Glass syringes for prefilled applications predominantly use silicone oil as a lubricant. A silicone oil-free glass prefilled device is highly desired, but before it would be accepted, stability testing with various pharmaceutical ingredients as well as particulate and force testing after extended storage is required. We propose the development of glass prefilled syringes with the TriboGlide(r) silicone-free lubrication system based on perfluoropolyether chemistry. The effect of accelerated storage conditions on break-loose and extrusion syringe forces along with comparison of the particulate generation between standard silicone oil lubricated and TriboGlide(r) silicone-free syringes is proposed. In collaboration with the University of Colorado Denver, UCD, TriboGlide(r) syringes will be compared to standard siliconized syringes as devices for packaging of protein formulations. Protein precipitation (UV/Vis spectroscopy), loss of soluble protein (SE-HPLC), influence of adsorbed protein on syringe forces, and pH shifts in water for injection will be assessed. The proteins selected for this study are human serum albumin, human IgG, insulin, and abatecept (monoclonal antibody by Bristol Myers Squibb). In phase II, we propose to evaluate the TriboGlide(r) glass syringes for effects on secondary and tertiary structural changes of the proteins, using circular dichroism and fluorescence spectroscopy. Differential scanning calorimetry will be used to detect changes in the thermodynamic stability of the proteins after extended storage in the syringes. Finally, with the extensive experience in vaccines brought by Dr. LaToya Jones Braun from UCD, we will evaluate the stability of various vaccine formulations stored in the syringes. The medical device and pharmaceutical industries have long desired a completely silicone-free system that does not affect the stability of the packaged drug in solution. If successful, TriboGlide will be the first universal silicone-free system for glass prefilled syringes with applications extending to other medical devices.

Public Health Relevance:
Patient controlled self-therapy is a big driving factor for drugs packaged in single-dose prefilled syringe formats for treatment of chronic ailments such as rheumatoid arthritis and diabetes. Other advantages include reduced errors, ease of use, accurate dosage, elimination of preservatives in case of multi-dose vaccines and above all reduced overfill of drugs that are required for packaging in vials. Silicone oil, which serves as a lubricant for easy operation of the syringe, can contaminate the drug product and adversely interact with the sensitive drugs. The proposed TriboGlide system will be the first silicone oil-free system for glass prefilled syringes that overcomes the problems of lubricant migration and drug contamination.

Public Health Relevance Statement:
Project Narrative Patient controlled self-therapy is a big driving factor for drugs packaged in single-dose prefilled syringe formats for treatment of chronic ailments such as rheumatoid arthritis and diabetes. Other advantages include reduced errors, ease of use, accurate dosage, elimination of preservatives in case of multi-dose vaccines and above all reduced overfill of drugs that are required for packaging in vials. Silicone oil, which serves as a lubricant for easy operation of the syringe, can contaminate the drug product and adversely interact with the sensitive drugs . The proposed TriboGlide system will be the first silicone oil-free system for glass prefilled syringes that overcomes the problems of lubricant migration and drug contamination.

Project Terms:
Abatacept; Address; Adhesions; Affect; Atrophic Arthritis; Automobile Driving; Biochemistry; Biological; Blood Plasma; Calorimetry, Differential Scanning; Cells; Chemistry; Chemistry, Biological; Chronic; Circular Dichroism; Collaborations; Colorado; Development; Devices; Diabetes Mellitus; Differential Scanning Calorimetry; Differential Thermal Analysis, Calorimetric; Dose; Drivings, Automobile; Drug Contamination; Drug Formulations; Drug Industry; Drug Packaging; Drug-sensitive; Drugs; Ensure; Environment; Fluorescence Spectroscopy; Formulation; Formulations, Drug; Gamma Globulin, 7S; Generations; Glass; Grant; Hormonal; Human; Human, General; Humulin R; Hydrogen Oxide; IgG; Immunoglobulin G; Industry; Industry, Pharmaceutic; Inflammatory Arthritis; Injection of therapeutic agent; Injections; Insulin; Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine-; Insulin, Regular; Life; Liquid substance; Lubricants; Lubrication; Man (Taxonomy); Man, Modern; Marketing; Measures; Medical Device; Medication; Moab, Clinical Treatment; Monitor; Monoclonal Antibodies; Novolin R; O element; O2 element; Operation; Operative Procedures; Operative Surgical Procedures; Oxygen; Particulate; Particulate Matter; Patients; Peptides; Performance; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Industry; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Plasma; Plastics; Precipitation; Procedures; Process; Property; Property, LOINC Axis 2; Proteins; Protocol; Protocols documentation; Research; Research Design; Reticuloendothelial System, Serum, Plasma; Rheumatoid Arthritis; SBIR; SBIRS (R43/44); Science of Chemistry; Self-control as a personality trait; Serum Albumin; Serum, Plasma; Silicone Oils; Silicones; Small Business Innovation Research; Small Business Innovation Research Grant; Solutions; Spectroscopy; Spectrum Analyses; Spectrum Analysis; Study Type; Surface; Surgical; Surgical Interventions; Surgical Procedure; Syringes; System; System, LOINC Axis 4; Technology; Testing; Thermodynamic; Thermodynamics; Universities; Vaccines; Vial; Vial device; Water; base; biological systems; cross-link; crosslink; diabetes; dosage; driving; drug/agent; experience; fluid; gene product; insoluble aggregate; liquid; migration; perfluoropolyether; protein aggregate; protein aggregation; public health relevance; self control; stability testing; study design; surgery; water vapor

In the medical device industry, silicone oil is a ubiquitous lubricant used in the manufacture, assembly of medical components, and also as the terminal lubricant for proper device operation. In prefilled syringes, problems arise when micro-droplets of silicone oil migrate into the drug medium and act as a contaminant which can potentially react with the packaged drug. In the case of biological drugs, silicone oil contamination has been implicated in protein conformational changes and aggregation where even a small fraction of aggregated proteins can reduce biological activity and/or result in undesirable immunogenicity. Glass syringes for prefilled applications predominantly use silicone oil as a lubricant. A silicone-free glass prefilld device is highly desired, but acceptance of a new lubricant requires stability testing with various pharmaceutical ingredients, as well as particulate and force testing after extended storage. TriboFilm Research, Inc. proposes the development of their TriboGlide(R) silicone-free lubrication system for use in glass prefilled syringes. The TriboGlide(R) technology is based on perfluoropolyether chemistry and gas plasma immobilization to create a lubricating coating that is resistant to migration and leads to less lubricant extraction into the drug product. In Phase I TriboFilm Research demonstrated a proof-of-concept for a silicone-free glass prefilled syringe. In collaboration with the University of Colorado at Denver, the superior performance of TriboGlide(R) versus Silicone Oil was demonstrated with respect to protein aggregation and syringe extrusion forces. In Phase II, a scalable manufacturing process for producing TriboGlide(R) coated glass syringes will be developed. Initially, the TriboGlide(R) lubrication process will be optimized using a design of experiments to produce coatings with low syringe extrusion forces and low particle counts. Particles will be measured using light obscuration (HIAC) as well as microflow imaging to determine the number of particles present and distinguish between lubricant particles and aggregated proteins. With an optimized coating process, protein stability will be evaluated using various therapeutic proteins. The TriboGlide(R) lubrication system will be compared to Silicone Oil to establish superiority of the lubrication process. Protein stability will be examined using fluorescence spectroscopy, mass spectrometry, and microflow imaging. Finally, a pilot scale lubrication machine will be built to demonstrate the scale-up and manufacturability of this process. The medical device and pharmaceutical industries have long desired a completely silicone-free syringe system that does not affect the stability of the packaged drug in solution. If successful, TriboGlide(R) will be the first universal silicone-free system for glass prefilled syringes with applications extending to other fields.

Public Health Relevance:
Patient controlled self-therapy is an enticing factor for packaging drugs in single-dose prefilled syringe formats which treat chronic ailments, such as rheumatoid arthritis, multiple sclerosis, and diabetes. Other advantages of prefilled syringes include reduction in medical errors, ease of use, accurate dosage, elimination of preservatives, and reduction in the amount of drug overfill required when pharmaceutical products are packaged in vials or ampoules. Silicone oil, which serves as a lubricant for easy operation of the syringe, can contaminate the drug product and adversely interact with sensitive pharmaceutical products. The proposed TriboGlide(R) system will be the first silicone-free system for glass prefilled syringes that overcomes the problems of lubricant migration and drug contamination.