SBIR-STTR Award

Improved Silicone Lubrication to Reduce Sub-Visible Particles in Parenteral Containers
Award last edited on: 5/15/2020

Sponsored Program
SBIR
Awarding Agency
NIH : NEI
Total Award Amount
$1,753,084
Award Phase
2
Solicitation Topic Code
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Principal Investigator
Jackson D Thornton

Company Information

Tribofilm Research Inc

625 Hutton Street Suite 105
Raleigh, NC 27606
   (919) 838-2844
   info@tribofilmresearch.com
   www.tribofilmresearchinc.com
Location: Single
Congr. District: 04
County: Wake

Phase I

Contract Number: 1R43EY024461-01A1
Start Date: 2/2/2015    Completed: 1/31/2016
Phase I year
2015
Phase I Amount
$222,626
In the medical device industry, silicone oil is a ubiquitous lubricant used in the manufacture and 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. These particles and conformational changes are especially troubling in ophthalmic applications where the use of intravitreal injections for the treatment of retinal disorders has become a common procedure. Silicone oil droplets have been reported to remain in the eye long after the intravitreal injection, causing several complications. Syringes for prefilled applications predominantly use silicone oil as a lubricant because of its inert and lubricious properties along with its long-term stability data and well known toxicology profile. However, silicone oil droplets in drug formulations pose a significant problem for many drugs where a prefilled format is preferred. Therefore, an advanced silicone lubrication technology for prefilled devices is highly desired. TriboFilm Research, Inc. proposes the development of their advanced silicone lubrication system, TriboLink", for use in prefilled syringes. The TriboLink" technology is based on crosslinking a silicone oil lubricant using an inert gas plasma technology to create a lubricating coating that is resistant to migration and leads to less lubricant extractin into the drug product. In Phase I, TriboFilm Research will optimize the TriboLink" coating and provide syringes with similar force profiles and dramatically reduced particle loads compared to standard siliconized syringes. In collaboration with Professor LaToya Jones Braun, TriboLink" will be analyzed in a variety of commonly used excipients and model protein formulations to establish the feasibility of using this advanced coating in parenteral containers. The TriboLink" 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 and microflow imaging to determine the number of particles present and distinguish between different types of particles. With an optimized coating process, longer term stability data will be accumulated to establish the superiority of the TriboLink" lubrication process compared to standard silicone oil. Activity assays with a model protein will give insight into the effects that the reduced particulate burden, observed in TriboLink" syringes, has on the efficacy of a protein molecule. In Phase II, therapeutic protein stability will be examined using fluorescence spectroscopy, mass spectrometry, and microflow imaging. Toxicity and function of therapeutic proteins stored in TriboLink" lubricated syringes will also be examined using in vitro (cell-based) and in vivo (rodent) models. The medical device and pharmaceutical industries have long desired an advanced silicone lubrication technology for prefilled syringes that does not affect the stability of the packaged drug in solution. If successful, TriboLink" will provide te advanced lubrication needed to package sensitive biopharmaceuticals in prefilled syringes.

Public Health Relevance Statement:


Public Health Relevance:
Ease of use, reduction in drug wastage, minimization of medical dosing errors, along with many other enticing factors provide compelling reasons for packaging drugs in single-dose prefilled syringe formats. 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. Contamination of drug products with lubricant molecules is especially detrimental in ophthalmic medicants where the use of intravitreal injections of monoclonal antibodies for the treatment of retinal disorders has become a common procedure. The proposed TriboLink" coating system provides an advanced lubrication alternative that overcomes the problems of lubricant migration and drug contamination in intravitreal injections and a broad range of other parenteral applications.

Project Terms:
Address; Affect; base; Biological; Biological Assay; Biological Products; Cells; Collaborations; Comparative Study; crosslink; Data; density; design; Development; Devices; Dose; Drug Contamination; Drug Delivery Systems; Drug Formulations; Drug Industry; Drug Packaging; Drug Storage; Excipients; Eye; Fluorescence Spectroscopy; Gases; Generations; Glass; Goals; Image; Immobilization; immunogenicity; improved; In Vitro; in vivo; Industry; Injectable; innovation; insight; intravitreal injection; Life; Light; Link; Lubricants; Lubrication; Mass Spectrum Analysis; Measures; Medical; Medical Device; migration; Modeling; Monoclonal Antibodies; Movement; Noble Gases; operation; particle; Particulate; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plasma; Plastics; Procedures; Process; process optimization; professor; Property; protein aggregate; protein aggregation; protein profiling; Proteins; public health relevance; Reporting; Research; research study; Resistance; Retinal Diseases; Rodent Model; Rods (Retina); Rubber; Safety; Silicone Oils; Silicones; Solutions; stability testing; Surface; Syringes; System; Technology; Testing; therapeutic protein; Thick; Time; Toxic effect; Toxicology

Phase II

Contract Number: 2R44EY024461-02A1
Start Date: 2/2/2015    Completed: 7/31/2020
Phase II year
2018
(last award dollars: 2019)
Phase II Amount
$1,530,458

In the medical device industry, silicone oil is a ubiquitous lubricant used in the manufacture and 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 undesired immunogenicity. These particles and conformational changes are especially troubling in ophthalmic applications where the use of intravitreal injections for the treatment of retinal disorders has become a common procedure. Silicone oil droplets have been reported to remain in the eye long after the intravitreal injection, causing several patient related complications such as “visual floaters”. Syringes for prefilled applications predominantly use silicone oil as a lubricant because of its inert and lubricious properties, along with its long-term stability data and well known toxicology profile. However, silicone oil droplets in drug formulations pose a significant problem for many drugs where the prefilled format is preferred. Therefore, an advanced silicone lubrication technology for prefilled devices is highly desired. TriboFilm Research, Inc. proposes the development of our advanced silicone lubrication system, TriboLink-Si™, for use in prefilled syringes. The TriboLink-Si™ technology is based on crosslinking the medical grade silicone oil lubricant using an inert, atmospheric gas plasma technology 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 optimized the TriboLink-Si™ coating system to provide syringes with similar force profiles and dramatically reduced particle loads compared to standard siliconized syringes. In collaboration with Professor LaToya Jones Braun, TriboLink-Si™ was analyzed in a variety of commonly used excipients and model protein formulations to establish the feasibility of using this advanced coating in parenteral containers. The TriboLink-Si™ lubricant proved to be comparable to silicone oil in terms of plunger force performance and the stability of model proteins, while reducing the particulate contamination by up to two orders of magnitude and meeting the USP <789> requirements for particulates in ophthalmic containers. Phase II will build on the Phase I findings to prove the commercial viability of the TriboLink-Si™ technology from a manufacturing standpoint. The TriboLink-Si™ coating parameters will be optimized using scalable processing equipment to achieve extremely low particulate levels and acceptable plunger forces. The compatibility of the TriboLink-Si™ coating with respect to general formulation parameters, protein stability, and aggregation will be examined using a pharmaceutically relevant therapeutic protein to build further customer confidence and market adoption. Additionally, an extraction study will be performed on TriboLink-Si™ coated syringes to evaluate the toxicological safety of the coating while generating data for use in regulatory filings. This project will culminate with the production of a pilot coating machine to demonstrate how all TriboLink-Si™ coating parameters can be integrated into a continuous manufacturing process. The pilot machine will document the know-how for full-scale manufacturing that can be transferred to potential licensees, while also producing TriboLink-Si™ coated syringes that can be provided to customers for evaluation. The medical device and pharmaceutical industries have long desired an advanced silicone lubrication technology for prefilled syringes that does not affect the stability of the packaged drug in solution. If successful, TriboLink-Si™ will provide the advanced lubrication needed to package sensitive biopharmaceuticals in prefilled syringes.

Public Health Relevance Statement:
PROJECT NARRATIVE Ease of use, reduction in drug wastage, minimization of medical dosing errors, along with many other enticing factors provide compelling reasons for packaging drugs in single-dose prefilled syringe formats. 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. Contamination of drug products with lubricant particles is especially detrimental in ophthalmic drugs where the use of intravitreal injections of monoclonal antibodies for the treatment of retinal disorders has become a common procedure. Patient complaints, such as sustained increases in intraocular pressure and silicone oil ‘floaters’ in the field of vision, are prevalent after intraocular injection of anti-VEGF compounds for the treatment of macular degeneration. The proposed TriboLink-Si™ coating system provides an advanced lubrication alternative that overcomes the problems of lubricant migration and drug contamination in intravitreal injections and a broad range of other parenteral applications.

Project Terms:
Address; Adoption; Antibody Therapy; base; bevacizumab; Biological; Biological Products; Collaborations; crosslink; Data; Development; Devices; Dose; Drug Contamination; Drug Delivery Systems; Drug Formulations; Drug Industry; Drug Packaging; Drug Storage; Drug usage; Equipment; Evaluation; Excipients; Eye; Fluorescence Spectroscopy; Formulation; Gases; Glass; High Pressure Liquid Chromatography; Image; Immobilization; immunogenicity; improved; Industry; Injectable; Injections; innovation; Intellectual Property; intravitreal injection; Licensing; Life; Link; Lubricants; Lubrication; Macular degeneration; Manufacturer Name; manufacturing process; Medical; Medical Device; meetings; migration; Modeling; Molecular Conformation; Monitor; Monoclonal Antibodies; Movement; operation; ophthalmic drug; Outcome; particle; Particulate; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physiologic Intraocular Pressure; Plasma; Procedures; Process; process optimization; Production; professor; Property; protein aggregate; protein aggregation; Protein Conformation; Proteins; Protocols documentation; Reporting; Research; Resistance; Retinal Diseases; Rubber; S Phase; Safety; scale up; Silicon; Silicone Oils; Silicones; Speed; Surface; Syringes; System; Techniques; Technology; Testing; therapeutic protein; Time; Toxicology; Vision; Visual; vitreous floater