SBIR-STTR Award

Improper or incomplete sterilization of manufacturing facilities is a major cause of pharmaceutical product recalls. The economic and societal impact of these recalls is significant and difficult to quantify. Many pharmaceutical companies use vapor phase hydrogen peroxide (VPHP) to decontaminate and sterilize production facilities, including barrier isolators. A reliable instrument with a large dynamic range and high sensitivity for monitoring VPHP during barrier isolator decontamination would be invaluable to manufacturers to improve product sterility assurance and quality. Physical Sciences Inc. (PSI) proposes to develop a commercial prototype sensor that will facilitate rapid and reliable development of decontamination cycles, equipment qualification and continuous monitoring of barrier isolators, enabling significant improvements to sterility assurance, drug quality and availability. The instrument will measure VPHP and water vapor using tunable diode laser absorption spectroscopy (TDLAS) with novel quantum cascade lasers and cavity enhanced spectroscopy. VPHP is a commonly used decontamination agent which must be carefully monitored to ensure sterility assurance and must be removed to very low levels prior to pharmaceutical filling operations due to its deleterious effects on pharmaceutical products. The sensor will be used to study vapor phase decontamination agent flow within an isolator and the effects of hydrogen peroxide destruction, adsorption and desorption for materials commonly used to fabricate isolators and in pharmaceutical fill/finish packaging operations. This Small Business Innovation Research Phase I / Phase II project addresses an immediate need for real-time measurement of trace amounts of VPHP in pharmaceutical filling and packaging systems. Barrier isolators are finding increasing use in the production and packaging of new biologic drug products. The instrument will enable production of a critical database of information for use in the pharmaceutical industry. The specific program innovation is the use of new quantum cascade laser technology with cavity enhanced spectroscopy to enable ultra-sensitive detection of critical decontamination parameters throughout the cycle and allow investigation of real-world fill/finish parameters (such as packaging material uptake of VPHP). Additional applications of the sensor include decontamination monitoring of lyophilizers and VPHP destruction of Meticillin-Resistant Staphylococcus Aureus (MRSA) contamination in hospital wards. No commercially available sensor can provide continuous VPHP measurements throughout the entire decontamination and purge cycles in manufacturing scale operations. The proposed sensor will provide this capability, allowing real-time process monitoring and control. This development targets the USFDA process analytical technology (PAT) initiative for building quality into pharmaceutical products, increasing the availability of critical drug products like vaccines and reducing the costs of prescription drug products.

Public Health Relevance:
The proposed research will produce a commercial VPHP sensor with the potential to improve drug availability through improved manufacturing and save millions of dollars in manufacturing costs by enabling more rapid development of decontamination cycles and accelerating FDA approval for novel drugs. The sensor will be used to monitor the decontamination process in pharmaceutical manufacturing and allow fewer opportunities for microbial contamination during processing operations. The resulting improved drug quality, efficacy, availability, and lower manufacturing cost will be directly beneficial to the general public.

Thesaurus Terms:
Absorption;Address;Adsorption;Algorithms;Analysis, Data;Biotechnology;Calibration;Computer Programs;Computer Software;Coupling;Data Analyses;Data Banks;Data Bases;Databank, Electronic;Databanks;Database, Electronic;Databases;Decontaminant;Decontamination;Decontamination Agent;Detection;Development;Devices;Documentation;Drug Industry;Drugs;Economics;Electromagnetic, Laser;Electronics;Ensure;Equipment;Evaluation;Experimental Models;Experimental Models, Other;Fda;Food And Drug Administration;Food And Drug Administration (U.S.);General Population;General Public;Goals;Government;H2o2;Hosp;Hospitals;Hydrogen Peroxide;Hydrogen Peroxide (H2o2);Hydroperoxide;Individual;Industry, Pharmaceutic;Instruction;Investigation;Laboratories;Lasers;Length;Light;Manuals;Manufacturer;Manufacturer Name;Marketing;Measurement;Measures;Medication;Moab, Clinical Treatment;Modeling;Models, Experimental;Monitor;Monoclonal Antibodies;Optics;Performance;Persons;Pharmaceutic Preparations;Pharmaceutical Agent;Pharmaceutical Industry;Pharmaceutical Preparations;Pharmaceuticals;Pharmacologic Substance;Pharmacological Substance;Phase;Photoradiation;Process;Process Of Absorption;Production;Programs (Pt);Programs [publication Type];Proteins;Radiation, Laser;Research;Resistance;S. Aureus;S.Aureus;Sbir;Sbirs (R43/44);Small Business Innovation Research;Small Business Innovation Research Grant;Software;Source;Spectroscopy;Spectrum Analyses;Spectrum Analysis;Staphylococcus Aureus;Sterility;Sterilization;System;System, Loinc Axis 4;Technology;Testing;Time;Usfda;United States Food And Drug Administration;Vaccines;Validation;Variant;Variation;Absorption;Clinical Data Repository;Clinical Data Warehouse;Commercialization;Computer Program /Software;Computer Program/Software;Cost;Data Repository;Design;Designing;Detector;Drug /Agent;Drug Quality;Drug/Agent;Gene Product;Improved;Innovate;Innovation;Innovative;Instrument;Interest;Manufacturing Facility;Manufacturing Process;Meetings;Microbial;Model;Monoclonal Antibody;Novel;Operation;Packaging Material;Physical Science;Prescription Drug Costs;Programs;Prototype;Purge;Purging;Quality Assurance;Quantum;Relational Database;Resistant;Sensor;Sterile;Uptake;Vapor;Ward;Water Vapor

Improper or incomplete sterilization of manufacturing facilities is a major cause of pharmaceutical product recalls. The economic and societal impact of these recalls is significant and difficult to quantify. Many pharmaceutical companies use vapor phase hydrogen peroxide (VPHP) to decontaminate and sterilize production facilities, including barrier isolators. A reliable instrument with a large dynamic range and high sensitivity for monitoring VPHP during barrier isolator decontamination would be invaluable to manufacturers to improve product sterility assurance and quality. Physical Sciences Inc. (PSI) proposes to develop a commercial prototype sensor that will facilitate rapid and reliable development of decontamination cycles, equipment qualification and continuous monitoring of barrier isolators, enabling significant improvements to sterility assurance, drug quality and availability. The instrument will measure VPHP and water vapor using tunable diode laser absorption spectroscopy (TDLAS) with novel quantum cascade lasers and cavity enhanced spectroscopy. VPHP is a commonly used decontamination agent which must be carefully monitored to ensure sterility assurance and must be removed to very low levels prior to pharmaceutical filling operations due to its deleterious effects on pharmaceutical products. The sensor will be used to study vapor phase decontamination agent flow within an isolator and the effects of hydrogen peroxide destruction, adsorption and desorption for materials commonly used to fabricate isolators and in pharmaceutical fill/finish packaging operations. This Small Business Innovation Research Phase I / Phase II project addresses an immediate need for real-time measurement of trace amounts of VPHP in pharmaceutical filling and packaging systems. Barrier isolators are finding increasing use in the production and packaging of new biologic drug products. The instrument will enable production of a critical database of information for use in the pharmaceutical industry. The specific program innovation is the use of new quantum cascade laser technology with cavity enhanced spectroscopy to enable ultra-sensitive detection of critical decontamination parameters throughout the cycle and allow investigation of real-world fill/finish parameters (such as packaging material uptake of VPHP). Additional applications of the sensor include decontamination monitoring of lyophilizers and VPHP destruction of Meticillin-Resistant Staphylococcus Aureus (MRSA) contamination in hospital wards. No commercially available sensor can provide continuous VPHP measurements throughout the entire decontamination and purge cycles in manufacturing scale operations. The proposed sensor will provide this capability, allowing real-time process monitoring and control. This development targets the USFDA process analytical technology (PAT) initiative for building quality into pharmaceutical products, increasing the availability of critical drug products like vaccines and reducing the costs of prescription drug products.