ABOUT US

LIGHTHOUSE offers complete solutions for headspace Oxygen Monitoring, Container Closure Integrity Testing, Moisture Determination and Microbial Contamination inspection of media vials. Our solutions include feasibility studies, process and packaging studies, method development, method validation protocols, automated or benchtop lease platforms, on-site trouble shooting and support.

Rapid, nondestructive, laser-based headspace analysis is suitable for applications specific to the sterile pharmaceutical industry. It is a useful analytical tool to generate statistical process and product data in all stages of the product life cycle, from Development to Manufacturing and Quality Control. LIGHTHOUSE Instruments is the leading provider and manufacturer of headspace analysis platforms and measurement services.

Contact us for a free demo, feasibility study, or other information.

SOLUTIONS AND SERVICES

What is your Container Closure Integrity (CCI) strategy? Recent regulatory revisions have put emphasis on appropriately designed CCI studies and robust method validation. LIGHTHOUSE offers complete solutions for CCI testing throughout the product life cycle, from Development to Manufacturing and Quality Control. 

The need to monitor headspace oxygen levels in parenteral containers arises from the requirement to ensure the stability and potency of oxygen-sensitive product. LIGHTHOUSE offers complete solutions for (in-process control) oxygen monitoring of oxygen-senstive formulations, from Development to Manufacturing and Quality Control. 

Residual product moisture content is a critical parameter when considering the stability and shelf life of lyophilized pharmaceutical product, sterile powders, or solid dosage product. Lighthouse offers complete solution for moisture determination of dry product.

Media Fill Inspection in the pharmaceutical industry has long been based on growth media culture methods. The general approach to media fill inspection is to incubate media filled vials for 14 days and then determine potential contamination with a visual inspection of the media sample. Over the last decade a number of Rapid Microbial Methods based on various analytical techniques have been implemented. These provide quicker, more sensitive, accurate, and reproducible test results when compared with conventional, growth-based methods. Recently, it has been demonstrated that laser-based headspace provides yet another alternative approach for detecting microbial contamination in sterile pharmaceutical product. 

Rapid, nondestructive, laser-based headspace analysis enables determination of headspace Oxygen, Moisture/Pressure, Carbon Dioxide and Water Activity. Using laser absorption, light from a near-infrared laser is tuned to match an internal absorption frequency of various molecules and passed through a glass sample container in the headspace above the product. The amount of laser light absorbed is proportional to the concentration of the specified gas in the headspace.

The PULSAR line of automated headspace inspection machines provides a reliable, compact, and flexible platform for 100% inspection of headspace oxygen, moisture, pressure, and carbon dioxide levels in sealed parenteral containers. Automated nondestructive, laser-based, headspace inspection enables robust process studies in development as well as 100% batch inspection to guarantee the quality of finished product. 

WEBINARS

The headspace gas composition in parenteral product containers is critical for sterile oxygen-sensitive drug product. This webinar reviews how oxygen levels in finished parenteral drug containers can be determined and controlled throughout the product life cycle by using laser-based headspace analysis. From development to manufacturing and QC, the optimization and control of oxygen levels can play an important role in achieving optimal shelf life and protecting drug efficacy.

Recent regulatory guidance has triggered changes in industry best practices in the area of container closure integrity (CCI) testing. A more science-based holistic approach that includes robust design & qualification of the process and the implementation of appropriate process controls is required. This webinar will describe a framework to enable such a holistic approach to CCI that assures both the primary packaging and the process contribute to good CCI of sterile injectable vial product.

When working on live viral vaccines, gene therapies or product that contains active cells cold storage is often required to maintain stability and/or activity. Deep cold storage, at dry ice (-80°C) or even cryogenic (-196 °C) temperatures, poses a significant challenge to packaging components and can result in CCI failures. Watch this webinar for a detailed presentation on this topic.

Water activity determination is increasingly being used in the pharmaceutical industry as evidenced by a newly drafted USP <922> Chapter for Water Activity measurement. This webcast presents how a water activity measurement can be implemented to give insight into the impact of moisture on critical product quality attributes including stability, dissolution rate, and physical properties of tablets, pills, capsules, and other solid pharmaceutical material.

Imagine a blue dye test, but replace the dye with a tracer gas. Headspace Gas Ingress Testing is a robust detection method of critical leaks. It is a rapid, non-destructive, analytical measurement and can be scientifically validated. Are you considering to upgrade your blue dye test, and do you want to learn more about this approach? Watch this webinar.

This webinar describes the use of positive controls as an important element of CCI studies designed to validate packaging components for CCI or to qualify processes for producing good CCI.

This webinar presents how to design and conduct studies to assess the total oxygen permeation rate of your pre-filled syringes, and how to determine if the permeation is primarily through the plunger or through the tip.  Protecting oxygen-sensitive formulations during filling will also be discussed. 

This webinar describes how non-destructive headspace moisture analysis can be used for characterizing batch moisture distributions, for lyo cycle development and optimization, and for freeze dryer moisture mapping and validation.

This webinar will review how oxygen levels in finished parenteral drug containers can be determined and controlled throughout the product life cycle by using laser-based headspace analysis.

Recent regulatory revisions have also put emphasis on robust method validation for container closure Integrity test methods. This webinar covers approaches that can be used for method development for CCI testing in all phases of the product life cycle.

The new language in EU Annex 1 will likely have a significant impact on your CCI testing practices. In this webinar CCI testing strategies and the proposed revisions to EU Annex 1 are discussed.

Increased regulatory scrutiny and exciting new analytical technologies have altered the landscape of container closure integrity testing. In order to provide guidance to this new environment the US Pharmacopoeia revised Chapter <1207> Sterile Product Package Integrity.  View this webinar recording to learn about the new guidelines and how they will impact your approach to sterile product package integrity.

APPLICATION NOTES

Headspace moisture analysis is a rapid nondestructive analytical method that addresses the limitations of traditional methods used for residual moisture determination. This article describes how rapid non-destructive headspace moisture determination enables the generation of insightful data for product life cycle activities related to lyo cycle optimization, lyo chamber moisture mapping, freeze dryer qualification, formulation development and product stability studies.

If CCI is lost during -80°C storage, non-sterile, cold, dense gas from the storage environment (i.e. air from a -80°C freezer or carbon dioxide from dry ice) can leak into the stored vial. It is therefore critical that robust development work is done to understand the CCI performance of any primary packaging components used for product needing deep cold storage and transport temperatures.

Pharmaceutical formulations, especially delicate large molecule biopharmaceuticals, may have some level of oxygen-sensitivity leading to degradation of the active pharmaceutical ingredient. Laser-based headspace oxygen analysis enables accurate, efficient determination of oxygen consumption curves. Accurate measurement of the oxidation rate supports the determination of headspace oxygen specifications and end-of-shelf life stability.

Laser-based headspace provides yet another alternative approach for detecting microbial contamination in sterile pharmaceutical product allows for quicker, more sensitive, accurate, and reproducible test results when compared with conventional, growth-based methods.

This application note describes how laser-based headspace analysis is used for the rapid non-destructive determination of headspace oxygen levels in pre-filled syringes. Data is presented demonstrating two major applications of this technique: 1) headspace oxygen monitoring on a pre-filled syringe line filling oxygen-sensitive product, and 2) container closure testing of pre-filled syringes.

This app note describes the application of the PULSAR inspection platform to perform 100% headspace oxygen monitoring during the filling of oxygen-sensitive formulations, 100% container closure inspection of suspect batches, moisture inspection of freeze dried product, and automated media fill inspection.

Large molecule biopharmaceuticals can be prone to oxidation and to prevent this from occurring, the headspace is often purged with an inert gas during filling to ensure a longer shelf life.

Using a high sensitivity detection technique known as Frequency Modulation Spectroscopy (FMS), LIGHTHOUSE rapid non-destructive headspace oxygen inspection can help streamline the monitoring of purge performance on the filling line. This paper demonstrates the correlation of the FMS rapid non-destructive technique for analyzing headspace oxygen levels with the most commonly used conventional destructive techniques for headspace oxygen inspection.

Non-destructive headspace analysis is a powerful method for monitoring container closure integrity in finished vials of freeze dried product and for building quality into the manufacturing operation.

This application note details FDA released guidance titled “Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products."

CONTACT INFORMATION

Lighthouse Instruments

2030 Avon Court

Charlottesville, VA 22902

UNITED STATES

Phone: 434-293-3081

Contact: Sales

FEATURED APPLICATION NOTES

FEATURED CASE STUDIES

  • A new biological product, in pre-filled glass syringes, had demonstrated oxygen sensitivity in stability studies. Therefore, the headspace was purged with nitrogen during filling, and the client wanted to validate the batch production process and assess the nitrogen purge efficiency. In this study we demonstrate by performing a 100% inspection on the engineering batches using non-destructive headspace oxygen analysis you could gather the data needed before a commercial launch.

  • Rapid non-destructive headspace moisture analysis from LIGHTHOUSE enables fast moisture determination of statistical numbers of lyo samples.

  • How non-destructive headspace analysis information can be critical for QC groups performing stability studies, or for packaging development groups responsible for choosing the optimal packaging.

  • A vaccine-focused biotechnology company needed assistance to investigate a phenomenon observed in liquid vaccine product stored at -80°C. During QC testing, a number of vials were found to have an overpressure. This phenomenon represented a serious safety risk and they needed to identify the root cause.

WHITE PAPERS

  • To ensure patient safety, good container closure integrity (CCI) is of great importance for all sterile injectable products. Recent regulatory guidance has made clear that there is no ‘gold standard’ for CCI testing. As a CCI test method, headspace analysis is based on detecting changes in the headspace gas composition that result from gas ingress through a leak. Non-destructive headspace analysis, using laser-based spectroscopy, can be used to directly quantify the gas concentration inside a sealed parenteral package. It can be applied to a range of product configurations, and formulations, and has historically been used for detecting leak defects in modified headspace product.

  • Laser-based headspace analysis is a deterministic CCI test technique described in USP <1207> that measures gas which ingresses into a container through a leak defect. More recently, general headspace CCI test methods have been developed that both resemble and improve upon the traditional blue dye ingress test .This article describes the headspace gas ingress testing approach which is increasingly being implemented to replace blue dye ingress as a general CCI test method.

  • Recent regulatory guidance has triggered changes in industry best practices in the area of container closure integrity testing (CCIT). However, assuring good CCI of sterile injectable product goes beyond CCI testing. A more science-based holistic approach that includes robust design & qualification of the process and the implementation of appropriate process controls is required. This article describes a framework enabling such a holistic approach to CCI that assures both the primary packaging and the process contribute to good CCI of sterile injectable vial product.

  • Non-sterile pharmaceutical products are subject to microbiological examination prior to release and during stability testing. While the tests described in these chapters cannot be eliminated from protocol completely, USP <1112>, Application of Water Activity Determination to Nonsterile Pharmaceutical Products, suggests that water activity determination can be used to reduce the need for frequent microbial limit testing and screening.

  • The draft of the new general chapter USP<922> states that water activity determination can be used to assess the level of protection provided by primary packaging for an oral solid dosage (OSD) product over its entire shelf life. Water activity (Aw) measurements provide unique information, and therefore expand and complement the data collected from USP<670> Auxiliary Packing Components and USP<671> Containers - Performance Testing.

  • The newly drafted USP <922> General Chapter describes the specific methods that pharmaceutical companies will use to calibrate, qualify, and use water activity instruments in their testing protocols. USP <922> includes a description of Tunable Diode Laser Absorption Spectroscopy (TDLAS) measurements and states that it is the only method to reliably and accurately measure water activity when the sample contains other volatile compounds. The Lighthouse FMS-Water Activity Analyzer uses TDLAS to non-destructively and directly measure the water activity non-invasively of samples in a sealed glass vial.

  • Generally, a variety of specific tests are necessary to evaluate the chemical and physical characteristics of an oral solid dosage (OSD) throughout the product life cycle. This article will present three case studies to show that direct water activity measurements can determine the impact of moisture on potency and dissolution.

  • Controlling water content in oral solid dosage (OSD) products, and dry pharmaceutical products in general, is essential to maintaining efficacy and safety. Measuring the water activity at multiple time points during the product life-cycle will correlate to changes in critical quality attributes such as degradation of the active ingredient, changes in the dissolution or disintegration rate, and changes in physical properties such as hardness or friability.

  • This article summarizes the current state of container closure integrity testing in the pharmaceutical and biopharmaceutical industries and outlines possible approaches for developing a CCIT strategy.

  • With no ‘gold standard’ container closure integrity (CCI) test, learn how to creating a toobox of CCI testing methods will allow you to be best prepared for every situation.

  • To ensure patient safety, pharmaceutical products must be kept properly packaged prior to use. Proper packaging prevents ingress of contaminants. Unfortunately, these contaminants are not always visible to the human eye and container closure integrity (CCI) tests must be performed to ensure the package has not been compromised. One way to test for proper CCI is to analyze the headspace gas composition of the vial.

  • Rapid water vapor determination with an optical method could replace the slow destructive traditional methods for the moisture analysis of freeze-dried product. A description of industry applications of headspace moisture analysis including freeze drying cycle optimization, lyo chamber moisture distribution mapping, and 100% moisture inspection of commercial freeze-dried product.

  • Gain insight into the process, ensure the maintenance of sterility for finished product after capping, and meet current regulatory guidance using laser-based headspace inspection.

CASE STUDIES

  • A new biological product, in pre-filled glass syringes, had demonstrated oxygen sensitivity in stability studies. Therefore, the headspace was purged with nitrogen during filling, and the client wanted to validate the batch production process and assess the nitrogen purge efficiency. In this study we demonstrate by performing a 100% inspection on the engineering batches using non-destructive headspace oxygen analysis you could gather the data needed before a commercial launch.

  • The accurate determination of oxygen concentration as a critical quality parameter for oxygen-sensitive products is important across the product life cycle activities. Traditional methods for determining headspace oxygen levels in parenteral containers, such as electrochemical methods or gas chromatography, are slow and destructive. This article describes several case studies comparing non-destructive laser-based oxygen headspace analysis with electrochemical oxygen analysis and gas chromatography.

  • The increased implementation of deterministic analytical methods for container closure integrity (CCI) testing has enabled deeper insight into the performance of primary packaging with respect to CCI. However, ensuring good CCI of sterile injectable product goes beyond CCI testing during the product life cycle. This case study describes how packaging development and process study data of a pharmaceutical vial product requiring deep cold storage can be combined in a holistic approach.

  • A vaccine production facility needed to replace an old freeze dryer in an existing facility during running operations. Activity involved a scale up of freeze-drying capacity from 14 m2 to 28 m2. With the application of non-destructive headspace moisture analysis small scale proof of concept studies were used to minimize project risk and the number of full-scale runs in the freeze-drying validation process.

  • A gene therapy clinical trial was halted due to CCI issues in deep cold storage. A CCI test method was developed that enabled non-destructive CCI testing of product vials at these cold temperatures. The capability to non-destructively test clinical product in deep cold storage enabled troubleshooting studies leading to corrective actions that assured good CCI.

  • A manufacturer of a syringe product received complaints about discolored product that was nearing the end of shelf life. A root cause investigation was started and product syringes were put on stability. The headspace oxygen levels were monitored over time. The laser-based headspace analysis proved to be a useful tool to check package integrity and for the presence of reactive headspace gases that can degrade the formulation.

  • A client had an existing filling line and wanted to optimize the nitrogen purge process to decrease headspace oxygen levels to 2%. In addition, frequent line stoppages resulted in a need to identify and reject high oxygen vials that had lost the nitrogen headspace during the stoppage. A purging process qualification study was performed using rapid non-destructive headspace oxygen analysis in an at-line set-up with samples being measured immediately from the line.

  • Regulators are paying closer attention to the proper design of robust Container Closure Integrity (CCI) studies and the validation of CCI test methods. 

  • Vacuum in finished sterile product containers is critical for certain pharmaceutical formulations to ensure proper reconstitution before administration to the patient, or to prevent interactions between the formulation and headspace gas. A loss of vacuum can be a clear indicator of a container closure integrity defect or an issue with the original sealing process. Using a LIGHTHOUSE headspace analysis platform for non-destructive headspace pressure determination verifies the maintenance of vacuum while preserving the product sample.

  • A vaccine-focused biotechnology company needed assistance to investigate a phenomenon observed in liquid vaccine product stored at -80°C. During QC testing, a number of vials were found to have an overpressure. This phenomenon represented a serious safety risk and they needed to identify the root cause.

  • How non-destructive headspace analysis information can be critical for QC groups performing stability studies, or for packaging development groups responsible for choosing the optimal packaging.

  • Rapid non-destructive headspace moisture analysis from LIGHTHOUSE enables fast moisture determination of statistical numbers of lyo samples.

  • In cases where oxidation of the formulation causes discoloration and eventual degradation of the product, non-destructive headspace analysis tests can give deep insight into the root cause. Since the samples are not destroyed by the headspace analysis, further testing can be done to accurately correlate headspace conditions with other product characteristics.

  • A leading contract manufacturer approached LIGHTHOUSE for help after a suspected raised stopper issue motivated the manufacturer to place several batches into quarantine. A decision was made to perform 100% container closure inspection of the product vials with the help of LIGHTHOUSE.

FEATURED WEBINARS

  • Increased regulatory scrutiny and exciting new analytical technologies have altered the landscape of container closure integrity testing. In order to provide guidance to this new environment the US Pharmacopoeia revised Chapter <1207> Sterile Product Package Integrity.  View this webinar recording to learn about the new guidelines and how they will impact your approach to sterile product package integrity.

  • This webinar presents how to design and conduct studies to assess the total oxygen permeation rate of your pre-filled syringes, and how to determine if the permeation is primarily through the plunger or through the tip.  Protecting oxygen-sensitive formulations during filling will also be discussed. 

  • This webinar will review how oxygen levels in finished parenteral drug containers can be determined and controlled throughout the product life cycle by using laser-based headspace analysis.

  • This webinar describes how non-destructive headspace moisture analysis can be used for characterizing batch moisture distributions, for lyo cycle development and optimization, and for freeze dryer moisture mapping and validation.

  • Recent regulatory revisions have also put emphasis on robust method validation for container closure Integrity test methods. This webinar covers approaches that can be used for method development for CCI testing in all phases of the product life cycle.

  • The new language in EU Annex 1 will likely have a significant impact on your CCI testing practices. In this webinar CCI testing strategies and the proposed revisions to EU Annex 1 are discussed.