An alternative sterility assessment for parenteral drug products using isothermal microcalorimetry

Brueckner, David; Krähenbühl, Stephan; Zuber, Ulrich; Bonkat, Gernot; Braissant, Olivier

doi:10.1111/jam.13520

Cited by 8 publications

(3 citation statements)

References 20 publications

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“…The application of membrane filtration for bacterial quantification using IMC has to our knowledge not yet been described. However, qualitative IMC monitoring of the growth of mycobacteria on nylon filters (Solokhina et al, 2017), as well as the qualitative sterility testing of membrane filters (Brueckner et al, 2017) and experiments with three different species on pure titanium disks placed on solid media (Astasov-Frauenhoffer et al, 2012, 2014) could be considered as preparatory work in that direction.…”

Section: Introductionmentioning

confidence: 99%

Rapid Calorimetric Detection of Bacterial Contamination: Influence of the Cultivation Technique

2019

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Modern isothermal microcalorimeters (IMC) are able to detect the metabolic heat of bacteria with an accuracy sufficient to recognize even the smallest traces of bacterial contamination of water, food, and medical samples. The modern IMC techniques are often superior to conventional detection methods in terms of the detection time, reliability, labor, and technical effort. What is missing is a systematic analysis of the influence of the cultivation conditions on calorimetric detection. For the acceptance of IMC techniques, it is advantageous if already standardized cultivation techniques can be combined with calorimetry. Here we performed such a systematic analysis using Lactobacillus plantarum as a model bacterium. Independent of the cultivation techniques, IMC detections were much faster for high bacterial concentrations (>102 CFU⋅mL–1) than visual detections. At low bacterial concentrations (<102 CFU⋅mL–1), detection times were approximately the same. Our data demonstrate that all kinds of traditional cultivation techniques like growth on agar (GOA) or in agar (GIA), in liquid media (GL) or on agar after enrichment via membrane filtration (GF) can be combined with IMC. The order of the detection times was GF < GIA ≈ GL ≈ GOA. The observed linear relationship between the calorimetric detection times and the initial bacterial concentrations can be used to quantify the bacterial contamination. Further investigations regarding the correlation between the filling level (in mm) of the calorimetric vessel and the specific maximum heat flow (in μW⋅g–1) illustrated two completely different results for liquid and solid media. Due to the better availability of substrates and the homogeneous distribution of bacteria growing in a liquid medium, the volume-related maximum heat flow was independent on the filling level of the calorimetric vessels. However, in a solid medium, the volume-related maximum heat flow approached a threshold and achieved a maximum at low filling levels. This fundamentally different behavior can be explained by the spatial limitation of the growth of bacterial colonies and the reduced substrate supply due to diffusion.

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Section: Introductionmentioning

confidence: 99%

Rapid Calorimetric Detection of Bacterial Contamination: Influence of the Cultivation Technique

2019

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“…Isothermal microcalorimetry, a non‐specific method, becomes highly selective through the application of chemical and thermal pre‐treatments (Leoni and Legnani, 2001) and the use of selective media (Descours et al , 2014). The application of membrane filtration as an enrichment process and subsequential cultivation with the aim of shortening detection times was firstly demonstrated in liquid medium by Brueckner and co‐workers using IMC (Brueckner et al , 2017). Recently, heat flow measurements demonstrating the potential of membrane filtration were performed on solid medium after enrichment via membrane filtration for anaerobic cultures (Fricke et al , 2019).…”

Section: Resultsmentioning

confidence: 99%

Rapid culture‐based detection of Legionella pneumophila using isothermal microcalorimetry with an improved evaluation method

Fricke

Jiang

et al. 2020

Microbial Biotechnology

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The detection and quantification of Legionella pneumophila (responsible for legionnaire's disease) in water samples can be achieved by various methods. However, the culture-based ISO 11731:2017, which is based on counts of colony-forming units per ml (CFUÁml -1 ) is still the gold standard for quantification of Legionella species (spp.). As a powerful alternative, we propose real-time monitoring of the growth of L. pneumophila using an isothermal microcalorimeter (IMC). Our results demonstrate that, depending on the initial concentration of L. pneumophila, detection times of 24-48 h can be reliably achieved. IMC may, therefore, be used as an early warning system for L. pneumophila contamination. By replacing only visual detection of growth by a thermal sensor, but otherwise maintaining the standardized protocol of the ISO 11731:2017, the new procedure could easily be incorporated into existing standards. The exact determination of the beginning of metabolic heat is often very difficult because at the beginning of the calorimetric signal the thermal stabilization and the metabolic heat development overlap. Here, we propose a new data evaluation based on the first derivation of the heat flow signal. The improved evaluation method can further reduce detection times and significantly increase the reliability of the IMC approach.

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“…There are records of deaths in Pakistan due to contaminated tablets of antimalarial drugs 17 , also warned about by Almuzaini et al 10 in 2014. Injectable drugs have the highest quality requirements (including sterility of the solution), yet SM reports for these products are also frequent 45 .…”

Section: Discussionmentioning

confidence: 99%

Reports of substandard medicines: a lexicographic analysis of the Brazilian Health Surveillance Report System

Fedalto

Mendes

Tonin

et al. 2021

Rev. Ciênc. Farm. Básica Apl.

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Regulatory agencies are responsible for collecting and evaluating spontaneous reports of suspected problems related to medications, including those from substandard medicines (SM). Objectives: The aim was to evaluate the profile of SM reports submitted to the Brazilian Health Surveillance Notification System (Notivisa) and classify these reports objectively by means of lexicographic analysis. Methods: Was extracted all SM reports available in Notivisa during the period 1 January 2007 to 31 December 2017. Descriptive statistics were performed and the reasons for SM reporting were standardized (using OpenRefine and Microsoft Excel). The following analyses were performed using IRAMuTeQ 0.7 alpha2: lexicographic analysis to obtain the frequency of active words; descending hierarchical classification (DHC) to categorize the active words into lexical classes; factorial correspondence analysis (FCA) to obtain graphs of the classes. Approved by the Ethics Committee of the Hospital do Trabalhador/SES/PR CAAE 81873417.3.0000.5225 (protocol number: 2.506.594). Results: A total of 61,775 reports were analyzed, most of them reported by hospitals (46%). The DHC of the reasons for SM produced four classes visualized in the FCA: (i) packaging problems (16%) mainly leakages/opening issues; (ii) inadequate drug identification (22%), such as illegible label information; (iii) stability and contamination issues (11%) such as presence of particles; (iv) damaged tablets/blisters (23%) mainly broken tablets. Most SM (52%) were solutions for parenteral use; sodium chloride (9%), glucose and dipyrone (3%) were the products with most complaints. Conclusions: The reasons for SM reporting can be objectively classified into classes that represent the main problems submitted to Notivisa. This classification could guide the standardization of SM reporting and contribute to improving surveillance reporting systems worldwide.

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An alternative sterility assessment for parenteral drug products using isothermal microcalorimetry

Cited by 8 publications

References 20 publications

Rapid Calorimetric Detection of Bacterial Contamination: Influence of the Cultivation Technique

Rapid Calorimetric Detection of Bacterial Contamination: Influence of the Cultivation Technique

Rapid culture‐based detection of Legionella pneumophila using isothermal microcalorimetry with an improved evaluation method

Reports of substandard medicines: a lexicographic analysis of the Brazilian Health Surveillance Report System

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