Standardized pyrogen testing of medical products with the bacterial endotoxin test (BET) as a substitute for rabbit Pyrogen testing (RPT): A scoping review

Spoladore, Janaína; Gimenes, Izabela; Bachinski, Róber; Negherbon, Jesse; Hartung, Thomas; Granjeiro, José Mauro; Alves, Gutemberg Gomes

doi:10.1016/j.tiv.2021.105160

Cited by 10 publications

(7 citation statements)

References 43 publications

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“…The most frequent deficiency observed for sterile products in this subsection is the request to include the limit for bacterial endotoxin in the FPP specifications. Endotoxins released from Gram-negative bacteria are the main reason of contamination in pharmaceutical products and as a result of this, an endotoxin test is required to be performed on sterile products especially those which are to be injected in the body so as to avoid bringing adverse effects to human [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)

Moeti

Litedu²,

Joubert

2022

J of Pharm Policy and Pract

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Background The aim of the study was to investigate the common deficiencies observed in the Finished Pharmaceutical Product (FPP) section of generic product applications submitted to SAHPRA. The study was conducted retrospectively over a 7-year period (2011–2017) for products that were finalised by the Pharmaceutical and Analytical pre-registration Unit. Methods There were 3148 finalised products in 2011–2017, 667 of which were sterile while 2089 were non-sterile. In order to attain a representative sample for the study, statistical sampling was conducted. Sample size was obtained using the statistical tables found in literature and confirmed by a sample size calculation with a 95% confidence level. The selection of the products was according to the therapeutic category using the multi-stage sampling method called stratified-systematic sampling. This resulted in the selection of 325 applications for non-sterile products and 244 applications for sterile products. Subsequently, all the deficiencies were collected and categorised according to Common Technical Document (CTD) subsections of the FPP section (3.2.P). Results A total of 3253 deficiencies were collected from 325 non-sterile applications while 2742 deficiencies were collected from 244 sterile applications. The most common deficiencies in the FPP section for non-sterile products were on the following sections: Specifications (15%), Description and Composition (14%), Description of the Manufacturing Process (13%), Stability Data (7.6%) and the Container Closure System (7.3%). The deficiencies applicable to the sterile products were quantified and the subsection, Validation and/or Evaluation (18%) has the most deficiencies. Comparison of the deficiencies with those reported by other agencies such as the USFDA, EMA, TFDA and WHOPQTm are discussed with similarities outlined. Conclusions The overall top five most common deficiencies observed by SAHPRA were extensively discussed for the generic products. The findings provide an overview on the submissions and regulatory considerations for generic applications in South Africa, which is useful for FPP manufacturers in the compilation of their dossiers and will assist in accelerating the registration process.

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Section: Discussionmentioning

confidence: 99%

Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)

Moeti

Litedu²,

Joubert

2022

J of Pharm Policy and Pract

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“…Biological detection techniques include rabbit pyrogen test, Limulus amebocyte lysate (LAL) assay, [114] and bovine whole blood assay, which use natural methods of endotoxin detection and are still in use today. [115] Biosensor techniques rely more on recent scientific achievements rather than traditional biological processes. These techniques represent the up-and-coming detection methods along with the advances in target sensing strategies.…”

Section: Contaminantmentioning

confidence: 99%

“…Current contaminants detection methodology can be divided into biological detection and biosensing techniques for classification. Biological detection techniques include rabbit pyrogen test, Limulus amebocyte lysate (LAL) assay, [114] and bovine whole blood assay, which use natural methods of endotoxin detection and are still in use today [115] . Biosensor techniques rely more on recent scientific achievements rather than traditional biological processes.…”

Section: Contaminantmentioning

confidence: 99%

Advances in sensor developments for cell culture monitoring

Kim,

Yeo

2023

BMEMat

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Cell culture encompasses procedures for extracting cells from their natural tissue and cultivating them under controlled artificial conditions. During this process, various factors, including cell physiological/morphological properties, culture environments, metabolites, and contaminants, have to be precisely controlled and monitored for the survival of cells and the pursuit of the desired properties of the cells. This review summarizes recent advances in sensor technologies and manufacturing strategies for various cell culture platforms using traditional plastics, microfluidic chips, and scalable bioreactors. We share the details of newly developed biological sensors, chemical sensors, optical sensors, electronic chip technologies, and material integration methods. The precise control of parameters based on the feedback by these sensors and electronics enhances cell culture quality and throughput.

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“… 1 , 2 Pyrogen testing is a statutory requirement listed in pharmacopoeias for controlling the safety of parenteral drugs and research on feasible pyrogen tests is urgently needed. 3 , 4 …”

Section: Introductionmentioning

confidence: 99%

A novel alternative for pyrogen detection based on a transgenic cell line

He,

Yu,

et al. 2024

Sig Transduct Target Ther

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Pyrogen, often as a contaminant, is a key indicator affecting the safety of almost all parenteral drugs (including biologicals, chemicals, traditional Chinese medicines and medical devices). It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted ‘reduction, replacement and refinement’ principle, which has been highly considered by regulatory agencies from different countries. We used NF-κB, a central signalling molecule mediating inflammatory responses, as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal. Here, we show that this test can quantitatively and sensitively detect endotoxin (lipopolysaccharide from different strains) and nonendotoxin (lipoteichoic acid, zymosan, peptidoglycan, lectin and glucan), has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals (group A & C meningococcal polysaccharide vaccine; basiliximab; rabies vaccine (Vero cells) for human use, freeze-dried; Japanese encephalitis vaccine (Vero cells), inactivated; insulin aspart injection; human albumin; recombinant human erythropoietin injection (CHO Cell)). The within-laboratory reproducibility of the test in three independent laboratories was 85%, 80% and 80% and the interlaboratory reproducibility among laboratories was 83.3%, 95.6% and 86.7%. The sensitivity (true positive rate) and specificity (true negative rate) of the test were 89.9% and 90.9%, respectively. In summary, the test provides a novel alternative for pyrogen detection.

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Standardized pyrogen testing of medical products with the bacterial endotoxin test (BET) as a substitute for rabbit Pyrogen testing (RPT): A scoping review

Cited by 10 publications

References 43 publications

Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)

Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)

Advances in sensor developments for cell culture monitoring

A novel alternative for pyrogen detection based on a transgenic cell line

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