Quality Assurance for In Vitro Alternative Test Methods: Quality Control Issues in Test Kit Production

In the quality control of vaccine batches, the potency testing of inactivated vaccines is one of the areas requiring very large numbers of animals, which usually suffer significant distress as a result of the experimental procedures employed. This article deals with the potency testing of diphtheria and tetanus toxoids, two vaccines which are used extensively throughout the world. The relevance of the potency test prescribed by the European Pharmacopoeia monographs is questioned. The validity of the potency test as a model for the human response, the ability of the test to be standardised, and the relevance of the test in relation to the quality of the product are discussed. It is concluded that the potency test has only limited predictive value for the antitoxin responses to be expected in recipients of these toxoids. An alternative approach for estimating the potency of toxoid batches is discussed, in which a distinction is made between estimation of the immunogenic potency of the first few batches obtained from a seed lot and monitoring the consistency of the quality of subsequent batches. The use of animals is limited to the first few batches. Monitoring the consistency of the quality of subsequent batches is based on in vitro test methods. Factors which hamper the introduction and acceptance of the alternative approach are considered. Finally, proposals are made for replacement, reduction and/or refinement (the Three Rs) in the use of animals in the routine potency testing of toxoids.

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Quality Assurance and Quality Control in the In Vitro Fertilization Laboratory

In Vitro Fertilization ◽

10.3109/9781420004960-18 ◽

2006 ◽

pp. 365-380

Author(s):

Karen Martin

Keyword(s):

Quality Control ◽

Quality Assurance ◽

In Vitro Fertilization ◽

Vitro Fertilization

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Bioethical Aspects of Improving the Production of Rabies Immunoglobulin in Russia

BIOpreparations Prevention Diagnosis Treatment ◽

10.30895/2221-996x-2020-20-2-89-96 ◽

2020 ◽

Vol 20 (2) ◽

pp. 89-96

Author(s):

S. V. Generalov ◽

E. G. Abramova ◽

Yu. K. Gavrilova

Keyword(s):

Quality Control ◽

Product Quality ◽

Specific Activity ◽

Test Methods ◽

Detection Methods ◽

Post Exposure Prophylaxis ◽

In Vitro Test ◽

International Trends ◽

Animal Use

The main objective of the present research was to review the studies that look into ways of improving production of anti-rabies immunoglobulin in terms of bioethical principles: ensuring patients’ right to receive quality pharmaceutical care, and compliance with the 3R principles. At the same time, compliance with bioethical principles should contribute to the improvement of production technology and the product quality, which is especially important for antirabies immunoglobulin due to the existing high demand for it. The paper analyses the current trends in avoidance of animal use in the production of rabies immunoglobulin. It summarises the main methods of production of serum products for post-exposure prophylaxis of rabies. The example of heterologous rabies immunoglobulin is used to substantiate the need to improve quality control of drugs by following the 3R principles. The paper highlights the potential use of cell cultures for determination of rabies immunoglobulin specific activity. The authors formulated the objectives that include development and use of pyrogen detection methods which do not involve animal use and are consistent with the current pharmacopoeial standards. They assessed the possibility and feasibility of removing Abnormal Toxicity Test for heterologous rabies immunoglobulin in accordance with the current international trends. The formulated objectives imply optimisation of production of heterologous rabies immunoglobulin in Russia in order to improve the quality of antirabies measures. The objectives include higher production volumes to ensure the availability of the product to patients, reduction of the product reactogenicity by using cell-culture technologies for obtaining rabies antigen, as well as development and implementation of in vitro test methods for product quality control in terms of Specific activity, Pyrogenicity, and Abnormal toxicity

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Skin Sensitization Potential and Cellular ROS-Induced Cytotoxicity of Silica Nanoparticles

Nanomaterials ◽

10.3390/nano11082140 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2140

Author(s):

Sung-Hyun Kim ◽

Dong Han Lee ◽

SeoYoon Choi ◽

Jun-Young Yang ◽

Kikyung Jung ◽

...

Keyword(s):

Silica Nanoparticles ◽

Test Methods ◽

Skin Sensitization ◽

Accurate Identification ◽

Silica Nanomaterials ◽

High Protein Binding ◽

In Vivo Analysis ◽

Alternative Test

Nowadays, various industries using nanomaterials are growing rapidly, and in particular, as the commercialization and use of nanomaterials increase in the cosmetic field, the possibility of exposure of nanomaterials to the skin of product producers and consumers is increasing. Due to the unique properties of nanomaterials with a very small size, they can act as hapten and induce immune responses and skin sensitization, so accurate identification of toxicity is required. Therefore, we selected silica nanomaterials used in various fields such as cosmetics and biomaterials and evaluated the skin sensitization potential step-by-step according to in-vitro and in-vivo alternative test methods. KeratinoSensTM cells of modified keratinocyte and THP-1 cells mimicking dendritic-cells were treated with silica nanoparticles, and their potential for skin sensitization and cytotoxicity were evaluated, respectively. We also confirmed the sensitizing ability of silica nanoparticles in the auricle-lymph nodes of BALB/C mice by in-vivo analysis. As a result, silica nanoparticles showed high protein binding and reactive oxygen species (ROS) mediated cytotoxicity, but no significant observation of skin sensitization indicators was observed. Although more studies are needed to elucidate the mechanism of skin sensitization by nanomaterials, the results of this study showed that silica nanoparticles did not induce skin sensitization.

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Determination of Disk Diffusion and MIC Quality Control Guidelines for High-Dose Cefepime-Tazobactam (WCK 4282), a Novel Antibacterial Combination Consisting of a β-Lactamase Inhibitor and a Fourth-Generation Cephalosporin

Journal of Clinical Microbiology ◽

10.1128/jcm.00788-17 ◽

2017 ◽

Vol 55 (10) ◽

pp. 3130-3134 ◽

Cited By ~ 2

Author(s):

Stefan Riedel ◽

Michael D. Huband ◽

Helio S. Sader ◽

Robert K. Flamm ◽

Ronald N. Jones

Keyword(s):

Quality Control ◽

Generation Cephalosporin ◽

Test Methods ◽

Disk Diffusion ◽

Fourth Generation ◽

High Dose ◽

Gram Negative ◽

Lactamase Inhibitor

ABSTRACTHigh-dose cefepime-tazobactam (1:1; WCK 4282), a novel antibacterial combination consisting of the β-lactamase inhibitor tazobactam and a fourth-generation cephalosporin, is under clinical development for the treatment of serious Gram-negative infections. A quality control (QC) study was performed to establish disk diffusion and MIC ranges for cefepime-tazobactam for multiple QC reference strains. The cefepime-tazobactam QC ranges for a fixed tazobactam MIC of 8 μg/ml and disk diffusion (30/20-μg disk) test methods were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing in January 2015 and January 2016. These QC ranges will be important for accuratein vitroactivity evaluations of cefepime-tazobactam when tested against clinical Gram-negative bacteria during clinical studies and routine patient care.

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The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM): A Review of the ICCVAM Test Method Evaluation Process and Current International Collaborations with the European Centre for the Validation of Alternative Methods (ECVAM)

Alternatives to Laboratory Animals ◽

10.1177/026119290203002s04 ◽

2002 ◽

Vol 30 (2_suppl) ◽

pp. 23-32 ◽

Cited By ~ 16

Author(s):

William S. Stokes ◽

Leonard M. Schechtman ◽

Richard N. Hill

Keyword(s):

International Adoption ◽

Evaluation Process ◽

Test Methods ◽

Test Method ◽

Alternative Methods ◽

Laboratory Animals ◽

European Centre ◽

The Usa ◽

Alternative Test

Over the last decade, national authorities in the USA and Europe have launched initiatives to validate new and improved toxicological test methods. In the USA, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and its supporting National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), were established by the Federal Government to work with test developers and Federal agencies to facilitate the validation, review, and adoption of new scientifically sound test methods, including alternatives that can reduce, refine, and replace animal use. In Europe, the European Centre for the Validation of Alternative Methods (ECVAM) was established to conduct validation studies on alternative test methods. Despite differences in organisational structure and processes, both organisations seek to achieve the adoption and use of alternative test methods. Accordingly, both have adopted similar validation and regulatory acceptance criteria. Collaborations and processes have also evolved to facilitate the international adoption of new test methods recommended by ECVAM and ICCVAM. These collaborations involve the sharing of expertise and data for test-method workshops and independent scientific peer reviews, and the adoption of processes to expedite the consideration of test methods already reviewed by the other organisation. More recently, NICEATM and ECVAM initiated a joint international validation study on in vitro methods for assessing acute systemic toxicity. These collaborations are expected to contribute to accelerated international adoption of harmonised new test methods that will support improved public health and provide for reduced and more-humane use of laboratory animals.

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