Animal Models and Alternatives in the Quality Control of Vaccines: Are In Vitro Methods or In Vivo Methods the Scientific Equivalent of the Emperor's New Clothes?

1995 ◽  
Vol 23 (1) ◽  
pp. 61-73
Author(s):  
Coenraad Hendriksen ◽  
Johan van der Gun
Keyword(s):  
Quality Control ◽  
Test Methods ◽  
In Vitro Test ◽  
Large Numbers ◽  
Alternative Approach ◽  
Inactivated Vaccines ◽  
Vitro Test

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.

In Vitro Toxicology and the Test Guidelines

1996 ◽  
Vol 24 (3) ◽  
pp. 435-438
Author(s):  
Kimmo Louekari
Keyword(s):  
Cost Effective ◽  
Test Methods ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
Effective Manner ◽  
Genotoxic Carcinogens ◽  
Vitro Test

Ethical, economical and scientific considerations should encourage the development of alternative and in vitro test methods. Before their adoption, in vitro methods need to be validated and scientifically justified. Demand for rigorous validation schemes for in vitro tests must be emphasised, even more than in the case of in vivo tests. The OECD has adopted in vitro guidelines for testing genotoxicity; several endpoints and mechanisms can be studied in a cost-effective manner in vitro. Similar advantages could be afforded if acute irritation and corrosion, as well as the non-genotoxic carcinogenic effects of chemicals, could be studied in vitro. Evaluation of the validation status of various methods used to study non-genotoxic carcinogens was begun by the Nordic Working Group on In Vitro Methods for Non-genotoxic Mechanisms in 1996. In some established OECD test guidelines (for example, the dermal irritation/corrosion test), there is already room for the application of in vitro methods which have not been formally validated. In January 1996, the OECD Workshop on Harmonisation of Validation and Acceptance Criteria for Alternative Toxicological Test Methods set the basis for internationally acceptable principles to be followed in the validation of in vitro test methods.

scholarly journals Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics

2015 ◽  
Vol 25 ◽  
pp. 347-355 ◽  
Author(s):  
Atsuo Ito ◽  
Yu Sogo ◽  
Atsushi Yamazaki ◽  
Mamoru Aizawa ◽  
Akiyoshi Osaka ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Test Methods ◽  
In Vitro Test ◽  
Calcium Phosphate Ceramics ◽  
Interlaboratory Studies ◽  
Vitro Test

Lack of Influence of Povidone-Iodine on Tests of Thyroid Function

1978 ◽  
Vol 6 (5) ◽  
pp. 406-408 ◽  
Author(s):  
D P Lividas ◽  
G D Piperingos ◽  
J Sfontouris ◽  
D A Koutras
Keyword(s):  
Thyroid Function ◽  
Povidone Iodine ◽  
Test Methods ◽  
Thyroid Function Tests ◽  
In Vitro Test ◽  
External Application ◽  
Vitro Test ◽  
Antiseptic Agent

The external application of povidone-iodine, an antiseptic agent, was tested for its influence on thyroid function. Previous workers have described some in vitro changes in thyroid function tests following its use. In the present study topical application of povidone-iodine did not affect thyroid function as measured some days later using both in vivo and radio-active iodine in vitro test methods, despite the fact that the latter are notorious for being influenced by exogenous iodine.

Development and Evaluation of a Novel Artificial Catheter-Deliverable Prosthetic Heart Valve and Method for in Vitro Testing

2009 ◽  
Vol 32 (5) ◽  
pp. 262-271 ◽  
Author(s):  
Thomase Claiborne ◽  
Danny Bluestein ◽  
Richard T. Schoephoerster
Keyword(s):  
Heart Valve ◽  
State Of The Art ◽  
Prosthetic Heart Valve ◽  
Test Methods ◽  
In Vitro Testing ◽  
In Vitro Test ◽  
Vitro Test ◽  
Percutaneous Heart Valve

Background This work presents a novel artificial prosthetic heart valve designed to be catheter or percutaneously deliverable, and a method for in vitro testing of the device. The device is intended to create superior characteristics in comparison to tissue-based percutaneous valves. Methods The percutaneous heart valve (PHV) was constructed from state-of-the-art polymers, metals and fabrics. It was tested hydrodynamically using a modified left heart simulator (LHS) and statically using a tensile testing device. Results The PHV exhibited a mean transvalvular pressure gradient of less than 15 mmHg and a mean regurgitant fraction of less than 5 percent. It also demonstrated a resistance to migration of up to 6 N and a resistance to crushing of up to 25 N at a diameter of 19 mm. The PHV was crimpable to less than 24 F and was delivered into the operating LHS via a 24 F catheter. Conclusion An artificial PHV was designed and optimized, and an in vitro methodology was developed for testing the valve. The artificial PHV compared favorably to existing tissue-based PHVs. The in vitro test methods proved to be reliable and reproducible. The PHV design proved the feasibility of an artificial alternative to tissue based PHVs, which in their traditional open-heart implantable form are known to have limited in vivo durability.

In Vitro Toxicology Methods in Risk Assessment

1996 ◽  
Vol 24 (3) ◽  
pp. 325-331
Author(s):  
Iain F. H. Purchase
Keyword(s):  
Risk Assessment ◽  
Hazard Assessment ◽  
Human Health Risk ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
New Concepts ◽  
Vitro Test

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined, and risk can then be assessed. In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames Salmonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification. The future development of in vitro methods is likely to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed in vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, will be more difficult to replace.

scholarly journals Tablet Scoring: Current Practice, Fundamentals, and Knowledge Gaps

2019 ◽  
Vol 9 (15) ◽  
pp. 3066 ◽  
Author(s):  
Emmanuel Reginald Jacques ◽  
Paschalis Alexandridis
Keyword(s):  
Prescription Drugs ◽  
In Vitro Test ◽  
Dose Administration ◽  
Solid Dosage ◽  
Non Invasive ◽  
Health Care Practitioners ◽  
Tablet Splitting ◽  
Vitro Test

Oral solid dosage formulations and/or tablets have remained the preferred route of administration by both patients and health care practitioners. Oral tablets are easy to administer, they are non-invasive and cause less risk adversity. Because of the lack of commercially available tablet dose options, tablets are being split or partitioned by users. Tablet scoring refers to the breakage of a tablet to attain a desired efficacy dose and is an emerging concept in the pharmaceutical industry. The primary reason for the tablet scoring practice is to adjust the dose: dose tapering or dose titrating. Other reasons for tablet partitioning are to facilitate dose administration, particularly among the pediatric and the geriatric patient population, and to mitigating the high cost of prescription drugs. The scope of this review is to: (1) evaluate the advantages and inconveniences associated with tablet scoring/portioning, and (2) identify factors in the formulation and the manufacturing of tablets that influence tablet splitting. Whereas tablet partitioning has been a common practice, there is a lack of understanding regarding the fundamentals underpinning the performance of tablets with respect to splitting. Several factors can influence tablet partitioning: tablet size, shape, and thickness. A requirement has recently been set by the European Pharmacopoeia and the U.S. Food and Drug Administration for the uniformity of mass of subdivided tablets. For breaking ease, an in-vivo reference test and a routinely applicable in-vitro test need to be established.

Characteristics and Biocompatibility of the Hydroxyapatite Based Two Ternary Biocomposites

2016 ◽  
Vol 720 ◽  
pp. 130-140
Author(s):  
Berrak Bulut ◽  
Ziya Engin Erkmen ◽  
Eyup Sabri Kayali
Keyword(s):  
Mechanical Properties ◽  
Physical And Mechanical Properties ◽  
Secondary Phase ◽  
In Vitro Test ◽  
Compression Tests ◽  
Vitro Test ◽  
Dental Applications ◽  
The Ideal

Hydroxyapatite (HA) is a very popular bioceramic for orthopedic and dental applications. Although HA has excellent biocompatibility, its inferior mechanical properties make it unsuitable for load-bearing implant applications. Therefore, HA should be strengthened by a secondary phase for robust mechanical properties. The aim of this study was to compare the properties of HA-Al2O3 (HAC) and HA-ZrO2 (HZC) composites with the addition of 5 and 10 wt% commercial inert glass (CIG); independently. The mixture powders were pressed and then, the pellets were sintered between 1000-1300 °C for 4 hours. Microstructural characterizations were carried out using SEM + EDS and XRD, while hardness and compression tests were done to measure mechanical properties. In order to investigate the biocompatibility behavior of the samples in vitro and in vivo tests were performed. The mechanical properties of HAC composites increased with rising CIG content and increasing sintering temperature. For HZC composites, increasing CIG content caused an elevation in hardness and a decrease in compressive strength values at 1300 °C. The composites having the best physical and mechanical properties also showed improved bioactive properties at in vitro test. In this study, the ideal composite was selected as HZC5 sintered at 1200 °C depending on the microstructure, mechanical and biocompatibility properties.

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