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Biomedical subjects

J Milstien

Publications and source records attributed to J Milstien.

13 recordsLinked to original sources
PubMed2002

Regulatory processes and three Rs alternatives.

Previously, the role of the laboratory in the regulation of vaccines and other biological products was key to assuring vaccine quality, where tests for potency and safety in animals were used to predict vaccine efficacy and safety in humans. In the past, regulation of inherently variable biological products depended on the use of inherently variable biological tests. Today, the concepts of regulation are evolving. Systems in place to assure product consistency are required; this is reflected in the need to have Good Manufacturing Practice as a part of quality assurance. Regulation now depends more strongly on experience in the clinic, including large post-marketing studies for safety. It also means that laboratory tests, especially in cases where there are no direct correlates of safety and efficacy, are more properly used for confirmation of consistency. In addition, the products themselves have changed. Many biological products can be produced in a form which allows quantification of characteristics, thus allowing more physical tests to be done. Thus, regulation of biological products in future will probably see a replacement, reduction and refinement (the 3 Rs) of animal testing.

Animal Testing Alternatives↗
PubMed2001

Laboratory testing of whole cell pertussis vaccine: a WHO proficiency study using the Kendrick test.

Whole cell pertussis vaccine (WCV), commonly in combination with vaccines for diphtheria and tetanus, has an important role in reducing morbidity and mortality among children in most parts of the world. Testing to assure the efficacy of such vaccines is essential. We have, therefore, carried out, under the Global Training Network (GTN) of the Department of Vaccines and Biologicals at the World Health Organization (WHO), a proficiency study involving 13 laboratories in 12 countries that routinely test WCV. Two vaccine samples were tested in this study and represented samples which were expected clearly either to pass (sample B, a full strength vaccine) or to fail (sample A, 1/8 strength of vaccine B). Data from this study showed good performance by the majority of participants. Most assays were statistically valid and were carried out to the level of precision achieved for these assays in previous studies. This study also indicated that, relative to the assay precision, the in-house reference (IHR) preparations are in general accurately calibrated. Statistically valid assays of the sub-potent vaccine, A, showed it to fail in all except one laboratory. Statistically valid assays of the potent vaccine, B, showed it to pass in all laboratories. Nevertheless, the between laboratory variability of estimates for vaccine B, and for comparisons of the two vaccine samples suggested that there are some differences in results in different laboratories. The introduction of a common working standard may assist in reducing inter-laboratory variation. This study has shown clearly satisfactory performance by most laboratories. However, a serious problem was detected in one laboratory where the sub-potent vaccine A could have been passed and was not distinguished from the eight-fold more potent vaccine B. There were also indications of possible problems in several other laboratories, where IHR preparation may not be accurately calibrated or where vaccine samples A and B may not be completely distinguished. Although this study provides reassurance that most laboratories perform well, it demonstrates the essential role of ongoing proficiency studies in high-lighting problems.

Animals↗
PubMed1999

Availability of quality fixed-dose combinations for the treatment of tuberculosis: what can we learn from studying the World Health Organization's vaccine model?

SETTING: In efforts to promote the use of fixed-dose combinations (FDCs) for the treatment of tuberculosis (TB), the World Health Organization (WHO) and partners address the issue of quality assurance. OBJECTIVE: To provide guidance for the development of strategies for quality assurance of FDCs. DESIGN: This review examines the WHO strategies for and experience with quality assurance and supply of vaccines. RESULTS: Several elements in the strategies for quality assurance and supply of vaccines may be applicable for FDCs. At national level, the important strategies are to strengthen National Regulatory Authorities (NRA) and procurement systems and develop planning activities. Stressing quality assurance of FDCs in training activities for regulatory personnel and recommending that aid agencies require adherence to quality assurance policies as conditions for support would promote the implementation of quality assurance of FDCs at country level. At the global level, pre-qualification of manufacturers of FDCs should be explored as a mechanism to assure quality. The pre-qualification process should include evaluation of product files, initial testing for compliance and consistency of specifications, and site visits to producers and NRAs. The vaccine model defines criteria for reassessment that can be used for FDCs.

Antitubercular Agents↗
PubMed1996

WHO activities towards the three Rs in the development and control of biological products.

WHO supports the concept of replacement, reduction and refinement of the use of in vivo methods for biologicals production and control, and regularly conducts reviews of its recommended procedures to allow reduction in the use of animals. The coordination of collaborative studies, publication of standardized methods, and holding of workshops on the use of these methods contributes to their use. The neurovirulence test for oral poliovaccine is probably the single most visible animal test for which alternative methods are sought. Collaborative studies on alternative methods for screening products are currently being sponsored by WHO. The use of Vero cells rather than primary monkey kidney cells for poliovaccine production can avoid the use of many monkeys. Cell banks of Vero and HEp-2 cells have been developed by WHO, tested for virus sensitivity and freedom from adventitious agents, and are available for vaccine production and control, replacing primary animal cells. For the future, final product testing will increasingly be directed towards establishment of consistency of production rather than potency. By supporting the validation and use of this approach, WHO can effectively influence more rational animal use in biological production and control.

Animal Testing Alternatives↗
PubMed1994

The relationship between dose and response of standard measles vaccines.

A considerable number of field trials have been published over the last 30 years, showing measles vaccines to be highly effective. Due to inconsistencies in methodology, comparisons between these studies have often been difficult with regard to the potencies used and the sero-response of vaccinated children. This article reviews key studies which have measured the response of children to different potencies of vaccine. The review concludes that increasing the titre of vaccine above log10 3.0 does not appear to improve vaccine efficacy. It is recommended that standard titre measles vaccine should be administered with a minimum potency of log10 3.0 TCID50 or PFU per dose at 9 months of age or later. This recommendation is endorsed by the Global Advisory Group and the Research and Development Group of the Expanded Programme on Immunization.

Child↗
PubMed1979

Characterization of the WIDR: a human colon carcinoma cell line.

We describe the establishment and characterization of WiDr, a cell line derived from a human colon carcinoma. It produces carcinoembryonic antigen in culture, and has a doubling time of 15 hr with plating efficiency of 51%. The HLA antigenic profile and the allozyme genetic signature (composed of eight gene-enzyme systems) of WiDr cells are different from those of HeLa cells. Furthermore, WiDr cells possess three marker chromosomes, again distinct from the HeLa marker chromosomes. Finally, it is highly tumorigenic in four different xenogeneic animal models. Based on these studies, WiDr represents a useful model cell line for tumor cell biology investigations.

Carcinoembryonic Antigen↗
PubMedDate not supplied

A systematic method for evaluating the potential viability of local vaccine producers.

Vaccine production exists in > 55 countries, but many production facilities cannot assure a reliable supply of existing or new vaccines. By analysing the characteristics of successful producers, we have identified seven critical elements for viability, each defined by several indicators. Each indicated weakness implies an investment to correct it. Thirty-one manufacturers were assessed based on these viability indicators and the implied investment costs. Three general groupings were found. 'Viable' producers scored well in all seven categories. Those with a 'low probability' of viability are weak in all areas. Facilities regarded as 'potentially viable' may produce sufficient vaccine to meet national needs, but must develop appropriate structures to effectively manage change. This analysis provides a logical system for governments and donors to evaluate the potential effectiveness of further investment in local vaccine production.

Humans↗