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J B Milstien

Publications and source records attributed to J B Milstien.

At least 19 recordsLinked to original sources
PubMed2001

Ensuring vaccine safety in immunization programmes--a WHO perspective.

Ever since vaccines were firstly used against smallpox, adverse events following immunization have been reported. As immunization programmes expand to reach even the most remote communities in the poorest countries, it is likely that many more events will be temporally linked with vaccine administration. Furthermore, the profound shift in the general public and media interest in adverse events may lead to undue concerns and allegations which may ultimately jeopardize immunization programmes world-wide. While the health professional has understood this issue for some time, the public and the media have now also become all too aware of the significance of vaccine-related adverse events. The familiar vaccines, well-tested over decades, have not changed--but the perception regarding their safety has shifted. Claims outrageous or reasonable are being made against both the old and the newly-introduced vaccines. At the same time, the immunological and genetic revolution of the last decade may well bring to our notice some hypothetical risks that need to be addressed at pre-clinical level. WHO has been at the leading edge to guarantee vaccine safety for the last 30 years and will continue to do so. The Organization's plans for the next decade and beyond include the Safe Injection Global Network (SIGN), the development and introduction of safer technologies, and the prevention, early detection and management of AEFIs. The new technologies include needle-containing injection devices such as the autodisable syringe, as well as mucosal and transcutaneous immunization. Training will continue to be at the centre of WHO's efforts, limiting human error to a minimum. Mechanisms have been set in place to detect and respond to new and unforeseen events occurring. Above all, there is a willingness to respond to new climates and new technologies so that the Organization is in the best position to ensure safe immunization for all the world's children.

Drug Contamination↗
PubMed2000

New challenges in assuring vaccine quality.

In the past, quality control of vaccines depended on use of a variety of testing methods to ensure that the products were safe and potent. These methods were developed for vaccines whose safety and efficacy were based on several years worth of data. However, as vaccine production technologies have developed, so have the testing technologies. Tests are now able to detect potential hazards with a sensitivity not possible a few years ago, and an increasing array of physicochemical methods allows a much better characterization of the product. In addition to sophisticated tests, vaccine regulation entails a number of other procedures to ensure safety. These include characterization of starting materials by supplier audits, cell banking, seed lot systems, compliance with the principles of good manufacturing practices, independent release of vaccines on a lot-by-lot basis by national regulatory authorities, and enhanced pre- and post-marketing surveillance for possible adverse events following immunization. These procedures help assure vaccine efficacy and safety, and some examples are given in this article. However, some contaminants of vaccines that can be detected by newer assays raise theoretical safety concerns but their presence may be less hazardous than not giving the vaccines. Thus risk-benefit decisions must be well informed and based on scientific evidence.

Humans↗
PubMed2000

Developing a national system for dealing with adverse events following immunization.

Although vaccines are among the safest of pharmaceuticals, the occasional severe adverse event or cluster of adverse events associated with their use may rapidly become a serious threat to public health. It is essential that national monitoring and reporting systems for vaccine safety are efficient and adequately coordinated with those that conventionally deal with non-vaccine pharmaceuticals. Equally important is the need for an enlightened and informed national system to be in place to deal with public concerns and rapid evaluation of the risk to public safety when adverse events occur. Described in this article is the outcome of efforts by the WHO Global Training Network to describe a simple national system for dealing with vaccine safety and with emergencies as they arise. The goals of a training programme designed to help develop such a system are also outlined.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

Alternatives and developing countries.

Alternative tests have a role in vaccine testing, especially to confirm production consistency. Given the characteristics of these alternative tests and of the products for which they may be used, there are several factors which will influence their use. These include a good understanding of the test and the product to be tested, strong national regulatory infrastructure, a laboratory run in accordance with the principles of laboratory quality systems, and the ability to validate the alternative method. This means that national regulatory authorities will need strong expertise in epidemiology and quality assurance to complement laboratory experience.

Animal Testing Alternatives↗
PubMed1999

Auto-disable syringes for immunization: issues in technology transfer.

WHO and its partners recommend the use of auto-disable syringes, "bundled" with the supply of vaccines when donor dollars are used, in all mass immunization campaigns, and also strongly advocate their use in routine immunization programmes. Because of the relatively high price of auto-disable syringes, WHO's Technical Network for Logistics in Health recommends that activities be initiated to encourage the transfer of production technology for these syringes as a means of promoting their use and enhancing access to the technology. The present article examines factors influencing technology transfer, including feasibility, corporate interest, cost, quality assurance, intellectual property considerations, and probable time frames for implementation. Technology transfer activities are likely to be complex and difficult, and may not result in lower prices for syringes. Guidelines are offered on technology transfer initiatives for auto-disable syringes to ensure the quality of the product, the reliability of the supply, and the feasibility of the technology transfer activity itself.

Disposable Equipment↗
PubMed1997

Development of a more thermostable poliovirus vaccine.

In 1991, a goal of improved thermostability of oral poliovirus vaccine (OPV) was set, and the Product Development Group was established under the Children's Vaccine Initiative to achieve this goal. Several initial research strategies were unsuccessful. The substitution of deuterium oxide for water in the final blending stage of vaccine production resulted in a significantly more stable product at temperatures of > or = 37 degrees C. A large body of clinical data shows the safety of deuterium at the dosage that would be given with this vaccine. However, reservations about the public acceptability of the vaccine, combined with the progress achieved in polio eradication with the current vaccine and the availability of vaccine vial monitors to indicate time and temperature exposure of every vial of OPV, have resulted in a recommendation that vaccine development cease. This product development activity has been instructive for the process of introduction of new vaccines.

Deuterium Oxide↗
PubMed1996

Global DTP manufacturing capacity and capability. Status report: January 1995.

A recently completed survey of 63 manufacturers of diphtheria-tetanus-pertussis (DTP) vaccine and its components in 42 countries shows that there is potentially a large excess installed capacity for DTP production. However, many manufacturers are not producing to capacity, and demand and supply for this vaccine are not matched in individual countries. About half of all countries producing DTP vaccine and its components do not have fully functional national control systems, and some countries are performing none of the critical functions for an effective control of quality. Thus, potential for export of excess capacity is limited. The data collected indicate much homogeneity in the preparation of diphtheria and tetanus toxoids. Nearly all manufacturers use the same seeds and similar purification methods, but there is variability in whether purification is done before or after conversion of toxin to toxoid. About 10% of all manufacturers do not meet WHO-defined standards of purity for these toxoids. There is much more heterogeneity in the pertussis seed strains and the methods of purification used. The formulation of DTP vaccine differs considerably among producers. Potency testing is not being done by the WHO-recommended method by about 50% of manufacturers on lots of diphtheria and tetanus toxoids for release. Testing of irreversibility of conversion of toxin to toxoid, a WHO-specified safety test, is also not being done on each lot of diphtheria toxoid by 15% of manufacturers surveyed nor on each lot of tetanus toxoid vaccine by 30% of manufacturers surveyed. Access to technology to develop new DTP-based combination vaccines will be delayed if these manufacturers cannot ensure consistent high quality vaccine for their target populations. The results and conclusions suggest areas for future activities to strengthen the supply and quality of DTP and DTP-based combination vaccines.

Chemistry, Pharmaceutical↗
PubMed1996

Regulatory considerations for new stabilised poliovaccines.

As the least heat stable vaccine used by national immunization programmes, oral poliovaccine (OPV) is a target for improved stability. Dilution of OPV trivalent bulk vaccines meeting all international requirements in 87% deuterium oxide results in a significant stability increase of up to 1000-fold after incubation for one week at 45 degrees C. Regulatory considerations for a new formulation focus generally on the safety, potency and efficacy of the individual components (OPV and deuterium oxide) and ruling out any untoward and unexpected interactions between them. As the characteristics of OPV and deuterium oxide are well established, preclinical and clinica, data should address potential interactions. Because this stabilised vaccine is under development by two European manufacturers, initial regulatory discussions are being conducted with the European Medicines Evaluation Agency and its Committee on Proprietary Medicinal Products.

Child, Preschool↗
PubMed1996

Performance and potency of tetanus toxoid: implications for eliminating neonatal tetanus.

Neonatal tetanus (NT) is a major cause of mortality in developing countries, with over 400,000 deaths estimated to occur annually. WHO has adopted the goal of eliminating NT worldwide, and a major strategy for its prevention is the administration of at least two properly spaced doses of tetanus toxoid (TT) to women of childbearing age in high-risk areas to protect passively their newborns at birth. In certain countries the locally produced TT vaccine has been shown to be subpotent, while other countries have reported NT among infants born to vaccinated women. An extensive review of production and quality control procedures was carried out between 1993 and 1995 in 8 of 22 TT-producing countries that also report NT cases, with a more superficial assessment being carried out in the remaining 14 countries. Only 4 of the 22 countries have a functioning national control authority to monitor TT production and vaccine quality. A total of 80 TT lots from 21 manufacturers in 14 of the 22 NT-reporting countries were tested for potency. Of these, 15 lots from eight manufacturers in seven countries had potency values below WHO requirements. TT potency can also be compromised by improper vaccine handling. To eliminate neonatal tetanus worldwide requires assurance that all doses of TT meet WHO production and quality requirements and that the field effectiveness of TT is monitored through systematic NT case investigations and assessment of coverage.

Adolescent↗
PubMed1994

Paralytic poliomyelitis: seasoned strategies, disappearing disease.

With more than 2 years having elapsed since the last case of paralytic poliomyelitis occurred in the Western Hemisphere, significant progress has been made towards the global eradication of wild polioviruses. Poliomyelitis is disappearing from Europe, North Africa, Southern Africa, the Middle East, China, and the Pacific. Reported poliomyelitis cases declined to 15,587 cases in 1992. Current eradication strategies recommended by the World Health Organization include national mass campaigns administering oral poliovaccine to all children under 5 years of age, enhanced surveillance to detect cases of acute flaccid paralysis, creating a network of laboratories for viral diagnosis, and targeted immunisation to areas and populations where poliovirus transmission is likely to persist. The major obstacles to eradication include inadequate political support for eradication and insufficient funding, especially for the purchase of vaccine. With additional support for the international eradication effort, epidemics of poliomyelitis will cease in developing countries, and industrialised countries will be able to save the large sums spent each year on poliovaccine and rehabilitation.

Global Health↗
PubMed1994

The crisis in vaccine supply: a framework for action.

Immunization programmes, having made significant progress in protecting over 80% of the world's children against six vaccine-preventable diseases, are now facing a crisis in funding for their vaccine supply. Contributing to this situation are changing donor priorities, rising prices, increased needs for vaccines. The Task Force on Situation Analysis for Vaccine Supply (TFSA) of the Children's Vaccine Initiative (CVI) has developed a framework which provides a logical division of countries into groups that might share similar vaccine supply systems. This framework provides a basis on which to analyse the needs and potential solutions for vaccine supply in countries based on their populations, national wealth, and current ability to produce vaccine. This framework has facilitated the development of strategies to strengthen national vaccine supply systems. It has also provided guidance for governments, donors and development agencies on the most appropriate actions for assuring the objective of sustainable vaccine supply.

Child↗
PubMed1994

The thermostability of vaccines. Technologies for improving the thermostability of the oral poliovirus vaccine.

Technologies that promise to enhance the stability of vaccines are likely to be determined by the product-specific physical structure and biological functions of the specific vaccine immunogens. Research may define the extent to which the stability of oral poliovirus vaccine may be improved by the addition of certain antiviral components that bind to the poliovirus capsid or by the application of novel drying technologies.

Capsid↗
PubMed1993

The WHO-EPI initiative for the global eradication of poliomyelitis.

Since the development of attenuated oral polio vaccine, Dr Albert Sabin consistently maintained that the global eradication of wild poliovirus was possible, but that to achieve polio eradication in developing countries would require the mass administration of the oral vaccine. Experience in Cuba and Czechoslovakia proved the effectiveness of this technique, but it was only with its deployment in Brazil in 1980 that its role in eradicating the virus from a broad geographical area started to be realized. With the declaration in 1985 of a target of regional polio eradication, extension of this policy, allied with the development of effective surveillance of acute flaccid paralysis in children, with laboratory confirmation of diagnosis rapidly led to apparent interruption of wild poliovirus transmission throughout the Americas. The World Health Assembly in 1988 committed WHO to the global eradication of poliomyelitis. Based on experience in the Americas and building on the solid foundation established by the Expanded Programme on Immunization, WHO has defined the strategies through which the global target could be achieved. Progress is encouraging and where the advocated strategies have been fully implemented, the incidence of poliomyelitis has declined dramatically. Significant geographical areas in Western Europe, the Maghreb, the Arabian peninsula, the Pacific basin and Southern Africa, each incorporating several countries, are now thought to be free of the disease caused by wild poliovirus. The target of a world free of polio by the year 2000 can be achieved.

Developing Countries↗
PubMed1990

Quality control of BCG vaccine by WHO: a review of factors that may influence vaccine effectiveness and safety.

WHO oversees the quality control of BCG vaccine via a system that includes regular testing of products by in vitro methods and clinical trials. Three parent strains of BCG (Glaxo-1077, Tokyo-172, and Pasteur-1173P2) account for over 90% of the vaccines currently in use worldwide. Important characteristics of the vaccine preparations are summarized here, along with their physical-chemical properties. In instances where diagnostic criteria for tuberculosis are stringent, there is no evidence that when administered to newborns different preparations of BCG vaccine exhibit different efficacies; however, the incidence of BCG-associated adverse reactions does correlate with the type of preparation. Other factors, including dose, administration technique, and recipient characteristics are also important in determining vaccine-associated reactions.

BCG Vaccine↗