Developments in biological standardization最新文献

Biological materials are variable by their very nature. Serum in particular is a complex mix of substances and may contain adventitious agents. Serum for pharmaceutical use is controlled on a batch to batch basis given that each batch may have differing properties. Control points for slaughterhouse obtained bovine and foetal bovine serum exist with the disease status and disease surveillance of the country of origin, veterinary inspection for clinical disease, collection methods and post collection quality control. With these control points many batches of commercially available serum are contaminated with viruses such as BVD. The use of donor serum provides a mechanism to extend Good Manufacturing Practice principles back to the farm environment giving the manufacturer the ability to increase control on production parameters in the donor animal such as disease and specific antibody status, genetic type and history, age, diet, treatments and origin of feed. As well as providing a secure supply of serum for manufacture, donor herds provide added traceability and give the opportunity for in vivo manipulation of the serum and specialised selection of the animals for specific applications with more consistent reproducibility of performance. The BSE crisis of the last 10 years has highlighted the added control that donor serum producers can exert: Many producers of donor serum applied ruminant feed bans on their animals ahead of nation-wide bans in their own countries. SPF donor herds can be set up in several ways and the purchaser should make themselves familiar with the methods used. SPF herds with accompanying seronegative status allow quality control testing of product free from the interference of specific antibodies. Such specific antibody freedom may also allow better growth of viruses for vaccine manufacture.

Animal cell lines are increasingly used in the manufacture of viral vaccines. They may play a key role in the preparation of seed stock virus and vaccine production. However, the same animal cell substrates may also be used for diagnosis of viral infection and surveillance of prevalent virus strains. Quality control of cell lines intended for use in this range of procedures is vital to ensure the absence of contaminating organisms and correct identity of the substrate cells used. Furthermore, the qualification and validation of the procedures, facilities and staff involved in the cell culture and testing are also important issues addressed in regulatory guidelines and regulations. The standards to which these activities are performed are dependent on whether the cells are intended for diagnostic and surveillance work or for seed stock virus isolation and production. This paper indicates when and how some of the relevant quality standards and quality control issues apply to cell lines intended for the different procedures involved in virus isolation and vaccine production.

The Australia Influenza Vaccine Committee makes independent decisions concerning the influenza vaccine formulation for Australia. Large-scale cell culture using MDCK cells would improve response time for vaccine production in the face of a new pandemic. There must be a consensus with respect to the use of MDCK or other cells before the next pandemic. It is unrealistic to expect any national regulatory authority to determine what safety requirements should be met before approving a cell substrate for vaccine production during an influenza pandemic. Regulatory issues seen as obstacles to the approval of MDCK cells as an accepted cell substrate for influenza vaccine production are identified.

Research always depended on animals or directly on human beings for the generation of antibodies with new specificities. With the opportunity to clone the human antibody repertoire, it is now also feasible to tap the human immune system and to search for new antibody specificities in antibody gene libraries [1, 2]. Phage display technology has fostered these approaches as it allows even rare specificities to be identified in libraries of a complexity of 10(8) to 10(10) [3, 4]. While most of the work in this field is still based on immune libraries, that is, B-cells derived from immunised animals or human individuals, more recent approaches allow even the necessity for immunisation to be by-passed. Synthetic antibody libraries exist of a complexity comparable to the natural immune system of mammals, so that theoretically every imaginable antibody may be detected and then used either for diagnostic or therapeutic purposes [5-7]. Thus, these new gene technology approaches make it possible to generate antibodies completely independently of animals. It may be that animals will only be used in the future to study the immune system of the animal.

It is important, both morally, scientifically and legally, that animal experimentation causes the minimum amount of suffering necessary to achieve the scientific objective. This paper describes an approach that facilitates the recognition and assessment of animal pain and distress through the use of clinical signs. The score sheet system can help to indicate new scientific responses, as well as to determine and to validate humane end points in the safety testing of biological products using animals. Some examples are given.

The potency of several novel botulinum toxin-derived biological therapeutic products now in routine medical use is determined exclusively by in vivo methods. In addition, large numbers of animals continue to be used for the potency and safety testing of therapeutic antitoxins and toxoid vaccines. There is thus an increasing need to develop acceptable alternative assays for toxicity testing of clostridia neurotoxins which could be applied to different toxin derived therapeutic agents, including vaccines. Scientific advances in the understanding of the mode of action of clostridial neurotoxins have now provided the basis for improving conventional testing procedures.

Recounting the origination and development of the concepts and institutions to foster and control new and existing biological products is a fertile subject for historical review. It describes what was a necessary and functional activity that needed to be brought into being. The earliest examples of biologicals regulation were created by the eighteenth century inventors themselves and became progressively institutionalized by the creation of national control authorities which increased in number and sophistication during the past century. In 1948, the World Health Organization (WHO) was established and created biological standards and regulations as an advisory to member nations. This too has grown in sophistication and is now of central importance in the biologicals enterprise worldwide. The field of biological standardization and regulation can be viewed in its need and role to foster technological development and to assure that the products of that endeavour are worthy and are retained. In many respects, it is a tale of troubles, tragedies, and triumphs and this is recounted in the text.