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International audience; Infectious disease outbreaks, such as 'Coronavirus disease 2019' (COVID-19), can constitute major global health threats with far-reaching consequences. As outbreaks develop, the international scientific community must provide high-quality scientific research-ready biological samples to solve the existing clinical and epidemiological questions to better combat the pandemic. Such examples are provided by dedicated biobank facilities, the latter collecting increasingly high volumes of biological samples. However, the more significant concentrations of infectious or potentially infectious biological materials can create a safety risk. The current short report describes the first attempt to identify the published scientific works on biobanking and safety. Three broad thematic areas have been identified: the physical security relevant to staff and sample integrity, the data safety aspects, and the governance parameters relating to the previous two. While the current publications reflect a broad alignment with existing standards and best practices in the biobanking field, they also demonstrate an opportunity for further in-depth work on this field in the post-COVID-19 era.

Routine and catastrophic animal mortalities in animal-agriculture systems poses numerous challenges in terms of animal and public health. In addition, environmental pollution is a major issue. Controlling microbial contamination issues requires implementation of safe carcass disposal methods. The risk of pathogen contamination during composting and rendering of animal products is an important and contemporary issue and has evidenced a great interest among the researchers. Increasing interest in public health and food safety evidenced by a large number of recent publications clearly indicates to the necessity for comprehensive review studies that assimilate knowledge from multidisciplinary fields to cover the issues of pathogen contamination in carcass disposal methods in order to present and address the problem as a whole. Rendering process is the leading method for carcass disposal in developed and many developing countries. It is vital for the rendering industry to apply appropriate methods during rendering to produce the finished products which are free from pathogenic bacteria. Although the typical time-temperature combinations used in rendering industry are theoretically considered adequate to completely kill the prevalent pathogens, the incidences of pathogenic contamination in rendered products have been reported from time to time. This necessitates extra precautions for producing safe rendered products and examining the rendering process and premises overall. This study reviews the possibilities of microbial contamination of rendered products and the efficacy of rendering process in pathogen inactivation. While current rendering practices are extremely helpful in controlling pathogenic contamination in the rendered products, this study included the additional biological safety measures required to ensure pathogen-free rendered products.

Designing the biological safety program is our opportunity to define risk control. However, if our biological safety program is solely based on testing, it is then solely reactive. I test and discover that my product is likely biocompatible or has some issues that could compromise biological safety. I have a program based on pass or fail. I have wasted time and money only to find out that I have a problem. This is not the best approach. Biological safety is a control program. Therefore it is a feedback loop mechanism. The control of adverse events is based on intended use, the materials of construction, and the manufacturing materials and processes. Biological safety must be designed into the product. Equal emphasis must be placed on the materials and the process relative to intended use.

In China, current active regulation of biological evaluation of medical devices is CFDA announcement of 2017 No. 345. Submitted document requirements of biological evaluation have been identified in CFDA announcement of 2014 No.43. These two regulations were introduced in this chapter. Biological safety testing in China should conform to GB/T 16886 series standards. Although GB/T 16886 series standards are adopted equivalently from ISO 10993 series standards, there are still some time gap and version differences. In addition, there are also some specific requirements or standards in China for biocompatibility tests. This chapter also outlines the Chinese standards and requirements for biological safety tests of medical devices.

ISO 10993-1:2009, Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing within a Risk Management Process states that this “document should serve to be the framework of a plan for a biological evaluation.” ISO 10993-1 indicates that such a plan “should minimize the number and exposure of test animals by giving preference to chemical constituent testing and in vitro models in situations where these methods yield equally relevant information to that obtained from in vivo models.” It stresses the fact that animal testing should not be used to uncover information that is already known. The document also states that biological safety evaluations “must be planned” in advance. It is a working document of execution. It should document what should be done, when it should be done and why. Thus the overall value of the biological safety evaluation plan is that it defines the evaluation of the unknown so that a sufficient amount of information can be evaluated and risk can clearly be understood and characterized.

Medical devices and the materials they are composed of need to be evaluated for their safety within the context of a risk management process. Safety issues related to toxicity can be evaluated using the ISO 10993 series of international standards for biological evaluation of medical devices. It provides an approach that combines the review and evaluation of existing data from all sources with, where necessary, the selection and application of additional tests, thus enabling a full evaluation to be made of the biological responses to each medical device, relevant to its safety in use. This chapter focuses on the various test methods, both in vitro and in vivo, that can be used for this evaluation. In addition to general in vitro cytotoxicity tests, more specific in vitro tests for genotoxicity, interaction with blood, and irritation are highlighted. Furthermore, in vivo tests for irritation and sensitization, haemocompatibility, genotoxicity, implantation and systemic toxicity are described in detail.

Several chemical hazards have been fount to be related to cured meat products. N-nitroso-compounds (NOCs) and polycyclic aromatic hydrocarbons (PAHs) were considered to increase the odds of colorectal cancer, as recently reviewed by the International Agency for Research on Cancer. This health concern involves products in which nitrites, nitrates, and smoking are used, but is especially linked to ready-to-eat meat products, namely dry-cured products (DCPs), where both of these risk factors are used simultaneously. Although the dry-curing process was a way to preserve meat products for a longer time, nowadays they earned their own status, being widely spread in gastronomy. Nitrite and smoking are used in DCP for safety and organoleptic purposes. The necessary reduction or elimination of nitrite and smoking in DCP must consider the control of significant foodborne pathogens, namely Clostridium botulinum, Staphylococcus aureus, Listeria monocytogenes, and Salmonella, and the sensory quality of DCP must meet the consumer’s acceptability criteria. This review aims to present strategies to reduce the use of nitrite and smoking in DCP, while assuring biological safety and maintaining the quality of these traditional products, namely through the use of natural ingredients, bacteriocins, edible active coatings, high hydrostatic pressure, and other emergent technologies.

Ceramics have been successfully used for more than 40 years for orthopedic prostheses, as articulating bearing surfaces against ceramic or polymer components. Nowadays, ceramics remain one of the most used biomaterials in the orthopedic field. Despite the outstanding performance of ceramics, some issues related to their failure still remain, requiring the strong contribution of scientific research to provide resolution to such issues. This paper traces the history of the ceramic materials used in orthopedic clinics, highlighting their mechanical properties and the chemical and physical characteristics, emphasizes the different innovations that have occurred over the years, and finally provides a detailed analysis of the main causes of failure of ceramic hip implants. Alumina was selected as a biomaterial around 40 years ago for its unsurpassed biological safety and stability in the living environment. However, the intrinsic properties of pure alumina limit its mechanical properties, especially the low fracture toughness. For this reason, development of composites was pursued, as a new class of ceramic biomaterials to be used in orthopedics. However, total hip implants present some failures due various causes: i.e., mismatch in female-to-male taper, roundness, roughness or linearity errors in the taper, severe traumatic accidents, etc., which are revised and discussed in the frame of this chapter. Therefore, the aim of this contribution is to illustrate the properties of the ceramics used in total hip arthroplasty and to revise the causes of failures of these biomaterials.

The features of manufacturing for cell therapy and regenerative medicine are described by considering stability of operations to take process consistency and maintenance of aseptic environment to prevent the extrinsic contamination, processing independency to prevent cross-contamination and operational confusion, biohazard containment for nonproliferation of contaminants, and their routine managements. In addition, the facility designs using biological safety cabinet and isolator for cell processing are discussed. The advantages of isolator technology lead to the development of the flexible modular platform, realizing the flexible combination of isolator modules such as the manual operation module and incubator module to enhance process versatility accompanied by safety, security, and cost-saving.

Emerging trends in medical plastic engineering may be triggered by many different reasons, whereas the whole world of regulatory affairs is definitely a key player within. Medical devices in general and plastic medical devices in special are regularly under scrutiny regarding actual benefits and risks. For dozens of years, many regulations for medical devices have been established around the world with the USA and European Union playing major roles. Introducing new legislation and simply to its huge market size, China will get more important as well. The aim of this chapter is to introduce the targeted reader into the world of regulations for medical devices first. Afterward, the focus shifts to the deriving impacts of these regulations or changing rules on future medical devices and therefore they do affect emerging technologies fundamentally.

Burkholderia cepacia is regarded as a genetically distinct but phenotypically similar bacteria group referring to Burkholderia cepacia complex (Bcc), which is found not only in clinic but also in rice growing environment. It is very important in microbial safety of rice for us to understand the genomovar status of Bcc. Genomovar analysis was performed among 87 Bcc isolates by means of Hae Ⅲ-recA RFLP assays and species-specific PCR tests. Three genomovars were found from the rice rhizosphere includingⅠ, ⅢB and Ⅴ, and genomovar Ⅴ was predominant. GenomovarsⅠ, ⅢA and ⅢB existed in the clinical samples, and genomovar ⅢA was the most popular. It showed that genomovar composition was different between the Bcc strains from the rice rhizosphere and clinical environment. Simultaneously, the results revealed the genetic diversity of Bcc strains from the rice rhizosphere, and genomovar Ⅲ referred as virulent species in clinic also existed in the rice rhizosphere.

The beginning of this chapter provides an overview of the processes, directives, and standards that are relevant for the market authorization of implants. Since standards are very important for marketing authorization of implants, the next section focuses on their meaning, classification, development, and use. The second part of the chapter discusses the biological evaluation of degradable magnesium implants and possible modifications of standard International Organization for Standardization protocols, especially for the cytotoxicity testing of magnesium alloys. Finally, a short review of the current scientific test methods summarises the options for the evaluation of the biological safety of innovative magnesium implant materials.

Successful cleaning of medical devices and instruments requires both careful selection of materials and consistent monitoring of the procedures used to process them. Chemical characterization of residues that may be adsorbed onto surfaces and mechanical testing to ensure functionality should provide sufficient information to evaluate the potential success of cleaned and disinfected/sterilized medical devices. By using a combination of chemical and mechanical analysis techniques, both manufacturing and decontamination processes can be optimized to insure a safe and effective product. Choosing the optimal testing protocols, interpreting results, selecting the appropriate chemistries, and implementing rugged, reliable processes require experienced advice and input. It is important to note that no test, however foolproof its design, can ever be considered a definitive predictor of clinical performance. This chapter will examine various kinds of contaminants associated with medical devices and explore various analytical techniques to detect their presence or absence. The use of toxicological risk assessment as a way to set residue limits and as a method to evaluate the overall biological safety of any remaining or detected contaminants left on medical devices will be discussed.

ISO 10993-1:2009, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process states that this ‘document should serve to be the framework of a plan for a biological evaluation’. ISO 10993-1 indicates that such a plan ‘should minimize the number and exposure of test animals by giving preference to chemical constituent testing and in vitro models in situations where these methods yield equally relevant information to that obtained from in vivo models’. It stresses the fact that animal testing should not be used to uncover information that is already known. The document also states that biological safety evaluations ‘must be planned’ in advance. It is a working document of execution. It should document what should be done, when it should be done and why. Thus the overall value of the biological safety evaluation plan is that it defines the evaluation of the unknown so that a sufficient amount of information can be evaluated and risk can clearly be understood and characterized.

This chapter presents the concepts of biorepositories, biosafety, and professional ethics. A biorepository is a collection of human specimens and associated data for research purposes, the physical structure where the collection is stored, and all relevant processes and policies. Biorepositories pose specific ethical issues. The participant donating a specimen, be it blood, urine, or tissue, expects that the specimen will be valued, that it will be handled and stored appropriately, and distributed as needed so it will contribute to scientific knowledge. Further, the participant expects that the users of the donated specimens will respect his or her privacy, and that the specimen(s) will be used only in ways consistent with the consent granted. Biological safety means using infectious and other hazardous materials safely in the laboratory, and reducing or eliminating the exposure of laboratory personnel, other personnel, and the outside environment. The primary principle is that of containment. Professional ethics for epidemiology and public health are not regulated. However, there is a code of ethics for the practice of epidemiology that has been adopted by several epidemiology societies and for public health professionals, which has been approved by the American Public Health Association. These general principles are summarized in the chapter, with particular examples relating to molecular epidemiologic studies.

Medical devices and medical device materials must be designed to achieve specific criteria for safety and performance. The criteria themselves may be constrained by physical, chemical, and material limitations, and by biochemical, molecular, and cellular processes within the body recognized to take place upon blood contact. In the latter case, responses can be favorable or unfavorable, partially controlled by learned approaches, for example antithrombotic drugs, or be uncontrollable by current experience and know-how. As such, determining what testing is required and which test results are acceptable and meaningful in the development of a new medical device can be complex. This chapter highlights some of the main considerations in the specific area of evaluation of blood-contacting medical devices and materials. It discusses the main factors that may impact the blood-device/material responses that can occur, and it provides examples of some of the most common observations and approaches to manage the response. As the international standard ISO 10993-4 has been and continues to be a major driving influence behind this aspect of the biological safety evaluation of materials and devices, the evolving direction of the standard is covered and controversies in testing are reviewed. Ultimately, appropriate care taken to evaluate and understand critical blood-device/material interactions in each unique application leads to predictive and safe use in humans.

In this chapter the traditional methods to assess biological safety are placed in the context of a new way forward with test procedures that reflect the biomaterials of the future, since both our understanding of biocompatibility phenomena, and the uses and expectations of these new biomaterials, are undergoing radical change. The main issue here is that, historically, biomaterials have been designed to be as inert as possible, but this approach is of limited value in applications that demand some form of biological functionality. The problems of existing in vitro and in vivo test procedures are explained within the framework of a new understanding of the mechanisms of biocompatibility.

In Japan, unified and original guidelines for biological safety evaluation based on ISO 10993 of medical devices have been implemented since 1995. Since then, the Japanese authorities issued and revised Japanese guidelines, but there have been no marked changes in the basic way of thinking. In recent years international mutual understanding has progressed, Japan’s safety evaluation way such as exhaustive extraction method has been introduced into various parts of the ISO 10993 series, and the latest ISO 10993 has been adopted for Japanese guidance. The basic test methods used in Japan do not differ from those used outside Japan for most test items. However, there is a perception gap in sample preparation applied to these tests. In Japan, the basic stance is to eliminate all risks systematically. This stance is especially prominent in cytotoxicity tests, sensitization tests and genotoxicity tests. In addition, there is a perception gap also in classification of medical devices. Focusing on these points, this chapter outlines the Japanese guidance for biological safety tests of medical devices.

The importance of materials to the medical device industry cannot be over emphasized. Along with increased demand for medical grade materials, the medical device industry has renewed its awareness and concern for the safety of materials used. An essential part of establishing biological safety is the implementation of chemical and material characterization testing. Chemistry is often called the central science because of its role in connecting the physical sciences, which include chemistry, with the life sciences and applied sciences such as medicine and engineering. This role of chemistry as the central science is very important to medical device evaluations and is noticeably evident in the ISO 10993 approach to the biological safety evaluation of medical devices and biomaterials. Parts 18 and 19 of the 10993 series of standards are receiving even more emphasis, as they become an integral part of the biological evaluation of medical devices. An important step in the process is that of characterizing the material and identification of chemicals that can migrate or extract from the polymer components. Such basic information is critical to understanding the biological response and toxicological risk of the device since adverse effects caused by materials are generally chemical effects. In recent years there has been a great deal of discussion of the merits of chemical and material characterization. Considering the intrinsic worth of chemistry and materials characterization to biocompatibility, it seems very likely that chemical characterization will receive even more attention in the future.

Designing the biological safety program is our opportunity to define risk control. However, if our biological safety program is solely based on testing, it is then solely reactive. I test and discover that my product is likely biocompatible or has some issues that could compromise biological safety. I have a program based on pass or fail. I have wasted time and money only to find out that I have a problem. This is not the best approach. Biological safety is a control program. Therefore it is a feedback loop mechanism. The control of adverse events is based on intended use, the materials of construction, and the manufacturing materials and processes. Biological safety must be designed into the product. Equal emphasis must be placed on the materials and the process relative to intended use.

Although the origin of the development of alumina as a biomaterial can be traced back to 1930, its successful use as a biomaterial is based on the studies carried out in the early 1970s in France, Germany, and Japan. Alumina has 40 years of clinical record in the field of orthopedics, where it is used in the manufacture of balls and cups for hip replacements and has proven its effectiveness in limiting the bearing wear. The arthroplasty of the hip is one of the most successful surgeries, with very positive outcomes but its success is hampered in a number of cases by the insurgence of osteolysis, a device-induced pathology, which also arises out of the reactions induced by the wear debris. This explains the interest shown in minimizing the wear of bearings in arthroplasty and the continuous efforts taken to improve the materials selected for this task. This chapter outlines, from an historical perspective, the development of alumina as a biomaterial, reviews the properties of this ceramic that are relevant for its clinical use, with emphasis on the studies performed on the biological safety of alumina and of its wear debris. Special attention is devoted to the use of alumina in total hip replacement (THR) bearings, which is the main application of alumina as a biomaterial today, while a section is devoted to the use of this ceramic biomaterial in the knee and to the ongoing development of alumina matrix composites.

Publisher Summary This chapter explains how researchers can plan and make choices appropriate to their experimental, environmental, and financial resources. Cell culture needs a commitment of energy and resources to be undertaken in a professional manner for any continuous period. Small cell culture facilities can be engineered without making significant modifications to laboratory rooms. Eukaryotic cells are also very sensitive to the primary and secondary metabolic products of microbes. Bacteria and fungi are therefore the biggest problem, for those growing eukaryotic cells. Eukaryotic cells can potentially harbor sub cellular microbes that could cause disease in human beings or animals. Ventilation and airflow in the cell culture environment are critical to the operation. At its simplest, there must be no disruption to the laminar airflow pattern in the biological safety cabinet and no undue circulation of dust and dirt that could occur with, for example, significant staff movement around the unit or location near drafts or vents.

Summary - In July of 1992 representatives of most countries in the world will attend in the city of Rio de Janeiro, Brazil, the UNCED - United Nations Conference on Environment and Development. The agenda for this conference will certainly include controversial issues which have been discussed for decades by developing and developed countries, without a foreseeable consensus. These are, however, the issues of this decade and can be no longer postponed. They include matters such as environment protection, germplasm conservation and availability, biological safety, intellectual property rights, technological and economical development. At the root of all the discussions are expectations among developed countries that a significant effort is necessary on the part of developing countries that will lead to a common understanding and strategy to approach the first four items. Developing countries view the need to reconcile this effort with goals which ultimately lead to social and economical development. As a scientist and as a member of the Working Party on Biotechnology for the UNCED, I have discussed these matters on several occasions at international meetings. Our observations indicate that the interfaces among these issues are so significant that no isolated solutions will be possible. I will present my view and a very brief update on some of these matters, from the perspective of a scientist working in a developing country (Brazil) of Latin America.

Publisher Summary This chapter discusses guidelines, legislation, and labor relations of the Genetic Manipulation Advisory Group (GMAG). The safeguards proposed by Ashby and his colleagues in Ashby Report in 1976 included a knowledge of the techniques of handling pathogens; equipment necessary for the containment of pathogens; funding bodies to enquire any new research proposals whether any new research proposals involve any biological hazard; the designation of a biological safety officer within each institution to advise on the appropriate level of precautions; an active search for improvements in biological containment; the performance of tests of pathogenicity on animals and of health monitoring of workers involved in the research; and long-term epidemiological studies on the health records of those involved in the work. The William Working Party in its Report, published in 1976, elaborated in detail the practical implementation of these safeguards and advocated the central code of practice.