Select agent regulations

In recent years, there has been an increase in research with biological agents, particularly those that pose a potential for use by terrorists. In this environment, laws have been enacted and regulations developed to ensure the appropriate use of specified "select agents and toxins" for legitimate research. Within this regulatory environment, it has been necessary for institutions and investigators to adapt to an entirely new set of requirements to begin or continue to work with these pathogens. Registration and approval for use of select agents and toxins, security and safety requirements, and daunting record-keeping requirements are only some of the regulatory challenges that researchers face in working with these agents. A brief overview of recent regulations is presented, as well as where to obtain additional information on regulations, standards, and guidelines related to work with select agents and toxins.     

Administrative issues related to infectious disease research in the age of bioterrorism

The recent unprecedented growth in infectious disease research funding and infrastructure has resulted in part from an outgrowth of concern about newly emerging and re-emerging diseases and the progressive development of antibiotic-resistant pathogens. However, the most compelling impetus is the suspected and demonstrated capability and will of unknown individuals, groups, or states to use biological agents and/or toxins as weapons. Although the actual number of known victims and fatalities from bioterrorism in the United States has been miniscule compared with many other daily hazards, biological agents have the potential to cause human mass casualties, severely damage segments of our economy or agricultural infrastructure, poison or compromise our food or water supply, and, perhaps most damaging, disrupt our society physically and psychologically. The significant institutional commitment necessary to participate in infectious disease research is described, with a focus on programs that involve research with pathogens thought to have potential for use by bioterrorists. Administrative considerations are described, and include obtaining necessary research funding to offset high operating costs; complying with "select agent" regulations, security screening of employees; building or renovating a biocontainment facility; finding skilled professional and technical manpower; providing adequate physical security in a threat environment; conducting targeted training; overcoming potential internal and external dissent; developing and/or providing sufficient occupational health and safety programs; achieving and maintaining compliance standards in a fluid regulatory environment; mitigating potentially hazardous working conditions; understanding personal and institutional liability; and reassuring and dealing with a concerned, skeptical, or even hostile public.     

Comparison of requirements in the European Union and United States of America for pre-clinical viral safety testing of veterinary vaccines

Of paramount importance in ensuring the safety of live and inactivated veterinary vaccines is demonstration of freedom from extraneous agents in biological starting materials used in their production. Both the European Union (EU) and United States of America (US) provide regulations and guidelines on extraneous agent testing of veterinary vaccines including guidance from the Committee for Medicinal Products for Veterinary Use (CVMP), the European Pharmacopoeia (Ph. Eur.) and the USDA Code of Federal Regulations, Title 9 (9CFR). There are distinct requirements prescribed in EU and US regulations and guidelines. The differences in EU and US requirements for extraneous agent testing of starting materials are such that there may be occasions when no one test may satisfy both sets of regulations for a given scenario. For compliance with both, for global licensing purposes it may therefore be necessary to perform additional tests and/or to justify methods chosen from one set of regulations over another, based on a variety of factors.     

Best practices for the use and exchange of invertebrate biological control genetic resources relevant for food and agriculture

The Nagoya Protocol is a supplementary agreement to the Convention on Biological Diversity that provides a framework for the effective implementation of the fair and equitable sharing of benefits arising out of the utilization of genetic resources, including invertebrate biological control agents. The Protocol came into force on 12 October 2014, and requires signatories and countries acceding to the Protocol to develop a legal framework to ensure access to genetic resources, benefit-sharing and compliance. The biological control community of practice needs to comply with access and benefit sharing regulations arising under the Protocol. The IOBC Global Commission on Biological Control and Access and Benefit Sharing has prepared this best practices guide for the use and exchange of invertebrate biological control genetic resources for the biological control community of practice to demonstrate due diligence in responding to access and benefit sharing requirements, and to reassure the international community that biological control is a very successful and environmentally safe pest management method based on the use of biological diversity. We propose that components of best practice include: collaborations to facilitate information exchange about what invertebrate biological control agents are available and where they may be obtained; knowledge sharing through freely available databases that document successes (and failures); cooperative research to develop capacity in source countries; and transfer of production technology to provide opportunities for small-scale economic activity. We also provide a model concept agreement that can be used for scientific research and non-commercial release into nature where access and benefit sharing regulations exist, and a model policy for provision of invertebrate biological control agents to other parties where access and benefit sharing regulations are not restrictive or do not exist.     

农业生态安全及其生态管理对策探讨

对生态安全和农业生态安全的基本内涵进行了探讨。认为生态安全是指不同尺度的生态系统及其生物要素、环境要素、资源要素等在数量、质量及其相互作用关系上的一种和谐、健康、稳定的状态和水平。农业生态安全包括农业环境安全、农业资源安全、农业生物安全和农业产品安全等几个方面的内容。提出了一系列农业生态安全管理对策 ,包括 :①加强农业生态安全管理 ,发展生态产业 ;②加强对现有资源与生态系统的保护、培育与可持续利用 ;③保护农业生物多样性 ,保障生物安全 ;④加强农业综合抗灾能力建设 ;⑤加强农业生态安全监测与法律法规体系建设 ;⑥建立良好的、和谐的社会、经济和政治关系。     

毒素战剂的生防疫苗简

毒素战剂是重要的生物战剂之一,其最大的威胁来自它的高毒性和缺乏有效的防治手段。在毒素战剂中,肉毒毒素、志贺毒素、蓖麻毒素、相思子毒素等属于致死性生物战剂,葡萄球菌肠毒素B属于失能性生物战剂。生防疫苗作为毒素战剂的一种重要的有效预防手段,一直备受关注,但目前绝大部分毒素战剂的疫苗都还在研制中,随着分子生物学技术的快速发展,几种重要毒素战剂的重组疫苗研究已获得重要突破。我们重点介绍肉毒毒素、志贺毒素、蓖麻毒素、相思子毒素、葡萄球菌肠毒素B等毒素战剂生防疫苗的研究与发展。     

Manufacturing and characterization of extracellular vesicles from umbilical cord–derived mesenchymal stromal cells for clinical testing

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) may deliver therapeutic effects that are comparable to their parental cells. MSC-EVs are promising agents for the treatment of a variety of diseases. To reach the intermediate goal of clinically testing safety and efficacy of EVs, strategies should strive for efficient translation of current EV research. On the basis of our in vitro an in vivo findings regarding the biological actions of EVs and our experience in manufacturing biological stem cell therapeutics for routine use and clinical testing, we discuss strategies of manufacturing and quality control of umbilical cord–derived MSC-EVs. We introduce guidelines of good manufacturing practice and their practicability along the path from the laboratory to the patient. We present aspects of manufacturing and final product quality testing and highlight the principle of “The process is the product.” The approach presented in this perspective article may facilitate translational research during the development of complex biological EV-based therapeutics in a very early stage of manufacturing as well as during early clinical safety and proof-of-concept testing.     

Chemical safety in animal care,use, and research

Chemical safety is an essential element of an effective occupational health and safety program. Controlling exposures to chemical agents requires a careful process of hazard recognition, risk assessment, development of control measures, communication of the risks and control measures, and training to ensure that the indicated controls will be utilized. Managing chemical safety in animal care and use presents a unique challenge, in part because research is frequently conducted in two very different environments--the research laboratory and the animal care facility. The chemical agents specific to each of these environments are typically well understood by the employees working there; however, the extent of understanding may not be adequate when these individuals, or chemicals, cross over into the other environment. In addition, many chemicals utilized in animal research are not typically used in the research laboratory, and therefore the level of employee knowledge and proficiency may be less compared with more routinely used materials. Finally, the research protocol may involve the exposure of laboratory animals to either toxic chemicals or chemicals with unknown hazards. Such animal protocols require careful review to minimize the potential for unanticipated exposures of the research staff or animal care personnel. Numerous guidelines and regulations are cited, which define the standard of practice for the safe use of chemicals. Key chemical safety issues relevant to personnel involved in the care and use of research animals are discussed.     

AGAINST RISK-BENEFIT REVIEW OF PRISONER RESEARCH

The 2006 Institute of Medicine (IOM) report, 'Ethical Considerations for Research Involving Prisoners', recommended five main changes to current US Common Rule regulations on prisoner research. Their third recommendation was to shift from a category-based to a risk-benefit approach to research review, similar to current guidelines on pediatric research. However, prisoners are not children, so risk-benefit constraints on prisoner research must be justified in a different way from those on pediatric research. In this paper I argue that additional risk-benefit constraints on prisoner research are unnecessary: the current Common Rule regulations, omitting category-based restrictions but conjoined with the IOM report's other four main recommendations, ensure that prisoner research is as ethical as non-prisoner research is. I explain why four problems which which may be more prevalent in prisons and which risk-benefit constraints may seem to address – coercion, undue inducements, exploitation, and protection from harm – are in fact not solved by adding further risk-benefit constraints on prisoner research.     

Patented Biologically-inspired Technological Innovations： A Twenty Year View

1 Introduction Biomimetics or bionics is having an increasing role in innovation[1]. It offers the promise of novel routes to technological innovation; a recent paper highlighted the potential of studies of biological systems to initiate patents in the engineering sciences and technology[2]. Media coverage, particularly in business periodicals is increasing, for example, The Economist recently re- ported on the growth of biomimetics and its impact on technology[3]. There are two principal rou…     

Biorisk assessment of natural science laboratories of Bicol University College of Science,Philippines

A biorisk assessment of natural science laboratories in Bicol University was conducted as an initial step towards improvement of laboratories and contributing to a culture of safety in the university. Survey among laboratory workers and ocular inspection of natural science labs was done. Results showed that gaps exist in the safety knowledge and practices of laboratory workers. Microbial assets pose the lowest risk, while equipment and the use of chemicals in biological assays pose the highest risk. The likelihood that such events will occur ranges from low to moderate while consequences range from moderate to high. The research recommends that a policy on biological safety be formulated and be integrated in the overall safety guidelines of the university, that existing guidelines and SOPs be improved and that their implementation be monitored, to introduce a course for undergraduates that will tackle the basics of safety and security in the laboratory, and that the equipment and physical design be improved to reduce the risks to acceptable levels.     

Disclosure of genetic information obtained through research

The rapid expansion of information and knowledge of genetics has implications for the question of whether, and under what circumstances, information discovered in the course of genetic research should be conveyed to research participants and/or their relatives. The aim of this paper is to propose an ethically defensible solution to a specific case example illustrating this problem. To do this we reviewed the literature to find answers to the following three questions: (1) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research to research participants? (2) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research to the relatives of research subjects? and (3) What do current regulations, guidelines, and commentary say about the disclosure of genetic risk information obtained through research about former research participants who are now deceased? Our conclusion is that current U.S. federal guidelines governing the use of human subjects in research, as well as much of the current literature, do not adequately address the familial dimension inherent in genetic research, are virtually silent on the issue of sharing information of relevance to family members, and do not protect the deceased. It is our belief that this omission needs to be corrected and that explicit guidance on this issue needs to be provided to institutional review boards and researchers alike.     

Avoiding conflicts between insect and weed biological control: selection of non-target species to assess host specificity of cabbage seedpod weevil parasitoids

Abstract:  Classical biological control of insect pests and weeds may lead to potential conflicts, where insect pests are closely related to weed biological control agents. Such a conflict may occur in the classical biological control of the cabbage seedpod weevil, Ceutorhynchus obstrictus (Marsham) in North America, which belongs to the same subfamily, Ceutorhynchinae, as a number of agents introduced or proposed for introduction against non-indigenous invasive weed species. We propose a step-by-step procedure to select non-target species and thereby to develop a non-target species test list for screening candidate entomophagous biological control agents of a herbivore pest insect in a way that would simultaneously evaluate non-target potential on weed biological control agents and other non-target species. Using these recommendations, we developed a non-target test list for host specificity evaluations in the area of origin (Europe) and the area of introduction (North America) for cabbage seedpod weevil parasitoids. Scientifically based predictions on expected host–parasitoid interactions and ecological information about the ecological host range in the area of origin can help avoid conflicts, while still allowing the introduction of safe and effective agents against both insect pests and weeds.     

Viral safety and extraneous agents testing for veterinary vaccines: Rationale for requirements,the European approach

Freedom from extraneous agents is a high priority for any medicinal product. For veterinary vaccines, extraneous agents testing is addressed by different regulations of the European Pharmacopoeia and guidelines issued by the European Medicines Evaluation Agency. This article provides a brief review of the relevant texts.     

The role of organizational culture in compliance with the principles of the 3Rs

In order for their research to be legitimate, scientists carrying out research using animals must comply with rules and regulations. The 3Rs (replacement, reduction and refinement) are one set of guidelines that help to promote the ethical use of animals for research. An important question is whether implementing the principles of the 3Rs in legal regulations, such as a Directive of the European Parliament and of the Council on the protection of animals used for scientific purposes, will increase compliance with the principles of the 3Rs in research organizations. Previous work suggests that organizational culture is just as important for directing behavior as are formalized rules and regulations. This article introduces the concepts of compliance and organizational culture and discusses their consequences on the implementation of the principles of the 3Rs.     

Nonhuman primate quarantine: its evolution and practice

Nonhuman primates (NHPs) are imported to the United States for use in research, domestic breeding, and propagation of endangered populations in zoological gardens. During the past 60 years, individuals responsible for NHP importation programs have observed morbidity and mortality typically associated with infectious disease outbreaks. These outbreaks have included infectious agents such as tuberculosis, Herpesvirus sp., simian hemorrhagic fever, and filovirus infections such as the Ebola and Marburg viruses. Some outbreaks have affected both animal and human populations. These epizootics are attributable to a variety of factors, including increased population density, exposure of na?ve populations to new infectious agents, and stress. The practice of quarantining animals arriving in the United States was first applied by individual research programs to improve animal health and ensure the quality of animals entering research programs. The development of government regulations for nonhuman primate quarantine accompanied the recognition that imported NHPs could pose a risk to public health. This article briefly reviews the history of US NHP importation and the factors behind the development of NHP quarantine regulations. The focus is on regulations concerned with infectious disease, public health, and the health of domestic primate colonies. These regulations have had the dual benefit of protecting public health as well as reducing animal morbidity and mortality during importation and quarantine. We review current practices and facilities for nonhuman primate quarantine and identify challenges for the future.     

Import and export of biological samples from tropical countries–considerations and guidelines for research teams

‘Biodiversity’ is increasingly perceived as an important resource for research and conservation, but also for economy. Conservation, access and sustainable use of biodiversity (genetic resources, species, samples) are negotiated on different political levels, resulting in an internationally binding legal framework. Resulting legislation is binding for all parties involved in biological sampling, i.e. researches and (and in italics) countries, and especially applies for tissue or DNA samples and dervied products thereof. Understanding and awareness of export and import permits for biological samples is increasingly important for biologists to perform research projects legally and timely. Nevertheless, some biologists are still exporting and importing biological samples ignoring or non-compliant with national and international legislation, conventions, and regulations. Resulting difficulties may not only cause serious problems during field work, but may also delay the export, import or exchange of samples. Comprehensive a priori information regarding legal requirements helps to avoid or at least diminish potential problems. We identified four major factors facilitating export/import permits: (1) good personal (mutually trusted) contacts in the country of origin, (2) understanding and compliance with all relevant laws and regulations; (3) access to information regarding knowledge on permits, regulations and laws including their circulation within the researcher communities; and (4) access to consistent and up to date regulations     

Exotic biological control agents: A solution or contribution to arthropod invasions?

Biological control is a valuable and effective strategy for controlling arthropod pests and has been used extensively against invasive arthropods. As one approach for control of invasives, exotic natural enemies  from the native range of a pest are introduced to areas where control is needed. Classical biological control began to be used in the late 1800s and its use increased until, beginning in 1983, scientists began raising significant concerns and questions about nontarget and indirect effects that can be caused by these introductions. In recent years, similar issues have been raised about augmentative use of exotic natural enemies. Subsequently, international guidelines, national regulations and scientific methods being used for exotic natural enemies in biological control have changed to require appropriate specificity testing, risk assessment and regulatory oversight before exotic natural enemies can be released. National and international standards aimed at minimizing risk have increased awareness and promoted more careful consideration of the costs and benefits associated with biological control. The barriers to the implementation of classical and augmentative biological control with exotic natural enemies now are sometimes difficult and, as a consequence, the numbers of classical biological control programs and releases have decreased significantly. Based in part on this new, more careful approach, classical biological control programs more recently undertaken are increasingly aimed at controlling especially damaging invasive arthropod pests that otherwise cannot be controlled. We examine evidence for these revised procedures and regulations aimed at increasing success and minimizing risk. We also discuss limitations linked to the apparent paucity of post-introduction monitoring and inherent unpredictability of indirect effects.