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.     

基因表达时间延迟调控关系识别软件ITdGR

基因表达调控网络的深入研究有利于分子药物靶标的发现以及推新药的研发,是未来生物医学研究的重要内容。针对基因表达调控的时间延迟问题,我们初步设计开发了一套基于基因表达谱数据识别基因表达时间延迟调控关系的软件ITdGR(Identification of Time-delayed Gene Regulations)。并已经成功地将该软件应用于酿酒酵母细胞周期的基因表达谱数据中,识别出的调控关系与已有的知识相符。该软件为基因调控网络重构以及基因表达动态研究提供了一个方便和快捷的工具。     

Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants

The use of genetically modified (GM) plants to synthesize proteins that are subsequently processed, regulated and sold as pharmaceuticals challenges two very different established regulatory frameworks, one concerning GM plants and the other covering the development of biotechnology-derived drugs. Within these regulatory systems, specific regulations and guidelines for plant-made pharmaceuticals (PMPs) - also referred to as plant-derived pharmaceuticals (PDPs) - are still evolving. The products nearing commercial viability will ultimately help to road test and fine-tune these regulations, and might help to reduce regulatory uncertainties. In this review, we summarize the current state of regulations in different countries, discuss recent changes and highlight the need for further regulatory development in this burgeoning, new industry. We also make the case for the harmonization of international regulations.     

History and future of genetically engineered food animal regulation: an open request

Modern biotechnology resulted from of a series of incremental improvements in the understanding of DNA and the enzymes that nature evolved to manipulate it. As the potential impact of genetic engineering became apparent, scientists began the process of trying to identify the potential unintended consequences. Restrictions to recombinant DNA experimentation were at first self-imposed. Collaborative efforts between scientists and lawyers formalized an initial set of guidelines. These guidelines have been used to promulgate regulations around world. However, the initial guidelines were only intended as a starting point and were motivated by a specific set of concerns. As new data became available, the guidelines and regulations should have been adapted to the new knowledge. Instead, other social drivers drove the development of regulations. For most species and most applications, the framework that was established has slowly allowed some products to reach the market. However, genetically engineered livestock that are intended for food have been left in a regulatory state of limbo. To date, no genetically engineered food animal is available in the marketplace. A short history and a U.S.-based genetic engineer’s perspective are presented. In addition, a request to regulatory agencies is presented for consideration as regulation continues to evolve. Regulators appear to have shown preference for the slow, random progression of evolution over the efficiency of intentional design.     

Generating a taxonomy of regulatory responses to emerging issues in biomedicine

In the biomedical field, calls for the generation of new regulations or for the amendment of existing regulations often follow the emergence of apparently new research practices (such as embryonic stem cell research), clinical practices (such as facial transplantation) and entities (such as Avian Influenza/'Bird Flu'). Calls for regulatory responses also arise as a result of controversies which bring to light longstanding practices, such as the call for increased regulation of human tissue collections that followed the discovery of unauthorised post-mortem organ retention. Whilst it seems obvious that new regulations should only be generated if existing regulations are inadequate (a practice referred to in this paper as 'regulatory syncretism'), this does not always occur in practice. This paper examines the conceptual steps involved in generating regulatory responses to emerging phenomena. Two decision points are identified. First, a stance is taken as to whether the emerging phenomenon raises unique ethical or legal issues (exceptionalism versus non-exceptionalism). Second, the decision is made as to whether new regulation should be generated only for truly unique phenomena (syncretism versus asyncretism). It is argued here that it is important to make a careful assessment of novelty, followed by a reflective and deliberative choice of regulatory syncretism or asyncretism, since each type of regulatory response has advantages which need to be harnessed and disadvantages which need to be managed--something that can only occur if regulators are attentive to the choices they are making.     

Public health and carrageenan regulation: a review and analysis

The status of carrageenan in the regulatory sphere influences how and where it may be used, with implications for seaweed farmers, carrageenan manufacturers and consumers. Over the period 1935 to the present the status of carrageenan has been effected by changes in the regulatory environment that reflect new understandings about carrageenan, health and health risks as well as broader trade, social and political changes. This paper reviews regulatory progress from the 1930s to the present. It reflects, in particular, the shifting priorities in public health and their effects on the regulatory status of carrageenan. Four case studies of public controversies about carrageenan safety are discussed in relation to regulatory responses and their public health significance. It is concluded that current assessments of risk associated with carrageenan have, in some contexts, failed to take into account the full spectrum of safety assessments that have been carried out and the maturing of food additive regulations thereby allowing a myth of risk to continue.     

Regulatory aspects of gene editing in Argentina

Argentina is a world leader in regards to regulation and adoption of genetically modified (GM) crops. As a consequence, the regulatory aspects of gene editing applied to agriculture were considered proactively by the Argentinian regulators, who implemented simple but solid pioneering regulatory criteria for gene edited crops. At present, the Argentine regulatory system is fully able to establish if a gene-edited crop should be classified (and handled) either as a GM crop or a conventional new variety. To this end, the concept of “novel combination of genetic material” derived from the Cartagena Protocol on Biosafety is of decisive importance. After some pilot cases that have been managed under this criteria, now applicants appreciate the ease, speed and predictability of the regulation. Moreover, it has been considered by other countries in the course of developing their own regulations, thus acting also as a harmonization factor for the safe and effective insertion of these technologies in the global market.

     

低空气湿度下气孔运动的调控

植物气孔应答气候环境因子的机制,一直是植物抗逆生理研究领域的热点课题。空气湿度是主要的气候环境因子之一,人们很早就发现降低空气湿度能导致气孔开度变小,但到目前为止,对调控这一生物学过程的机制还知之甚少。本文概述近年来在植物气孔应答低空气湿度信号的运动规律、水被动反馈假说、水主动反馈假说、水力调节与代谢调节的关系等方面的进展,并基于进化学的理论,提出了水力调节和代谢调节的反向消长模式,以期解释大量物种气孔对低空气湿度的不同应答反应。     

Expert Views on Regulatory Preparedness for Managing the Risks of Nanotechnologies

The potential and promise of nanotechnologies depends in large part on the ability for regulatory systems to assess and manage their benefits and risks. However, considerable uncertainty persists regarding the health and environmental implications of nanomaterials, hence the capacity for existing regulations to meet this challenge has been widely questioned. Here we draw from a survey (N=254) of US-based nano-scientists and engineers, environmental health and safety scientists, and regulatory scientists and decision-makers, to ask whether nano experts regard regulatory agencies as prepared for managing nanomaterial risks. We find that all three expert groups view regulatory agencies as unprepared. The effect is strongest for regulators themselves, and less so for scientists conducting basic, applied, or health and safety work on nanomaterials. Those who see nanotechnology risks as novel, uncertain, and difficult to assess are particularly likely to see agencies as unprepared. Trust in regulatory agencies, views of stakeholder responsibility regarding the management of risks, and socio-political values were also found to be small but significant drivers of perceived agency preparedness. These results underscore the need for new tools and methods to enable the assessment of nanomaterial risks, and to renew confidence in regulatory agencies’ ability to oversee their growing use and application in society.     

Antimicrobial peptides and plant disease control

Several diseases caused by viruses, bacteria and fungi affect plant crops, resulting in losses and decreasing the quality and safety of agricultural products. Plant disease control relies mainly on chemical pesticides that are currently subject to strong restrictions and regulatory requirements. Antimicrobial peptides are interesting compounds in plant health because there is a need for new products in plant protection that fit into the new regulations. Living organisms secrete a wide range of antimicrobial peptides produced through ribosomal (defensins and small bacteriocins) or non-ribosomal synthesis (peptaibols, cyclopeptides and pseudopeptides). Several antimicrobial peptides are the basis for the design of new synthetic analogues, have been expressed in transgenic plants to confer disease protection or are secreted by microorganisms that are active ingredients of commercial biopesticides.     

Protecting vernal pools: a model from Massachusetts,USA

Ephemeral ponded wetlands, often referred to as vernal pools in the wetland’s lexicon of the northeastern United States, are in need of protection from outright loss, catastrophic alteration, and disruption of natural processes in the surrounding landscape, because of their great importance to a characteristic wildlife fauna. The state of Massachusetts, USA provides a useful model for vernal pool protection. Vernal pools have been specifically protected under state wetlands regulations since 1987 and many of the state’s municipalities have added additional, more stringent protection under local wetland bylaws. Some vernal pools are also protected under federal wetlands protection law. The protection of vernal pools in Massachusetts is based on a certification process in which biological data are collected to demonstrate that a wetland provides vernal pool functions. Once certified, and if a pool meets jurisdictional requirements, regulatory restrictions are placed on development and other activities proposed within the pool. The regulatory protection for vernal pools in Massachusetts has resulted in the prevention of outright loss and degradation of many vernal pools across the state. However, a 2001 US Supreme Court decision, referred to as the SWANCC decision, may result in a loss of federal jurisdiction over many vernal pools, protection that is especially valuable for pools that do not meet state regulatory criteria. Of significant importance is a lack of protection in existing regulations of the upland non-breeding habitat surrounding vernal pools, which has been shown to be of critical importance to the animals that rely on the pools. Despite the shortcomings of the regulatory protection model in Massachusetts, it has been especially effective as a catalyst for environmental and wildlife awareness, public participation in the wetlands regulatory process, and as an extremely valuable tool in environmental education and outreach.     

Source of information in heart research 1978 and 1988.

Several regulatory provisions have been introduced during the last decade that might interfere with the conduct of experimental medical science. In order to study their impact on the source of information within one major field, heart research, a total of 3579 abstracts from the 1978 and 1988 Scientific Sessions of the American Heart Association were analysed with respect to their source of information. There was no change in overall fractions of classical patient studies (45%) or experimental animal studies (30%) for the 2 years although regulations have been introduced in both areas. There was no evidence that the volume of circulatory physiology, a subset that extensively utilizes animal experimentation, declined relative to other subsets of the composite information base. The fraction of cell culture studies clearly rose over the period at the expense of in vitro laboratory studies but not as replacement for animal experimentation. Particularly tight regulations on experiments with selected species apparently explains why dogs and cats are less frequently used relative to rats, rabbits, ferrets and pigs which represent the alternatives. Nevertheless, the absolute number of dog studies doubled over the 10-year period and this species still remains the most widely used experimental model in heart research. The study does not reveal directly what is actually performed within the research community but rather identifies the source of information for those studies that are considered to bring about pertinent new information in modern heart research.     

Current state of Health Canada regulation for cellular and gene therapy products: potential cures on the horizon

We provide an overview of the regulatory framework, pathways and underlying regulatory authority for cell, gene and tissue-engineered therapies in Canada. Canada's regulatory approach uses three sets of regulations, namely, the Cells, Tissues and Organs Regulations, the Food and Drug Regulations and the Medical Devices Regulations. We provide an overview of each these sets of regulations as they apply to clinical investigation to post-market product lifecycle stages. Information is provided on the current sources of relevant Health Canada guidance documents. We highlight several regional success stories including Prochymal, a cell therapy product that achieved Canadian regulatory approval using the conditional marketing approval system. We also examine the perceived gaps in the Canadian regulations and how those gaps are being addressed by interactions between the government, stakeholders and international bodies. We conclude that the risk-benefit approach used by Health Canada for regulatory approval processes is sufficiently flexible to enable to development of novel cell and gene therapy products in Canada, yet stringent enough to protect patient safety.     

Current status of regulating biotechnology-derived animals in Canada: animal health and food safety considerations

Development of an effective regulatory system for genetically engineered animals and their products has been the subject of increasing discussion among researchers, industry and policy developers, as well as the public. Since transgenesis and cloning are relatively new scientific techniques, transgenic animals are 'novel' organisms for which there is limited information. The issues associated with the regulation of transgenic animals pertain to environmental impact, human food safety, animal health and welfare, trade and ethics. It is a challenge for the developers to prove the safety of the products of biotechnology-derived animals and also for regulators to regulate this increasingly powerful technology with limited background information. In principle, an effective regulatory sieve should permit safe products while forming a formidable barrier for those posing an unacceptable risk. Regulatory initiatives for biotechnology-derived animals and their products should be able to ensure high standards for human and animal health, a sound scientific basis for evaluation; transparency and public involvement, and maintenance of genetic diversity. This review proposes a regulatory regime that is based on scientific risk based assessment and approval of products or by-products of biotechnology-derived animals and its application in context to Canadian regulations.     

The precautionary principle: a double edged sword?

There is no doubt that the introduction of quality system principles and regulation to blood and tissue services in the 1990’s has brought about significant improvements in the control of processes and the quality of products being released for patient care. But, as regulation extends into new areas of cellular and tissue therapy, it is perhaps time to review the regulatory paradigm within which we work, and the principles that underpin it. At what point do the costs of regulation exceed the benefits to be gained? At what point to regulations cease to yield measurable benefits to patient care and safety at all, but instead become simply a burden on service providers and businesses, and ultimately the community as a whole? And is there a point at which regulation actually compromises patient care and safety, or the development of new technologies? In the early stages of regulation, there is demonstrable cost-benefit as assessed by product quality and patient outcomes. However, there is inevitably a “law of diminishing returns”, whereby the degree of improvement that can be achieved decreases and the cost of achieving that benefit increases. What has not yet been determined is whether, as regulations and regulators become more precise and more demanding, there remains a measurable net cost benefit over time, or whether there is a point at which the cost of further improvement matches, or even exceeds, the benefits to be gained. A key underpinning of the regulatory philosophy is the “Precautionary Principle”. This paper will focus on the application of the Precautionary Principle in the area of blood and tissues, which encompasses the burgeoning field of cellular therapies.     

Novel GM animal technologies and their governance

Scientific advances in methods of producing genetically modified (GM) animals continue, yet few such animals have reached commercial production. Existing regulations designed for early techniques of genetic modification pose formidable barriers to commercial applications. Radically improved techniques for producing GM animals invite a re-examination of current regulatory regimes. We critically examine current GM animal regulations, with a particular focus on the European Union, through a framework that recognises the importance of interactions among regulatory regimes, innovation outcomes and industry sectors. The current focus on the regulation of risk is necessary but is unable to discriminate among applications and tends to close down broad areas of application rather than facilitate innovation and positive industry interactions. Furthermore, the fields of innovative animal biosciences appear to lack networks of organisations with co-ordinated future oriented actions. Such networks could drive coherent programmes of innovation towards particular visions and contribute actively to the development of regulatory systems for GM animals. The analysis presented makes the case for regulatory consideration of each animal bioscience related innovation on the basis of the nature of the product itself and not the process by which it was developed.