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Documents on bioterrorism and biosecurity
EBRCN Resource Legislation.
The European Biological Resource Centre Network Information Resource
The safe handling and distribution of micro-organisms and the law
There is extensive legislation concerning the safe handling and distribution of micro-organisms at the national, regional and international levels. Micro-organisms of hazard groups 2, 3 and 4 are hazardous substances and as such fall under the EU Biological Agents Directive and are dangerous goods as defined by the International Air Transport Association (IATA) Dangerous Goods Regulations where requirements for their packaging are defined. Further, there are restrictions on distribution imposed by National Postal Authorities where more and more countries prohibit receipt of Infectious materials formerly Infectious, Perishable Biological Substances (IPBS) and, in some cases, Perishable Biological Substances formerly Non-infectious Perishable Biological Substances (NPBS). More recently the use of microorganisms in bioterrorism has lept to the forefront reminding us of the control measures in place for access to dangerous pathogens. The legislation and supporting documents are often difficult to find and understand. The European Biological Resource Centre Network (EBRCN) offer advice and interpretation to help the implementation of such legislation.
Background..... 1
Health and Safety..... 2
Classification of Micoorganisms on the Basis of Hazard.....2
Quarantine regulations..... 3
Postal Regulations and Safety..... 3
Packaging..... 3
Regulations governing distribution of cultures.....4
Legislation on the Proliferation, Distribution and Misuse of Dangerous Pathogens..... 4
Export Licensing Measures.....4
Convention on Biological Diversity.....6
Ownership of Intellectual Property Rights (IPR).....6
Safety information provided to the recipient of microorganisms..... 7
Summary.....7
References..... 8
Background
Microorganisms are isolated, grown, characterised, preserved and stored and transported between laboratories. They are shipped by various means, by mail, courier or by hand, from one laboratory to another within countries and often across borders or continents. They are sent for identification, reference, research or for production purposes from colleague to colleague, from and to culture collections. All these actions must be carried out safely and compliant with the various legislation and regulations that control these matters. Not only does the legislation exist but from time to time it is changed or added to (http://wdcm.nig.ac.jp/wfcc/wfccreports.pdf).
The importance of a laboratory’s health and safety procedures stretch beyond the laboratory to all those who may come in contact with substances and products from that laboratory. A microorganism in transit will put carriers, postal staff, freight operators and recipients at risk, some organisms being relatively hazard free whilst others quite dangerous. It is essential that safety and shipping regulations are followed to ensure safe transit. There are several other pieces of legislation that restrict the distribution of microorganisms of which a microbiologist must be aware. Attention is drawn to these and information sources are provided to ensure that microbiologists remain within the law.
Guidelines on the operation of culture collections
It is critical that biological resource centres operate to high standards and currently there are some guidelines available for adoption and use. One of the goals of the EBRCN project is to establish a European Standard for the operation of biological resource centres. Some examples of guidelines and quality management systems are:
CABRI http://www.cabri.org/guidelines/gl-framed.html
WFCC http://wdcm.nig.ac.jp/wfcc/GuideFinal.html
UKNCC http://www.ukncc.co.uk/html/Information/docs/UKNCCQAP.doc
Table 1 List of some of the regulations governing microbiological activities
Cartagena Protocol on Biosafety http://www.biodiv.org/biosafety/protocol.asp
Budapest Treaty on the International Recognition of the Deposit of Micro-organisms for the Purposes of Patent Procedure (done at Budapest on April 28, 1977 and amended on September 26, 1980) http://www.cnpat.com/worldlaw/treaty/budapest_en.htm
Convention on Biological Diversity http://www.biodiv.org/convention/articles.asp
EC Directive 93/88/EEC on Biological Agents http://eur-op.eu.int/opnews/395/en/r3633.html for purchase through Celex
EC Directive 90/679/EEC setting mandatory control measures for laboratories http://eur-op.eu.int/opnews/395/en/r3633.html for purchase through Celex
Accord Européen relatif au transport international des merchandises dangereuses par routes (ADR). http://eur-op.eu.int/opnews/395/en/r3633.html for purchase through Celex
IATA Dangerous Goods Regulations (DGR) http://www.iata.org/cargo/dg/dgr.htm
UK Management of Health and Safety at
Work (MHSW) Regulations 1992 (Anon, 1992) http://www.hmso.gov.uk/cgi-bin/htm_hl3?URL=http://www.hmso.gov.uk/si/si1999/19993242.htm&
STEMMER=en&WORDS=management+health+safeti+work+&
COLOUR=Red&STYLE=s#muscat_highlighter_first_match
UK Control of Substances Hazardous to Health (COSHH) regulations (1988)
EU Council Regulation 3381/94/EEC on the Control of Exports of Dual-Use Goods from the Community of 19th December 1994 (Official J. L 367, p1) and amendments http://eur-op.eu.int/opnews/395/en/r3633.html
EEC Directives 90/219/EEC. Contained use of genetically modified microorganisms (GMO's), *L117 Volume 33, 8 May 1990. http://biosafety.ihe.be/Menu/BiosEur1.html
EEC Directives 90/220/EEC. Release of GMO's, *L117 Volume 33, 8 May 1990.
http://biosafety.ihe.be/Menu/BiosEur1.html
Health and Safety
Whether it is compliance with the law or duties of a caring employer the basic requirements in order to establish a safe workplace are:
· Adequate assessment of risks.
· Provision of adequate control measures.
· Provision of health and safety information.
· Provision of appropriate training.
· Establishment of record systems to allow safety audits to be carried out.
· Implementation of good working procedures.
Good working practice requires assurance that correct procedures are actually being followed and this requires a sound and accountable safety policy. http://www.hse.gov.uk/pubns/hsc13.htm
Microorganisms as hazardous substances
The UK Management of Health and Safety at Work (MHSW) Regulations 1992 (Anon, 1992) are all encompassing and general in nature but overlap and lead into many specific pieces of legislation. The Control of Substances Hazardous to Health (COSHH) regulations require that every employer makes a suitable and sufficient assessment of the risks to health and safety to which any person whether employed by them or not may be exposed to through their work (Anon, 1996b), a risk assessment. These assessments must be reviewed regularly in addition to and when changes in procedures or regulations demand, and must be recorded when the employer has more than five employees. The distribution of microorganisms to others outside the workplace extends these duties to protect others. The organism must be assessed for all types of hazard it presents not on infection but also on the basis of toxin production for example the mycotoxins or bacterial toxins.
Classification of Microorganisms on the Basis of Hazard
Various classification systems exist which include:
World Health Organisation (WHO) www.who.org/emc/biosafe/index.htm;
United States Public Health service (USPHS);
Advisory Committee for Dangerous Organisms (ACDP);
European Forum for Biotechnology (EFB)
EC Directive (93/88/EEC) on Biological Agents
In Europe the EC Directive
(93/88/EEC) on Biological Agents sets a common base line which has been
strengthened and expanded in many of the individual member states. In the
EU legislation on GMOs:
COUNCIL DIRECTIVE (90/219/EEC) on the contained use of genetically modified micro-organisms 23 April 1990
COUNCIL Directive (90/220/EEC) on the deliberate release into the environment of genetically modified organisms 3 April 1990
COMMISSION DIRECTIVE 94/51/EC of 7 November 1994, adapting to technical progress Council Directive 90/219/EEC on the contained use of genetically modified micro-organisms
COMMISSION DECISION (94/730/EC) of 4 November 1994, establishing simplified procedures concerning the deliberate release into the environment of genetically modified plants pursuant to Article 6 (5)of Council Directive 90/220/EEC
This and other EU Legislation concerning transport of GMOs or pathogenic organisms and that pertaining to biotechnological safety can be found at:
http://biosafety.ihe.be/Menu/BiosEur.html
United Nations Industrial Development Organisation
· Voluntary code of conduct for the release of organisms into the environment
The text can be found at http://binas.unido.org/binas/regs.php3
Quarantine regulations
Quarantine legislation is in place in countries
world wide restricting the import of non-indigenous plant and animal
pathogens. Those who wish to import
such organisms must hold the relevant import permit which can be obtained from
the relevant country authority for example – Canada, UK, USA. Information on the transport of plant
pathogens throughout Europe can be obtained from the European and Mediterranean Plant,
Protection Organisation (EPPO), 1 rue le Nôtre, 75016 Paris,
Postal Regulations and Safety
Countries have their own regulations governing the packaging and transport of biological material in their domestic mail. International Postal Regulations regarding the postage of human and animal pathogens are very strict on account of the safety hazard they present. There are several organisations that set regulations controlling the international transfer of such material. These include the International Air Transport Association (IATA), International Civil Aviation Organisation (ICAO), United Nations Committee of Experts on the Transport of Dangerous Goods, the Universal Postal Union (UPU) and the World Health Organisation (WHO). It is common place to send microorganisms by post, as this is more convenient and less expensive than air freight. However, many countries prohibit the movement of biological substances through their postal services. The International Bureau of the UPU in Berne publishes all import and export restrictions for biological materials by national postal services. This information can also be found in the countries table published in the DSMZ Shipping of infectious, non-infectious and genetically modified biological materials International Regulations (http://www.gbf.de/dsmz/shipping/shipping.htm).
Packaging
IATA Dangerous Goods Regulations (DGR) require that packaging used for the transport of hazard group 2, 3 or 4 must meet defined standards, IATA packing instruction 602 (class 6.2) (IATA, 2002). Packaging must meet EN 829 triple containment requirements for hazard group 1 organisms. However, microorganisms that qualify as dangerous goods (class 6.2) must be in UN certified packages. These packages must be sent by air freight if the postal services of the countries through which it passes do not allow the organisms in their postal systems. They can only be sent airmail if the National Postal authorities accept them. There are additional costs above the freight charges and package costs if the carrier does not have its own fleet which will require the package and documentation to be checked at the airport DGR centre.
Regulations governing distribution of cultures
The IATA Dangerous Goods Regulations require that shippers of microorganisms of hazard groups 2, 3 or 4 must be trained by IATA certified and approved instructors. They also require shippers declaration forms, which should accompany the package in duplicate, and specified labels are used for organisms in transit by air (IATA, 2002). There are several other regulations that impose export restrictions on the distribution of microorganisms. These include control of distribution of agents that could be used in biological warfare, EU Council Regulation 3381/94/EEC on the control of export of dual-use goods (Official J. L 367, p1) and more generally countries are currently implementing Access Regulations to Genetic Resources under the Convention on Biological Diversity, transport of goods by road. It is critical that microbiologists are aware of and follow such legislation.
Some cultures represent a health hazard, and for post and packaging purposes these are placed into four classes by the UPU.
Web links to further information on transport and shipping
Legislation on the Proliferation, Distribution and Misuse of Dangerous Pathogens
There is considerable concern over the transfer of selected infectious agents capable of causing substantial harm to human health. There is potential for such organisms to be passed to parties not equipped to handle them or to persons who may make illegitimate use of them. Of special concern are pathogens and toxins causing anthrax, botulism, brucellosis, plague, Q fever, tularemia and all agents classified for work at Biosafety Level 4 (hazard group 4). There is control legislation in place and some of this is described below.
The American Society for Microbiology (ASM) provide information for example "Contact Information for Select Agent Preservation" is available at the WFCC site http://www.wfcc.info/ and "Biosafety" section of http://www.wdcm.org/. The document is on the issue of preserving
(dangerous) agents for research for the
human welfare. The title of the menu in the Web page is "
Biological Weapons Convention
The Biological Weapons Convention (BWC) (The Biological and Toxin Weapons
Convention ) was signed in London, Moscow and Washington on 10 April 1972 and entered into
force on 26
March 1975. There are currently 162 country
signatories of which 18 are still to ratify.
· Convention on the prohibition of the development, production and stockpiling of bacteriological (biological) and toxin weapons and on their destruction
The text can be found at http://binas.unido.org/binas/regs.php3
Following the signing of the BTWC countries have introduced new control legislation or procedures to prevent unauthorised access to strains that could be misused in this way. An Ad Hoc Group is currently discussing a verification protocol for the BWC, such a protocol is now in place for the CWC.
"Countering Bioterrorism: DOE - Funded DNA-Based Technologies Track Identity, Origin of Biological Agents" is retrievable at Human Genome Web site
http://www.ornl.gov/hgmis/publicat/hgn/v12n1/01bioterror.html
Article III of the BWC obliges the States Parties not to transfer to any recipient what so ever, directly or indirectly, and not in any way to assist, encourage, or induce any States, group of States or international organizations to manufacture or otherwise acquire any of the agents, toxins, weapons, equipment or means of delivery specified in article I of the Convention.
This is a legally binding obligation. A number of countries have implemented national export licensing measures as an effective means of implementing these obligations and to avoid the possibility of the inadvertent supply of any item which could be used in a BW program.
Export licenses are not bans. They operate to deter proliferation by monitoring trade of relevant materials, and provide authority to stop a sale in the infrequent cases where a prospective export is likely to contribute to a BW program. It is also in the interest of industry and research institutes to ensure that such firms and institutes are not inadvertently supplying pathogens and dual-use equipment for use in the production of BW.
The Geneva Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases, and of Bacteriological Methods of Warfare.
http://www.opcw.nl/fact/rel_conv.htm
The USA have rules that
include a comprehensive list of infectious agents, registration of facilities
that handle them, requirements for transfer, verification and disposal and that
carry criminal and civil penalties. In the
The
In response to a Congressional mandate in 1997, CDC
promulgated a regulation, Additional
Requirements for Facilities Transferring or Receiving Select Agents. The select agents were drawn from the Australia List
and includes forty or so microorganisms, a dozen toxins, and certain
recombinant DNA molecules. Institutions were provided Registration Packages
that included a self-assessing laboratory survey form based on the CDC/NIH
publication, Biosafety in Microbiological
and Biomedical Laboratories. Each registered facility is to be inspected by
personnel from the OHS during a three year cycle. To date there are 67
laboratories registered. This presentation will provide a status report on the
activities associated with implementing this regulation. CDC is currently
working to develop a plan to address the role of Public Health to meet the
growing national concerns about bioterrorism.
Additional Requirements for Facilities Transferring or Receiving Select Agents : 42 CFR Part 72.6, 1996
Public
Health Chapter I--Public Health Service, Department of Health and Human
Services Part 71--Foreign Quarantine-Subpart
F--Importations Sec. 71.54 Etiological agents, hosts, and
vectors. (a) A person may not import into the
European
The European Union has adopted a common position with the Biological and Toxic Weapons Convention http://projects.sipri.se/cbw/docs/btwc-EU-commpos.html
Delivery of microorganisms which could be used as biological weapons is controlled by the EU Council Regulation 3381/94 <documents/EuropeanCouncilRegulationl.rtf> on the Control of Exports of Dual-use Goods from the Community and by the resp. EU Council Decision of December 1994 with its Annex I <documents/annexes.pdf>(Publication L367/8/EEC of 31.12.1994 and amendments).
France
Control procedures:
UKNCC control of Dangerous Pathogens
The
Some biosafety related sites:
The European Federation Biotechnology Working Party on Safety in Biotechnology http://www.boku.ac.at/iam/efb/
The European Biological Safety Association http://www.ebsa.be/
The American Biological Safety Association http://www.orcbs.msu.edu
The Belgian Biosafety Server with lots of links http://biosafety.ihe.be/
World Health Organisation WHO http://www.who.ch
UNIDO Bio Informations Network http://binas.unido.org/binas/binas.html
International Centre for Genetic Engineering and Biotechnology (ICGEB) in Trieste
http://www.icgeb.trieste.it/~bsafesrv/
Some BTWC related sites:
The Department of Peace Studies at the University of Bradford
http://www.brad.ac.uk/acad/sbtwc/home.htm
Pugwash Study Group on CBW http://fas-www.harvard.edu:80/~hsp/pugwash.html
CBIAC (The Chemical and Biological Defense Information Analysis Center)
http://www.cbiac.apgea.army.mil
SIPRI (Stockholm International Peace Research Institute) Chemical and Biological Warfare Project
The Henry L. Stimson Center, Chemical and Biological Weapons Nonproliferation Project
Biological and Toxin Weapons Working Group, Federation of American Scientists
http://www.fas.org/bwc/index.html
ASA (Applied Science and Analysis, Inc.) Newsletter http://www.asanltr.com/
Chemical and Biological Arms Control Institute http://www.cbaci.org/
Convention on Biological Diversity
Text: http://www.biodiv.org/convention/articles.asp
The Convention on Biological Diversity (CBD) was established to support the conservation and utilisation of biodiversity ensuring fair and equitable sharing of benefits arising from the latter. The CBD assigns sovereign rights to the country of origin and requires that Prior Informed Consent (PIC) is received from the country in which access to organisms is requested. Mutually Agreed Terms (MAT) on the conditions under which access is granted and on which benefits will be shared should they accrue from the use of the organisms must be put in place. Benefit sharing may include monetary elements but may also include information, technology transfer and training. The supply of organisms must also be under agreed terms under Material Transfer Agreements (MTA) between supplier and recipient to ensure benefit sharing with, at least the country of origin. This is a significant role for public service collections potentially bearing critical responsibilities to ensure traceability. Many culture collections have operated benefit sharing since they began giving organisms in exchange for deposits and re-supplying the depositor with the strain if they require a replacement. An EU DG XII project, Microorganisms Sustainable Use and Access Regulation International Code of Conduct (MOSAICC) (http://www.belspo.be/bccm/mosaicc/) is working toward standard material transfer agreements to facilitate access to genetic resources whilst adhering to the spirit of the CBD and National and International law governing the distribution of microorganisms (Davison et al. 1998).
Many countries are putting in place legislation to control access to their genetic resources. This normally includes certification processes and can help by identifying the relevant authorities for PIC and help set the terms and conditions of access. However, some legislation has been bureaucratic and has served to restrict access. National Focal Points on access and benefit sharing are beginning to appear that should make the process simpler. To date most collections have adopted a wait and see attitude as their role is still not clear.
Ownership of Intellectual Property Rights (IPR)
Organisms originating from different habitats all over the world are deposited in collections. On deposit the issue of ownership of intellectual property associated with them must be addressed. The CBD bestows sovereign rights over genetic resources to the country of origin, but intellectual property rights covering their use in processes is another matter. The CBD requires that the country of origin has a share in benefits accruing from such use, but there may be several other stakeholders. These may include the landowner where the organism was isolated, the collector, those involved in purification and growing the organism, the discoverer of the intellectual property, the collection owner where the organism was preserved and the developer of the process. It is clear that all stakeholders do not all have an equal stake, this will depend upon the input of each one to the discovery or process. This has implications for the sharing of benefits arising from exploitation of the genetic resource. The collection has a role to play in the protection of IPR even if it is merely informing the recipient of any existing material transfer agreement or the citation of the strain in a patent. The implementation of the CBD is still being discussed by delegates from the countries who are signatory and who meet at the Conference of the Parties and their workgroups. Information on the progress of these discussions can be found on the CBD web site (http://www.biodiv.org/).
As a form of protecting IPR patents may be taken out. In many cases the organism involved must be part of the disclosure and many countries either recommend or require by law that a written disclosure of an invention involving the use of organisms be supplemented by the deposit of the organism into a recognised culture collection. Most patent lawyers recommend that the organism is deposited, regardless of it being a requirement, to avoid the possibility of the patent being rejected. To remove the need for deposit of organisms in a collection in every country where patent protection is desired, the “Budapest Treaty on the International Recognition of the Deposit of Micro-organisms for the Purpose of Patent Procedure” was concluded in 1977 and came into force towards the end of 1980. This recognises named culture collections as “International Depository Authorities” (IDA) and a single deposit made in any one is accepted by every country party to the treaty. Any collection can become an IDA providing it has been formally nominated by a contracting state and meets certain criteria. There are 29 IDAs around the world and 23 in Europe which accept patent deposits of human and animal cell lines, algae, bacteria, cyanobacteria, fungi, nematodes, non-pathogenic protozoa, plant seeds and yeasts.
It is quite clear that every intermediary in an improvement or development process is entitled to a share of the IPR, which adds another dimension to ownership. Therefore, it is critical that clear procedures on access, mutually agreed terms on fair and equitable sharing of benefits and sound material transfer agreements are in place to protect the interested parties.
Further information: http://link.springer.de/link/service/journals/00253/bibs/1057004/10570443.htm
Safety information provided to the recipient of microorganisms
A safety data sheet must be despatched with
organism indicating which hazard group it belongs to and what containment and
disposal procedures are necessary. In the
· The hazard group of the
organism being despatched as defined by EU Directive 90/679/EEC Classification
of Biological Agents and by the national variation of this legislation for
example, in the
· A definition of the hazards and assessment of the risks involved in handling the organism.
· Requirements for the safe handling and disposal of the organism.
- Containment level
- Opening cultures and ampoules
- Transport
- Disposal
- Procedures in case of spillage
Safety Data Sheets content is described in EU Directive 93/112/EC of 10 December 1993 (OL L314/93) which amends the 91/155/EC. An explanation of the Directive can be found at http://www.vgt.nl/msds/msdsregs.htm.
Summary
In the interests of the progress of science microbiologists must be able to exchange their organisms upon which their hypotheses and results are based but they must do this in a way that presents minimum risk to those who come into contact with the organism. They must not fall fowl of the laws that control the shipping of microorganisms as this will inevitably result in even more restrictive legislation that will make their exchange impossible. Health and Safety, packaging and shipping and controlled distribution legislation may be extensive and sometimes cumbersome but is there to protect us and must be followed.
References
Alexander, M.T. & Brandon, B.A. (eds.) (1986) Packaging and shipping of biological materials at ATCC. Rockville, Maryland: American Type Culture Collection.
Anon (1993a). Chemicals (Hazard Information and Packaging) Regulations 1993: Approved Supply List: Information approved for the classification and labelling of substances and preparations dangerous for supply. Health and Safety Executive. Sudbury: HSE Books.
Anon (1993b). CHIP for Everyone. Chemicals (Hazard Information and Packaging) Regulations 1993). Health and Safety Executive. Sudbury: HSE Books.
Anon (1993d) Royal Mail International (RMI) Service Guide. pp. 501-502. London: Royal Mail International.
Anon (1996a) Categorisation of pathogens according to hazard and categories of containment. Fourth edition. Advisory Committee on Dangerous Pathogens (ACDP). London: HMSO.
Anon (1996b). COSHH (General ACOP), Control of Carcinogenic substances, Biological Agents: Approved Codes of Practice (1996). London: HSE. ISBN 0 11 885468 2.
Anon (1996c). Industrial Property Statistics, 1994, Part II. Geneva: World Intellectual Property Organisation (WIPO).
Anon (1997a). Sichere Biotechnologie, Eingruppierung biologischer Agenzien: Bakterien. Berufsgenossenschaft der chemischen Industrie. Merkblatt B 006, 2/97, ZH 1/346. Heidelberg: Jerdermann-Verlag.
Anon (1997b). Sichere Biotechnologie, Eingruppierung biologischer Agenzien: Fungi. Berufsgenossenschaft der chemischen Industrie. Merkblatt B 006, 2/97, ZH 1/346. Heidelberg: Jerdermann-Verlag.
Anon (1997c). EH40/73 Occupational exposure limits 1993: Sudbury: HSE Books.
Anon (1997d). Orange Book, Recommendations on the Transport of Dangerous Goods, Tests and Criteria. 10th edition. New York: UNO.
Anon (1998) Shipping of infectious, non-infectious and genetically modified biological materials, International Regulations DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Braunschweig, Germany.
IATA (1998) Dangerous Goods Regulations. 39th edition. Montreal; Geneva: IATA.
G.S. de Hoog (1996) Risk assessment of fungi reported from humans and animals. Mycoses 39, 407-417.
Collier, L., Balows, A. & Sussman, M. (eds) (1998). Topely and Wilson’s Microbiology and Microbial Infections. 9th edition. London: Arnold.
Collins C H (1983). Laboratory-acquired infections. London: Butterworths.
Collins C H (1990). A review. COSHH and the microbiologist. Letters in Applied Microbiology 10, 109-112.
Collins C H; Hartley E G; Pilworth R (1974). The prevention of laboratory acquired infection. PHLS Mongraph Series 6. London: HMSO.
Davison,
A. Brabandere, J. de., & Smith, D. (1998) Microbes, collections
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EC Council Directive 94/55/EC on the approximation of the laws of Member States on the transport of dangerous goods by road. Official Journal of the European Communities L319, 7.
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L374 Volume 33, 31 December 1990.
EEC Directives 90/679/EEC. Protection of workers from risks related to biological agents
L117 Volume 33, 8 May 1990.
EEC Directives 90/219/EEC. Contained use of genetically modified microorganisms (GMO's)
EEC Directives 90/220/EEC. Release of GMO's
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Biosafety Manual (1993). Second edition.
Medical aspects of occupational asthma. Guidance Note MS25 from the Health and Safety Executive. 1991. London: HMSO.
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Smith, D. (ed.) (1996). Committee on postal, quarantine and safety regulations report 1996, Postal, quarantine and safety regulations: status and concerns. World Federation for Culture Collections (WFCC). pp39.
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Information on the European Biological Resource Centre Network
BACK to text
The European Biological Resource Centre Network (EBRCN) is a project running under the Quality of Life and Management of Living Resources of the EU Framework 5 Programme due for completion May 2004. The project addresses important issues raised by the current OECD Initiative on Biological Resource Centres (BRCs) requiring collections to adapt to support biosciences for the 21st century. It will establish a thematic network that will allow Europe to exploit its expertise in BRCs and Information Technology. It will provide an infrastructure with one gateway to reach quality assured European biological resource centres. It will allow links to be made between the BRC catalogues and other data sets and ensure that the large amount of specialised information that is presently hidden is made accessible for all to use. The European Biological Resource Centres Network (EBRCN) will be established with a critical mass of high quality BRCs to act as a focal point for common policy development. It will use the Common Access to Biological Resources and Information (CABRI) database, a recently completed EU demonstration project as its central electronic contact point (http://www.cabri.org) and on which it will base the European ‘virtual’ BRC.
Objectives
1. Establish a network of biological resource centres initiated with a minimum of 11 living organism collections (ca. 150000 living specimens), holders of nucleic acids, probes etc. and associated data to respond to OECD initiatives in the international environment.
2. Develop the European Standard for BRCs based on existing collection quality management systems to be adopted by a minimum of eleven national collections of European states.
3. Establish a framework to maximise complementarity and minimise unnecessary duplication among European BRCs.
4. Introduce new techniques in information technology to the EBRCN to add value to current catalogue information and enhance accessibility to 11 catalogue databases and at least one literature and one molecular database.
5. Collate and disseminate information on legislation on access to, and distribution of, living organisms and health and safety to BRCs and users through a central web site.
It is essential that European public service collections work together to address common problems and become more effective and efficient by sharing tasks and collaborating together to provide a comprehensive service. Collection organisations such as the European Culture Collection Organisation (ECCO) and the World Federation for Culture Collections (WFCC) do not co-ordinate the operations of collections. However, two European countries do have collections co-ordinated on a more integral basis, the Belgian Co-ordinated Collections of Micro-organisms (BCCM) and the UK National Culture Collection (UKNCC). The EBRCN will enhance such collaboration and extend it European-wide to enable Europe to offer a premier service to its member states and to the world. The technology now exists for such co-operation. Web-based interactions between European centres will lead to a Virtual Biological Resource Centre, which will provide the focal point Europe needs to gain the most from its divergent expertise and investments.
The project work is split into 5 work packages, which aim at building the EBRCN platform forming a comprehensive network. The network will set the European Biological Resource Collection (BRC) Standard. Common policies will be established to address legislation governing collection activities and services and to co-ordinate activities leading to an effective resource to underpin European Biotechnology. Finally there is a need to take full advantage of available information technology and ensure that linking to, and from, literature and other relevant biological information databases enhances collection information.
The partner BRCs are currently providing services and products to the scientific community whilst developing mechanisms to improve these and designing new approaches to meet the changing needs of their users. This project will co-ordinate such processes and increase effectiveness and efficiency. Research and development will continue in these centres, information will be gathered and data generated to add value to holdings. Strain property and molecular information will be gathered and stored in databases. The project will provide the mechanisms for such information to be made available to the scientific community in a user friendly and comprehensive way. The overall aim is to develop the European ‘virtual’ Biological Resource Centre that will increase efficiency in partner BRCs and facilitate user access. The project will offer solutions to critical problems in biotechnology and biodiversity.
Information on microbiologists and law
BACK to text
Handling and distribution of micro-organisms and the law to disseminate information on our legal responsibilities while collecting and distributing microorganisms (Smith, D. Rohde, C. & Holmes, B. (1999). Microbiology Today 26, 14-16). A fuller version of this paper is available on the Society for General Microbiology web site, this will be periodically updated, http://www.socgenmicrobiol.org.uk
Information on COSHH
The effect of COSHH on Culture Storage and Supply
The COSHH regulations (1988)
aim to stimulate and enforce an improvement in Health and Safety in the
workplace. All principles embodied
in the COSHH regulations are contained in the UK HSW Act 1974. COSHH formalises, enforces and in some
instances extends certain sections of this act. COSHH requires a suitable and
sufficient risk assessment for all work that is liable to expose an employee to
any substance that may be hazardous to health. This
It can be much simpler dealing with a known chemical than with a named microorganism. The full metabolic and biochemical potential of a microorganism is rarely known and therefore assessing the risk when the hazard is not clearly defined becomes difficult. This is where the COSHH regulations are realistic leaving room for interpretation. The regulations incorporate terms `as far as reasonably practicable', `adequate control', and `suitable measures' which enables the employer to set relevant safe procedures that are workable. Microorganisms present different levels and kinds of hazard and leaving an enormous, but necessary, task for microbiologists. A risk assessment for example, must take into account the production of potentially hazardous toxins. In the last analysis a safe laboratory is the result of applying good techniques, a hallmark of technical excellence. Containment level 2 is easily achievable and should be standard practice in all microbiological laboratories. Good aseptic techniques applied by well-trained personnel will ensure pure and clean cultures and will minimise contact with the microorganism. However, the unexpected, the accident, must also be taken into account when assessing the risk involved. The employment of good laboratory practice, good housekeeping, workplace and equipment maintenance and ensuring that staff have the relevant information and training, will minimise the risk of accidents. The establishment of emergency procedures to reduce potential harm is an additional and sensible approach.
Information on risk assessment
Risk assessments are carried out on all microorganisms worked with and held in laboratories. This requires the assignment of each strain to a hazard group including a positive inclusion into hazard group 1 following a thorough risk assessment. The risk assessment should include an assessment of all hazards involved not just infection but also the production of toxic metabolites and the ability to cause allergic reactions. Organisms that produce volatile toxins or aerosols of spores or cells present a greater risk. It is the responsibility of the microbiologist to provide such assessment data to a recipient of a culture to ensure its safe handling and containment.
Microorganisms are normally classified on their potential to cause disease, their human pathogenicity, into four groups (Anon, 1996a). - ACDP classification BACK to text
Group 1 A biological agent that is most unlikely to cause human disease.
Group 2 A biological agent that may cause human disease and which might be a hazard to laboratory workers but is unlikely to spread in the community. Laboratory exposure rarely produces infection and effective prophylaxis or treatment is available.
Group 3 A biological agent that may cause severe human disease and present a serious hazard to laboratory workers. It may present a risk of spread in the community but there is usually effective prophylaxis or treatment.
Group 4 A biological agent that causes severe human disease and is a serious hazard to laboratory workers. It may present a high risk of spread in the community and there is usually no effective prophylaxis or treatment.
The containment level numbers correlate with the risk group in which the organism falls (i.e. organisms in Risk Group 1 require Containment level 1 and so forth see Table 1 below).
The species of bacteria and
fungi falling into hazard groups 2 and 3 are defined (Anon, 1996a, 199b). All
bacteria from the approved list have been assigned to an appropriate hazard
group in
The COSHH regulations work well and can be easily applied in establishments with designed laboratories but may not work so well in the industrial environment where very large volumes and more hazardous techniques may be used. Total containment is rarely applicable.
Microorganisms are more difficult to name, less predictable and more difficult to enumerate or measure than chemicals. Virulence and toxicity may vary from strain to strain. In addition to the risk of infection other hazards exist, such as mycotoxin production, allergenicity.
Information on containment levels – Back to text
Table 2 Summary of laboratory containment levels
for the
CONTAINMENT REQUIREMENT |
CONTAINMENT LEVEL |
|||||
1 |
2 |
3 |
4 |
|||
Laboratory site: isolation |
No |
No |
Partial |
Yes |
||
Laboratory: sealable for fumigation |
No |
No |
Yes |
Yes |
||
Ventilation: inward airflow/negative pressure Ventilation: through safety cabinet mechanical: direct mechanical: independent ducting |
Optional No No No |
Optional Optional No No |
Yes Optional Optional Optional |
Yes No No Yes |
||
Airlock Airlock: with shower |
No No |
No No |
Optional No |
Yes No |
||
Wash hand basin |
Optional |
Yes |
Yes |
Yes |
||
Effluent treatment |
No |
No |
No |
Yes |
||
Autoclave site: on site in suite in lab: free standing in lab: double ended |
Yes No No No |
No Yes No No |
No Yes Optional No |
No No No Yes |
||
Microbiological safety cabinet/enclosure Class of cabinet/enclosure* |
No - |
Optional Class I |
Yes Class I/III |
Yes Class I/III |
||
* Guidance on the use of Class II microbiological safety cabinets is given in the Advisory Committee on Dangerous Pathogens Report (1996).
To meet COSHH requirements a step by step evaluation of a laboratory procedure or an industrial process must be carried out. This is necessary as different organisms provide different hazards and different size inocula are required to cause a problem. The assessment must cover the procedure from the original inoculum or seed culture to the final product or the point where the organism is killed and disposed of. It is not adequate to say that the microorganism is of ACDP hazard group 2 or less and therefore work can be carried out on the laboratory bench apart from those procedures that may create aerosols. Some individuals may respond differently to exposure, being more sensitive than others are. It is therefore critical that the full potential of organisms is taken into account and this related to the effect they may have on the particular individual carrying out the work.
Information on mycotoxin production - BACK to text
One of the better known hazards associated with fungi is the ability to produce toxic secondary metabolites. The presence of these in culture media adds to the hazard status of the growing organisms. The toxins produced may be carcinogenic, nephrotoxic, hepatotoxic, haemorrhagic, oestrogenic or cause inflammatory effects. The most commonly known is aflatoxin which is considered to be carcinogenic, hepatotoxic and potentially mutagenic and is produced by strains of Aspergillus flavus and A. parasiticus. Table 2 lists some mycotoxins that may be present in growth media and present additional problems in both use and disposal.
Mycotoxicoses are poisonings caused by the ingestion of food contaminated (and sometimes rendered carcinogenic) by toxin producing microfungi. Toxins are also produced by many other fungi for example citreoviridin, citrinin, islanditoxin and patulin by species of Penicillium, ochratoxin by Aspergillus and trichothecenes and zearelenone by species of Fusarium, and various other compounds including cochliodinol by Chaetomium. It should always be remembered that many fungi have not been studied chemically and because mycotoxins are not reported for a species does not mean it does not produce them. The handling of materials contaminated by these toxins can lead to their ingestion and subsequent poisoning. Inhalation of mycotoxins can also be dangerous. Toxins from Aspergillus and Fusarium species have caused problems in patients when inhaled. The death of 2 factory workers from liver disease was associated with the inhalation of dust containing aflatoxin.
Table 3 Some common mycotoxins and examples of fungi producing them.
Mycotoxin Organisms
Aflatoxin Aspergillus flavus, A. parasiticus
Aflatrem Aspergillus flavus
Altenuic
acid Alternaria alternata
Alternariol Alternaria alternata
Austdiol Aspergillus ustus
Austamide Aspergillus ustus
Austocystin Aspergillus ustus
Bentenolide Monographella nivalis
Brevianamide Aspergillus ustus
Citrinin Aspergillus carneus, A. terreus, Penicillium citrinum, P. hirsutum, P. verrucosum
Citreoviridin Aspergillus terreus, Penicillium
citreoviride
Cochliodinol Chaetomium cochliodes
Crotocin Acremonium crotocinigenum
Cytochalasin
E Aspergillus clavatus
Cyclopiazonic
acid Aspergillus versicolor
Destruxin
B Aspergillus ochraceus
Fumagilin Aspergillus fumigatus
Fusarin Fusarium
moniliforme
Gliotoxin Aspergillus fumigatus
Islanditoxin Penicillium islandicum
Malformin Aspergillus niger
Maltoryzine Aspergillus spp.
Moniliformin Fusarium moniliforme, F. oxysporum, F.
equiseti
Ochratoxin Aspergillus ochraceus, Penicillium
viridictum
Oxalic
acid Aspergillus niger
Patulin Aspergillus clavatus, Penicillium expansum,
P.
roquefortii, P. claviforme, P. griseofulvum
Penicillic
acid Aspergillus ochraceus
Penitrem Penicillium crustosum
Roridin Myrothecium roridum, M. verrucaria
Dendrodochium spp., Cylindrocarpon spp.,
Stachybotrys spp.
Rubratoxin Penicillium rubrum
Rubroskyrin Penicillium spp.
Rubrosulphin Penicillium viridicatum
Rugulosin Penicillium brunneum, P. kloeckeri,
P.
rugulosum
Satratoxin Stachybotrys chartarum
Slaframine Rhizoctonia leguminicola
Sterigmatocystin Aspergillus flavus, A. nidulans, A.
versicolor,
Penicillium rugulosum
Trichodermin Trichoderma viride
Trichothecin Trichothecium roseum
Trichothecenes Fusarium acuminatum, F. roseum, F.
sporotrichioides
T2
toxin
deoxynivalenol
(vomitoxin)
nivalenol
diacetoxyscirpenol
fusarenone
3-acetyldeoynivalenol
15-acetyldexoynivalenol
Tryptoquivalene Aspergillus clavatus
Verrucarin Myrothecium verrucaria, Dendrodochium spp.
Verruculogen Aspergillus fumigatus
Viopurpurin Trichophyton spp., Penicillium viridicatum
Viomellein Aspergillus spp., Penicillium aurantiogriseum, P. crustosum, P. viridicatum
Viriditoxin &n