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Table of contents
Foreword 5
13
Risk assessment and classification of activities involving genetically modified or pathogenic organisms
17
27
Microbiological identification of naturally occurring human pathogens in diagnostics, food and environmental samples
31
36
51
55
59 61 62 63 64 65
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Foreword
Karoline Dorsch
Executive Secretary, Swiss Expert Committee for Biosafety Biosafety Officers (BSOs) have an important function in monitoring that work with pathogenic and genetically modified organisms is performed properly in order to protect people and the environment. The Swiss Federal Office for the Environment (FOEV), jointly with the Swiss Federal Office of Public Health (SFOPH) and the Swiss Expert Committee for Biosafety (SECB) have organised training courses for BSO and other interested persons since the coming into force of the Ordinances relating to biotechnology in 1999. These training courses have a longstanding tradition in Switzerland since the predecessor of the EFBS, the Swiss Interdisciplinary Committee for Biosafety in Research and Technology (SCBS) has organised similar courses before that. The aim of these courses is to provide participants with a basic understanding of the current situation regarding Swiss regulatory requirements, notification procedures, principles of risk assessment, safety measures and tasks of BSO. Participants form previous courses have requested that the teaching materials of the course for BSO should be made available in written form. Consequently, the present manual contains the contents of the training courses in a more elaborate and selfexplanatory form. We hope that this manual facilitates the tasks of BSO by explaining the existing ordinances and guidelines. However, in contrast to ordinances, the papers presented here are not considered to be legally binding. The manual together with the presentations of the BSO-meeting of 2006 will also be made available on the internet site of the Federal Coordination Center for Biotechnology: http://www.umwelt-schweiz.ch/buwal/de/fachgebiete/biotechnologie/ouc/bureau/index.html) They will be updated as needed.
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Introduction
On the basis of the Law on Epidemics, the Law relating to the Protection of the Environment, the Federal Law on Accident Insurance and the Labour Law, three ordinances have been force since 1 November 1999, regulating the different aspects of biosafety in the handling of genetically modified or pathogenic organisms:
Ordinance on the Contained Use of Organisms (Containment Ordinance, CO) Ordinance on the Occupational Safety in Biotechnology (OOSB) Ordinance on the Release of Organisms into the Environment (Release Ordinance, RO)
With the revised Law relating to the Protection of the Environment and theLaw on Epidemics the Federal Council decided to introduce at the level of ordinances a reporting and authorisation procedure for the handling of genetically modified or pathogenic organisms. Until these ordinances came into force, activities using genetically modified organisms were reported to the Swiss Interdisciplinary Committee for Biosafety in Research and Technology (SKBS). Projects using pathogenic organisms were not recorded. Monitoring of such activities occurred through the Ordinance on Major Accidents (OMA). The cantons are responsible for enforcement of the OMA. Within the European Union, comparable regulations have been in force since 1990. The guidelines that apply in the EU are:
Council Directive 98/81/EC of 26 October 1998 amending Directive 90/219/EEC on the contained use of genetically modified micro-organisms Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work (seventh individual directive within the meaning of Article 16(1) of Directive 89/391/EEC) Directive 2001/18/EC of the European Parliament and of the Council on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC
In contrast to the CO, the EU Directives regulate the handling of pathogenic organisms and genetically modified organisms separately (Directives 2000/54/EC and 90/219/EEC). The EU also restricts its regulations to the handling of micro organisms.
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2.1
2.2
Ordinance on the Release of Organisms into the Environment (Release Ordinance, RO)
The purpose of the RO is to protect people and the environment against harmful effects or nuisances of the use of organisms in the environment. This applies to field trials and marketing, both of which require a risk analysis and assessment of the possible effects on people and the environment. In addition, monitoring procedures must be described and precautionary measures taken. Field trials and marketing both require authorisation. The licensing authority for field trials in SAEFL. Various federal agencies are responsible for marketing, according to the intended use: SFOPH, SAEFL, SFOA and the FVO. In the case of immunobiological products in the veterinary sector, the responsible agency would be the FVO. The SFOPH (for population) and SAEFL (for environment) also issue statements on possible hazards to people and the environment.
2.3
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Enforcement of the CO
The CO regulates the contained use of genetically modified or pathogenic organisms. Anyone involved in the contained use of organisms must take all due care to ensure that organisms, their metabolic and waste products do not endanger people or the environment. Anyone who wishes to use organisms must carry out a risk assessment in advance. The general safety measures listed in Appendix 4 of the CO apply to all kinds of use. Furthermore, additional safety measures must be adhered to, according to the class of activity. The classification determines whether a proposed project is subject to the recording and notification obligation, or if necessary the authorisation obligation. The federal authorities examine the risk assessment and authorise the activity and if necessary, the omission of safety measures. Respect for the obligation to take due care and adherence to safety measures are monitored through inspections carried out by the cantonal authorities.
3.1
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3.2
Safety measures
Assigning the activity to a Class establishes the safety measures. The general safety measures must be taken for any activity. These include adhering to the facilitys safety concept, employment of a person to be responsible for supervising biosafety, and adherence to good microbiological practice according to Appendix 3 of the OOSB (protective clothing, prohibition of eating, minimising the production of aerosols, use of disinfectants etc.). Additional safety measures according to Appendix 4 of the CO must also be taken. These depend on both the classification and the type of the activity (laboratory, greenhouse, animal unit, production). Class 2 research activities, for example, require a microbiological safety cabinet, the presence of an autoclave, regular disinfection of work surfaces, and the inactivation of microorganisms for disposal. Class 3 activities are generally carried out in laboratories with negative air pressure and HEPA filtering of exhaust air. Class 1 production activities require the working area to be so constructed that spillage of the total contents of the primary closed system is contained. On request, particular additional safety measures may be omitted under certain conditions. For example, in a Class 3 activity using non-aerogenically transmissible organisms (enterohaemorrhagic E. coli), negative air pressure in the laboratory or HEPA filtering of exhaust gases may be omitted. The application for authorisation must be justified, and alternative safety measures of equal value must be taken if necessary.
3.3
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3.4
Further obligations
Class 3 and 4 activities require legal liability of 20 million Swiss francs to be guaranteed. These activities are also subject to the summary reports required under the Ordinance on Major Accidents.
3.5
Inspections
According to Article 20 of the CO, the cantonal agencies are responsible for monitoring the obligation to take due care and adhere to the safety measures.
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Patrick Krhenbhl
Federal Coordination Center for Biotechnology
Principles
The recording, notification and authorisation obligation is laid down in Art. 9 of the CO. The following activities are subject to the notification/authorisation obligation (research, production, diagnostics etc.):
Non-genetically modified organisms Activity Class 1 Class 2 Classes 3 + 4 First time Notification Authorisation Each time 1 Authorisation2 Genetically modified organisms First time Notification Notification Authorisation Each time 1 Notification Authorisation
Table 1 : Notification and authorisation obligation under the CO First activity under Art. 9 Para. 2 letter a, and para. 3 letter a CO Each activity under Art. 9 Para. 2 letters b and c, and Para. 3 letter b CO
The duty to take due precaution applies to all activities involving organisms in contained systems. These organisms must therefore be handled in such a way that they, their wastes or metabolic products cannot pose a risk to people or the environment. A notification or a licence application must be submitted as early as possible. In contrast to an activity that requires a licence, one that requires notification may be taken up immediately. The only exception is a first activity of Class 2. These activities may only be commenced if the Federal Office responsible raises no objections within 45 days of submitting the notification. If additional details are necessary for examination of the risk assessment, the deadline is extended accordingly. Authorisation applications for first activities should thus be submitted at least 90 days before the desired start of the activity, and all others at least 45 days in advance.
1 2
These activities do, however, still need to be recorded. For medical microbiological diagnostics, authorisation of the first activity is sufficient.
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Figure 1
Notifications or applications for authorisation are submitted to the Federal Coordination Centre for Biotechnology (KBB). The procedure for this will be according to the information published at the time in question on the KBBs Website http://www.contactbiotech.ch. Notifications or applications for authorisation are submitted to the federal coordination centre for Biotechnology (KBB). The procedure for this will be in accordance to the information given at the time on the KBB's Website http://www.contactbiotech.ch.
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All the necessary forms can be obtained from this Website. The notifications or applications for authorisation must be submitted to the KBB in writing. For reasons of legal security, one signed original and two additional copies of the whole document should be submitted. The copies are for sending on to the enforcement authorities. To simplify data acquisition and traffic, an electronic version (www.ecogen.ch) should be submitted as well. Supplements to existing notifications must also be reported to the KBB. The KBB examines the documents for their completeness and may request more information if necessary. The receipt of the notifications or applications for authorisation is published on the Internet and in the Federal Gazette. The KBB determines the federal agency responsible for the complete dossiers, and forwards the dossier to these other agencies for their opinion (see Fig. 1). If the risk to the public is foremost, the SFOPH in consultation with SAEFL shall decide. This is the case for handling humanpathogenic organisms. If the risk to the environment is foremost, SAEFL decides in consultation with the SFOPH and SFOA (for activities involving plant-pathogenic organisms). The SFOPH, SAEFL and the cantons in question receive all notifications and applications. The Federal Veterinary Office and the Federal Office of Agriculture, as well as the Federal Ethics Committee on Non-Human Gene Technology, receive notifications and applications concerning activities involving animals and plants and organisms that are pathogenic to animals and plants. The EFBS issues statements on all applications concerning Class 3 or 4 activities. The authorities examine the risk assessment and in particular the classification of the activity. The SFOPH or SAEFL, respectively, make their decision concerning the risk assessment, taking into account statements from the authorities involved, and may authorise the omission of safety measures. The competent authority informs the applicant of its decision on a notification or authorisation application. All the other offices involved receive a copy of the decision. The KBB registers the decision and updates the information on the Internet accordingly.
Confidentiality
Under Art. 15 Para. 2d of the CO, all non-confidential details of notifications and authorisation applications received shall be publicly accessible. A register of all notifications will also be published on the Internet and the receipt of notifications published in
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the Federal Gazette. Under Article 24 of the CO, details will be treated confidentially where there are reasons to do so. These details must be marked. The reasons for confidentiality must be justified. There are also a few specified details that are never confidential (Art. 24 Para. 5): the names of those responsible for carrying out the activity and for monitoring biosafety; the address of the institution and its installation (site of the activity); the type of installation, safety measures and waste disposal measures; a general description of the organisms and their properties; a general description of the activity, in particular the purpose and the approximate scale (e.g. culture volume); a summary of the risk assessment; the class of the activity.
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Risk assessment and classification of activities involving genetically modified or pathogenic organisms
Karoline Dorsch
Executive Secretary, Swiss Expert Committee for Biosafety, SECB
Carmen Spycher
Federal Office for the Environment, FOEN
Introduction
The basis for safe work in the laboratory is the risk assessment prior to and during work being done. The Contained Use Ordinance (CO) states in Art. 8, para. 1 as follows: Anyone involved in the contained use of genetically modified or pathogenic organisms must assess in advance the possible damage to people and the environment, as well as the extent of potential damage and the probability of its occurrence (risk assessment).
1.1
Definitions
Risk is the combination of the probability that damage occurs and the extent of the damage. Damage is the impairment of value or function due to the occurrence of a hazard. Hazard is any characteristic that could lead to harm/damage. For risk assessment of work with pathogenic and/or genetically modified organisms, it is primarily the biological properties (i.e. the risk an organism poses to humans and the environment) and secondarily the possible risk caused by the activity (what is done with an organism), which must be taken into consideration. Due to the many factors involved, quantitative measurement of biological risk is difficult, because organisms can reproduce and interact with other organisms. The probability that damage occurs depends on different events: Organisms are released and spread within the plant and may consequently be a hazard to workers. Such risks are primarily dealt with by the Ordinance on Occupational Safety in Biotechnology (OOSB). Organisms are released from the plant. In this case, human health and the environment may be affected depending on several factors including: Survival of the released organism Propagation Establishment of organisms in the environment
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In principle, risk assessment of work with pathogenic and/or genetically modified organisms in the laboratory comprises, according to the containment ordinance, the following two steps: Assignment of the organisms to a group, followed by Classification of the activity in a class.
2
2.1
Classification of organisms
Classification of natural organisms into 4 groups
Organisms have traditionally been grouped into four (risk) groups according to the risk they present to humans, while newer lists also take into account the pathogenicity of organisms to animals and plants. A very early list was elaborated by the U.S. Department of Health, Education and Welfare, Public Health Service, Centers for Disease Control, Office of Biosafety: the Classification of Etiologic Agents on the Basis of Hazard, (4th edition, July 1974, Atlanta, Georgia 30333). Classifications based on this list are used in most countries, although classifications of certain organisms may differ due to climate, occurrence of organisms, occurrence of vectors etc. Table 1 shows schematically how organisms are assigned to groups. It also demonstrates that each group contains a broad spectrum of organisms with a somewhat varying degree of pathogenicity.
Risk that organisms present Group 1 Group 2 Group 3 Group 4 No or negligible risk Low risk Moderate risk High risk Examples E. coli K12, Saccharomyces cerevisiae, phage lambda Clostridium tetani, Measles virus, Candida albicans Bacillus anthracis, Mycobacterium tuberculosis, HIV, Hepatitis C, Histoplasma capsulatum Smallpox, Ebola virus (Group 4 only contains viruses)
Lists with the classifications of organisms are provided by FOEN (Art. 22 CO): 1 FOEN, in agreement with FOPH, seco, FVO, SFOA and SUVA and after consulting EFBS/CFSB, shall maintain a publicly available list in which: a. organisms are assigned to four groups according to the criteria given in appendix 2.1; and b. biological containment systems are given that meet the specifications listed in Appendix 2.2. 2 It shall take into account existing lists, in particular those of the European Union. The lists of bacteria, parasites, fungi and virus are available on the internet: Bacteria:
http://www.umwelt-schweiz.ch/imperia/md/content/stobobio/biotech/15.pdf
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Parasites:
http://www.umwelt-schweiz.ch/imperia/md/content/stobobio/biotech/12.pdf
Fungi:
http://www.umwelt-schweiz.ch/imperia/md/content/stobobio/biotech/20.pdf
Virus:
http://www.umwelt-schweiz.ch/imperia/md/content/stobobio/biotech/25.pdf
The Swiss lists are based on the lists elaborated by different countries and organizations as well as the organism lists of the Swiss Expert Committee for Biosafety (EFBS/CFSB) issued in 1992. In the Swiss lists specific local situations have been taken into account. (SKBS/CSSB), 1992 (amended 1995) US NIH guidelines, and amendments US Public Health Service, CDC, Atlanta, 1974, and amendments WHO, Geneva, 2004 Council Directive 2000/54/EC on the protection of workers from risks related to exposure to biological agents Germany: Bundesministerium fr Gesundheit Germany: Berufsgenossenschaft der chemischen Industrie (see References) UK Health and Safety Executive Health Canada
2.2
Most organisms routinely used in research or diagnostics can be found in either the Swiss lists or in international lists. In only a few cases will organisms have to be classified. Among these are emerging organisms, rarely used organisms, or organisms which have been attenuated naturally or by genetic modification. In cases where an organism has to be classified, a detailed description of the organisms properties or an experts report must be submitted, taking into account the above points. Some of these points are discussed here in more detail.
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Pathogenicity Pathogenicity is defined as the (inheritable) property of an organism of causing disease in a specific host. The main factors involved are: ability to survive and to multiply in a host; production of damaging products. frequency of infections/severity of disease; genetic determinants (there are pathogenic and apathogenic species belonging to the same genus, which can be closely related). In most cases, several genetic determinants are necessary to determine the pathogenicity of an organism; host specificity.
Virulence Virulence is the extent of pathogenicity of a given organism, i.e. it provides a quantitative measure of pathogenicity. The microorganisms invasiveness, toxicity and ability to multiply determine virulence. Individual strains of organisms can be avirulent, weakly or highly virulent. Transmission Possible routes of transmission are: direct contact (mucous membranes, skin); body fluids; aerosols; indirect (water, soil, food, air); vectors (e.g. insects).
Depending on the route of transmission, the risk varies and different safety measures must be taken. Availability of prophylaxis and treatment The availability of vaccines and/or antibiotics against specific organisms may have an influence on assigning pathogenic and genetically modified organisms to groups. In the case of HIV, for example, no vaccine is available, but HIV is not transmitted by the airborne mode. In addition, it survives poorly in the environment and is not highly infectious. Due to the absence of a vaccine it is assigned to Group 3, but otherwise it might be assigned to Group 2.
2.2.1
Group 1 organisms
Work with Group 1 organisms presents no risk or a negligible risk for people and the environment. Organisms that do not cause diseases are consequently assigned to Group 1. Specific bacterial and viral strains of Groups 2 and 3 which have lost their virulence permanently and which do not revert easily will also be assigned to Group 1. Examples are Escherichia coli K12 (see below) and other E. coli strains. De-
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rivatives of LT-2 strains of Salmonella typhimurium which have stable mutations in the genes aroA, galE or cya and crp are also assigned to Group 1. The same is true for specific Salmonella typhi (Group 3) strains carrying two independent deletions in genes coding for essential metabolic functions (aroC and aroD) with or without an additional deletion in the heat shock gene htrA (involved in the regulation of the virulence). In this case, multiplication of the mutants in the host and in the environment is prevented. Furthermore, clinical data show that the uptake of high doses of these bacteria poses no risk to people or the environment. A further example of reclassification in Group 1 is the Shigella flexneri strain carrying the stable deletion virG (no survival in epithelial cells following invasion), sen/set (enterotoxin genes), guaBA (purine biosynthesis is deleted). As a general rule, the minimal requirements for reclassifying pathogenic bacteria from Groups 2 or 3 into Group 1 are the presence of two independent mutations, one in virulence genes and the other in metabolic genes; data from toxicity/pathogenicity studies.
Bacteria or fungi which have been used for large scale production for a long time and whose safety has thereby been proven, such as certain Lactobacillus strains. Saccharomyces cerevisiae and Pichia pastoris also belong to Group 1. Some viral vectors are also assign to Group 1, e.g. due to their ability to replicate in only very few cell lines, such as NYVAC (a highly attenuated derivative of the Copenhagen vaccinia virus strain) or ALVAC (an attenuated variant of a canary pox vector).
2.2.2
Salmonella typhimurium Lethality Virulence Infectious dose Host range Transmission Drug resistance Classification Rarely lethal High 100-1000 organisms Humans, animals Food borne Exists Group 2
Mycobacterium tuberculosis High, lethal High 10 organisms Primarily humans Airborne Exists Group 3
A number of organisms classified in Group 3 are not airborne transmitted. They are marked with ** as in the EU Directive 2000/54/EC. For these organisms certain safety measures assigned to level 3 can be omitted, such as negative air pressure or exhaust passing through a HEPA filter (Appendix 4 CO, Table 1, points 7 and 8).
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3
3.1
Classification of activities
Definition of use under the CO
Any deliberate activity using organisms in contained systems according to the CO is defined as use3. Examples are research, development, production, diagnostics (medical-microbiological diagnostics, analysis of food and environmental samples) and teaching (laboratory courses). Work in a facility may be limited to one such activity or comprise different categories with fluid transitions (e.g. research in an university that also teaches laboratory courses to students).
3.2
In particular culturing, processing, multiplication, modification, detection, transport, storage and disposal are listed.
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Risk of activity
Class of activity
Measures
Class 1
Good laboratory technique Minimize emissions Reversible and restricted regarding both duration and area Irreversible but restricted regarding area Irreversible
Class 2
Class 3 Class 4
3 4
3.3
3.4
3.4.1
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e. f. g. h. i. j. k. l.
tential, independence of infectivity; stability and expression of the recombinant genetic material; mobilisation potential of the recombinant genetic material; selection pressure for the recombinant genetic material; techniques for detecting, identifying and monitoring recombinant genetic material; geographic spread, interaction with other organisms or involvement in biogeochemical processes resulting from the genetic modification; known or assumed spread of the recombinant genetic material in the environment through sexual reproduction or horizontal gene transfer; potential for survival, replication and dissemination of the genetically modified organism in the environment, in particular the formation of structures for survival or dormancy; potential for regeneration of eukaryotic cells to higher organisms.
3.5
3.5.1
3.5.2
Examples
Host organism: Escherichia coli K12 In laboratory work, the combination of Escherichia coli K12 together with the narrow host range plasmid pBR322 or derivatives thereof (such as pBluescript) is very commonly used. They are described here in more detail. E. coli K 12 is genetically defective with respect to many pathogenicity determinants as compared to pathogenic E. coli strains. These defects include the absence of
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the fimbria necessary for attachment to the epithelial cells of the gut the K surface antigen factors determining invasion toxins (endotoxins/enterotoxins) serum resistance surface (O) and capsid antigens.
Many K12-derived strains are recombination deficient (recA) or auxotrophic. Consequently multiple recombination events would be necessary to restore pathogenicity of E. coli K12.
Plasmid vector: pBR322 and its derivatives such as pUC, pBluescript, pET
The tra genes (a complex of at least 20 different functions) are deleted (tra genes code, among others, for the F-pili which are responsible for active transfer of plasmids). The mob gene, coding for the so-called mobilizing protein, is deleted. The mob region can be complemented in trans by another plasmid present in the same cell as long as the nic-bom region is present and allows the binding of the mob protein. The nic-bom region is still present in pBR322. The bom region is necessary as a cis-active region for DNA transfer. It contains the nic site, which is the site of DNA strand break. Deletion of nic-bom would provide even greater safety.
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If rop (repression of plasmid) is deleted, a higher number of plasmid copies can be produced per cell. The oriV (origin of replication) is necessary for the autonomous replication of a plasmid. Amp and Tet resistance are of selectable markers.
Plasmid vectors for eukaryotic cell lines usually contain the following components: Bacterial origin of replication Genetic markers, e.g. antibiotic resistance gene(s) to facilitate replication and selection in bacteria Eukaryotic enhancer sequences Eukaryotic promoter sequences Eukaryotic splice sites Eukaryotic polyadenylation sequences
Shuttle vectors contain, in addition, a eukaryotic replicon to facilitate replication of the vector in eukaryotic cells. In many cases these vectors contain well defined eukaryotic regulatory sequences often originating from Group 2 viruses (such as SV40, cytomegalovirus, retroviruses etc) Consequently, the properties regarding the safety of these plasmid vectors are in most cases not significantly changed by the addition of these sequences. However, because these vectors can be expressed in eukaryotic cells, particular attention has to be paid to the inserts.
Examples
Escherichia coli K12 Bacillus subtilis Streptomyces coilicolor Examples Saccharomyces cerevisiae Aspergillus nidulans Established cells (CHO, Hela, BHK) Nicotiana tabacum Spodoptera frugiperda (SF9)
Eukaryotic systems
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Eukaryotic cells, in contrast to bacteria, only survive under well-defined and rather complex growth conditions (media composition, CO2 concentration, temperature), and thus are of little risk if released accidentally into the environment.
3.6
Example 1
Donor organism Insert Vector Recipient organism GMO Class of activity Reasons
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Example 2
Donor organism Insert Vector Recipient organism GMO Class of activity Reasons
Example 3
Donor organism Insert Vector Recipient organism GMO Class of activity Reasons
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Example 4
Donor organism Insert Vector Recipient organism GMO Class of activity Reasons
Example 5
Donor organism Insert Vector
Naturally occurring plants and higher animals generally belong to Group 1. This means that the classification of activities involving genetically modified animals and plants primarily depends on the risk of the inserted sequences. Activities with plants and animals can be assigned to Class 1 if the donor and recipient organisms and the inserts are all assigned to Class 1, if the vectors are not horizontally transferable, if the GMO fulfils the requirements of a Group 1 organism, and does not release organisms of higher groups. If these criteria are not fulfilled the risk assessment can lead to a higher classification of the activity.
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Microbiological identification of naturally occurring human pathogens in diagnostics, food and environmental samples
Urs Spahr
Swiss Federal Office of Public Health When handling clinical samples it must always be kept in mind that Group 2 or 3 microorganisms could be present. The risk of possible infection or accidental exposure is thus real. In addition, there are regular reports of cases of infection of personnel in contained systems by inhalation of infectious aerosols, percutaneous inoculation, contact with mucous membranes, or by ingestion. In addition, certain working methods may contribute to an enhanced risk of transmission of a pathogenic agent in a medical microbiological diagnostics laboratory: enrichment of the microorganisms in the clinical specimen for isolation purposes, use of reference cultures for identification purposes, laboratory work practices that are likely to produce aerosols (homogenisation, centrifugation, sonication etc.), use of hypodermic syringes, inoculation of animals. Conversely, analyses that involve the use of diagnostic kits, without enrichment of the microorganisms or use of reference strains considerably reduce the risk of accidental infection. As a general rule, analyses of clinical material are assigned to Class 2, unless Group 3 organisms are enriched for diagnostic purposes and this is associated with an enhanced risk to people and the environment (CO, Appendix 2.3, Chapter 1, para. 4). In this case, the activity shall be assigned to Class 3. Here the mode of transmission of the Group 3 pathogenic organisms is a key element in the classification of medical microbiological diagnostic activities. Microorganisms for which an airborne transmission has been proven must be considered fully in the risk assessment and the safety measures that must be applied. Microbiological analyses of Group 4 organisms are in all cases to be assigned to Class 4. The application of the CO has allowed to progressively specify the content of theses provisions. Thus, for microbiological analyses of Group 2 microorganisms as well as those of Group 3 that are normally not airborne transmitted or for which such a mode of transmission has not been demonstrated, level 2 safety measures are sufficient (Class 2). This includes the enrichment of microorganisms, the use of reference cultures, resistance tests etc. The boundary between a Class 2 and a Class 3 activity is thus situated where Group 3 microorganisms that are airborne transmitted (for example Mycobacterium tuberculosis, Brucella spp., Coccidioides immitis) are isolated by culture and identified using methods that require a certain number of additional steps (passaging, extraction, characterisation of resistance) and where reference cultures are used. Such activities are therefore to be assigned to Class 3 and the additional safety measures of level 3 according to Appendix 4, table 1 of the CO4 have to be applied. Activities carried out in reference centres for Group 3 organisms (for example, reference centres for Mycobacteria, prions, or enteropathogenic bacteria) are always to be assigned to Class 3. These activities, as a result of their extent, use of reference strains, and the development and
Some additional safety measures may be modified, substituted or omitted. The competent authority evaluates these on a case-by-case basis.
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validation of new detection methods, present an enhanced risk to people and the environment.
Special cases
Doctor's practices: the setting up and evaluation, for example, of closed urine cultures (Uricult, Urotubes) or other similar systems of minicultures do not fall under the provisions of the CO. These minicultures are generally sent to medical microbiological laboratories for additional investigations and confirmation. By contrast, a medical practice that proposes a complete bacteriological analysis of stools is carrying out an activity in the sense of the CO. Haematology, serology, PCR: for these activities, potentially infectious material must be handled and prepared, for example with a view to extracting nucleic acids. This may prove to be particularly critical in the case of a direct detection (without culture or enrichment) of the M. tuberculosis complex, of pathogenic microorganisms present in blood and serum, as well as of Group 4 microorganisms (viruses that cause haemorrhagic fevers, for example). Here, the risk is related to a possible exposure to the pathogenic organisms, a problem that is regulated by the OOSB. To ensure the protection of personnel working with pathogenic microorganisms, the employer is required to specify the safety measures adapted to the given conditions (but no assignment to safety levels), in particular if large quantities of samples are handled or if suspect samples are frequently analysed. For Group 4 organisms, however, and in accordance with the CO, additional safety measures of level 4 must be applied as long as these pathogenic agents have not been completely inactivated (for example by lysis).
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Methods used
1. Primary cultures on selective agars (McConkey/XLD/Hektoen/chro 2. Identification of suspect colonies using biochemical tests (TSI, API 20E, VITEK) and characterisation using agglutination tests. 3. Resistance testing (antibiograms) and possibly serotyping.
2 Only analyses of Group 2 and 3 organisms that are not airborne transmitted (designated by 3** in European Directive 90/679/EEC as well as in the SAEFL list of bacteria). A therapy is available in any cases.
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Example 2
Organisms (groups) analysed
Microbiological analyses of sputum, urine, bronchial lavages for the presence of M. tuberculosis
M. tuberculosis complex (M. tuberculosis, M. bovis, M. africanum, M. canetti, M. microti): group 3. Other species of mycobacteria (M. avium, M. marinum): group 2.
Methods used
1. Decontamination of specimens by treatment with N-acetyl-Lcysteine NaOH; centrifugation. 2. From the sediments: primary cultures (Lwenstein-Jensen agar) to isolate the agents, enrichment in the BACTEC system; microscopic staining (Ziehl-Neelsen); PCR; in vitro diagnostics (Genotype; MTB tests). 3. The suspect primary cultures are sent to the Mycobacteria Reference Centre for further investigations (identification/ confirmation/ characterisation). 4. Possibly: microscopic preparation from suspect primary cultures to confirm the presence of acid-resistant rods.
2 Most of the handling is carried out in closed tubes/containers; the centrifugation steps are secured; for the BACTEC system, reading of primary cultures is completely automated; all the laboratory work practices likely to produce aerosols (inoculation of primary cultures, extraction of nucleic acids etc.) are carried out in the microbiological safety cabinet. 1. Setting up of cultures to isolate and definitively identify the pathogenic agents (reference strains, inoculation and further growth on agar of BACTEC-positives, resistance testing, etc.). 2. Manipulation and preparation of suspect primary cultures for analysis by PCR, in vitro diagnostics (for example Accuprobe).
Further activities
3 Pathogenic agents are transmitted by air; work with open cultures and material enriched with pathogenic agents; work practices that are likely to produce aerosols.
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Example 3
Organisms
Activity
Further activity
Classification and safety measures concerning the diagnostic of bovine spongiform encephalopathy (BSE) in food samples, see the statement by the EFBS in the appendix
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1.
Introduction
The transport of genetically modified or pathogenic microorganisms is regulated by art. 14 of the ordinance on the contained use of organisms (SR 814.912): "1 Anyone transporting genetically modified or pathogenic microorganisms must observe applicable, national and international transport regulations regarding labelling and packaging.
2
These transport regulations apply by analogy to the transport of genetically modified or pathogenic organisms, in particular genetically modified animals and plants, and plant-pathogenic microorganisms".
Table 1 presents the relevant national and international transport regulations, as far as Switzerland and the European Union are concerned. The regulations do not exclusively apply to the carriage of dangerous goods. Preliminary and downstream processes like consigning, packing, accepting, (un-) loading and filling of dangerous goods are also subject to these regulations. Transport regulations are mode specific (Table 1). In general, the various regulations are consistent with the UN Recommendations on the Transport of Dangerous Goods (Model regulations, Manual of tests and criteria), the so called "Orange book". Due to historical evolution, different committees elaborating the regulations, and mode specific properties, however, the regulations are not identical. Differences exist especially with respect to obligations, training, labeling, packing and documentation. Even the classification of dangerous goods is not consistent in every case (e.g. aquatic pollutants). Furthermore, national legislation provides in some cases deviations from the international regulations.
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Table 1: International and national regulations for the transport of dangerous goods Transport mode Road Regulations international: - European Agreement Concerning the International Carriage of Dangerous Goods by Road (ADR) national (CH): - Ordinance on the Transport of Dangerous Goods by Road (SDR, SR 741.621) international: - Regulations Concerning the International Carriage of Dangerous Goods by Rail (RID) national (CH): - Ordinance on the Transport of Dangerous Goods by Rail (RSD, SR 742.401.6) international: - International Civil Aviation Organisation (ICAO) Technical Instructions (TI) - International Air Transport Association (IATA) Dangerous Goods Regulations (DGR) national (CH): - Ordinance on Transport by Air (LTrV, SR 748.411) international: - International Maritime Dangerous Goods Code (IMDG) national (CH): - none international: - European Agreement Concerning the International Carriage of Dangerous Goods on the river Rhine - European Agreement concerning the International Carriage of Dangerous Goods by Inland Waterways (not yet ratified by CH) national: - Ordinance on the enactment of the ADNR (SR 747.224.141.1) - Ordinance on the police on the river Rhine - Ordinance on the navigation on swiss inshore waters (BSV, 747.201.1)
Rail
Air
Sea
Fluvial
2.
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6. 7. 8. 9.
Requirements for construction and testing of packagings, IBC, tanks Provisions concerning conditions of carriage, loading, unloading and handling Requirements for vehicle crews, equipment, operation and documentation Requirements concerning construction and approval of vehicles
The following chapters will present the most important regulations for the transport of infectious substances, referring thereby in general to the ADR version 2007 (enters into force at 1.1.2007). However, not every detail or every possibility can be treated within the scope of this manual.
3.
Consignee: (means the consignee according to the contract for carriage. If the consignee designates a third party in accordance with the provisions applicable to the contract for carriage, this person shall be deemed to be the consignee within the meaning of ADR. If the transport operation takes place without a contract for carriage, the enterprise which takes charge of the dangerous goods on arrival shall be deemed to be the consignee)
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Participant Loader: (means any enterprise which loads dangerous goods into a vehicle or large container)
Obligations He shall hand the dangerous goods over to the carrier only if they are authorized for carriage in accordance with ADR He shall, when handing over for carriage packed dangerous goods or uncleaned empty packagings, check whether the packaging is damaged. He shall not hand over a package the packaging of which is damaged, especially if it is not leakproof, and there are leakages or the possibility of leakages of the dangerous substance, until the damage has been repaired; this obligation also applies to empty uncleaned packagings He shall, when loading dangerous goods in a vehicle, or a large or small container, comply with the special requirements concerning loading and handling He shall, after loading dangerous goods into a container comply with the requirements concerning danger markings He shall, when loading packages, comply with the prohibitions on mixed loading taking into account dangerous goods already in the vehicle or large container and requirements concerning the separation of foodstuffs, other articles of consumption or animal feedstuffs. He shall comply with in particular: the requirements concerning packing conditions, or mixed packing conditions; and when he prepares packages for carriage, the requirements concerning marking and labelling of the packages.
Packer: (means any enterprise which puts dangerous goods into packagings, including large packagings and intermediate bulk containers (IBCs) and, where necessary, prepares packages for carriage)
4.
Infectious substances (ADR section 2.2.62) Infectious substances are assigned to class 6.2. For the purposes of ADR, infectious substances are substances (biological products, genetically modified (micro-) organ-
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isms, cultures, clinical or medical waste, diagnostic specimens, infected live animals) which are known or are reasonably expected to contain pathogens. Pathogens are defined as micro-organisms (including bacteria, viruses, rickettsiae, parasites, fungi) and other agents such as prions, which can cause disease in humans or animals. Substances which meet the criteria of class 6.2 are divided into two categories: Category A: an infectious substance which is carried in a form that, when exposure to it occurs, is capable of causing permanent disability, life-threatening or fatal disease to otherwise healthy humans or animals. Category B: an infectious substance which does not meet the criteria for Category A.
The assignment of a substance to Category A has to be based on the known medical history and symptoms of the source human or animal, endemic local conditions, or professional judgment. International transport regulations like ADR present an indicative list of infectious substances included in Category A (2.2.62.1.4.1). Assignment should in any case be based on available data (e.g. WHO hazards and risks analysis). In case of uncertainties, the assignment should be made in accordance with the competent authority (Federal Office of Public Health, Federal Office for the Environment) Category A substances are to be assigned to two different UN numbers: UN 2814 "INFECTIOUS SUBSTANCE AFFECTING HUMANS" UN 2900 "INFECTIOUS SUBSTANCE AFFECTING ANIMALS only"
Category B substances have to be assigned to the following UN number: UN 3373 "BIOLOGICAL SUBSTANCE", CATEGORY B (from January 2007) Medical or clinical wastes containing Category A infectious substances are to be assigned to UN 2814 or UN 2900 as appropriate. Wastes containing category B substances are to be assigned to the following UN number: UN 3291 "CLINICAL WASTE, UNSPECIFIED, N.O.S." or "(BIO) MEDICAL WASTE, N.O.S." or "REGULATED MEDICAL WASTE, N.O.S."
In case of the indicative list the term cultures (laboratory stocks) is important. For the purposes of transport regulations, cultures are the result of a process by which pathogens are amplified or propagated in order to generate high concentrations. This definition refers to cultures prepared for the intentional generation of pathogens and does not include cultures intended for diagnostic and clinical purposes. Exemptions The following substances are not subject to the provisions of ADR unless they meet the criteria for inclusion in another class: Substances which do not contain infectious substances or substances unlikely to cause diseases in humans or animals Substances containing microorganisms which are non-pathogenic to humans or animals Substances in a form that any present pathogens have been neutralized or inactivated such that they do no longer pose a health risk
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Substances with a low probability of presence of infectious substances, or with concentrations of infectious substances at natural level (e.g. food stuff, water samples, living persons) Dried blood spots or faecal occult blood screening tests and blood (components) which have been collected for the purposes of transfusion or for the preparation of blood products to be used for transfusion or transplantation and any tissues or organs intended for use in transplantation Human or animal specimens for which there is minmal likelihood that pathogens are present, if the specimen is carried in a packaging which will prevents any leakage and which is marked with the words Exempt human specimen or Exempt animal specimen, as appropriate. Biological products (products derived from living organisms, used either for prevention, treatment or diagnosis of disease, investigational purposes) carried for purposes of final packaging or distribution and use for personal health care by medical professionals or individuals.
Examples of classification The following Table 3 presents some examples of classification of infectious substances.
Table 3: Classification of infectious substances, examples.
Material Blood for transfusion Blood for routine analysis (e.g. clinical chemistry, hematology, immunology) Patient specimens: Suspected of containing B. anthracis or Mycobacterium tuberculosis Known of containing B. anthracis or Mycobacterium tuberculosis Suspected of containing Marburg or Ebola Known of containing Marburg or Ebola Sample from far East, new Influenza strain suspected pandemic Suspected of containing Staphylococcus aureus, Pseudomonas aeruginosa, Borrelia, etc. Known of containing Staphylococcus aureus, Pseudomonas aeruginosa, Borrelia, etc. Enrichment from primary diagnostics shipped to reference centre for confirmation Positive for B. anthracis or M. tuberculosis Positive for St. aureus, Ps. aeruginosa, etc. B. anthracis, M. tuberculosis cultures shipped for contained use and: Diagnostic purposes (reference cultures) Research purposes Category none none UN number none none ADR Packing Provisions exempt exempt
B B A A A B B
B B
UN 3373 UN 3373
P650 P650
A A
UN 2814 UN 2814
P620 P620
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Material St. aureus, Ps. aeruginosa cultures (or any cultures of Cat. B substances) shipped for contained use and: Diagnostic purposes (reference cultures) Research purposes MRSA (drug resistant St. aureus) cultures shipped from BE to Lausanne for contained use Medical or clinical wastes containing Cat. A infectious substances Medical or clinical wastes containing Cat. B infectious substances Medical or clinical wastes containing Cat. B infectious substances in culture Inactivated wastes (containing Cat. A or B) Environmental samples, suspected bioterrorism Live vaccines, attenuated strains: Cat. A Cat. B
Category
UN number
UN 2814 UN 2814 UN 2814 UN 2814 UN 3291 UN 2814 none UN 2814 (none) (none)
P620 P620 P620 P620 P621 P620 exempt P 620 exempt exempt
Blood or blood components for purposes of transfusion are not subject to provisions of ADR (2.2.62.1.5.5). Blood for routine analysis is not subject to provisions of ADR unless it is known or there are reasons to expect pathogens in concentrations clearly above natural level (2.2.62.1.5.4). Patient specimens can in general be attributed to Category B (UN 3373), if the pathogens do not meet the criteria of Category A, or if a Category A pathogen is referred to "cultures only" ( 2.2.62.1.4.1; 2.2.62.1.4.2) Enrichments of pathogens from primary diagnostics transported to reference centre can be attributed to Category B if they meet the criteria "cultures only" of the indicative list (2.2.62.1.4.1) and are intended for diagnostic and clinical purposes (2.2.62.1.3). Pathogens which meet the criteria "cultures only" of the indicative list (2.2.62.1.4.1) of ADR have to be assigned to Category A, if the cultures are prepared for the intentional generation of pathogens (e.g. "pure" cultures), otherwise they have to be assigned to Category B. All Category B substances are assigned to UN 3373, including cultures prepared for intentional generation of pathogens (2.2.62.1.3). Medical wastes containing Category B cultures are assigned to UN 3291. Biological products (like vaccines) carried for purposes of final packaging or distribution and use for personal health care by medical professionals or individuals are not subject to ADR provisions.
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5.
In ADR the specific provisions and requirements are presented for each UN number in chap. 3.2.
5.1
To determine the correct packing provision, it may be useful to answer first the following questions: Is it known or are there reasons to believe that the substance contains pathogens? Does the substance represent an exemption according to 2.2.62.1.5 ADR? To which Category the substance has to be attributed? To which UN number the substance has to be attributed? Do any special provisions exist? Special provisions may be part of international transport regulations (ADR 3.3), national regulations or even internal regulations of the carrying company (especially in case of air fright)
UN 2814 and UN 2900: Packing provision P 620 Substances attributed to UN 2814 or UN 2900 have to be packed according to packing provision P 620 (see below). Inner and outer packagings have to meet specific requirements for testing, construction and marking (chap. 6.3 ADR). The outer packaging has to be marked and labelled according to 5.1.2 and 5.2 ADR. The following information have to be put on the consignment: Addresses of the consignor and the consignee UN number Label No. 6.2 (hazard) and in case of liquids No. 11 (orientation of the packaging) (ADR 5.2.2) Construction and test marking (ADR 6.3) Eventually additional labels UN numbers, e.g. in case of use of liquid nitrogen or dry ice for cooling
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According to ADR 4.1.8.3 a detailed list of the content of the packaging has to be put between the secondary and the outer packaging.
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fields for addresses Label for orientation of packaging field for UN number labelling class 6.2 marking of packaging
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UN 3373: Packing provision P 650 Substances attributed to UN 3373 have to be packed according to packing provision P 650 (see below). Inner and outer packagings should meet the specific requirements for testing, construction and marking of chap. 6.3 ADR. The outer packaging has to be marked and labelled according to 5.1.2 and 5.2 ADR. Infectious substances which are assigned to UN 3373 and meet the requirements of packing provision P 650 are not subject to other provisions of ADR (see chap. 5.2 of this manual).
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It is recommended to obtain packagings which meet the requirements of P 620 or P 650 from specialized companies. A list of such companies can be found at the Robert Koch Institute (http://www.rki.de/cln_006/nn_226928/DE/Content/Infekt/Biosicherheit/Seuchenalarm /Anhang/Verpackung,templateId=raw,property=publicationFile.pdf/Verpackung; http://www.rki.de).
5.2
The consignor is responsible for the elaboration of the documentation and the delivery to the carrier. A dangerous goods transport documentation contains the following information: Name and address of the consignor Name and address of the consignee and the name and telephone number of a responsible person (ADR 5.4.1.2.4) Quantity and description of the packaging UN number, proper shipping name, biological denotation, class (e.g. UN 2900 INFECTIOUS SUBSTANCE AFFECTING ANIMALS only (Foot and mouth disease virus), 6.2 Volume or Mass of each dangerous substance with different UN number Gross weight and dimensions of the packaging
The transport documentation does not need any specific form. Many carriage companies provide their own forms.
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Instructions in writing: Instructions in writing indicating the behaviour in case of accidents or incidents have to be given to the driver. The consignor is responsible for a handout of the instructions during loading at the latest. Instructions in writing are to be elaborated according to ADR 5.4.3.8 and include following information: load (official denotation, class, UN number) kind of danger personal protection equipment general and specific safety measures equipment behaviour in case of fire first aid additional instructions or information
It is recommended to coordinate the instructions in writing in accordance with the competent authority or any accredited institute with respect to the kind of danger.
6.
Transport
Substances assigned to UN 3373 can in principle be transported with a private or a company owned car. In this case however, the driver has to be instructed and trained. Substances of UN 2814 and UN 2900 can in general only be transported by specialized companies. The Swiss postal services are only transporting substances assigned to UN 3373.
7.
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8.
http://www.unece.org/trans/danger/publi/adr/adr2005/05ContentsE.html http://www.astra.admin.ch/html/de/news/gefahrengut/index.php
RID
http://www.otif.org/html/e/pub_cotif_09_05_1980.php http://www.bav.admin.ch/themen/verkehrspolitik/00709/00882/index.html?lang=d e
IATA DGR
ICAO TI
IMDG
http://www.imo.org/HOME.html http://www.eda.admin.ch/sub_dipl/g/home/organ/sea.html
ADN ADNR
http://www.unece.org/trans/danger/adnreg2005.html
http://www.bav.admin.ch/dokumentation/grundlagen/00869/index.html?lang=de& showdetail=74
http://www.unece.org/trans/danger/publi/unrec/rev14/14files_e.html
http://www.who.int/csr/resources/publications/biosafety/WHO_CDS_CSR_LYO_ 2005_22/en/index.html
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Starting point
Legal basis: According to Article 20 of the Containment Ordinance, the cantons are responsible for monitoring the contained use of organisms and observance of the safety measures. The cantons may carry out spot checks and take samples, giving notice of them in advance or not. The inspections will be coordinated as far as possible with other monitoring (e.g. of safety at work, accreditation, GLP, industrial accident prevention). The facilitys notifications and applications for authorisation submitted to the Federal Coordination Centre for Biotechnology (KBB), and the decisions on classification of the activity in the case of notification (Classes 1 and 2) and licences (Classes 3 and 4) of the federal authority responsible, serve as a basis for inspection. The polluter-pays principle (LPE, Art. 2) applies to monitoring and sampling, i.e. they are subject to a fee. Whether in practice fees are levied, and how high they are, depends on the enforcement practice of the canton in question. Uniformity: There has long been a drive towards intercantonal harmonisation of inspections. The Intercantonal experience exchange group for technical agencies involved in biotechnology and gene technology (ERFA Bio, http://www.erfa-bio.ch) has established appropriate guidelines. Through practices of joint inspection, this should promote a uniformity of enforcement practice within Switzerland and at international level.
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The results of the sample analysis, including any consequences arising from it, will generally be communicated to the facility.
Possible consequences
Measures: If an inspection ascertains that legal provisions are being contravened, there are deficiencies, or the safety measures do not reflect current safety technology, the cantonal agency may order measures of a binding nature for the facility. If the cantonal agency concludes that under the given circumstances, the protection of people and the environment is not assured, the facility must be closed until the required measures have been implemented. The cantonal agency will inform the Federal Coordination Centre for Biotechnology (KBB) of complaints. It will also inform the KBB if unnotified activities are being carried out at the facility (Art. 20, CO). If there are less severe deficiencies, the agency may recommend improving the existing measures. Consequences of sampling: Evidence of contamination with organisms can be an indicator of inappropriate working practices (e.g. not observing good microbiological practice, or use of unsuitable appliances). Visible soiling noticed while viewing the laboratory can also be substantiated by the sampling results. If the values measured lie clearly above those usually found in similar facilities, it indicates that the required safety measures are not being adequately implemented. In such cases the cantonal agency may order measures to improve, for example, the hygienic conditions in the facility (periodic cleaning of laboratory/appliances, tightening up the hygiene plans etc.). More minor contamination that lies below these critical values may result in recommendations for improving safety measures. Previous experience has shown that sampling has positive effects on the safety standards for handling organisms. Proven contamination heightens employees risk awareness of particular vulnerable points in the laboratory. Penalties: The penalties under Art. 60 LPE apply: A person who deliberately contravenes the regulations on substances or organisms (letter e), handles organisms in such a way that they, their metabolites or wastes can endanger the environment or, indirectly, persons (letter f), or in handling genetically modified or pathogenic organisms fails to take all necessary containment measures (letter l), shall be liable to imprisonment or a fine. These provisions also apply if the conditions imposed by order of the agency are not implemented.
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29 June 1994, Lausanne. A goods train pulling a variety of tank wagons derails at 3 am while crossing a set of points in Lausanne station. 13 wagons - four of them loaded with hazardous chemicals - jump off the track. Two wagons containing epichlorohydrin overturn, spilling their cargo. The chemicals leak into the ballast beneath the track and penetrate the drainage pipes. Epichlorohydrin is a highly toxic, corrosive and carcinogenic liquid which also emits highly flammable vapors. Owing to the ensuing risk of explosions, around 3'000 people are evacuated from the districts downwind of the station.
1.
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In the field of biology, the OMA concerns the activities of class 3 or 4 according to the Containment ordinance (CO), but also the activities of lower classification if they can cause severe damage under certain circumstances or in combination with other risks The OMA does not only apply to fixed installations with chemical and biological hazard potentials, but also to the transportation of hazardous goods by rail, road and along the Rhine river. The OMA is designed to prevent accidents as much as possible by appropriate measures, but it also governs the management of accidents, where the latter arise despite all safety measures taken, as shown below.
2.
3.
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of chemical or hazardous biological substances must first of all provide the enforcement authority with a summary report describing the hazard potential and the safety measures that have been taken. The summary report must notably include the following elements: A description of the enterprise, a situation map and information on the neighborhood; A precise description of the activities; A description of the dangerous goods used (quantitative and qualitative aspects), together with their place of storage; A description of the safety measures (equipment, organization, staff training, emergency); A plan for the intervention forces; A description of the potential hazards linked to the activities and an assessment of the potential scale of an accident at the plant. If the authority concerned judges the damage that might occur to be to great, then a specific risk assessment must be undertaken as the second stage in the procedure. In order to assess the risk, it is necessary to determine the extent of any damage that might occur as a result of accidents and to set it in relation to its likelihood If the authority should deem this risk to be unacceptable, it will require the owners to overhaul the facility in question, or should supplementary measures fail to elicit the desired level of risk reduction it will either impose restrictions or else prohibit production altogether.
Short report drawn up by owners If the expected scale of damage is large Risk assessment drawn up by owners
4.
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He also coordinates the activities and the duties of the enterprise in the frame of the different regulations as far as biosafety is concerned, in particular the Ordinance on containment of organism, the OMA, the Ordinance on occupational safety in biotechnology, the Ordinance related to the impact on the environment, the Ordinance on the release of organisms into the environment and the Ordinance on dangerous goods safety adviser.
5.
Concluding remarks
Despite this positive overall picture, it should not be assumed that we have achieved a position of absolute safety. In Switzerland we are still surrounded by both stationary and mobile potential chemical hazards, which could endanger the public and the environment. These hazards continue to demand the utmost circumspection and this level of caution can only be guaranteed if companies handling potentially hazardous chemicals establish safety and environmental protection as integral management objectives in every area of their operations. This poses a particular challenge in the current business climate, with industry and authorities alike facing massive pressures to cut costs and to reorganize. For the enforcement of the OMA a strong collaboration is needed between the owners of the enterprises, the cantonal authorities, the local fire department and the federal authorities The cantonal office responsible for the enforcement of the OMA plays a role of coordination between all theses actors. In the field of biotechnology the enforcement of the OMA is ensured by the cantonal authorities responsible for the enforcement of the containment ordinance. The addresses can be found on the following web site: http://www.umweltschweiz.ch/buwal/eng/fachgebiete/biotechnologie/adresse/cant/index.html
6.
Note
Some parts of this text are based on the publication of the Swiss Agency for the Environment, Forests and Landscape "Environment Switzerland 2002, Chapter 3. Environment under pressure" available at the following address: http://www.umwelt-schweiz.ch/buwal/eng/medien/umweltbericht/druck/index.html
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Appendix
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References
World Health Organisation, WHO, Laboratory Biosafety Manual, 3rd ed., 2004
http://www.who.int/csr/resources/publications/biosafety/WHO_CDS_CSR_LYO_2004_11/en/
ACGM Compendium of Guidance, Guidance from the health and safety commissions advisory committee on genetic modification, Health and Safety Executive (HSE) http://www.hse.gov.uk/biosafety/gmo/acgm/acgmcomp/ Adelmann S. and Schulze-Halberg H.; Arbeitsschutz in Biotechnologie und Gentechnik, Springer, 1996. Biosafety in Microbiological and Biomedical Laboratories (BMBL), 4th edition; US DHHS, CDC and NIH, May 1999. http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4toc.htm Fleming, D.O. and Hunt, D.L. (eds) 2000. Laboratory Safety. Principles and Practices. Third Edition. American Society for Microbiology, Washington D.C., ISBN 1-55581180-9. Murray et al. (eds) 1995. Manual of Clinical Microbiology. ASM Press, ISBN 1-55581086-1. Systematic collection of federal law (in French, Italian and German) http://www.admin.ch/ch/f/rs/rs.html Sichere Biotechnologie, Einstufung gentechnischer Arbeiten: Gentechnisch vernderte Organismen, BG Chemie, Merkblatt B 008 4/93, Jedermann-Verlag, Postfach 10 31 40, 6900 Heidelberg. Statements of the German Zentrale Kommission fr die Biologische Sicherheit (ZKBS) http://194.95.226.234/GENTEC/ZKBS/ZKBS.HTM
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EFBS Statements
Statement of the Swiss Expert Committee for Biosafety on the classification of work with genetically modified viral vectors Risk assessment and safety measures for activities with oncogenic and cytokineencoding sequences Classification of work using prion genes and prion proteins Statement of the Swiss Expert Committee for Biosafety on BSE diagnostics: classification and safety measures Statement of the Swiss Expert Committee for Biosafety on waste disposal in medical microbiology diagnostic laboratories Statement on the terms used in the Containment Ordinance and on the siting of autoclaves in containment level 3 and 3** laboratories Guidelines for work with cell cultures in research laboratories
http://www.umweltschweiz.ch/buwal/eng/fachgebiete/fg_efbs/rubrik_dokumentation/dok_stell_allg/index.html
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Institutions
American Biological Safety Association: http://www.absa.org/ American Society for Microbiology http://www.asm.org/ Belgian Biosafety Server: http://biosafety.ihe.be/ ERFA Bio http://www.erfa-bio.ch/ European Biosafety Association: http://www.ebsaweb.eu Centers for Disease Control and Prevention: http://www.cdc.gov/ French Commission de Gnie Gntique http://www.recherche.gouv.fr/commis/genetique/default.htm Federal Coordination Centre for Biotechnology: http://www.contactbiotech.ch Health & Safety Executive UK http://www.hse.gov.uk/biosafety/index.htm Robert Koch Institute: http://www.rki.de/ Word Health Organization, Epidemic and Pandemic Alert and Response http://www.who.int/csr/en/ World Organisation for Animal Health http://www.oie.int/eng/en_index.htm
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Abbreviations
Legal Statutes
ADR CO GTL LPE OMA OOSB RID RO RSD SDR European Agreement concerning the International Carriage of Dangerous Goods by Road Ordinance on the Contained Use of Organisms (Containment Ordinance) Federal Law relating to Non-human Gene Technology (Gene Technology Law) Federal Law relating to the Protection of the Environment OMA Ordinance on Occupational Safety in Biotechnology Convention concerning the international rail transport of dangerous goods Ordinance on the Release of Organisms into the Environment (Release Ordinance) Ordinance concerning the transport of dangerous goods by rail Ordinance concerning the transport of dangerous goods by road
Federal Offices
KBB FVO seco SFOA SUVA Federal Coordination Centre for Biotechnology Federal Veterinary Office State Secretariat for Economic Affairs Swiss Federal Office for Agriculture Swiss National Accident Insurance Organisation
Committees
ECNH SECB Swiss Federal Ethics Committee on Non-human Gene Technology Swiss Expert Committee for Biosafety (Eidgenssische Fachkommission fr biologische Sicherheit, EFBS)
Cantons
ERFA Bio Intercantonal experience exchange group for agencies involved in biotechnology and gene technology
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