BSO Manual

Introductory Information Meeting for New Biosafety Officers Thursday, 23 November, 2006, Hotel Ador, Bern
BSO Manual 2006
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Table of contents
Foreword 5
Biosafety Regulations in Switzerland
Notification and authorisation procedures
13
Risk assessment and classification of activities involving genetically modified or pathogenic organisms
17
Additional biological containment systems
27
Microbiological identification of naturally occurring human pathogens in diagnostics, food and environmental samples
31
Transport regulations for class 6.2, infectious substances
36
Cantonal inspections: practical aspects and experiences
51
Cantonal enforcement of the Ordinance on Major Accidents (OMA)
55
Appendix 1 2 3 4 5 References EFBS Statements Internet Links on Organisms Institutions Abbreviations
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.
Bern, 23 November 2006
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Biosafety Regulations in Switzerland

Urs Spahr
Swiss Federal Office of Public Health
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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An overview of the three ordinances

The three ordinances cover different areas of application. This is shown in Figure 1. As soon as genetically modified or pathogenic organisms are used in contained systems, the activity falls within the area of validity of the CO. Use is defined as any deliberate activity using organisms, in particular culturing, processing, multiplication, modification, detection, transport, storage or disposal. Certain activities that form part of medical microbiological diagnostics, production and biomedical research fall within the area of validity of the CO. If the work entails possible contact with micro organisms and there may thus be a risk to the safety or the health of employees (exposures), the activity then falls within the area of validity of the OOSB. These include work in hospitals such as taking blood samples, where there may also be a risk of infection through exposure. Organisms are cellular or noncellular biological entities able to replicate or transfer genetic material. These include animals, plants and micro organisms (bacteria, algae, fungi, protozoa, viruses and viroids). Cell cultures, parasites, prions and biologically active genetic material are considered to be micro organisms. A contained system is a containment measure using physical barriers or a combination of physical and chemical or biological barriers to limit or prevent contact between organisms and people or the environment.
Figure 1: Areas of validity of the three ordinances
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2.1
Ordinance on the Contained Use of Organisms (Containment Ordinance, CO)

The purpose of the CO is to protect people and the environment against harmful effects or nuisances of the contained use of organisms. Contained systems are generally laboratories, but they may also be production facilities, animal houses or greenhouses. However, the CO does not cover e.g. the food industry or sewage treatment plants, since the activity involving microorganisms in such facilities, due to many years of experience or according to the Release Ordinance, does not have to be carried out in a contained system. Anyone who carries out an activity must undertake a risk assessment. This leads to its classification and so determines the additional safety measures of the corresponding safety level. The Ordinance stipulates a notification and authorisation obligation.
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
Ordinance on the Occupational Safety in Biotechnology (OOSB)

The purpose of the OOSB is to protect employees from the hazards of microorganisms through exposure (possible contact) and handling (deliberate activity). It lays down an employers responsibilities and tasks. Determination of the hazard and a risk assessment must be carried out. This establishes the required safety measures. The OOSB requires notification of the use of microorganisms, which in practice is combined with notification or licence application under the CO. The specific enforcement of the OOSB is the responsibility of the Swiss National Accident Insurance Association (SUVA).
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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
Risk assessment and classification of activity

The first step of the risk assessment consists of ascertaining which organisms are to be used. The handling of organisms assigned to Group 1 presents no or a negligible risk to people or the environment. Pathogenic organisms assigned to Group 2 show a small risk. Properties such as virulence, pathogenicity, infectivity and possibility of treatment are taken into account. The organisms assigned to Group 3 are assumed to present a moderate risk. These organisms may sometimes cause severe to lifethreatening diseases. Organisms in Group 4 can cause severe diseases, and their use is associated with a high risk. As yet, only viral pathogens have been assigned to this Group. If genetically modified organisms are to be used, it must be ascertained whether this will involve a biological safety system. Various criteria for the recipient (host) organism and vectors are defined in Appendix 2.2 of the CO. A safety system is, for example, E. coli K12 in combination with derivatives of the plasmid pBR322. Once the Group of the organisms has been established, the activity is assigned to one of the 4 Classes (the criteria for this are given in Appendix 2.3 of the CO). As a rule, the Class of activity corresponds to the Group to which the organisms are assigned, in particular for research activities. Medical microbiological diagnostics are generally placed in Class 2 and the examination of food and environmental samples in Class 1, as long as these activities are not associated with an increased risk.
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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
Recording, notification and authorisation obligation

The use of genetically modified or pathogenic organisms is associated with a recording and notification obligation. The records must contain various details such as the name and qualification of the person responsible, the type of organisms used and the risk assessment. The precise details for each class of activity are set down in Appendix 3 of the CO. The records must be stored for five years after the activity ends. All activities in Class 1 that use genetically modified organisms for the first time must be notified. Every Class 2 activity that uses genetically modified organisms must also be notified. All Class 3 and 4 activities must be authorised. Anyone who handles pathogenic organisms must notify every first Class 2 activity, and have permission for every Class 3 or 4 activity. The entry and exit point for all notifications and applications for authorisation is the Federal Coordination Centre for Biotechnology, which passes the documents on to the relevant authorities. Figure 2 shows the enforcement of the CO schematically.
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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.
Figure 2: Enforcement of the CO
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Notification and authorisation procedures
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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The notification and authorisation procedure

Figure 1 shows schematically the notification and authorisation procedure according to the CO.
Figure 1
Notification and authorisation procedure according to the CO
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.
Tasks of the Federal Coordination Centre for Biotechnology

The Federal Coordination Centre for Biotechnology is the entry and exit point for all notifications and licence applications under the two Ordinances (CO, OOSB). It is therefore the first point of contact for all questions and problems concerning the submission of notifications and licence applications. It also functions in the course of a notification procedure as an information point about the process and state of notifications. Further KBB tasks are: examining notifications and licence applications for completeness; monitoring deadlines and management of notifications and authorisations; publishing the notifications and authorisations received on the Internet and in the Federal Gazette; serving as an information point for further questions.
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.
The Ordinance on Fees

Services carried out under the CO are subject to a fee. The fees are set in the Ordinance of 15 October 2001 on fees for services under the Containment Ordinance (SR 814.912.35). The most important fees are:
Examination of a notification / authorisation application for: Class 1 activities Class 2 activities Class 3 und 4 activities Omission of safety measures Cost in Swiss francs: 100 500 100 500 300 1500 100 2000
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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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Displacement of other organisms Interaction with other organisms
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:
Fungi:
Virus:
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
Criteria for classification of natural organisms

A number of properties are being used for classification of the organisms (Appendix 2.1 CO and OOSB): a. b. c. d. e. f. g. h. i. j. k. l. pathogenicity and lethality; virulence or attenuation; mode of infection, effective infection dose and the infection route; production of noncellular components such as toxins and allergens; the reproductive cycle and survival structures; host range; the degree of natural or acquired immunity of the host; pattern of resistance or sensitivity to antibiotics and other specific agents; availability of appropriate prophylaxis and therapy; the presence of oncogenic nucleic acid sequences; the shedding of viruses in the case of cell lines; parasitic properties.
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.
Other important factors determining the extent of the pathogenicity of an organism:
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
Group 2 and 3 organisms

The table below shows the characteristics of two organisms that distinguish them between Group 2 and 3:
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
Risk assessment of activities

The classification of an activity depends first on the properties of the organisms used, and second on the activity carried out using these organisms. The risk assessment of an activity should include the type of activity and its extent. The type of activity is determined in part by classifying the work into one of the categories of research, diagnostics, production, development etc. The individual work steps also determine the type of activity. Hazardous work steps (e.g. production of aerosols through pipetting, subculturing, vortexing, centrifugation), or culture volumes, must be considered in the assessment. Furthermore, for Class 3 or 4 activities an assessment should be made of possible impacts of the organisms used on the location of the facility. Criteria such as the capacity of the organisms to survive, reproduce and spread in the environment, interactions with other organisms, and their involvement in biogeochemical processes should be assessed. Further criteria for the classification of activities are given in Appendix 2.3 of the CO. The Ordinance describes the procedures for classification, divided according to activities, using naturally occurring organisms and those involving genetically modified organisms. The risk assessment leads to classification of the activity in one of the four classes. The classification determines the safety measures of levels one to four to be applied (Appendix 4 CO).
In particular culturing, processing, multiplication, modification, detection, transport, storage and disposal are listed.
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Risk of activity
Class of activity
Safety measures: containment level
Measures
Effect on people and environment in event of escape from contained systems
No or negligible risk Low risk Moderate risk High risk
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
Prevent emissions Prevent emissions
3.3
Activities involving organisms that occur naturally

The class of an activity with naturally occurring organisms generally corresponds to the group of the organism used. If organisms of different groups are used, the class generally corresponds to that of the most hazardous organism. Exceptions such as the classification of diagnostic activities are given in the CO. The classification of medical-microbiological diagnostics is described in a separate chapter. The analysis of soil, water, air and food samples is assigned to Class 1, if it is not associated with an elevated risk for people and the environment. One example of a Class 1 activity is the analysis of products for contamination with pathogenic organisms, if such contamination is not normally expected. There is an increased risk in samples taken to confirm suspected contamination, in the cultivation of Group 2 or 3 reference strains, in the identification and serotyping of microorganisms, and in the development and validation of methods for Group 2 to 3 organisms. The classification in these cases is carried out analogously to medical-microbiological diagnostics.
3.4
3.4.1
Activities involving genetically modified organisms

Definition of a GMO under the CO
A GMO is any organism in which the genetic material has been altered in a way that does not occur under natural conditions by mating or natural recombination. The CO defines in Appendix I the processes that lead to a GMO in the sense of this Ordinance. Processes that do not produce a GMO in the sense of the CO such as mutation are also listed there.
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3.4.2. Risk assessment of activities involving genetically modified organisms

In addition to the criteria given above, the risk assessment of activities involving genetically modified organisms should consider the components used to construct a GMO, and subject them to a complete evaluation. According to Appendix 2.3 Section 2 Para. 1 CO, these components are: a. b. c. d. donor and recipient organism; genetic material introduced (inserts); vector or vector-recipient system; genetically modified organism.
3.4.3. Components of a GMO

The donor organism is the organism from which the foreign nucleic acid to be inserted into the recipient organism originates. Assignment of the donor organism to a group is set down in the list of organisms or is carried out according to the criteria given in Appendix 2.1 of the CO. The classification of an insert into a group depends on the type of sequence inserted, as well as its level of expression and activity. If the nucleic acid of the entire donor organism is used, its properties and their possible transmission to the recipient must be included in the risk assessment. The risk assessment should also cover whether an insert demonstrates toxic, allergenic or oncogenic potential. The recipient organism is the organism into which the foreign nucleic acid is inserted. Assigning it to a group is set down in the list of organisms or is carried out according to the criteria given in Appendix 2.1 of the CO. Plants and animals generally come under Group 1. A vector is a biological carrier with which the foreign nucleic acid can be inserted into a recipient organism. Commonly used vectors are plasmids, cosmids, viruses and phages. Risk assessment of activities using vectors should include the following properties: original vector, vector maps, regulatory elements (e.g. replicon, promotor, enhancer), mobilisability, cotransfer, transfer system, selection marker, host specificity and infectivity. The Swiss Expert Committee for Biosafety (EFBS/CFSB) has carried out a classification of activities with commonly used viral vectors (see EFBS/CFSB Statements). Plasmids derived from the narrow host range pBR322 based plasmid, such as pUC or pBluescript can generally be assigned to Group 1. For recombinant genetic material the function of the insert, stability, expression and selection pressure should be assessed. If, for example, an oncogene is not expressed in an organism, the use of this GMO presents less hazard than one in which the protein is expressed and is biologically active. The criteria for classifying activities involving genetically modified organisms are given in Appendix 2.3 Section 2 Para. 2 CO: a. b. c. d. nature, extent and purpose of the activity; function of the genetic modification; degree of purity and characterisation of the genetic material used for recombination; for vectors: the host specificity, presence of a transfer system, mobilisation po-
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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
Biological containment systems

Definition
Biological containment systems are recipient organisms or vectors, or a combination of both, with biological barriers that lead to a reduced risk posed by the GMO. These organisms are assigned to Group 1, yet they provide additional safety compared to regular Group 1 organisms, which is especially important for work with toxic sequences or for large-scale production. The criteria are listed in Appendix 2.2 CO as follows: Host organisms a. must be characterised scientifically and classified taxonomically; b. must require conditions for its replication that never or seldom occur outside the contained system; c. must not be pathogenic or display properties that might endanger people and the environment in another way; d. must show no or negligible horizontal gene exchange with animal- or plantassociated organisms The vector: a. must have genetic material which has been extensively characterised; b. must have a very high host specificity; c. must, especially in the case of vectors for bacteria and fungi, have no transfer system, a low rate of cotransfer and low mobilisation; d. must, in the case of viral vectors for eukaryotic cells, show no independent infectivity and only a low transfer rate by endogenous helper viruses; e. must, in the case of viral vectors, be unable to regain infectivity or replication ability through recombination.
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.
from: BG Chemie, Merkblatt B009
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.
Additional biological containment systems

Prokaryotic systems
Gram-negative bacteria Gram-positive bacteria
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
Fungi Mammalian cells Plant cells Insect cells
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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
Examples of the classification of activities

Classification of activities using viral vectors (see EFBS/CFSB Statements) Classification of activities using genetically modified PrP genes (see EFBS/CFSB Statement on the classification of work using prion genes and prion proteins) Risk assessment and safety measures for activities with oncogenic and cytokine-encoding sequences (see EFBS/CFSB Statements) Classification of activities using various inserts / donor organisms:
Expression of the RNaseH gene of the Hepatitis C virus (HCV)
Hepatitis C virus (Group 3) RNase H pSP64 (original vector pBR322) E. coli K12 Recombinant E. coli K12 1 The vector-host system corresponds to a biological containment system The subgenomic nucleic acid fragment is characterised and without potential hazard.
Example 1
Donor organism Insert Vector Recipient organism GMO Class of activity Reasons
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Example 2
Establishment of a genomic library of Streptococcus pyogenes

Streptococcus pyogenes (Group 2) Subgenomic fragments (shotgun-cloning) pUC18 E. coli K12 Recombinant E. coli K12 1 Streptococcus pyogenes is the pathogen causing scarlet fever. This organism is pathogenic because of exotoxins encoded by single genes. Transmission of a whole toxin gene to the recipient organism cannot be ruled out. But because the insert in this vector-recipient system is not expressed, the activity can be assigned to Class 1. Note: The classification of an activity like this requires careful risk assessment. A case-by-case evaluation, including further work steps and the resulting expression potential as well as the activity of the insert should be carried out. If the risk assessment shows that the activity can be given a lower classification than the donor organism, valid reasons should be given.
Example 3
Cloning of HIV-1 DNA

HIV-1 (Group 3) Entire genome of HIV-1 Plasmid vector (pBR derivative) COS 7 (established monkey cell line, Group 1) Monkey cell line with the entire genome of HIV-1 3 The entire provirus DNA is inserted into the cell line. The donor organism belongs to Group 3.
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Example 4
Manipulation of in vitro naked HIV DNA

HIV-1 (Group 3) Entire genome of HIV-1 (full length intact molecule) Plasmid vector (pUC18 derivative) E. coli K12 Recombinant E. coli K12 2 The entire provirus DNA is inserted into the plasmid vector. Expression of insert and production of viral particles are not possible. Lentiviral naked DNA is much less infectious than intact viral particles.
Example 5
Donor organism Insert Vector
Expression of human Tumour Necrosis Factor (TNF) using retroviral vectors

Human (Group 1) TNF LNSX (retroviral vector with sequences from pBR322, bacterial neomycin resistance gene, 3 and 5 LTR of a murine retrovirus) Amphotropic murine packaging cell line GP+AM12 (Group 1) Cell line producing recombinant, amphotropic retroviruses (Group 2) 2 After transfection, the recombinant vector is packaged into an amphotropic, infectious, replication-deficient Group 2 retrovirus and released from the cell line. The viruses are able to infect human cells.
Recipient organism GMO
Class of activity Reasons
Classification of activities using genetically modified plants and animals
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).
Food and environmental microbiology

With regard to the rare presence of human pathogenic micro-organisms in samples of food, water, soil and air, the CO in appendix 2.3, chapter 1, paragraph 3a stipulates that the analysis of such samples can generally be assigned to class 1 unless these activities are associated with an increased risk to humans and the environment. This will apply for routine analyses of food samples, e.g. in a laboratory of a production site where the quality control aims to demonstrate the absence of specific microorganisms in intermediate and finished food products. These laboratories do not normally subcultivate suspect colonies for further identification and do not cultivate reference strains. On the contrary, a more specialized laboratory with higher diagnostic skills and where reference strains of pathogenic cultures are held will assign its diagnostic activity to class 2. This will be the case in Cantonal laboratories that often have to analyse food and environmental samples in the course of a food poisoning outbreak. Such samples may contain pathogenic micro-organisms in great numbers and therefore will pose an enhanced risk of people and the environment.
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Summary: decision tree
Examples of classification of activities

Example 1
Organisms (groups) analysed
Microbiological stool analyses

Salmonella sp. (group 2). Salmonella typhi (group 3). E. coli O157:H7 enterohaemorrhagic (group 3). Shigella sp. (groups 2-3).
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
Analysis of food and environmental (soil, water, air) samples

E. coli, Salmonella spp., Shigella spp., P. aeruginosa, L. monocytogenes, L. pneumophila, etc. (Group 2 and 3) Routine analysis of samples for the absence or presence of pathogenic micro-organisms (no samples taken to confirm suspect colonies, no reference strains). 1 Rare presence of target micro-organisms; no increased risk for people and the environment. Analysis to confirm suspect colonies including cultivation of Group 2 and 3 reference organisms, identification and serotyping of micro-organisms, development and validation of methods. 2 Comparable risks as for medical microbiological diagnostics; the cultivation of Group 2 and 3 micro-organisms represent an increased risk to humans and the environment. No airborne transmission of group 3 micro-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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Transport regulations for class 6.2, infectious substances

Tobias Schaller
Swiss Federal Office of Transport
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.
Structure and content of international transport regulations

The structure and contents of the international regulations mentioned in Table 1 are comparable. As an example, the table of content of ADR is shown below. 1. 2. 3. 4. 5. General provisions (scope, definitions, training, safety obligations, compliance, security, ) Classification (class specific provisions, test methods) Dangerous goods lists, special provisions and exemptions Packing and tank provisions Consignment provisions
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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.
Obligations of the participants

In chapter 1.4 of ADR, the participants and their obligations are determined. Table 2 presents a digested version. It is important to notice that the consignor, the enterprise or person who wants a dangerous good to be transported, has extended obligations. He is responsible for, among others, the correct classification, packing, marking, labelling and documentation.
Table 2: Participants and their obligations
Participant Consignor: means the enterprise which consigns dangerous goods either on its own behalf or for a third party. If the transport operation is carried out under a contract for carriage, consignor means the consignor according to the contract for carriage; Obligations The consignor shall in particular: ascertain that the dangerous goods are classified and authorized for carriage in accordance with ADR furnish the carrier with information and data and, if necessary, the required transport documents and accompanying document use only packagings, large packagings, intermediate bulk containers (IBCs) and tanks approved for and suited to the carriage of the substances concerned and bearing the markings prescribed by ADR comply with the requirements on the means of dispatch and on forwarding restrictions; If the consignor uses the services of other participants (packer, loader, filler, etc.), he shall take appropriate measures to ensure that the consignment meets the requirements of ADR. The consignee has the obligation not to defer acceptance of the goods without compelling reasons and to verify, after unloading, that the requirements of ADR concerning him have been complied with. He shall in particular carry out in the cases provided for by ADR the prescribed cleaning and decontamination of the vehicles and containers; If the consignee makes use of the services of other participants he shall take appropriate measures to ensure that the requirements of ADR have been complied with. If these verifications bring to light an infringement of the requirements of ADR, the consignee shall return the container to the carrier only after the infringement has been remedied.
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.
Classification of infectious substances

The classification of dangerous goods is based on the chemical, physical and biological characteristics of a substance and the potential effects (danger) it can present for humans, animals and the environment. Dangerous substances are divided into 13 classes and assigned to specific UN numbers (ADR, chap. 2.2). Provisions and requirements for the transport are determined according to the classification of a dangerous substance. "Biological" substances can be attributed in general to three different classes of dangerous goods: Infectious substances (class 6.2): substances which are known or are reasonably expected to contain pathogens Miscellaneous substances / genetically modified organisms (class 9 / M8): micro-organisms and organisms in which genetic material has been purposely altered through genetic engineering in a way that does not occur naturally. Toxic substances (class 6.1): e.g. toxins from plants or bacteria
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
UN 3373 UN 3373 UN 2814 UN 2814 UN 2814 UN 3373 UN 3373
P650 P650 P620 P620 P620 P650 P650
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
ADR Packing Provisions
A (B) A (B) A (B) A none A (none) none A, (none) (none)
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.
Provisions and requirements

Provisions and requirements for the transport of any classified dangerous substance are a function of the: dangerous good class (general provisions and requirements) UN number of the substance (specific provisions and requirements)
In ADR the specific provisions and requirements are presented for each UN number in chap. 3.2.
5.1
Packing provisions (ADR chap. 4.1)

Classification of an infectious substance results in the assignment of a UN number, which determines the relevant packing provision. In case of class 6.2 substances, the following provisions are decisive: UN 3373: UN 2814 / UN 2900: UN 3291: P 650 P 620 P 621 / IBC 620 / LP 621
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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Example of a packaging according to P 620:
leakproof primary receptable
absorbent and padding material leakproof secondary packaging
fields for addresses Label for orientation of packaging field for UN number labelling class 6.2 marking of packaging
rigid outer 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
Other requirements and provisions

Training of persons involved in the carriage of dangerous goods The consignor is regarded as a main participant of the transport of dangerous goods (ADR 1.4.2). All employees of the consignor have to be trained according to their responsibilities (ADR 1.3.1); especially persons who are concerned with classification, documentation and packaging of infectious substances. Security provisions In case of carriage of Category A substances, the provisions of ADR 1.10 (access authorization, security plan etc.) have to be met. Documentation The transport of UN 2814 or UN 2900 substances needs special documentation: Dangerous goods transport documentation (ADR 5.4.1) Instructions in writing (ADR 5.4.3, precaution against accidents)
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.
Dangerous good safety adviser

Each undertaking, the activities of which include the consigning, carriage, or the related packing, loading, filling or unloading, of dangerous goods by road shall appoint one or more safety advisers for the carriage of dangerous goods, responsible for helping to prevent the risks inherent in such activities with regard to persons, property and the environment (ADR 1.8.3, GGBV, SR 741.622). The carriage of substances assigned to UN 3373 and packed according to the provision P 650 are not subject to further provisions of ADR. Thus, an appointment of a dangerous goods safety adviser is not compulsory. In contrast, in case of carriage of UN 2814 or UN 2900 substances, the undertaking company needs to appoint a dangerous goods safety adviser.
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8.
Internet addresses for transport regulations and information

CH law ADR
http://www.admin.ch/ch/d/sr/sr.html
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
http://www.iata.org/ps/publications/9065.htm http://www.iata.org/ps/publications/9052.htm http://www.aviation.admin.ch/
ICAO TI
http://www.icao.org/icao/en/m_publications.html http://www.icao.int/anb/FLS/DangerousGoods/flsdg.cfm http://www.aviation.admin.ch/
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
UN Model regulations WHO: Transport of infectious substances
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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Cantonal inspections: practical aspects and experiences

Susanne Biebinger
Kantonales Laboratorium Basel-Stadt
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.
Objective and frequency of inspections

The aim of the inspection is to examine whether the required technical and organisational safety measures are being observed. The cantonal agency also checks the state of safety technology. In addition, the records required to be kept under CO, Art. 9, para. 1 will be subjected to spot checks for accuracy and completeness, and the guarantee of liability (for Class 3 and 4 activities). Monitoring will particularly consider whether there are unnotified/unauthorised projects, or a significant change in a notified project. The frequency of inspections will depend in part on the Class and extent of the activity. The inspections also serve to clarify specific issues relating to the facilitys safety concept, its activities using organisms, and special safety measures, particularly if there are indications that these are insufficient or have raised concern during previous inspections.
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The process of inspection

The cantonal agency may give notice of an inspection to the facilitys biosafety officer. He or she should involve further representatives of the facility (project leader, company manager or further safety officers) where necessary. He or she is obliged to provide information and documentation at the request of the agency, e.g. copies of the facilitys safety concept or company guidelines, company and site plans, or further information on the use of organisms (LPE, Art. 46, para. 1). The inspection is generally divided into a preliminary discussion, viewing the premises, and a final discussion. At the start, the representatives of the cantonal agency and the facility involved in the inspection generally discuss superordinate topics (the facilitys organisation of safety, responsibilities, the biosafety officers tasks, organisational measures). The inspector acquires an overview of the activities and facilities of the site and may ask questions about the individual projects (e.g. risk assessments, classification, critical steps). In principle any premises in which genetically modified or pathogenic organisms are handled may be viewed (laboratories, animal units, greenhouses, production facilities, as well as instrument, storage, cold rooms and incubation rooms, etc.). Technical safety aspects will be examined (the state, quality and suitability of installations and appliances), and organisational measures (work according to good microbiological practice, observance of general and additional safety measures of the CO and any rules specific to the facility, emergency planning). Finally the results of the inspection will be summarised and, if there are deficiencies, consequences such as measures, deadlines or sampling are discussed. After the inspection the facility will generally receive a written report from the cantonal agency. This will summarise the inspection, levy a fee and provide information about the results of any samples taken. If necessary, measures will be ordered or recommendations made.
Inspections with the taking of samples

Legal basis/objective: The taking of samples is an additional means of monitoring the observance of safety measures (CO, Art. 20, para. 1) and the completeness and accuracy of the records kept by the facility. Sampling is given priority in cases where there is an elevated risk in the handling of organisms (principle of proportionality) or if there is a justified suspicion that organisms are being handled inappropriately. Procedure for taking specimens: Before sampling, the cantonal agency will define its objectives, the organisms they are seeking, and the number and type of samples. Upon request, the facility must make samples, detection methods and details available to the agency (CO, Art.20, para. 3). All steps of sampling (recording, transport, analysis) take place according to validated standard procedures, and are minuted. The taking of samples should also be documented photographically. Sampling points may lie within the working area (e.g. centrifuge, bench), between the laboratory and its immediate surroundings (e.g. door handles, waste after inactivation), or in the environment. Organisms capable of replication, genetic material (DNA, RNA), or specific components (e.g. toxins, allergens) will be detected qualitatively and if necessary quantitatively.
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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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Cantonal enforcement of the Ordinance on Major Accidents (OMA)

Sylvain Rodriguez
Service de lenvironnement et de lnergie (SEVEN), Epalinges Potential hazards due to dangerous chemical or biological substances are all around us. The different accidents that have occurred in the last two decades in Switzerland and abroad have demonstrated the necessity for both enterprises and authorities to continue the efforts to prevent major accidents.
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.
Aim and scope of the OMA

The aim of the OMA is to protect humans and the environment against accidents that may occur in enterprises that handle chemical substances or pathogenic and genetically modified micro-organisms. Such enterprises include buildings containing production equipment, tank stores or facilities using ammonia for cooling purposes, e.g. refrigerated warehouses or outdoor swimming pools.
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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.
Monitored individual responsibility": a central principle of the OMA

The owners of the relevant facilities are required to take all appropriate risk reduction measures that are both compatible with best available safety technology and economically viable. This individual responsibility is monitored by cantonal authorities, which will judge what risks are acceptable, or alternatively what additional steps need to be taken in order to reduce these risks to acceptable levels. It is essential for an enterprise to take, under its own responsibility, safety measures that it considers expedient and necessary on the basis of its hazardous substances or micro-organisms. It notifies the authorities via a summary report or - if the potential danger is very great and severe harm to people and the environment cannot be ruled out in the event of an accident - via a risk assessment concerning planned safety measures. If the authorities discover deficiencies, they can order further measures.
3.
Cantonal enforcement of the OMA

The authorities have the task of monitoring whether the owners of a hazardous facility fulfill their obligations, and thus whether the OMA is, in fact, enforced. As mentioned before they have at their disposal for this purpose a two-stage monitoring and assessment procedure. All facilities containing potentially dangerous amounts
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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
Assessment by the cantonal authorities

Bio- and chemical safety, water protection, public health and fire prevention offices
Assessment by the cantonal authorities
If the risk is not acceptable Additional safety measures or ban
4.
The role of the biosafety officer

The primary role of the biosafety officer is the monitoring of the biological safety inside the facility. He coordinates the realization of the summary report and if necessary the risk assessment study. He is the authorities contact point for all technical questions in relation to the content of these documents.
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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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Internet Links on Organisms

American Type Culture Collection LGC Promochem: http://www.lgcpromochem-atcc.com/about/LGCATCCPart.cfm DSMZ, German Collection of Microorganisms and Cell Cultures: http://www3.dsmz.de/dsmzhome.htm European and Mediterranean Plant Protection Organization http://www.eppo.org/QUARANTINE/quarantine.htm European Collection of Cell Cultures http://www.ecacc.org.uk/ Flies http://flybase.bio.indiana.edu/docs/news/ Material Safety Data Sheets (Canada): http://www.phac-aspc.gc.ca/msds-ftss/index.html#menu ZKBS lists of microorganisms, vectors, cell lines:
http://194.95.226.234/GENTEC/ZKBS/ZKBS.HTM?ORGLISTE/VEKTORLI.HTM&1Literatur
Viruses http://www.virology.net/garryfavweb.html Cell lines http://www.biotech.ist.unige.it/cldb/cname-dh.html#H
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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
SFOEN Swiss Federal Office for the Environment
SFOPH Swiss Federal Office of Public Health
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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Introductory Information Meeting for New Biosafety Officers Thursday, 23 November, 2006, Hotel Ador, Bern

BSO Manual 2006

Biosafety Regulations in Switzerland

Notification and authorisation procedures

Additional biological containment systems

Transport regulations for class 6.2, infectious substances

Cantonal inspections: practical aspects and experiences

Cantonal enforcement of the Ordinance on Major Accidents (OMA)

Appendix 1 2 3 4 5 References EFBS Statements Internet Links on Organisms Institutions Abbreviations

Bern, 23 November 2006

Biosafety Regulations in Switzerland

An overview of the three ordinances

Figure 1: Areas of validity of the three ordinances

Ordinance on the Contained Use of Organisms (Containment Ordinance, CO)

Ordinance on the Occupational Safety in Biotechnology (OOSB)

Risk assessment and classification of activity

Recording, notification and authorisation obligation

Figure 2: Enforcement of the CO

Notification and authorisation procedures

The notification and authorisation procedure

Notification and authorisation procedure according to the CO

Tasks of the Federal Coordination Centre for Biotechnology

The Ordinance on Fees

Displacement of other organisms Interaction with other organisms

Criteria for classification of natural organisms

Other important factors determining the extent of the pathogenicity of an organism:

Group 2 and 3 organisms

Risk assessment of activities

Safety measures: containment level

Effect on people and environment in event of escape from contained systems

No or negligible risk Low risk Moderate risk High risk

Prevent emissions Prevent emissions

Activities involving organisms that occur naturally

Activities involving genetically modified organisms

3.4.2. Risk assessment of activities involving genetically modified organisms

3.4.3. Components of a GMO

Biological containment systems

from: BG Chemie, Merkblatt B009

Additional biological containment systems

Fungi Mammalian cells Plant cells Insect cells

Examples of the classification of activities

Establishment of a genomic library of Streptococcus pyogenes

Cloning of HIV-1 DNA

Manipulation of in vitro naked HIV DNA

Expression of human Tumour Necrosis Factor (TNF) using retroviral vectors

Recipient organism GMO

Class of activity Reasons

Classification of activities using genetically modified plants and animals

Food and environmental microbiology

Summary: decision tree

Examples of classification of activities

Microbiological stool analyses

Class of activity Reasons

Class of activity Reasons

Class of activity Reasons

Analysis of food and environmental (soil, water, air) samples

Class of activity Reasons

Class of activity Reasons

Transport regulations for class 6.2, infectious substances

Structure and content of international transport regulations

Obligations of the participants

Classification of infectious substances

UN 3373 UN 3373 UN 2814 UN 2814 UN 2814 UN 3373 UN 3373