Classification of Laboratories, Production Facilities, etc.
Guidelines for classification of laboratories, production facilities, etc. involving activities with genetically modified organisms.
The Danish Working Environment Authority’s guidelines concern the classification of laboratories, glasshouses/growth-rooms, animal units, facilities, and the like (referred to as a "room" in these guidelines), where employees will be carrying out activities involving genetically modified organisms (GMOs). The guidelines also describe the requirements that the legislation stipulates for this.
One classification is the Danish Working Environment Authority's approval that the room meets the requirements that apply to the given class. The purpose of a classification is to ensure that there are no adverse effects on human health or the external environment as a result of activities involving GMOs.
The Executive Order on Genetic Technology and the Working Environment contains the special rules for these activities. These guidelines are a supplement to the Executive Order and should be read in that context.
It is against the law to carry out activities involving GMOs in rooms that are not classified by the Danish Working Environment Authority.
In addition to the special rules on genetic engineering and the working environment, the rooms and the activities carried out in these must live up to the general provisions of the working environment legislation on the design of permanent workplaces, technical aids, the execution of activities, etc.
The Danish Working Environment Authority’s guidelines on risk assessment of genetic engineering research projects, etc. deal with risk assessment and notification of projects (1).
2. Working with Genetically Modified Organisms
Working with GMOs covers all activities that involve GMOs. This includes testing, research, analyses, storage, and the production of GMOs (referred to as a "project" in the guidelines).
2.1. What is a GMO?
A genetically modified organism is an organism (a micro-organism, a cell line, a plant or an animal) that has had its heritable material altered using recombinant techniques1 in vitro. This either means that an organism has received heritable material from another type of organism (e.g. a bacterium that has received a gene from a plant) or that special techniques have been used. The special techniques may include techniques for the direct introduction of DNA into an organism or for the fusion of two cells that are not able to fuse naturally.
1 Techniques where the heritable material (DNA and RNA) is cut up and reassembled so that combinations occur that do not occur naturally, e.g. when the gene for human insulin is inserted into a bacterium.
To be covered by the GMO rules, the organism must be viable, i.e. be able to reproduce. This means that naked DNA (pure DNA), for example, is not covered by the GMO rules. It is instead considered a chemical. Gene therapy using genetically modified vectors or viruses is covered by the rules.
Even if a company has not changed the heritable material itself, but has, for example, bought a transgenic mouse2, the activity is still covered by the GMO rules.
2 Animals that have had a so-called transgene inserted using biotechnological methods (genetic engineering), i.e. a gene that is foreign to the animal species in question.
Transport of GMOs is covered by the rules of the Danish Ministry of the Environment. This applies to both transport out of the country and transport between classified rooms. See www.mst.dk.
2.2. Working with GMOs
Examples of areas where activities that involve GMOs may be carried out:
- Animal units
- Climate chambers
- Rooms for gene therapy, i.e. rooms used in connection with gene therapy. These include preparation rooms, operating rooms, hospitals, sampling rooms and analysis laboratories.
- Production facility
- Facility for large-scale testing or pilot plant.
The classification should also include places where GMOs are stored. These include freezers, cold rooms, climate rooms and freezer rooms.
If several rooms are to be included in the same classification, the rooms should be in close proximity to each other.
The Danish Working Environment Authority does not classify ordinary offices, workshops, technical rooms, toilets, etc., because they are not used for activities that involve GMOs and are not designed so that they can be classified.
Once the GMO has been processed so that it is no longer viable, i.e. it has been inactivated, it is no longer covered by the Danish Environmental and Genetic Technology Act and therefore not by the Executive Order on Genetic Technology and the Work Environment, either. Activities with such material can take place in non-classified rooms.
There is no lower dilution or volume limit for the definition of GMOs.
2.3. Working with non-GMOs in classified rooms
It is permitted to carry out activities involving non-genetically modified organisms in classified rooms. However, employees must carry out the activities according to the rules and conditions of the classification.
Activities involving “natural” micro-organisms must be reported to the Danish Working Environment Authority pursuant to the Executive Order on Biological Agents and the Workplace.
A company must not start genetic engineering activities until it has received a classification from the Danish Working Environment Authority for the area where the project is to be carried out.
The Danish Working Environment Authority allocates a classification for one or more room(s) to a company.
The company must involve the occupational health and safety organisation or, where such does not exist, the employees, so that it or they can contribute to preparing the safety regulations, other regulations, procedures and any emergency response plans.
In order to obtain a classification, the company must go through the following phases:
3.1. Risk assessment
The company decides which class the Danish Working Environment Authority should classify the room for.
The company must carry out an assessment of the risk associated with future project(s) in order to select the right class. In this assessment, the company must consider both human safety and health as well as the risk of any impact on the external environment. The procedure for the assessment is discussed in Section 6 of the Executive Order on Genetic Technology and the Work Environment.
The company must also use the assessment when notifying the project, see the guidelines on risk assessment of genetic engineering research projects, etc. (1).
Classes 1-4 include activities involving genetically modified micro-organisms (GMMs):
- In Class 1, the company may carry out activities of no or negligible risk.
- In Class 2, the company may carry out activities of low risk.
- In Class 3, the company may carry out activities of moderate risk.
- In Class 4, the company may carry out activities of high risk.
In the “Animals” Class, the company may carry out activities involving genetically modified animals (GM animals).
In the “Plants” Class, the company may carry out activities involving genetically modified plants (GM plants).
If the company is to carry out activities that involve both GMMs and, for example, GM animals, the Danish Working Environment Authority must classify the room for both Classes 1-4 and for the "Animals" Class.
The company must submit the completed notification form to the Danish Working Environment Authority. Section 4 provides a more in-depth review of the form. The Danish Working Environment Authority registers the notification and receives an LAB ID number. This number is given to the company in connection with the classification. The company must use the number when contacting the Danish Working Environment Authority about the activities involving genetic technology or about approval of genetic engineering projects.
The Danish Working Environment Authority has registered the notified classified rooms and facilities in Denmark where companies carry out activities involving GMOs as well as the notified genetic engineering projects.
Once the company has notified the Danish Working Environment Authority, the notification is processed as quickly as possible and within a maximum of 45 days (however, 90 days for Classes 3 and 4). If the Danish Working Environment Authority is missing any information, the period is extended by the number of days that elapse before we have the missing information.
3.3. Classification and terms
The company must always follow the requirements in the Executive Order on the Risk Assessment of Genetic Engineering Research Projects, etc., the information in the notification form that is important for safety and human health, and any annexes. The Danish Working Environment Authority may provide a classification on certain conditions, which may be conditional on special circumstances. These conditions must always be observed by the company as well.
This means that the company, after receiving the classification, may use the room in question to carry out activities involving approved projects with GMOs in that class or a lower class specified by the classification, cf. the Principle in Section 2.3.
Other companies wishing to borrow or rent the room must obtain a classification of the room themselves.
3.4. Duration of classification
There is usually no time limit on a classification.
The Danish Working Environment Authority can make a classification temporary, e.g. when it is absolutely certain that the company will only be carrying out activities associated with a project for a limited period of time. At the same time, the classification will then be linked to that specific project. This is the case, for example, with gene therapy studies and studies with large animals such as pigs and horses.
In special situations, it may be practical for the Danish Working Environment Authority and the company to agree on procedures for temporary downgrading and subsequent upgrading of the room. This could, for example, be the case for seasonal work with GMOS. The agreed procedures must be included in the classification.
Permanent change of a classification is described in Section 6 on Notification of Significant Changes to the Danish Working Environment Authority.
4. Completing the Notification Form
This section is a guideline for companies for completing the notification form so that it provides the information required in the Executive Order on Genetic Technology and the Work Environment.
The notification form for all rooms in which companies will be carrying activities involving GMOs is called:
"Notification for Classification of Genetic Engineering Laboratories and Laboratory Areas as well as Facilities for Large-Scale Genetic Engineering, Testing or Production".
Notification must be made using the notification form available at www.virk.dk.
When completing the notification, the company must read Annex 2, Parts A and B to the Executive Order at the same time. The questions in the form reflect the information requirements of the Executive Order.
The company may answer some of the questions by ticking either "Yes" or "No". A tick in “Yes” does not mean that the procedure or the regulation must be attached, but the Danish Working Environment Authority will probably ask for it in connection with the inspection.
The form has a front page and is divided into six parts.
The front page and Part 1 must always be completed by the company.
Part 2 (animal units), Part 3 (glasshouses/growth-rooms), Part 4 (aquariums), Part 5 (Classes 3 and 4) and Part 6 (large-scale testing or production) is additional information, and the company should only complete this if relevant to the classification.
The company must attach the following annexes:
- Layout sketch/drawing of the area in the building where the classified room is located.
- Sketch/drawing of the classified area, indicating the location of fixed furniture, major technical aids, and any space for written work.
4.1. Part 1 of the form
The first part of the form must always be completed by the company. Note that there may be several answers in the “What will the company be working with?” section – the company may carry out activities that involve genetically modified micro-organisms on plants or animals, which may also be genetically modified.
Also note that the company usually carries out activities that involve the handling or storage of GMOs in several types of rooms, such as laboratories and storage rooms.
Description of proposed containment and other protection measures
This part of the form under the heading "Information on the design of the laboratory, etc." must include a brief description of what special measures are needed to be able to safely carry out activities that involve GMOs and prevent their spread or unintended release into the environment. The company may refer to safety regulations or cleaning regulations, etc.
Technical aids, including computers, must be designed so that they are easy to clean and disinfect. Their surfaces must be able to withstand disinfection. For Class 1, this only applies to the technical aids that may come into contact with GMOs.
Personal protective equipment
In a classified room, everyone must wear a lab coat, jacket, and pants or similar to protect and cover the person and regular clothing. This also applies to visitors and tradespeople visiting or working in the room. The company must describe what type of clothing persons in the classified room should wear.
The company must also describe when the persons must wear personal protective equipment and what kind, e.g. gloves and shoes.
If the personal protective equipment and footwear cannot be disinfected, the user must dispose of it and treat it as GMO waste when it becomes contaminated.
In unfortunate circumstances, unbalanced ventilation systems can carry air with GMOs into another room. If the ventilation ducts in Classes 2, 3 and 4 are common to the ventilation of several rooms, it must not be possible to pull/push air from the classified room into other rooms through the ventilation systems. This applies to both room and process ventilation, e.g. LAF benches3.
3 LAF bench: A protected work area, which in particular aims to protect the material contained in the bench. There are primarily two types of LAF benches – one has horizontal air flow and the other vertical flow. Benches with horizontal flow must only be used for activities where no air pollution can form.
The company can ensure that this does not happen, e.g. with a damper that closes immediately in case of imbalance. In case of new construction, the Danish Working Environment Authority recommends that the company establish separate ventilation ducts for each room for both process and room ventilation. This is a requirement for Classes 3 and 4.
The notification must state how the company has secured the ventilation systems so that they cannot return air from one room to another.
The rooms in Class 1 must live up to the general requirements of the working environment legislation for ventilation.
Waste and spillage
There must be disinfectants available in the room that are effective against the biological organisms, on which activities are being carried out. Employees must know how to use the disinfectants e.g. in case of spillage and sprays. They also must know how long it will take for the disinfectant to work.
The company must process and dispose of all material that is contaminated with biologically active material, such as GMO waste. This may include paper used to wipe up spillage, used gloves and other disposable equipment, broken glass, needles, cell cakes and liquids from vacuum suction. If there is any doubt as to whether the waste is contaminated with micro-organisms, the company must treat it as if it were contaminated. For Classes 3 and 4, all waste must be treated as GMO waste.
The company must ensure that spillage and waste is decontaminated before it can be treated as ordinary waste. Decontamination can be done through chemical disinfection (however, only in Class 1) or autoclaving4. Where neither of these procedures is possible, the company may bring Class 1 waste directly to a proper destruction facility (incineration).
4Autoclaving: A treatment with saturated water vapor at 121°C for 20 minutes or other combinations of temperature, pressure and time that have at least the same inactivating effect on biological organisms. The autoclaving must continue until the whole organism/solution reaches the required temperature, e.g. it may take up to 1.5 hours for all parts of an aqueous solution in a 5-litre container to reach the desired temperature.<1 } Viscous liquids require even longer.
The waste may be decontaminated by the company inside or outside the classified area. If the waste is to be transported outside to be decontaminated, the company must transport it in containers that comply with the Ministry of the Environment and Energy's rules on the transport of GMOs. That is, the containers must be closed, break-proof and labelled so that it is clear that they contain GMOs. The company should plan the transport carefully so that the material does not accidentally spread. For Classes 3 and 4, decontamination must take place within the classified area.
It is advisable to use the same procedure for transport out of the classified area, whether it concerns GMO waste, GMOs for storage or recyclable (glass) items.
Glassware and other items to be reused must be disinfected by the company before washing-up or washing. Items that may be contaminated must also be disinfected.
For Class 1, this may be a chemical disinfection, while for Classes 2-4 this must be done by autoclaving. “Animals” and “Plants” Classes require a concrete assessment by the company on how to handle the waste.
4.2. Parts 2, 3 and 4 of the form (working with animals, plants or fish)
Parts 2, 3 and 4 of the notification form must be completed by the company for laboratory areas where it will be carrying out activities involving animals, plants, or fish, respectively.
The description must clarify which animals, plants or fish are to be included in the activities. The company must describe how it intends to ensure that animals, plants, pollen, or fish will not escape into the surroundings.
In the case of animals, the notification form must also state the types of cages used and how the cages are ventilated and emptied.
With regard to plants, the company must describe the glasshouse/growth-room, especially how easy/difficult it is to clean and how it is secured against unintended release into the surroundings.
4.3. Part 5 of the form (Classes 3 and 4)
The description must include the safety measures that are essential to safeguard against any form of spread of GMOs. This includes a description of the differences in pressure between the laboratory and the surroundings, etc. In addition, very special requirements apply, cf. the Executive Order on the Risk Assessment of Genetic Engineering Research Projects.
4.4. Part 5 of the form (facilities for large-scale testing or production)
Annex 2 to the Executive Order on Genetic Technology contains requirements for the facility’s design, etc. The company must assess which requirements are relevant for safety and human health. This assessment must appear on the notification form together with information on the measures, which the company will hence be implementing.
In connection with the classification, the Danish Working Environment Authority will include the company's assessment.
5. Other Documents
These documents must not be attached to the notification by the company but must be available prior to the Danish Working Environment Authority's inspection in connection with the classification. The documents are necessary for the company's work on their working environment and should be included in the company's workplace assessment.
5.1. Safety regulations
The company must prepare safety regulations. These must be in writing and must describe how employees are to handle GMOs in a safe manner. Among other things, the regulations must describe the precautions which the company must always take in connection with spills and accidents. The regulations are typically a concrete elaboration of the requirements set out in Annex 2 to the Executive Order on Genetic Technology and the Work Environment.
The safety regulations should include provisions on:
- Access rules
- The actual activities
- Waste and recyclable articles
- Spills and accidents
- Storage and other transport of GMOs.
Suggestions for relevant questions and examples can be found in Annex 1 to these guidelines.
In addition, the safety regulations must contain other information that has emerged from the risk assessment or that is otherwise relevant. Finally, the Danish Working Environment Authority may assess that the company must add other provisions.
5.2. Cleaning regulations
The company must keep the classified room clean and, for Classes 2-4, establish procedures for this. Employees must clean the workplace itself efficiently every day and always after spills. They must use suitable cleaning supplies and disinfectants.
There may be different cleaning regulations for different staff groups, e.g. one for the cleaning staff and one for users of the room.
Suggestions for relevant questions can be found in Annex 2.
5.3. Description of ventilation and filter change
The rules for ventilation systems are described in the Danish Working Environment Authority’s Guidelines on Ventilation (2).
If the Danish Working Environment Authority accepts recirculation of the extract air from an LAF bench into the classified room, it will entail conditions for the classification. The condition will require that no activity be carried out in the bench, which can develop harmful or bothersome air pollution. This must appear on a notice on the LAF bench.
For Classes 2-4, the company must ensure that a written procedure is available for maintenance of the ventilation systems. The company must also have a written procedure for changing of the filters (HEPA filters5), both from process ventilation systems, room ventilation systems and air input systems. All employees who maintain the ventilation systems must follow the procedure.
Relevant examples can be found in Annex 3.
5 HEPA filters: Filters that can trap 99.9 percent of particles larger than 0.3 µm.
5.4. Emergency response plans
The company must prepare emergency response plans if the risk assessment shows that there are special risks to human health or safety or to the external environment. Emergency response plans must always be prepared for Classes 3 and 4.
When devising the emergency response plans, the company must involve the occupational health and safety organisation or, where such does not exist, the employees. The plans must be available to the employees, and the company must submit these together with the notification to the Danish Working Environment Authority.
7. Significant Changes
When significant changes are made to the information in a notification or in the terms of a classification, the company must notify these to the Danish Working Environment Authority. This must be done when the changes affect safety or human health, even when they improve conditions.
Significant changes may include:
- Cancellation of a classification
- Structural alterations to a room, e.g. demolition of walls
- Ventilation changes, e.g. additional LAF benches in the room
- Change of physical access conditions.
The Danish Working Environment Authority will assess the significance of the changes for the classification. The Danish Working Environment Authority shall notify the company of the result. If the changes require a classification in a higher class, the company must carry out a new notification and approval procedure. The same applies to changes to classifications from before June 2000 (allocated pursuant to either of the Executive Orders from 1987 or 1991).