Notification and Classification of Laboratories, Laboratory Areas, Facilities for Large-Scale Testing and Production, cf. Section 7, Subsection 1

Annex 2 to the Danish Working Environment Authority's Executive Order No. 910 of 11 September 2008 on Genetic Engineering and Working Environment.

Part A

General principles

Classification is done into four groups in relation to:

layout of the areas;
plans for the execution of the work, including emergency response plans;
technical aids of the areas; and
internal supervision and control.

Classification notification:

Information required in connection with the notification referred to in Section 7, Subsection 1:

name of the user(s) and the persons responsible for supervision and safety;
information about training and qualifications with regard to the persons responsible for supervision and safety;
information about occupational health and safety organisation;
address of the facility and general description of the buildings;
a description of the nature of the work to be carried out;
the class of contained use;
information about waste management;
any emergency response plans.

Tables 1a, 1b, 1c and 2 present the normal minimum requirements and measures necessary for each level of containment.

Containment is also achieved through the use of good work practices, training, containment equipment and special installation design. For all activities involving genetically modified micro-organisms, the principles of good microbiological practice and the following principles of good occupational safety and hygiene shall apply:

(i) all protective measures and protective equipment must be adequately inspected and maintained;

(ii) if necessary, testing must be carried out for the presence of viable process organisms outside the primary physical containment;

(iii) appropriate training of personnel must be provided;

(iv) local guidelines must be prepared and implemented for the safety of personnel, as required;

(v) appropriate records must be kept;

(vi) for safety reasons, written work instructions must be prepared as required.

The headings of the tables are indicative.

Table 1a present minimum requirements for laboratories and laboratory areas that carry out activities involving genetically modified organisms is carried out.

Table 1b presents additions and modifications to Table 1a for glasshouse/growth-room activities involving genetically modified micro-organisms.

Table 1c presents additions to and modifications to Table 1a for animal units and the like where activities involving genetically modified micro-organisms are carried out.

Table 2 present minimum requirements for facilities for large-scale testing and production involving genetically modified organisms.

In some particular cases, it might be necessary to apply a combination of measures from Tables 1a and 2 of the same level.

In some cases users may, with the agreement of the Danish Working Environment Authority, not apply a specification under a particular containment level or combine specifications from two different levels.

In these tables, 'optional' means that the user may apply these measures on a case-by-case basis, subject to the assessment referred to in Section 6. The Danish Working Environment Authority may, upon a specific assessment, require that the measures specified in the tables as 'optional' be applied.

Definitions

Autoclaving: Autoclaving means a treatment with saturated water vapor at 121 ^o C for 20 minutes or other combinations of temperature and time that have at least the same inactivating effect on biological material.

Disinfection: Disinfection means as a reduction in the number of harmful micro-organisms to such an extent that there will be no spreading of significance to safety or human health. Disinfection is most often carried out by exposure to heat or chemicals.

Part B

Containment and other protective measures for laboratories and laboratory areas, cf. Section 8

In this Annex, both 'laboratory' and 'laboratory area' are referred to as laboratories.

In addition to the requirements mentioned in the current class, the requirements in Classes 2, 3 and 4 include the requirements mentioned in the previous class or classes. When classifying a Class 3 or 4 laboratory, special requirements may be stipulated depending on the specific project to be carried out in the laboratory in addition to the general requirements stipulated in the annex.

A horizontal line means that the requirement from the lower class should not be transferred to the higher class, as it would be in conflict with other requirements in this class.

Table 1a. Containment and other protective measures for laboratories and laboratory areas.

Specifications	Containment level (class)
	1	2	3	4
ADMINISTRATIVE CONDITIONS
Access and transport into the laboratory.	Access of all unauthorised persons to the laboratory must be restricted.	Only access for the personnel necessary to carry out the work, as well as persons who are appropriately instructed.	Only access to specially nominated personnel necessary to carry out the work.
				A log must be kept of time spent in the facility by the staff.
			Access must only take place through a lock with shower and changing facilities.
			All material must be brought in through a lock, designed according to the same principles as entrance locks.
	Lab coat or other suitable special work clothing must be worn in the laboratory.		Special requirements for work clothing and personal protective equipment.
		Suitable footwear must be worn in the laboratory. Footwear must not be stored in the laboratory.
		Jewelry, wristwatches, handkerchiefs and the like must not be brought into the laboratory.
		Unauthorised material is not allowed in the laboratory.
	Tobacco, food and beverages must not be consumed, and cosmetics must not be applied in the laboratory. If brought into the laboratory, it must be stored in a special cabinet. However, food must not be stored in the laboratory.	Tobacco, food and beverages as well as cosmetics must not be brought into the laboratory.
		Animals and plants not involved in the work must not be present.
Exit and transport out of the laboratory	The special work clothing must be removed before eating and at the end of working hours.	The special work clothing and footwear must be removed before leaving the laboratory.	Exit must take place through a lock with shower and changing facilities. All staff must shower and change when exiting.
		Hands must be washed before leaving the laboratory.
			Transportation of material must take place through a lock.
	A procedure must be prepared for transporting biologically active material out of the laboratory and on how to label transport containers.			No material may be removed unless autoclaved. Special equipment for this must be available in the area.
	All waste containing biologically active material must be collected in suitable containers and autoclaved or disinfected properly before disposal.	All waste containing biologically active material must be collected in suitable containers and autoclaved before disposal.	All waste must be autoclaved in the classified area before disposal.
	If waste containing biologically active material is to be transported outside the classified area in order to be autoclaved or disinfected, it must be transported in tightly closed containers.	If waste containing biologically active material is to be transported outside the classified area in order to be autoclaved, it must be transported in tight, closed containers.	_________	_________
	Where autoclaving or disinfection is not practically possible, waste may be brought directly to a proper destruction facility. The transport must take place in suitable, tightly closed packaging.	_________	_________	_________
	Needles, disposable syringes, sharp objects and the like must be placed in closed containers immediately after use and autoclaved or disinfected before disposal or cleaning.	Needles, disposable syringes, sharp objects and the like must be placed in closed containers immediately after use and autoclaved before disposal or cleaning.	Needles, disposable syringes, sharp objects and the like must be placed in closed containers immediately after use and autoclaved in the classified area before disposal or cleaning.
	Utensils, glassware and the like, contaminated with biologically active material, must be autoclaved or disinfected before cleaning.	Utensils, glassware and the like, contaminated with biologically active material, must be autoclaved before cleaning.	Utensils, glassware and the like must be autoclaved in the classified area before cleaning.
			Any necessary auxiliary material must not be removed from the classified area until it has been autoclaved.	_________
		Special work clothing must be collected in a closed container and autoclaved securely before or during laundering.	Special work clothing must be collected in a closed container and autoclaved in the classified area before laundering.
		Exterior surfaces of transport containers must be properly disinfected before the containers are brought out of the classified area.
Training and instruction.		The work is subject to special supervision by a person with the necessary insight within the field of work area.	Special requirements for professional staff qualifications.
Safety instructions	If testing and the like take place without the presence of experts, it must be possible to call in a professionally competent person.			Testing and the like must not take place without the presence of a professionally competent person.
		A log must be kept of all accidents that have given rise to a risk to the safety or health of people or to the external environment.	A log must be kept of all accidents.
			The efficiency of autoclaving must be checked.
			Major accidents must be reported to the Danish Working Environment Authority immediately.
EXECUTION OF WORK	All work must be carried out so that the formation of aerosols is minimised.
	Mouth pipetting is prohibited.
		All work must be carried out in a cabinet equipped with its own ventilation system when there is a risk of harmful air pollution, including when: 1) There is a danger of the formation of aerosols with biologically active material; 2) Work is carried out with large amounts of liquid with biologically active material; or 3) Work is carried out with large concentrations of biologically active material.	Activities involving biologically active material outside closed systems must be carried out in a cabinet equipped with its own ventilation system.
	Needles, syringes, sharp objects and the like should be used as little as possible.
Cleaning etc.		Workplaces in the laboratory must be cleaned and disinfected daily according to a special procedure.
	The workplace must be kept tidy.		The classified area must be cleaned at least once a day.
	Appropriate disinfectants must be available in the laboratory.
	In case of spillage of biologically active material, disinfect immediately with a suitable disinfectant.		In the event of any spillage, disinfect effectively immediately with a suitable disinfectant.
Special work clothing and personal protective equipment		The special work clothing and footwear must not be brought outside the laboratory before being washed or destroyed.
	Suitable gloves must be worn when in contact with biologically active material.	Suitable gloves must be worn when there is a risk of contact with biologically active material and when working with animals.
		Footwear must be thoroughly disinfected with a suitable disinfectant in case of a spillage.
Personal hygiene.	Hands must be washed after contamination with biologically active material and spillage and contact with animals, as well as before breaks at work and at the end of working hours.			Special washing procedure.
Doors/windows.		Doors to the classified area must be closed when work is carried out.
WORKPLACE DESIGN		Windows must be either closed or equipped with insect screens.	_________	_________
Signage.	There must be signs marked 'Genetic Engineering Area, Class 1' on doors to the classified area.	There must be signs marked 'Genetic Engineering Area, Class 2' on doors to the classified area.	There must be signs marked 'Genetic Engineering Area, Class 3' on doors to the classified area.	There must be signs marked 'Genetic Engineering Area, Class 4' on doors to the classified area.
			The classified area must be specially separated from the rest of the building.	The classified area must be in a separate or specially isolated part of the building.
Design, technical aids and furniture.			The classified area must be designed so that it is extremely easy to clean.	Special requirements for cleaning procedures and staff qualifications.
		Only the necessary technical aids must be found at workplaces in the laboratory where biologically active material is used.
	Technical aids that may come in contact with biological activity material in the laboratory must, as far as possible, be designed so that they are easy to clean and disinfect.	Technical aids in the laboratory must be designed so that they are easy to disinfect and clean.
	Worktables, chairs, etc. in the laboratory must have a smooth surface that is easy to clean.
		Floors must be smooth and without cracks and with a rounded transition to the wall.
		Wall surfaces in the laboratory must be smooth and easy to wash. Transitions between fixed furniture and building parts must either be completely tight or so open that efficient cleaning is possible.
	The surface of the laboratory equipment and floors must be able to withstand acids, bases, organic solvents and moderate heat.
	Decontamination and washing options, including easy access to hand-washing sinks, must be provided in the work area.		Decontamination and washing options, including easy access to hand-washing sinks, must be provided in the work area. A hand-washing sinks must be located near the exit.
			Taps must not be hand-operated.
			Windows must be closed and sealed.	Windows must be break-proof.
			Locks must be equipped with self-closing doors and negative pressure in relation to the surroundings and overpressure in relation to the classified area.
				An observation window or alternative is to be present so that occupants can be seen from outside.
				The lock must have self-locking doors.
				Special requirements for lock design.
			It must be possible to seal the classified area to enable disinfection.	It must be possible to seal the classified area to enable disinfection by fumigation.
Plumbing				Special requirements for plumbing installations.
Ventilation systems		Extract air from room ventilation must not be returned to the room or other rooms. However, in special cases (e.g. sterile rooms) this may be accepted.	Ventilation air must not be led into the room or other rooms.
		There must normally be a small separate room with its own ventilation system in the laboratory. In special cases, however, it may be accepted that the extract air is led into the room (e.g. sterile benches).	Special requirements for ventilation systems.
			Special requirements for the closed systems.
		Extract air from cabinets with their own ventilation system must be filtered through absolute filters, and filters must be autoclaved before disposal.	All extract air should be filtered through absolute filters and filters must be autoclaved before disposal.	All extract and input air should be filtered through absolute filters and filters must be autoclaved before disposal.
		Procedures must be in place for checking and maintaining filters and for checking the efficiency of ventilation systems as well as for maintenance.	Special inspection and maintenance requirements.
Run-off water and drainage conditions	Biologically active material must not be poured into drains/sewers.	Physical protection must be established against unintended release into sewers from all drains. It must be possible to collect any accidentally released biologically active material and autoclave it. Drains from sinks used only for hand washing are exempt from this requirement.	Physical protection must be established against unintended release into sewers from all drains, including bathrooms. All run-off water must be collected and autoclaved.

Table 1b. Containment and other protective measures for glasshouses/growth-rooms and the like.

The terms glasshouse/growth-room and the like refer to a structure with walls, a roof and a floor designed and used for principally for growing plants in a controlled and protected environment.

All provisions of Table 1a shall apply with the following additions/modifications:

Specifications		Containment level (class)
		1	2	3	4
Building
1	Glasshouse: permanent structure¹⁾	No	Yes	Yes	Yes
Equipment
2	Entry via a separate room with two interlocking doors	No	Optional	Yes	Yes
3	Control of contaminated run-off water	Optional	Minimise run-off²⁾	Prevent run-off	Prevent run-off
System of work
4	Measures to control undesired species such as insects, rodents and arthropods	Yes	Yes	Yes	Yes
5	Procedures for transfer of living material between the glasshouse/growth-room, protective structure and laboratory shall control dissemination of genetically modified micro-organisms	Minimise dissemination	Minimise dissemination	Prevent dissemination	Prevent dissemination

1) The glasshouse shall consist of a permanent structure with a continuous waterproof covering, located on a site graded to prevent entry of surface-water run-off, and with self-closing lockable doors.

2) Where transmission can occur through the ground.

Table 1c. Containment and other protective measures for activities in animal units and the like.

All provisions of Table 1a shall apply with the following additions/modifications:

Specifications		Containment level (class)
		1	2	3	4
Facilities
1	Isolation of animal units³⁾	Optional	Yes	Yes	Yes
2	Animal facilities⁴⁾, separated by lockable doors	Optional	Yes	Yes	Yes
3	Animal facilities designed to facilitate decontamination (waterproof and easily washable material (cages, etc.))	Optional	Optional	Yes	Yes
4	Floor and/or walls easily washable	Optional	Yes (floor and walls)	Yes (floor and walls)	Yes (floor and walls)
5	Animals kept in appropriate containment facilities such as cages, pens or tanks	Optional	Optional	Optional	Special requirements for cage and unit conditions for test animals
6	Filters on insulators or insulated rooms⁵⁾	Optional	Yes	Yes	Yes
7	Respirators			Appropriate filtering respirators must be used	Appropriate filtering respirators must be used

3) Animal unit: a building or a separate area within a building containing facilities and other areas such as changing rooms, showers, autoclaves, food storage areas, etc.

4) Animal facility: a facility normally used to house stock, breeding or experimental animals or one which is used for the performance of minor surgical procedures.

5) Insulators: transparent boxes where small animals are contained within or outside a cage; for large animals, isolated rooms may be more appropriate.

Part C

Containment and other protective measures for large-scale testing and production facilities, cf. Section 9

The notification shall, where necessary, include information on the planned protective measures to protect against the risks associated with the use of the installation, including:

the expected culture volumes;
quantities, nature and consumption of raw materials, excipients, etc. to be used;
the processes used, including the formation of intermediate and waste products as well as by-products of importance for safety and human health;
the expected emissions in the workplace from installations and equipment of gaseous, liquid and solid substances and materials in connection with operation and accidents.

The requirements for the containment measures for organisms are set out in the categories listed below, depending on the organism and work in question.

Each operation in the process must be assessed. The characteristics of each operation are decisive for the physical containment to be used. This will make it possible to select and organise the process and the facility and operating procedures that are best suited to ensure adequate and secure containment. Two important factors that must be considered when selecting containment equipment are the risk and effects of failure of the equipment used. The more serious the consequences of a potential failure, the stricter requirements for manufacturing practices may be stipulated to reduce the risk of failure.

Table 2.

Specifications		Containment level (class)
		1	2	3	4
GENERAL
1	Viable micro-organisms should be contained in a system which separates the process from the environment (closed system)	Optional	Yes	Yes	Yes
2	Control of exhaust gases from the closed system	No	Yes, minimise dissemination	Yes, prevent dissemination	Yes, prevent dissemination
3	Control of aerosols during sample collection, addition of material to a closed system or transfer of material to another closed system	Optional	Yes, minimise dissemination	Yes, prevent dissemination	Yes, prevent dissemination
4	Inactivation of bulk culture fluids before removal from the closed system	Optional	Yes, using validated means	Yes, using validated physical or chemical means	Yes, using validated physical or chemical means
5	Seals should be designed so as to minimise or prevent release	No specific requirements	Minimise dissemination	Prevent dissemination	Prevent dissemination
6	The controlled area should be designed to contain spillage of the entire contents of the closed system	Optional	Optional	Yes	Yes
7	The controlled area should be sealable to permit fumigation	No	Optional	Optional	Yes
EQUIPMENT
8	Entry via airlock	No	No	Optional	Yes
9	Surfaces resistant to water, acids, alkalis, solvents, disinfectants and decontamination agents, and easy to clean	Yes (possibly table)	Yes (possibly table, floor)	Yes (possibly table, floor)	Yes (possibly table, floor, ceiling, walls)
10	Specific measures to adequately ventilate the controlled area in order to minimise air contamination	Optional	Optional	Optional	Yes
11	The controlled area should be maintained at an air pressure negative to the immediate surroundings	No	No	Optional	Yes
12	Intake and extract air from the controlled area should be HEPA filtered	No	No	Yes (extract air, optional for input air)	Yes (input and extract air)
13	A closed system must not be opened for maintenance unless it has been sterilised using a recognised method	Optional	Yes	Yes	Yes
14	Closed systems must have monitoring and sensing devices that measure the integrity of the enclosure during operation	Optional	Optional	Yes	Yes
15	The containment integrity of closed systems must be tested using the corresponding host organism before using the system	Optional	Optional	Yes	Yes
SYSTEM OF WORK
16	Closed systems should be located within a controlled area	No	Yes	Yes	Yes, designed for the purpose
17	Access should be restricted to nominated personnel only	No	Yes	Yes	Yes, via airlock
18	Biohazard signs should be posted	Yes, Class 1	Yes, Class 2	Yes, Class 3	Yes, Class 4
19	Personnel should shower before leaving the controlled area	No	No	Optional	Yes
20	Facilities designed to facilitate decontamination and washing for personnel	Yes	Yes	Yes	Yes
21	Personnel should wear protective clothing	Yes (work clothing)	Yes (work clothing)	Yes	Complete change of clothing before entry and exit
WASTE
22	Inactivation of genetically modified micro-organisms in effluent from hand-washing sinks and showers or similar effluents	No	No	Optional	Yes
23	Inactivation of genetically modified micro-organisms in contaminated material and waste, including process run-off water before final discharge	Optional	Yes, using validated means	Yes, using validated physical or chemical means	Yes, using validated physical means