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Permits and notifications

Biosafety Coordinator for EMV, IKVL and ILM: Emanuel Smeds

GMM

All types of handling of genetically modified microorganisms; GMM, shall be authorized by, or reported to, the Swedish Work Environment Authority. GMM refers to all micro-organisms and cell cultures which have been genetically modified in an unnatural manner. The genes must not necessarily have been integrated in the genome, or have been constructed by the user. On this page you can find the information you need when applying for a permit or a notification. The regulations for handling GMM are included, in their entirety, in the provisions Contained Use of Genetically modified Micro-organisms AFS 2011:2.

Definition of the term GMM

GMM (Genetically modified micro-organism): A micro-organism, of which the genetic material has been altered in a manner that would not occur naturally, through mating or natural recombination (SFS 2000:271).

Micro-organism: Each micro-biological unit, cellular or non-cellular, which can reproduce or transfer genetic material, including viruses, viroid and animal or plant cell cultures (SFS 2000:271).

Exceptions: What does not count as GMM? (SFS 2000:271)

•Organisms that are created through mutagens (using radiation or chemicals)
•Microorganisms that are created through cell fusion of prokaryotic species exchanging genetic material through known physiological processes.
•Microorganisms that are created through cell fusion of eukaryotic species, including the creation of hybridoma  and fusions of plant cells.
•Micro-organisms that have been genetically modified in nature, such as antibiotic resistant bacteria from a patient.
Find a list of micro-organisms in various risk groups in the Swedish Work Environment Authority’s provisions regarding Microbiological work environment risks.

Definition of the term ’Verksamhet’

’Verksamhet’ (‘activity’ in English) is an administrative concept that, inter alia, is limited by:

•A person held responsible
•An address
•A protection level
•A type of 'verksamhet', e.g., laboratory, teaching or animal testing
Experiments that are to be implemented in the laboratory as well as in the animal facility shall thus belong to two different 'verksamheter'. These must have separate risk assessments.

Definition of the term ’Användning’

’Användning’ (‘use’ in English) is equated to the same type of experiment.  It is the 'användning' that is assessed for risk, and as long as the 'användning' may be included in a well-drafted risk assessment, several similar experiments may be included. 'Användning' must be included in an approved 'verksamhet'. A 'verksamhet' may have several different 'användningar'.

Classification of negligible risk, low risk and risk filled verksamhet

The handling of GMM is divided into three 'verksamhet' levels: F (negligible risk), L (low risk) and R (risk-filled 'verksamhet').
Examples of how this division is made can be found below. Note that the risk assessment regulates which 'verksamhet' level to be applied.

  • E. coli (laboratory adjusted strand) with an insulin gene on a regular plasmid: negligible risk (F)
  • Human cell culture with GFP (green fluorescent protein), on a regular plasmid: negligible risk (F)
  • Listeria monocytogenes with a human gene: low risk (L) due to Listera belongs to risk group 2
  • Human cell cultures with a human immunomodulatory gene: either low or negligible risk (L or F). Consult the Biosafety Coordinator Emanuel Smeds. This is due to the insert which could be considered a risk to humans or the environment, which often requires a higher activity level.
  • Human cell culture, where a GFP is to be inserted into the genome through a replication-defect viral vector: low risk (L). This is because viral vectors that can be integrated into human cells are always classed, at least, as low risk. If, on the other hand, you will only handle the already genetically modified cell containing GFP, and all replication-defect viruses have been removed, this is normally classified as a negligible risk.
  • Mouse cell cultures, where GFP is to be integrated into the genome, with a replication-defect viral vector that cannot be integrated into human cells: negligible risk (F). This is because the replication-defect viral vectors that cannot be integrated into human cells are often classified as a negligible risk (F).

Procedure

  1. The verksamhet level is decided upon completion of the risk assessment. A guide to the probable verksamhet level of an experiment can be found under ’Classification of negligible risk, low risk and risk-filled activity’ above.
  2. If anything is unclear, the Biosafety Coordinator Emanuel Smeds may be contacted. When starting a new verksamhet, the Biosafety Coordinator shall be contacted.
  3. A risk assessment of the GMM shall always be made on the Swedish Work Environment Authority’s form. Risk assessments of experiments on 'verksamhet' level F are not required to be sent to the Swedish Work Environment Authority. Other risk assessments shall be sent to Emanuel Smeds, who then provides comment and submits the report to the Swedish Work Environment Authority.

Conducting GMM experiments with negligible risk (F)

First read the text above, in order to ensure that the experiments are likely to belong in 'verksamhet' level F, and that the terms ’verksamhet' and ’användning’ have been understood.

A risk assessment made on the Swedish Work Environment Authority’s form, must always precede the experiments. The forms may be used to assess the risk of more than one 'användning' at a time. Each GMM 'verksamhet' has its own 'verksamhet' ID. This ID is provided by the Biosafety Coordinator who simultaneously checks that the premises intended for use are covered by the approved 'verksamhet', and that the activity provisions, as described in the 'verksamhet' notification, are being followed. If there is no approved 'verksamhet' to connect the risk assessment to, the Biosafety Coordinatorr shall be contacted, in order to start one, or expand a previously approved 'verksamhet'.

The risk assessment shall be made available, in connection to the premises where the experiments are carried out, e.g., a laboratory binder. This shall be updated in the event of any changes, and be available to display at any protection rounds, and inspections by the Swedish Work Environment Authority.

Note that there are different 'verksamhet' IDs for laboratory and animal experiments. One risk assessment cannot cover both laboratory and animal experiments. The risk assessment for any animal experiment shall be available in the animal facility.

Conducting GMM experiments with low risk (L)

First read through the text above, in order to ensure that the experiment is most likely 'verksamhet level L, and that the terms ’verksamhet’ and ‘användning’ have been understood.

'Användning' in 'verksamhet' level L shall be limited by, e.g., the following:

  • a type of micro-organism (for virus vectors: a type of vector such as Lentivirus, Adenovirus, AAV, MMLV , rabies)
  • a limited type of insert, such as genes in a gene family/pathway/genetic function. Marker genes can also be added
  • a responsible group leader (or several)
  • a limited space

Experiments at this 'verksamhet' level shall always be limited by handling instructions as well. These can either be specific to 'verksamhet' or 'användning'. The notification shall clearly show which type of handling instructions that are to be applied.

  1. A biosafety group is  available in BMC, contact: Hans Hovenberg or Emanuel Smeds.
  2. A risk assessment on a Swedish Work Environment Authority form shall always precede the experiments. The forms are available at the Swedish Work Environment Authority website. The forms can be filled out in English. A short guide to completing the form for 'användning' in 'verksamhet' level L, called Quick-guide to the GMM-form LA can be found on the right.The form shall be sent, in it's entirety, to the EMV HMS coordinator.
  3. No experiment in level L may be initiated until a notification and its appendices have been sent to the Swedish Work Environment Authority. All risk assessments at level L must first be sent to the EMV HMS Coordinator. Thereafter, the coordinator shall send the documentation to the Swedish Work Environment Authority.

Once the documentation has been sent to the Swedish Work Environment Authority, a copy shall be made available in connection to the premises where the experiments are carried out, e.g., in a laboratory binder. This should be available at protection rounds and inspections by the Swedish Work Environment Authority.

When planning an experiment which is no longer covered by an approved 'användning', either make a new 'användning' notification, or update an existing 'användning'. This is also applicable if the handling instructions are altered. Documentation on this type of alteration shall also first be sent to the Biosafety Coordinator for review. Thereafter, the coordinator shall send the documentation to the Swedish Work Environment Authority.

Note that there are different 'verksamhet' IDs for laboratory and animal experiments. One risk assessment cannot cover both laboratory and animal experiments. The risk assessment for animal experiments shall be made available in the animal facility.

The approval of a report by the Swedish Work Environment Authority can take anything from a couple of days to a few months. The approval is sent via e-mail and is then titled 'Underrättelse om mottagen anmälan för ny användning i L-verksamhet’ ('Notice of received notification for new 'användning' in 'L-verksamhet’' in English). This document shall also be available in connection to the experiments. Note that the experiments may be initiated as soon as the documentation has been sent to the Swedish Work Environment Authority, however, this is not the case if there is no previously approved 'verksamhet' connectable to the report, see below.

If there is no approved L 'verksamhet' to which the report can be connected, an 'verksamhet' notification shall be made. Experiments conducted in an 'verksamhet', which has not yet been approved, may not be initiated until a reply has been received from the Swedish Work Environment Authority via e-mail titled ’Underrättelse om mottagen anmälan om innesluten användning av GMM' (Notification of received notification of contained use of GMM’ in English), or alternatively 45 days after the notification was sent

Micro-organisms

The handling of genetically modified, contagious micro-organisms requires notification (safety level 2) or permit (safety level 3-4) from the Swedish Work Environment Authority. A list of all micro-organisms belonging to risk group 2 and up, which thus require notification/permit, is available in the Swedish Work Environment Authority’s provisions

Note that this list is not complete.

Exceptions are granted for diagnostic activities, where the handling only entails the use of the original patient sample, e.g., for chemical analysis where no enrichment has been carried out. Research on micro-organisms in risk group 2 and up, generally require notification/permit.

In a work place that has a permit for, or has notified the handling of contagious micro-organisms, it is required

  • that the handling instructions that have been established in connection with the report are adhered to,
  • that only persons who have been informed of the risks are allowed to work there,
  • that the work is only carried out in the premises reported,
  • that the premises have been marked,
  • that the documentation regarding the report/notification shall be easily accessible, e.g., in a laboratory folder.

A permit application/notification shall contain a definition of the micro-organisms to be used. If you want to handle other micro-organisms in the same laboratory, or otherwise supplement/alter the application/notification, the application/notification must be updated.

In the provisions, as well as on the Swedish Work Environment Authority website, there is more information on which data is required in a report/notification application.  

Note that the department must be made aware of the micro-organisms on safety level 2 and up being handled, through the department’s HMS Coordinator (arbetsmiljösamordnare).

During safety rounds, or inspections by the Swedish Work Environment Authority, it should be possible to show the documentation regarding the permit as well as all routines involved in the report/notification, such as risk assessment/handling instructions

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