What must be done?
The biological risk assessment is carried out in four main stages. The Principal Investigator (PI) is responsible for this process, which involves identifying and analysing the risks associated with each experimental procedure. Based on this analysis, the PI determines the required biosafety level to safely carry out the activity.
Once the assessment is complete, the PI must formalise it in the form of a declaration of activities and submit it to the Institutional Biosafety Committee (IBC) for review and validation.
Biological risk assessment
If an activity is carried out solely with natural organisms, without any type of genetic modification, the biosafety level (BSL) attributed to it generally corresponds to the hazard group of the organisms used. When the activity involves the use of organisms from different groups, the classification of the activity generally corresponds to the group of the organism that presents the most danger.
The BSL might not correspond to the hazard group of the organisms due to the following criteria:
- The nature, scale and objective of the activity.
- The ability of organisms to survive, multiply and spread in the environment, in particular selective advantage and the formation of survival structures.
- Interaction with other organisms in the environment or participation in other biogeochemical processes.
The following activities are generally attributed to BSL1:
- The analysis of soil, water, air or food samples to the extent that they do not represent a danger to human health and the environment.
- Activities involving group 2 organisms to the extent that they have been proven, either experimentally or on the basis of long experience, to be as safe as those of group 1.
- The analysis of clinical samples (medical microbiological diagnosis) is generally considered a BSL2 activity. If group 3 pathogenic organisms are enriched, for a diagnostic purpose, and pose an additional risk to humans and the environment, the activity must be classified as BSL3. If working with group 4 organisms, in all cases the activity will be BSL4.
Each new cell line used in the laboratory must be subject to a detailed risk assessment, which will allow establishing the preventive measures that must be taken. This assessment must consider the following elements:
- Source of the cell line: The closer the genetic relationship of the cell culture is to humans, the higher the risk is to humans since contaminating pathogens usually have specific species barriers (in descending order of risk: autologous human, heterologous human, non-human primate, other mammals, birds, invertebrates).
- Tissue provenance: gives an indication of possible contaminants and latent viruses (oncogenes).
- Culture type: in descending order of risk -primary cell lines, continuous cell lines, very well characterized cell lines-.
- Number of cells per culture.
In the case of recombinant cell lines, it is also necessary to consider:
- The properties of the host cell line (in the case of hybridomas, the properties of each of the starting cells must be taken into account).
- The vector used for the transformation.
- The transfer of viral sequences.
- The transfer of virulence factors.
- The activation of endogenous viruses.
- The recombinant gene product.
- The presence of auxiliary viruses.
What do we mean by "biological agent"?
In the UAB, the concept of biological agent goes a little beyond what is defined in article 2 of RD 664/1997. Therefore, we consider a biological agent as any organism, including those which have been genetically modified, biotoxin, protein (ex. prion), allergen, cell cultures and endoparasite, which may be able to provoke any infection, allergy or toxicity in humans, animals, plants or harmful effects to the environment.
What do we mean by confined activities with biological agents?
It is an operation in which genetically modified or pathogenic organisms are cultured, stored, transported, destroyed, disposed or used in any other way, and for which specific containment measures are used to limit their contact with, and to provide a high level of safety for, the general population and the environment. An operation can take place in a laboratory (research, diagnosis), an animal facility (small and / or large animals), a greenhouse or a large-scale process facility (production).
What is a Genetically Modified Organism (GMO)?
Law 9/2003 defines GMO as "any organism, with the exception of human beings, which has been modified, through specific techniques of genetic manipulation, a modification of its genetic load (genome)". It is therefore induced modifications, different from those that occur naturally in mating, recombination or in any other biological process of transfer of genetic material. The modification may consist of a modification of the expression of their genes, deletions or partial losses thereof, or the incorporation of genetic material from other species or varieties.
What is self-cloning?
According to Directive 2009/41/EC (Annex II Part A), self-cloning in risk group 1 or multicellular organisms (excluding germ cells of human origin) consists in "the removal of nucleic acid sequences from a cell of an organism, which may or may not be followed by reinsertion of all or part of that nucleic acid (or a synthetic equivalent), with or without prior enzymatic or mechanical steps, into cells of the same species or into cells of the same species or of phylogenetically closely related species which can exchange genetic material by natural physiological processes where the resulting micro-organism is unlikely to cause disease to humans, animals or plants.
Self-cloning may include the use of recombinant vectors with an extended history of safe use in the particular micro-organisms.
Are the risk/hazard group and the biosafety/biocontainment level synonymous?
Previous versions of the WHO "Laboratory Biosafety Manual" described the classification of biological agents and laboratories in terms of risk/hazard groups and biosafety/containment levels. While this may be a logical starting point for the handling and containment of biological agents, it has led to the misconception that the risk group of a biological agent directly corresponds to the biosafety level of a laboratory. In fact, the actual risk of a given scenario is influenced not only by the agent being handled, but also by the procedure being performed and the competency of the laboratory personnel engaging in the activity.