Types and categories of biological agents

Biological agents are substances such as microorganisms which can create a hazard to human health, for example, through infection, allergy, toxicity, etc.

On this page

• What is a biological agent?
• What is genetically modified material?
• What is not considered to be genetically modified material?
• Samples from human or animals plants
• Schedule 5 
• Specified Animal Pathogens 
• Zoonoses
• Lab Animal Allergens

 What is a biological agent?

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Biological agents include:

• micro-organisms such as bacteria, viruses, fungi, parasites, prions, protozoa
• toxins produced by biological agents
• genetically Modified microorganisms
• cell cultures derived from humans / animals or insects
• the products of biological agents including animal dander, pollen or fluids such as urine, saliva or sap
• animals, arthropods (insects and arachnids) and plants used in research

Hazard groups 

This is the categorisation of wild type (naturally forming bacteria, viruses, fungi, parasites, protozoa and prions) are 1-4 with increasing hazard with the increasing number the groups are determined by the severity of disease. The higher the level of risk the more stringent controls are required to minimise the risk of exposure to as low as possible.    

Hazard group	Level of disease	Spread	Prophylaxis
1	Unlikely to cause harm	N/A	N/A
2	Can cause infection and disease but will recover	Unlikely to spread to the wider community	Effective and available prophylaxis
3	Cause serious disease	May spread to the wider community	Effective and available prophylaxis
4	Cause serious disease	Likely to spread to the wider community	Usually, no effective prophylaxis available

Categorisation of Biological Agents is determined by Approved List of biological agents

At UCL organisms up to and including Hazard Group 3 can be handled. There are no containment level 4 facilities at UCL to work with HG 4 organisms.

At UCL, only organisms up to Hazard Group 3 and Class 3 GMOs are handled. Only a limited number of facilities exist in the UK capable of containing Hazard Group 4 and Class 4 organisms.

The higher the risk rating, the more stringent the control measures are to ensure that the risk of exposure is kept as low as possible. There are standards for both procedures that have to be in place and the engineering controls that have to be present for each level of risk. These are referred to as the Containment levels.

What is Genetically Modified Material?

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This is where the nucleic acids of an organism have been artificially manipulated by humans to produce an organism which does not occur in nature through mating or natural recombination.

What is not considered to be Genetically Modified Material?

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Certain techniques are not considered to result in genetic modification:

• in vitro fertilisation
• natural transformation processes eg conjugation, transduction or transformation; and polyploidy induction
• mutagenesis
• cell fusions (including protoplast fusion) of eukaryotic species including the production of hybridomas and plant cell fusions
• self cloning where the resultant organism is likely to cause disease or harm to humans

In addition, there are certain techniques where the bulk of the Regulations do not apply, provided they do not use recombinant genetic material or GMOs in the first instance:

• mutagenesis;
• cell fusion (including protoplast fusion) of cells of any eukaryotic species, including the production of hybridomas and plant cell fusions; and
• self-cloning where the resultant organism is unlikely to cause disease or harm to humans.

Genetically Modified (GM) Materials  classification 

GM Materials do not occur naturally, so they do not fit into the hazard groups like naturally occurring microorganisms. Instead, they are categorised by Class. The Classes are also numbered 1 to 4 and again with the increasing number there is an increase in the level of risk. The Class of a GMO is determined by the hazards of the final construct to human health or the environment as well as the activity being carried out. The Class is determined by the control measures needed e.g. if a single measure or multiple measures from CL2 are required the GMO would be Class 2.

Class	Risk	Controls used
1	non or negligable	CL1
2	low	CL2
3	medium	CL3
4	high	CL4

Categorisation of GMM is determined by risk assessment. The highest risk material worked with at UCL is Class 2 which can only be conducted in specialised CL 3 facilities.

Samples from Humans and Animals

These are categorised according to the level of risk of pathogens being present that will impact human health or the health of the environment.

This will also be determined by the type of sample and potential diseases that could be present. 

All these materials should be treated as if they are potentially infectious and must have suitable controls in place to protect employees and other lab users. 

Hazard	Cell Type	Baseline containment
Low	Well characterised or authentic finite cell lines from human or primate origin with a low risk of pathogens being present and tested for the most serious pathogens	CL1
Medium	Finite and continuous cell lines or strains of human or primate origin not fully characterised or authenticated where there is a high risk of endogenous biological agents e.g. blood borne viruses	CL2
High	Cell lines with endogenous agents or deliberately infected cells Primary cells from blood or lymphoid cells of human or primate origin	Containment determined by the infective agent  containment determined by risk. A minimum of CL2

Where there is a risk of infectious aerosol the work should be carried out in a Microbiological Safety Cabinet.

Schedule 5

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Schedule 5 is part of the Anti-terrorism, crime and security Act. The purpose of Schedule 5 is to prevent the unauthorised acquisition and use of dangerous pathogens and toxins for malicious use. The list has a range of human and animal pathogens and includes nucleic acids from these agents. To order and work with biological agents that feature in Schedule 5 and application of licences please contact biochem@ucl.ac.uk.

• People who work with these agents should have appropriate experience and training.
• Only order what is needed and limit stocks to the minimum required
• Records should be kept on the amounts used and amounts disposed of, A regular check on Schedule 5 agents is carried out by Safety Services
• There should be a register of users with access to these agents
• These agents must be safely and securely stored to avoid unauthorised access

Schedule 5 Viruses 

Chikunga virus	Middleburg virus
Congo-crimean haemorrahagic fever virus	Mobala virus
Dengue virus fever	Monkey pox virus
Dobrava / Belgrade virus	Mucambo virus
Eastern equine encephalitis virus	Murray Valley encephalitis virus
Ebola virus	Ndumu virus
Everglades virus	Nipah virus
Getah virus	Omsk haemorrahagic fever virus
Guanarito virus	Polio virus
Hantaan virus	Powassan virus
Hendra virus (Equine morbillivirus)	Rabies
Herpes simiae (B virus)	Rift Valley fever virus
Influenza virus (pandemic strains)	Rocio virus
Japanese encephalitis virus	Sabia virus
Junin virus	Sagiyama virus
Kyasanur Forest virus	Sin Nombre virus
Lassa Fever virus	St Louis encephalitis virus (Russian Spring-Summer encephalitis virus)
Louping ill virus	Variola virus
Lymphocytic chloriomeningitis virus	Venezuelan equine encephalitis virus
Machupo virus	West Nile fever virus
Marburg virus	Western equine encepalitis virus
Mayaro virus	Yellow fever Virus

Rickettsiae

Coxiella burnettii	Rickettsia rickettsii
Rickettsia prowazeki	Rickettsia typhi (formerly R. mooseri

Bacteria 

Bacillus anthracis	Francisella tularensis
Brucella abortus	Multi drug resistant Salmonella paratyphi
Brucella canis	Mycobacterium tuberculosis
Brucella melitensis	Salmonella paratyphi A, B, C
Brucella suis	Salmonella typhi
Burkholderia mallei (Pseudomonas mallei)	Shigella boydii
Burkholderia pseudomallei (Pseudomonas pseudo mallei)	Shigella dysenteriae
Chlamydophila psittaci	Shigella flexneri
Clostridium botulinum	Vibrio cholerae
Clostridium perfringens	Yesinia pestis
Enterohaemorrhagic Escerichia coli, serotype 157 and Verotoxin producing strains

Fungi

Cladophialophora bantiana
Cryptococcus neoformans

Toxins

Abrin	Saxitoxin
Botulinum toxins	Shiga and shiga-like toxins
Clostridium perfringens eplison toxin	Staphylococcus enterotoxins
Clostridium perfringens enterotoxin	Tetrodotoxin
Conotoxin	Viscum Album Lectin 1 (Viscumin)
Modecccin toxin	Volkensin toxin
Ricin

 Zoonoses

Transmission of Zoonotic disease from laboratory animals is uncommon due to the health status of laboratory animals. However, there are a number of diseases that can be spread between animals and humans these include:

• Marburg Virus
• Simian Immunodeficiency Virus (SIV)
• Filoviruses
• Mycobacterium tuberculosis
• Herpes simae (monkey B virus)
• Transmissible Spongiform Encephalopathy (TSE’s) e.g. Bovine Spongiform Encephalopathy (BSE)
• SARS- CoV-2

Information on zoonosis can be found on the the HSE webpage https://www.hse.gov.uk/biosafety/diseases/zoonoses.htm or biochem@ucl.ac.uk.

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Specified Animal Pathogen Order (SAPO)

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SAPO is a specific element of the Animal Health Act. SAPO specifically lists animal pathogens that are not endemic to the Great Britain, and if introduced could have a significant impact and economic loss to the livestock industry e.g. Foot and Mouth outbreak in 2007. A list of SAPO agents can be found in Guidance for licence holders on containment and control of specified animal pathogens. SAPO includes the wild type microorganisms, attenuated strains and genetically modified forms of any of the listed pathogens.

Please contact biochem@ucl.ac.uk for further information about working with these agents and licence applications.

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Lab Animal Allergens (LAA)

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Working with animals and animal samples can lead to the exposure to Lab Animal Allergens. The symptoms can be itchy red and or watery eyes can be found in animal dander, urine, droppings and bedding. To be able to enter these facilities an LAA questionnaire must be completed and returned to Workplace Health this is typically part of the Job Hazard Form process completed by the Manager of the person working in these areas. Face fit testing and a Health questionnaire will also be required before starting work where there is a risk of exposure to LAA.  

For information on Respiratory Protective Equipment.