Marburg Biosafety and Biosecurity Scale (MBBS): A Framework for Risk Assessment and Risk Communication

Abstract

Current risk assessment and risk communication of biosafety and biosecurity concerns lack a convenient metric and conceptual framework. The absence of such a systematic tool makes communication more difficult and can lead to ambiguous public perception of and response to laboratory biosafety incidents and biosecurity threats. A new 7-category scoring scale is proposed for incidents and situations in laboratories related to the handling of human and animal pathogens. The scale aims to help clarify risk categories, facilitate coordination and communication, and improve public understanding of risk related to biosafety and biosecurity.

Risk assessment and risk communication of biosafety and biosecurity concerns currently lack a convenient metric and conceptual framework. The absence of such a systematic tool makes communication more difficult and can lead to ambiguous public perception of and response to laboratory biosafety incidents and biosecurity threats. The authors propose a 7-category scoring scale for incidents and situations in laboratories related to the handling of human and animal pathogens. The scale aims to help clarify risk categories, facilitate coordination and communication, and improve public understanding of risk related to biosafety and biosecurity.

International prevention and control of infectious diseases epidemics and pandemics such as influenza and in particular outbreaks of emerging and re-emerging highly infectious pathogens, such as SARS coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus, require a variety of health system capacities, including laboratories that can diagnose and conduct research on such pathogenic agents.^1,2 All member states of the World Health Organization (WHO) have recognized the importance of this capacity building in their adoption of the International Health Regulations (IHR 2005), which legally oblige all countries to build and maintain the capacity to prevent and respond to public health emergencies.² There is a general agreement that scientific investigation of human and animal pathogens is necessary for preparedness for and response to outbreaks. Thus, the implementation of biosafety and biosecurity measures in laboratories is of high priority to ensure safe and secure handling of biomaterials.

Concepts of Biosafety and Biosecurity

Biosafety “refers to principles, technologies, practices and measures implemented to prevent the accidental release of, or unintentional exposure to, biological agents or toxins, and biosecurity refers to the protection, control and accountability measures implemented to prevent the loss, theft, misuse, diversion or intentional release of biological agents and toxins and related resources as well as unauthorized access to, retention or transfer of such material.”^3(pp4-5)

Biocontainment

To ensure the safety of laboratory personnel and the environment, work on human and animal pathogens in laboratory settings is currently classified in biosafety levels 1 to 4 (BSL 1-4 and ABSL 1-4, respectively).⁴ The biosafety levels are designated in ascending order, by degree of protection needed for personnel, the environment, and the community.

This classification draws on the concept of biocontainment—that is, the difference between a pathogenic interior and a less pathogenic exterior, such as work/personnel or laboratory/environment, and a stable barrier between them.⁵ The physical containment of infectious pathogens or toxins is required to prevent accidental infection of workers or release of pathogens into the environment during scientific research or diagnostics.

Biosafety and Biosecurity Threats

Dangerous human and animal pathogens are handled in laboratories of high and highest biosafety levels. BSL-3 and ABSL-3 laboratories handle pathogens that cause severe diseases in humans and animals but for which there exist therapies and/or vaccines (eg, B. anthracis, rabies virus). BSL-4 and ABSL-4 laboratories handle pathogens for which no treatment or vaccines are available (eg, Ebola virus, Nipah virus). Those laboratories are necessary to diagnose infectious pathogens, guide infection control measures, and conduct research into new vaccines and treatment options. Very strict guidelines regulate BSL-3 and -4 laboratory operations. The mere existence of such high-containment laboratories is often perceived by authorities and the public as threatening. Concerns focus on incidents that could cause pathogens to physically escape the laboratory and contaminate the environment and accidents inside the laboratory that could lead to laboratory-acquired infections.^6-9 In the aftermath of the anthrax letters, biosecurity fears also have increased. Concerns have been raised about BSL-4 laboratories, in particular, as a potential source of security threats because their materials and technologies could be used to threaten societies.

Dual-Use Dilemma

Research and development in the field of biomedical sciences can sometimes pose a dual-use dilemma. While scientific discoveries can be used in beneficial ways to cure diseases and improve health, they also can be used for malicious purposes, as biological weapons. Dual use as a concept originated in the Cold War when it was applied to concerns related to nuclear material and its weaponization. Biomedical sciences in the postgenomic era bring a new dimension to the dual-use dilemma: Their dual-use potential is not only material-based (eg, possession of pathogens) but, more importantly, information-based (eg, possession of sequence information).¹⁰ The relevant dual aspects are not only physical possession of pathogens but also knowledge and information about how to modify or manipulate the original structure (eg, sequences of amino acids, mutations). These dual-use concerns were recently broadly discussed when researchers successfully introduced mutations to an avian influenza virus that enhanced its transmissibility (ie, gain-of-function experiments).^11,12

Risk Assessment and Risk Communication

Biosafety, biosecurity, and dual-use concepts are complex, lack standardization, and are often understood differently by scientific and security experts, policymakers, and the public. Current risk assessment and communication of laboratory biosafety and biosecurity can add ambiguity because they lack explicit metrics. To address this challenge, we have developed a new scale to help frame risk assessment and facilitate risk communication related to the classification of biosafety and biosecurity incidents and situations in laboratories.

Concept: Marburg Biosafety and Biosecurity Scale

Drawing on the concept of scaling nuclear events using the International Nuclear Event Scale (INES), we developed an explicit metric to assess biosafety incidents and biosecurity levels using a scale from 0 to 7, called the Marburg Biosafety and Biosecurity Scale (MBBS).

For biosafety, we evaluated the impact of laboratory-originated incidents on personnel, integrity of containment (in this context: biocontainment), and the environment. In order to avoid confusion with the BSL classification and to emphasize what we are measuring, we use a biosafety incident scale to classify the kinds of incidents that could occur in laboratories that handle human and animal pathogens and how severe they are in terms of impact on personnel, containment, and environment. Biosafety incidents 0 to 3 describe incidents that could, however unlikely, happen in routine laboratory operations; incident levels 4 to 7 describe accidents or attacks from external actors. From incident level 4 on, biosafety and biosecurity scales merge.

For biosecurity, we use levels to classify situations. Our starting point is the distinction between physical/material–based and intangible/information–based threats. We then further reflect issues related to the impacts on individuals, integrity of containment (in this context, control and effectiveness of response mechanisms), and the public. In contrast to the biosafety incident scale, the biosecurity levels 0 to 3 describe situations and not incidents. Only from biosecurity levels 4 and higher does the scale describe incidents. Botulinum toxin, for instance, is a biosecurity relevant pathogen that is currently in use for medical and cosmetic purposes. This is a biosecurity level 0. If botulinum toxin were to be used to intentionally harm a person (biosecurity level 4) or in synchronized attacks in one country (biosecurity 6) or several countries (biosecurity level 7), the biosecurity level would increase.

The first 4 scores (MBBS 0 to 3) of biosafety- and biosecurity-relevant incidents and situations develop (and would be reported) independently, while from MBBS 4 on, biosafety and biosecurity aspects move closer together, are less discrete, and have a similar common final path (locally contained, regional, national, and international impacts). Literally, the biosafety and biosecurity scale forms a Y-shape, where one arm of the Y is the biosafety branch and the other arm the biosecurity arm, both leading into a common final path (see Figure 1).

Figure 1.

Y-shape of Biosafety and Biosecurity Scale. Color images available online at www.liebertpub.com/hs

MBBS Biosafety Branch

The biosafety branch refers to work on human and animal pathogens in laboratories and provides a metric for evaluating incidents with regard to the impact they have on personnel, the integrity of the containment, and the environment (Table 1). Although this scale applies to all laboratories, only incidents in the high and highest containment laboratories are likely to have a significant impact on people, integrity of containment, and the environment. For this reason, examples presented are mainly drawn from work in BSL-3 and -4 laboratories.

Table 1.

Marburg Biosafety and Biosecurity Scale (MBBS), Biosafety Branch

Biosafety	Description	Impact on Personnel P	Impact on Integrity of Containment TO	Impact on the Environment U	Examples	Consequences
0	Internal technical incident No notification required	No or minor impact 0	No or minor impact 0	No 0	A hole in 1 of the 3 gloves	Adaption of organization; information provided to all staff
1	Low-impact incident Notification required	Minor impact 0	Minor impact I	No 0	A torn protection suit without infectious risk	Notification of laboratory authority and occupational health; information provided to all staff
2	Incident Notification required	Suspected case (limited loss of layered security measures) I	Minor impact I	No 0	Needle stick injury with infectious risk	Notification of laboratory, occupational, and health authorities; quarantine; information provided to all staff
3	Serious incident Notification required	Contamination and/or health threats; loss of layered security measures I	Minor impact I	Possible infection of contact persons I	Contagious staff without quarantine (probable case); leakage of sewage water or unsafe waste (eg, Pirbright)	Contact tracing; containment efforts; notification protocol; information provided to staff and public
4	Accident with local consequences	Staff not exposed (eg, during the night)	Damage to laboratory and integrity of containment	Release of pathogens to environment; potential exposure of the public	Sudden excess pressure (explosion); release of pathogens	Police and firefighters close off the local environment; emergency protocol; information provided to staff and public
5	Accident with wider consequences	Contamination of staff	Damage to laboratory and integrity of containment	Release of pathogens to environment; potential exposure of the public	Sudden excess pressure (explosion); release of pathogens	Police and firefighters close off the local environment; emergency protocol; information provided to staff and public
6	Serious accident	Contamination of staff	Serious damage to laboratory and integrity of containment	Release of pathogens to environment; cases in the public (1 country)	Sudden excess pressure (explosion); release of pathogens	National emergency response protocol; information provided to staff and public
7	Major accident	Contamination of staff	Severe damage to laboratory and integrity of containment	Release of pathogens to environment; cases in several countries	Sudden excess pressure (explosion); release of pathogens	International emergency response protocol; information provided to staff and public

Biosafety incident 0 classifies an incident of no or minor impact on personnel and integrity of containment and no impact on the environment. An example would be a hole in 1 of 3 gloves because of a material defect without contamination. In the laboratory such events are described as technical incidents and are recorded in the record book of each laboratory but do not require any notification to regulatory authorities. Nonetheless, all personnel are informed about such technical incidents. Reporting of such incidents, however minor, is very important for the safe operation of high-containment laboratories. From a safety control system perspective, such reporting should never have negative professional consequences, and, in fact, reporting should be encouraged to improve the overall adoption of safer working practices.

Incident level 1 classifies a situation where there is a minor impact on the integrity of biocontainment, no or a minor impact on personnel, and no impact on the environment. A torn protection suit without infectious risks would be an example. This kind of low-impact incident requires notification to the organizational authority of the laboratory, and information is provided for all staff.

Incident level 2 classifies a situation where there is an impact on personnel and the integrity of the biocontainment, but no impact on the environment. A needle-stick injury with infectious risk would be one example. Notifications of laboratory and health authorities are required for activation of response protocols, and appropriate treatment measures for the injured are activated. Information is provided for all personnel.

Incident level 3 classifies a serious incident that affects personnel, the integrity of the biocontainment, and the environment. This could be, for example, a case in which infected staff have not been quarantined and transmission of disease to people inside and outside the laboratory cannot be excluded but has not yet been reported.

The leakage of agriculturally relevant pathogens, such as foot-and-mouth-disease virus, from the laboratory into the environment because of a damaged sewage system, with limited infections, would be another example of an incident level 3 situation. Response measures include notification of laboratory and public health authorities, as well as national authorities, to activate containment measures and contact tracing. Information should be provided to personnel, local communities, and the general public.

Incident level 4 classifies situations that are the result of physical damage to the containment. A fire due to a defective electrical device that damages the integrity of the biocontainment and leads to a release of pathogens (if they are not inactivated by the heat of the fire) would be one example of this level of a local accident. Level 4 incidents are defined by situations in which the environment may be contaminated but personnel are not exposed, such as a fire that happens during the night. In such circumstances, the emergency response team would focus on measures to protect the local area. Organizational, health, and security authorities would work according to their emergency protocols. Information should be provided to personnel, the local community, and the public.

Incident level 5 classifies situations in which an accident has wider consequences and personnel and the public are exposed. Exposed individuals would be placed in quarantine, and contact tracing would be implemented. Similar emergency response measures would be taken as in level 4.

Incident level 6 is an escalation of level 5 in which disease cases as a consequence of exposure are reported indicating a sustained chain of transmission. Infections, however, are limited to 1 country. National emergency plans and response measures are taken to detect cases, stop the chain of transmission, and contain the outbreak.

Incident level 7 is the widest escalation, with cases detected in several countries. In this case national and international emergency response measures would be taken.

MBBS Biosecurity Branch

The biosecurity branch of the MBBS includes levels 0 to 7, where the first 4 biosecurity levels, MBBS 0 to 3, describe situations of laboratory development or manipulations, whereas biosecurity levels MBBS 4 to 7 classify incidents with wider implications. The biosecurity scale, however, does not include the wide-ranging long-term social and political ramifications and ripple effects that biosecurity incidents could have on society.

Biosecurity in this context refers to any activity, material, knowledge, or information that could be used for malicious purposes to pose threats or commit crimes or terror attacks.

As an initial distinction we discriminate between tangible, physical dimensions and intangible, information-based dimensions of biological threats. We evaluate biological threats against their effect on individuals, on the integrity of containment (this includes the ability to respond to infectious diseases and contain the pathogen), and on the public (Table 2).

Table 2.

Marburg Biosafety and Biosecurity Scale (MBBS), Biosecurity Branch

Biosecurity	Tangible/Physical	Intangible/Information	Impact on Individuals	Impact on Integrity of Containment	Impact on the Public	Examples	Possible Response Strategies and Consequences
0	Dual-use dilemma Material base		No or minor impact0	No or minor impact0	No0	Pathogens	Education and trainingRisk communicationPolicyAwareness
1		Dual-use dilemma Information baseDirect	No or minor impact0	Minor impactI	No0	Gain-of-function research and publication	Education and trainingRisk communicationPolicyAwareness
2		Dual-use dilemma Information baseIndirect	No or minor impactI	Minor impactI	No0	Lateral application of gain-of-function research and publication	Education and trainingRisk communicationPolicyAwareness
3	Serious incidentNotification required		Minor impactI	Minor impactI	Potential impactI	Theft of pathogenic material from a BSL-3 or -4 lab	Security and intelligence investigationsRisk communication
4	Attack with local consequences		Minor to major impact	Prophylaxis and/or treatment available	Minor	Intentional release of pathogens to attack individuals (eg, Markov ricin attack)	Security and intelligence investigationsRisk and crisis communication
5	Attack with wider consequences		Major	Prophylaxis and/or treatment available	Major	Intentional release of pathogens; several cases in 1 country	Security and intelligence investigationsEmergency protocolInforming of staff and public
6	Serious attack		Major	Prophylaxis and/or treatment unavailable	Major	Intentional release of pathogens; several cases in 1 country	National emergency response protocolInforming of staff and public
7	Major attack		Major	Prophylaxis and/or treatment unavailable	Major	Intentional release of pathogens; cases in several countries	International emergency response protocolInforming of staff and public

Biosecurity level 0 classifies the situation of the tangible, factual material existence of pathogens or toxins in the local community and/or environment—for example, ricin growing on bushes, anthrax found in the soil, C. botulinum in medical and cosmetic use, and naturally occurring avian influenza.

Biosecurity level 1 classifies the situation of intangible dual use, in which information can be used to modify pathogens based on direct, information-based application of common laboratory practice. As a result, pathogens can become more dangerous to humans. Examples are gain-of-function experiments that modify transmissibility or mortality in a laboratory setting.

Biosecurity level 2 describes an escalation of level 1, in which information-based scientific achievements are used in an interdisciplinary approach to modify characteristics. One example would be the anthrax letters: The anthrax spores were coated in a particular manner to avoid clumping, which presents a common problem in the dispersion of fine powder; this technique is used in a different science (engineering, physics), and the lateral application poses a different and new threat level.

Biosecurity level 3 classifies the situation of a material-based theft of pathogenic agents with minor impact on individuals and the integrity of the containment and potential impact on the public. In contrast to biosafety level 3, where pathogenic agents could be released incidentally, this biosecurity level 3 has a criminal or terrorist purpose.

Biosecurity level 4 classifies an attack with local consequences, such as an attack on an individual with a pathogenic agent. The impact on individuals would be minor to major, the impact on the public would be minor, and treatment and/or prophylaxis are available.

Biosecurity level 5 classifies the situation of intentional release of a pathogen to a group of the public with a major impact on individuals and the public; prophylaxis and/or treatment is available. The difference from level 4 is the occurrence of several cases, probably as a synchronized attack.

Biosecurity level 6 classifies the situation of an intentional release of a pathogen to a group of the public where treatment and/or prophylaxis is unavailable and several cases occur nationally. Difference from level 5 is that the epidemiologic containment measures are limited (no prophylaxis or causal treatment).

Biosecurity level 7 classifies the situation of an intentional release of a pathogen where cases occur in different countries and prophylaxis and/or treatment is not available.

Discussion

This proposed scale provides a unique framework for a rational and transparent classification of laboratory biosafety and biosecurity concerns. The scale can be applied both prospectively and retrospectively to contribute to the assessment and communication of biological risks. Applications might usefully include: (1) risk assessment of incidents and situations using the explicit rationale; (2) risk communication of these incidents and situations to relevant stakeholders including the general public; (3) action guidance for laboratory personnel and authorities; (4) system preparedness planning, such as informing other sectors with an interest in biosafety and biosecurity (other than the laboratory community).

Until now, there has been no convenient standardized related rating or scaling system for laboratory-related biological risks. On the input side, risk groups of pathogens have been identified that determine the containment level of work that has to be conducted with these agents. On the outcome side, current systems that classify incidents in laboratories (eg, internal technical incident, low-impact incident, accident) tend to be focused on (and confined to) laboratory experts. Moreover, criteria defining incidents/accidents are not standardized and are often not clear or are not clearly communicated. Current classification systems exclude a broader risk assessment and understanding of biosafety or any classification for biosecurity. The existing color coding to classify terrorism threats (eg, Homeland Security Advisory System or the UK threats) cannot be applied to biosafety or biosecurity, and the criteria for serious or severe, red or orange levels, are too vague.

Regarding response, in the field of biosafety, emergency protocols are in place and are exercised in different settings such as in lab or national exercises that form part of routine quality control procedures. In biosecurity such protocols are more vague, and there are no or few established routines to respond to these threats and test and evaluate the effectiveness of response measures.

Scope

The biosafety incident scale can contribute to a clearer understanding of the nature of incidents in the laboratory (incident levels 0 to 3) and accidents or attacks on laboratories (incident levels 4 to 7), while the biosecurity levels provide an overview of situations (biosecurity levels 0 to 3) and incidents (biosecurity levels 4 to 7). This scale provides an easy to understand, explicit rationale to assess and communicate biosafety and biosecurity concerns. Having clear criteria can contribute to more transparent and concise assessment, communication, and response. Both scales merge from incident level 4, where accidents at laboratories are the result of intentionally malicious purposes, such as an explosion in a BSL-4 laboratory. These represent common external factors, and therefore biosafety and biosecurity move closer together.

Assessment

The MBBS could be used to better understand incidents and consequences and to rethink strategic response measures. Having an explicit framework in place that illustrates where on the scale the situation actually is, how it could develop, and what actions might be necessary is important strategic information that can inform response strategies well ahead of escalating situations. Response mechanisms to biosecurity threats are not well articulated or standardized as yet. For this purpose, we suggest some basic response actions and include a column on possible strategies and consequences. This could be used by relevant institutions and groups to reflect and structure their response.

Reassessment

Working through scenarios, the scale could, for example, show that the former, often intuitive risk assessment that assumes that BSL-4 labs are more dangerous than BSL-3 labs could be misleading. BSL-4 work is highly regulated, and certain threats, such as explosions, should not happen (unless there is an attack), since all explosive materials are prohibited inside BSL-4 facilities. BSL-3 labs are less regulated and more widely distributed; having higher levels on the biosafety and/or biosecurity scale might lead to rethinking about needed security and response capacities and mechanisms among regulators and policymakers.

Quality Control

The notification and reporting that are required on the different levels could also be used to evaluate quality in laboratories. The assessment tool generates new data that can be analyzed and could inform decision making.

Improved Communication

A major feature of this scale is that it allows clearer and more consistent communication. Having the same explicit rationale in place facilitates coordination with institutions and communication with colleagues and the public.

Bioseverity Scale

In order to better understand the health implication of biosafety and biosecurity 4 to 7 and the severity of the epidemiologic situation, a third assessment and communication rationale would be necessary to classify clinical outbreak scenarios and guide public health response. This “bioseverity scale” is currently being developed to assess the clinical and epidemiologic situation for public health responses.

Limitations

The proposed MBBS is a conceptual evaluation framework and metric, and its applicability and benefit need to be demonstrated in further discussions and use. The MBBS does not include a way of measuring the social and political factors that shape both the identification of and responses to incidents, accidents, and attacks. In its current form, it is limited to developing a standardized measuring and communicating tool that could improve understanding and clarify risk assessment and communication related to biosafety and biosecurity. The scale could function in a similar way to the Richter scale for earthquakes: It is not just a strong or heavy or severe earthquake; it is an earthquake of 5.7 on the Richter scale. The MBBS can offer comparability and a better understanding of the impact an event can have. Having an explicit rationale in place could help conceptualize response measures.

An important question for security intelligence is how easily or likely it is that a biosecurity level 0 to 3 situation could develop into biosecurity 4 to 7, or how likely a biosafety incident 4 to 7 is. The MBBS does not provide an intelligence tool to assess how likely or feasible it is that situations may develop. The purpose of this scale at this stage is to provide an explicit rationale for assessment and communication.

Conclusion

Drawing on similar scales that rate and evaluate natural threats and nuclear events, this biosafety and biosecurity scale provides an explicit metric to rate biosafety and biosecurity to improve risk assessment and risk communication. It could also serve to improve quality assessment of laboratory work, inform policy and political decision makers, and help conceptualize and improve appropriate response measures.

References

Gulland

. Ebola outbreak claims more than 60 lives. BMJ, 2014 Mar 31; 348:g2473.

World Health Organization. International Health Regulations 2005. 2nd ed. Geneva: World Health Organization; 2005. http://www.who.int/ihr/about/en/. Accessed February 18, 2015.

Meeting of the States Parties to the Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction . Report of the meeting of states parties. Geneva, 2008. Contract No.: BWC/MSP/2008/5. http://www.opbw.org/new_process/msp2008/BWC_MSP_2008_5_E.pdf. Accessed February 18, 2015.

Centers for Disease Control and Prevention. Principles of biosafety. In: Biosafety in Microbiological and Biomedical Laboratories (BMBL). 5th ed. Washington, DC: US Department of Health and Human Services; 2009.

Patterson

, Fennington

, Bayha

, et al. Biocontainment laboratory risk assessment: perspectives and considerations. Pathog Dis, 2014; 71(2):102-108.

Dickmann

, Keith

, Comer

, Abraham

, Gopal

, Marui

. Report of the International Conference on Risk Communication Strategies for BSL-4 Laboratories, Tokyo, October 3-5, 2007. Biosecur Bioterror, 2009; 7(2):227-233.

Foot and mouth: mystery outbreak at Pirbright. Nature, 1970; 228(5270):403.

Gunther

, Feldmann

, Geisbert

, et al. Management of accidental exposure to Ebola virus in the biosafety level 4 laboratory, Hamburg, Germany. J Infect Dis, 2011; 204(Suppl 3):S785-S790.

Report of the Investigation into the Cause of the 1978 Birmingham Smallpox Occurrence (22 July 1980). London: Her Majesty's Stationery Office; 1980.

10.

Dickmann

. Biosecurity - Biomedizinisches Wissen zwischen Sicherheit und Gefährdung. Bielefeld: Transcript; 2012.

11.

Fouchier

, Herfst

, Osterhaus

. Public health and biosecurity. Restricted data on influenza H5N1 virus transmission. Science, 2012; 335(6069):662-663.

12.

Herfst

, Schrauwen

, Linster

, et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science, 2012; 336(6088):1534-1541.