LECTURE TIMETABLE
TRAINING COURSE BROCHURE

Lecturers

Martien Broekhuijsen

Romualdo Grande

Alessandra Lombardi

Alessandro Mancon

Davide Mileto

Angelo Moretto

Tatyana Novossiolova

Gijsbert van Willigen

Tutors

Giovanna Fotia

Mirko Palestrino

Luca Vitali

Please download the registration form here.

Thanks to generous sponsors, CLIMVIB is pleased to announce a public competition for two scolarships which aim at promoting the participation of scientists from low and low-middle-income countries. For more information click on the links below!

INSTRUCTIONS FOR APPLICANTS
APPLICATION FORM

Laboratory Biosafety
Martien Broekhuijsen

Laboratory Biosecurity, Dual Use of Biological Materials and Ethical Issues
Tatyana Novossiolova

The purpose of this two-hour lecture is to provide an overview of the following key concepts:

• Biosecurity;
• Dual Use;
• Ethical, Social, and Legal Responsibilities of Life Scientists.

The lecture looks into the core principles of biosecurity and the role of various stakeholders in promoting and sustaining biosecurity locally, nationally, and internationally.
The lecture further aims to foster an understanding of the concept of dual use and how it relates to the life sciences in the 21st century in terms of responsibilities and practices.
The lecture covers the basic elements of the new International Certification Programme in Biosecurity that was launched by the International Federation of Biosafety Associations (IFBA) in spring 2016.
The format of the lecture is participant-centred featuring practical tasks and discussion-based exercises, that are designed to encourage reflection, debate, and active engagement with the issues to be discussed.

Key Reference Reading:
Simon Whitby et al. Preventing Biological Threats: What You Can Do, (Bradford: University of Bradford, 2016).
Tatyana Novossiolova, Biological Security Education Handbook: The Power of Team-Based Learning, (Bradford: University of Bradford, 2016).[1]

[1] Both books are freely available at: http://www.bradford.ac.uk/social-sciences/peacestudies/research/publications-and-projects/guide-to-biological-security-issues/

Regulatory Aspects
Martien Broekhuijsen

Primary Barriers: PPE & Laboratory equipment
Martien Broekhuijsen

Secondary Barriers: Facility design and construction
Gijsbert van Willigen

Good Laboratory Practices
Martien Broekhuijsen

Good laboratory practices are all those methods and procedures that in combination with other measures (e.g. physical barriers or equipment) ensure the safe handling of hazardous biomaterials. In several countries the most often used description is Good Microbiological Practice (GMP), not to be confused with Good Manufacturing Practice. Other terms used include Standard Microbiological Practice (SMP) or Safe Microbiological Practice (also SMP).
Any biosafety procedure or biosafety equipment can be rendered useless if the user makes mistakes or does not use the equipment properly. The correct use of equipment and proper execution of methods by the microbiological worker is at the core of biosafety. A proper level of education and sufficient training are the most essential starting points for GMP.
Many international guidelines include paragraphs on GMP, such as from the WHO[1], CDC[2], and others. International biosafety associations such as ABSA and EBSA also publish guidelines for GMP.
GMP involves aspects such as training, peer control, procedures, SOP’s, and other elements. Several organisations offer training courses for GMP. Many use videos and photos to illustrate essential elements of GMP. GMP is not a replacement for a microbiological education, it is merely an extension, relying on a solid microbiological education as basis.

[1] http://www.who.int/csr/resources/publications/biosafety/WHO_CDS_CSR_LYO_2004_11/en/
[2] http://www.cdc.gov/biosafety/publications/bmbl5/

Biohazardous Waste Management
Gijsbert van Willigen

Solid (including sharps) or liquid biohazardous waste is unavoidably produced in facilities where laboratory experiments, experiments with animals are performed during the treatment of patients. For save handling of this waste it should be collected in such a way that it does not pose any risk for the people who handle or transport this waste inside or outside of the institute. Special bags, over packs and containers should be used for safe collection of biohazardous waste. They should be leak and puncture proof and can be used for various types of decontamination. Preferably they cannot be reopened. For biohazardous waste national and international legislation is in place for dealing with biohazardous waste.
For inactivation of biohazardous waste several methods are available ranging from chemical inactivation to various types of a physical process for inactivation. All these methods aim at rendering the biohazardous waste harmless for humans, animals and environment. Depending on the risk, this inactivation should take place outside the organisation (BSL1 and BSL2) or within the organisation (BSL3 and BSL4)
The method of choice for inactivation of biohazardous waste greatly depends on the composition and volume of the waste, the risk level of the waste, but also if the material that is being decontaminated is reusable or disposable. Also economic factors can be considered when choosing an inactivation method. After a method is chosen the inactivation process must be validated.
For a proper inactivation, validation and verification of the inactivation process should be in place. For this several methods can be used to demonstrate the effectiveness of the inactivation. One of them is the use of biological indicators when physical processes are used for inactivation
In the presentation all aspects of biohazardous waste management will be discussed. Also some of the commonly made mistakes will be shown.

Laboratory Accidents
Davide Mileto

The security of work place is one of the most important aspects of the working activity. The risk assessment for the scientific laboratory, chemical and biological, is linked with the presence of hazardous factors present in the daily lab activities. Among the different elements to be considered in a risk assessment, there are the agents, the equipment, the problems linked with the space limitations, organizational/management aspects and sometimes the lack of information, education and training of the staff. The presence of these factors in a laboratory setting could cause laboratory accidents, such as break of tubes in a centrifuge, projection of liquid in eyes, spills, accidental injection of a contaminated solution, aerosol of liquid solution that could generate the spread of agents into the laboratory environment thereby causing the infection of workers or the contamination of equipment and materials, etc. Accordingly, a relevant problem in the context of the laboratory accidents is all infection acquired through laboratory or laboratory-related activities regardless whether they are symptomatic or asymptomatic in nature. This infections are defined as Laboratory Acquired Infection (LAI) or laboratory-associated infections. Among the LAI, the bloodborne Pathogens are important especially for HBV, HCV and HIV infections.
A prevention plan is mandatory to minimize the risk of accidents. Every laboratory should perform a risk assessment in order to evaluate which are the risks that could be encountered inside the laboratory. Risk assessment must take in account every material, every procedures, workers, environment and the different protective equipment. In the context of laboratory accidents, personnel training plays a key role: the workers are directly exposed to risk in case of emergency and they are the first operators involved in emergency maneuvers.

Laboratory Acquired Infections
Romualdo Grande

Laboratory-acquired infections due to a wide variety of bacteria, viruses, fungi, and parasites have been described. Although the precise risk of infection after an exposure remains poorly defined, surveys of laboratory-acquired infections suggest that Brucella species, Shigella species, Salmonella species, Mycobacterium tuberculosis, and Neisseria meningitidis are the most common causes. Infections due to the bloodborne pathogens (hepatitis B virus, hepatitis C virus, and human immunodeficiency virus) remain the most common reported viral infections, whereas the dimorphic fungi are responsible for the greatest number of fungal infections. Because of the increasing attention on the role of the laboratory in bioterrorism preparation, I discuss the risk of laboratory-acquired infection with uncommon agents, such as Francisella tularensis and Bacillus anthracis. Physicians who care for a sick laboratory worker need to consider the likelihood of an occupationally acquired infection while advising exposed laboratory workers about postexposure prophylaxis. In addition, physicians should be aware of the importance of alerting the laboratory if infection with a high-risk agent is suspected.

Introduction to Occupational Medicine
Angelo Moretto

The aims of occupational medicine are the identification of health risks in the workplace, health surveillance of workers, diagnosis and treatment of occupational diseases, and in collaboration with professionals with other expertise (e.g. engineers, chemists, industrial hygienists, psychologists) participation to training programs and activities of risk management measures. Over the year, a shift has been observed in the attitude towards health and safety in the workplace. From the XVIII century Bernardino Ramazzini’s first textbook on occupational diseases to the modern legislation, the active involvement of the workers has been increased. In fact, in the XXI century workers are required to actively participate in the management of health and safety in the workplace. This has two consequences: on one hand workers are entitled to provide suggestions and participate in the planning of the activities related to their health and safety through their representatives; on the other hand workers also became responsible and liable of their behaviour with respect to their and their co-workers’ health and safety.
Accidents (injuries) in the workplace, and occupational or work-related diseases are taken care of by specific insurance schemes, that may differ between countries, even within the European Union. According to the Organisation of Economic Co-operation and Development (OECD) “An occupational injury is any personal injury, disease or death resulting from an occupational accident; an occupational injury is therefore distinct from an occupational disease, which is a disease contracted as a result of an exposure over a period of time to risk factors arising from work activity”. Instead, the term occupational disease “is linked to the identification of a specific cause-effect relationship between a harmful agent and the affected human organism. However, it is not easy – and considerably more difficult than in the case of accidents – to prove that a disease is occupationally conditioned, i.e. caused by conditions at, not outside work”. Because of the difficulty in proving a disease to be occupational in origin, most countries have produced lists of prescribed occupational diseases. These are generally limited to those diseases where a strong cause-effect relationship has been proven. However, with the number of categories ranging from 50 to 90, national lists vary in terms of those diseases recognised as occupational. Recommended lists developed by the International Labour Organisation and the European Communities seem to have led only to limited degree of harmonisation. In addition, in certain countries, including Italy, the list is not prescriptive, and any worker can claim a disease as occupational or work-related provided that she/he is able to prove the causal relationship. Each country has different legislative approaches related to registration, notification, and compensation for occupational injuries or diseases and their health consequences.
The risks related to exposure to biological agents at work are subjects to an EU directive (2000/54/EC of 18 September 2025). This Directive has general provisions that have been implemented by local legislation in EU member Countries. General provisions of the directive include the definitions and the assessment of risks. Employers’ obligations including replacement, reduction of risks, information to authority, provision of adequate hygiene and individual protection devices, information and training of workers, compilation of a list exposed workers, active participation of workers, and notification to the competent authority. In addition, health surveillance, measures for the workplace, classification of biological agents based on their characteristics. The class of the biological agent will determine the different provisions that should be taken to protect the health and safety of the workers, and the consequent administrative, technical, preventive and sanitary measures.

BSL3: Agents & Specificities
Alessandra Lombardi, Alessandro Mancon

Microorganisms are internationally classified by a risk group (1,2,3,4).
Different microorganisms (viruses and bacteria) are reported as high priority agents that pose a threat to national security. They can be easily disseminated or transmitted person-to-person, cause high mortality, with potential for major public health impact, might cause panic and social disruption and require special public health preparedness.
For their diagnosis different methods are used: microscopy, molecular tests, antigens and antibodies.

BSL 3 agents pose a risk for operators and communities. For this reason, their manipulation requires dedicated measures, in order to minimize the occurrence of laboratory acquired infections and the spread among the population. Different national and international institutions (i.e.: WHO, CDC) provide indications to properly work with these agents.
BSL 3 facilities can serve both research and diagnostic purposes; obviously, differences related to these aims exist, mainly concerning the use of animal models.
BSL 3 laboratories are enclosed environments: air and fluids systems are dedicated and not shared with other areas; moreover, only authorized personnel can enter. Such a condition can be obtained with an engineering planning before the construction building phase. Regarding the work in the laboratory, specific rules indicate which standards that must be followed as regards: Personal Protective Equipment, safety cabinets, decontamination agents, work procedures. Also emergency situations must be considered: they need particular measures, not adopted in daily routine activity.
In the Laboratory of Clinical Microbiology, Virology and Bioemergencies (CLIMVIB) at ASST Fatebenefratelli Sacco, a BSL 3 facility is present: its use is strictly related to diagnostic purpose, without any animal specificity. The examples presented refer to clinical experience and depict a real-life situation: Biosafety rules and indications are adapted to CLIMVIB needs and they could differ from other institutions. Naturally, each institution must meet Biosafety principles, in order to prevent personnel infections, epidemic and/or pandemic and related panic in the communities.

BSL4: Agents & Specificities
Romualdo Grande, Davide Mileto

The number of Biosafety level 4 containment labs is increasing in the world. In early 1980’s only two of such facilities were operational in the US and now an increasing number of these are present worldwide.
New diseases associated with high mortality and morbility have been recently discovered, whereas others, as Ebolavirus in Africa, re-emerged abruptly in recent times as enormous outbreaks that caused a huge number of deaths. As a consequence of such a spreading, the workload of laboratories in the world that are able to handle this kind of response also augmented, revealing the necessity of improving the redistribution of resources in order to allow a significant growth of research and diagnosis on BSL4.
This lecture will provide a short overview of the characteristics of the viruses to be handled in BSL4 laboratories.

The facilities of biosafety level 4 (BSL4) are designed in order to manage biological agents belonging to risk group 4 and patients infected by such kind of agents.
The main feature of this facility is related with the need to avoid the infection of workers but also with the requirement to prevent the spread of the level 4 biological agents into the environment.
Different international guidelines (WHO or CDC guidelines) describe all the specificities and the correct standards of behavior to be adopted for the BSL4 facilities.
Among them surely the need to have always almost two workers inside of the laboratory and an external support team outside of the laboratory. Communication between the two different teams, internal and external of the laboratory, is mandatory in order to monitor all the different steps and procedures and to act in case of emergency. Laboratory protective clothing must be of the type with solid-front or wrap-around gowns, scrub suits, coveralls, head covering and, where appropriate, shoe covers or dedicated shoes. All the personal protective equipment must be decontaminated before being disposed of. The complexity of the structure makes it mandatory to organize periodic training also to cope with accidents or illnesses.
Different technical features are need for the BSL4 laboratory.
A negative pressure system inside the laboratory guarantees the primary containment. This condition is also provided thanks to the system of interlocked door necessary to enter and exit from the laboratory. The biosafety cabinet of level III are used inside the laboratory whereas supplies and materials are introduced through a double-door autoclave or fumigation chamber. A HEPA filter system cleans incoming and outgoing air flows including the air flow need to work with the positive pressure suit. All effluents from the suit area, decontamination chamber, decontamination shower, or class III biological safety cabinet must be decontaminated before final discharge.Emergency power and dedicated power supply lines must be provided.

HOW TO REACH L. SACCO UNIVERSITY HOSPITAL
Via G.B. Grassi 74
20157 Milano

Railroad link
Stop Milano Certosa (4 km distant to L. Sacco University Hospital)
-Suburban line S5 (Varese – Treviglio )
-Suburban line S6 (Novara – Treviglio)

Trams
-Line 12, 19 (end of line in front of L.Sacco University Hospital)

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