IBC Resources

Biosafety Manual

The purpose of this manual is to define the biological safety policies and procedures pertaining to research operations at Boston University and Boston Medical Center. These policies and procedures are designed to safeguard personnel and the environment from biologically hazardous materials and to comply with federal, state, and local regulatory requirements. All BU and BMC principal investigators and laboratory workers must adhere to the biological safety policies and procedures in the conduct of their research and the management of their laboratories.

Regulations

Boston Public Health Commission: Biological Laboratory Regulations

The Boston Public Health Commission Biological Laboratory Regulations govern labs using biological agents and recombinant DNA in the city of Boston.

Centers for Disease Control and Prevention

Provides more resources on biosafety guidelines, such as Biosafety in Microbiological and Biomedical Laboratories (BMBL).

Dual Use Research of Concern

The Dual Use Research of Concern Program is a focal point for the development of policies addressing life sciences research that yield information or technologies with the potential to be misused to threaten public health or national security.

NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules

The NIH guidelines provide the IBC with the standards that guide containment and safe reserach practices for recombinant DNA research. The Recombinant DNA Program promotes scientific advancement and safety in the conduct of basic and clinical recombinant DNA research.

Office of Biotechnology Activities (OBA)

The NIH Office of Biotechnology Activities (now under the Office of Science Policy or OSP) promotes science, safety, and ethics in the development of public policies in three areas: Biomedical Technology Assessment, Biosafety and Biosecurity.

Select Agents

Federal Select Agent Program

The Federal Select Agent Program is jointly comprised of the Centers for Disease Control and Prevention/Division of Select Agents and Toxins and the Animal and Plant Health Inspection Services/Agricultural Select Agent Program. The Federal Select Agent Program oversees the possession, use, and transfer of biological select agents and toxins which have the potential to pose a severe threat to public, animal, or plant health, or to animal or plant products.

Agricultural Select Agent Program

APHIS issues permits for the import, transit, and release of regulated animals, animal products, veterinary biologics, plants, plant products, pests, organisms, soil, and genetically engineered organisms.

Final rule on Possession, Use, and Transfer of Select Agents and Toxins

Provides current select agent regulations and official interpretation of a specific provision regarding the select agent regulations.

Minutes

IBC Meeting Minutes

Risk Group Definitions

The investigator must make an initial risk assessment based on the Risk Group of an agent. Agents are classified into four Risk Groups according to their relative pathogenicity for healthy adult humans by the following criteria: More information can be found in the Appendix B of NIH Guidelines.

Risk Group 1

Agents that are not associated with disease in healthy adult humans

Risk Group 2

Agents that are associated with human disease which is rarely serious and for which preventive or therapeutic interventions are often available.

Risk Group 3

Agents that are associated with serious or lethal human disease for which preventive or therapeutic interventions may be available (high individual risk but low community risk)

Risk Group 4

Agents that are likely to cause serious or lethal human disease for which preventive or therapeutic interventions are not usually available (high individual and high community risk)

As a general rule, a biosafety level (BSL) should be used that matches the highest risk group classification of the agents involved.

Where to find the risk group of a specific pathogen?

US Department of Health and Human Services Risk Group Classification for Infectious Agent

Public Heath Agency of Canada Pathogen Safety Data Sheets and Risk Assessment

NIH OBA NIH Guidelines (Appendix B)

Glossary

Abandoned Laboratory: A clinical or research laboratory that is left vacant by a Principal Investigator or Laboratory Director and his or her laboratory staff, and has laboratory materials (biological, surplus chemical, radioactive), equipment or waste that has not been disposed of.

ABSL-2: Animal Biosafety Level 2 includes pathogenic agents of moderate hazard potential (CDC Biohazard Class 2) and chemical hazard agents of moderate hazard potential.

Associate Vice President, Research Compliance (AVP-RC):the individual responsible for overall research compliance oversight at BU.

Attenuated Strain: A debilitated, weakened or less virulent virus, bacteria or other pathogen

Biohazardous Material: Biohazardous materials and organisms include all infectious agents or biologically derived infectious materials that present either a risk or a potential risk to the health of humans or animals, either directly through infection or indirectly through damage to the environment.

• all human, plant, and animal pathogens
• all human blood, blood components and products, tissues and body fluids
• all human and animal cultured cells
• all infected animals and animal tissues
• all cultures/stocks of biological agents, including recombinant DNA material
• all biological toxins
• biomedical waste
• physically dangerous (sharp) waste

Biological products: those products derived from living organisms manufactured and distributed in accordance with the requirements of national governmental authorities (e.g., the FDA). They may have special licensing requirements and are used either for prevention, treatment, or diagnosis of disease in humans or animals, or for developmental, experimental, or investigational purposes related thereto.

Biological products manufactured and packaged in accordance with the requirements of appropriate national authorities; transported for the purposes of final packaging or distribution; and for personal health-care use by medical professionals are NOT subject to dangerous goods regulation. However, biological products not governed by national authorities and that are known or reasonably believed to contain infectious substances MUST be classified and shipped according to dangerous goods regulations.

Biological Safety Officer (BSO): An individual appointed by the institution to oversee management of Biosafety risks.

Biological Use Authorization (IBC Application)

Biosafety Level 3 (BSL-3): Classification of clinical, diagnostic, teaching, research, or production facilities where work is performed with indigenous or exotic agents that may cause serious or potentially lethal disease through the inhalation route of exposure. Laboratory personnel must receive specific training in handling pathogenic and potentially lethal agents, and must be supervised by scientists competent in handling infectious agents and associated procedures.

Biosafety Manual: The purpose of this manual is to define the biological safety policies and procedures pertaining to research operations at Boston University and Boston Medical Center. These policies and procedures are designed to safeguard personnel and the environment from biologically hazardous materials and to comply with federal, state, and local regulatory requirements. All BU and BMC Principal Investigators and laboratory workers must adhere to the biological safety policies and procedures in the conduct of their research and the management of their laboratories.

Boston Public Health Commission (BPHC)

Biological Safety Level (BSL): A description of the degree of physical containment and work practices employed to confine organisms containing recombinant DNA molecules and biohazardous materials and to reduce the potential for exposure to laboratory workers, persons outside of the laboratory, and the environment.

Completely Exempt Substances: materials that are totally exempt for consideration under the shipping regulations:

• Substances containing micro-organisms that are non-pathogenic to humans or animals
• Substances in a form so that any present pathogens have been neutralized or inactivated such that they no longer pose a health risk (Chemical itself may be regulated – Contact EHS prior to shipping)
• Environmental samples (including food and water samples) that are not considered to pose a significant risk of infection, and
• Dried blood spots, collected by applying a drop of blood onto absorbent material, fecal occult blood screening tests, blood or blood components intended or prep to be used for transfusion, and tissues or organs intended for transplantation.

Dangerous goods: articles or substances capable of posing significant risk to health, safety, property, or the environment when transported by surface or air. Most infectious or biological materials are considered dangerous goods and therefore are subject to shipping regulation.

Decommissioning: The process whereby a Principal Investigator or Laboratory Director and his or her laboratory staff decontaminate existing laboratory space and make a clinical or research laboratory safe prior to vacating the space.

Decontamination: The process whereby the Principal Investigator or Laboratory Director and his or her laboratory staff clean and disinfect laboratory surfaces and equipment so they are safe to handle.

Derivatives: Broadly defined as dead cells, DNA, RNA, proteins, and any other products secreted by or extracted from human embryonic stem cells.

Dry Ice: Commonly used a refrigerant.

DURC (Dual Use Research of Concern): The National Science Advisory Board for Biosecurity (NSABB) has defined Dual Use Research of Concern (DURC) as: “research that, based on current understanding, can be reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health and safety, agricultural crops and other plants, animals, the environment or materiel”.

An excellent short video discussing DURC is posted on the Biosafety and Biosecurity Policy website. All investigators are strongly recommended to view the video for a better understanding the issues.

EHS Director: the Director of Research Safety in the EHS of Boston University.

Environmental Health and Safety (EHS): Environmental Health and Safety’s mission is to provide a safe environment for students, employees, faculty, and staff as well as patients and others visiting our facilities and to help ensure compliance with federal, state, and local codes and regulations, in accordance with the Boston University Statement of Commitment to Environmental Health & Safety.

Environmental Health and Safety (EHS) comprises Campus & Clinical Safety, Emergency Response Planning, Environmental & Waste Management, Medical Physics, Radiation Safety, and Research Safety. These five divisions provide a full range of environmental, health, and safety services to the Boston University and Boston Medical Center communities.

Exempt Patient/Animal Specimens: patient or animal specimens for which there is a minimal likelihood that pathogens are present are exempt from most of the shipping regulations. However, they must be marked with the words “exempt human specimen” or “exempt animal specimen” and must be triple-packed as described below.

Expose or Exposure: any situation arising from, or related to, the work operation where an employee or community resident may ingest, inhale, absorb through the skin or eyes, or otherwise come into contact with any high-risk agent.

• Overt Exposure: a definitive contact with a Biosafety Level 2 (BSL-2) or higher recombinant biological agent. Examples of overt exposures include, but are not limited to:
  • needle sticks
  • splashes of rDNA agent on personnel
• Potential Exposure: a possible personal contact with a Biosafety Level 3 (BSL-3) or higher recombinant biological agent. Examples of potential exposures include, but are not limited to:
  • BSL- 3 or higher accidents,
  • equipment failure,
  • splash to intact skin

Genetically Modified Micro-Organism/Organisms (GMMO/GMO): materials in which genetic materials have been altered through genetic engineering which does not occur naturally.

High–Risk Agent: a select agent, defined as:

• Agents in Risk Group (RG) 4 as specified in the National Institute of Health’s Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules and Biosafety in Microbiological and Biomedical Laboratories 5th edition, published by the Centers for Disease Control and Prevention and the National Institutes of Health and the amendments and rulings made relative thereto from time to time.
• Highly pathogenic avian influenza
• SARS Co–V
• Any other agent identified by the Director of BPHC on a list to be posted on the BPHC

Hypodermic needles: syringes, blades, and needles with attached tubing

Inactivation: A process that documents the absence of infectious particles.

Infectious substances: substances known or reasonably expected to contain pathogens. Pathogens are defined as micro-organisms (including bacteria, viruses, rickettsiae, parasites, fungi) and other agents, such as prions, which can cause disease in humans or animals. For the purposes of shipping classification, infectious substances are broken into two categories:

• Category A: an infectious substance transported in a form that, when exposure to it occurs, is capable of causing permanent disability or life-threatening or fatal disease in otherwise healthy humans or animals.
• Category B: an infectious substance that does not meet the criteria for inclusion in Category A.

Institutional Biosafety Committee (IBC): An institutional committee created under the NIH Guidelines to review research involving recombinant DNA and/or biohazardous materials.

Institutional Review Board (IRB): The Committee with the responsibility for review and approval of all human subject research at BU and BMC that is subject to the HHS definition of “human subject research.”

Laboratory Safety Training (LST)

Medical Surveillance: the systematic assessment of employees exposed or potentially exposed to occupational hazards. This assessment monitors individuals for adverse health effects and determines the effectiveness of exposure prevention strategies. A medical surveillance program includes the analysis of both individual and aggregate surveillance data over time, with the goal of reducing and ultimately preventing occupational illness and injury.

NEIDL (National Emerging Infectious Disease Laboratories): The National Emerging Infectious Diseases Laboratories (NEIDL) is part of a national network of secure facilities studying infectious diseases that are—or have the potential to become—major public health concerns. The laboratories are dedicated to the development of diagnostics, vaccines, and treatments to combat emerging and re-emerging infectious diseases. In addition to BSL-2 and BSL-3 laboratories, the NEIDL houses a BSL-4 laboratory. The NEIDL adds to the growing life sciences industry in the region, throughout the Commonwealth of Massachusetts, and across the country.

NIH Human Embryonic Stem Cell Registry: These are hESC lines that are listed by the NIH in their registry as those eligible for federal funding and are also referred to as the Registry hESC lines.

NIH – OBA (NIH Office of Biotechnology Activities): The NIH office responsible for developing, implementing, and monitoring NIH policies and procedures for the safe conduct of recombinant DNA activities, including human gene transfer.

NIH – RAC (NIH Recombinant DNA Advisory Committee): An NIH advisory committee whose principal role is to provide advice and recommendations to the NIH Director on:

• Conduct and oversight of research involving recombinant DNA, including the content and implementation of the NIH Guidelines, and;
• Other NIH activities pertinent to recombinant DNA technology.

A major element of this role is to examine the science, safety, and ethics of clinical trials that involve the transfer of recombinant DNA to humans.

Occupational Health Officer (OHO): the physician(s) who is the Occupational Health Officer of ROHP at Boston University. The Occupational Health Officer may also name a designee to perform occupational health assessments or evaluations, provided that the designee is also a licensed physician experienced in occupational medicine or a registered nurse experienced in occupational health nursing.

Other potentially infectious materials (OPIM):

• Semen
• Vaginal secretions
• Cerebrospinal fluid
• Synovial fluid
• Peritoneal fluid
• Amniotic fluid
• Saliva in dental procedures
• Body fluid that is visibly contaminated with blood and all body fluids in situations where it is difficult or impossible to differentiate between body fluids.

Parenteral: Taken into the body or administered in a manner other than through the digestive tract, as by intravenous or intramuscular injection.

Human, Animal, and Plant Pathogens:

• viruses, including oncogenic and defective viruses (includes viral vectors)
• Rikettsiae
• Chlamydiae
• bacteria, including those with drug resistance plasmids*
• fungi
• parasites
• undefined or other infectious agents, such as prions
• toxins (bacterial, fungal, plant)
• All human blood, blood components and products, tissues and body fluids
• Cultured cells (all human and non-human primates) and potentially infectious agents these cells may contain
• Animals or animal tissues that may transmit zoonotic or human pathogens designated at BL-2 or higher
• Non-human primates and any tissues derived therefrom
• Sheep and any tissues derived therefrom

*Lab K-12 strains of E-coli are not included

PPE: Personal protective equipment

Purchased Services: Professional contract services; such as the services of consultants, laborers, or maintenance and repair technicians.

Qualified Vendor: A vendor who meets or exceeds the criteria in Section 6.

Receiver: The receiver, for the purposes of this policy, is the individual who receives the package. This individual is required to have shipping training. The receiver notifies the shipper upon receipt of the planned delivery of high-risk material.

Recombinant DNA Molecules: In accordance with the NIH Guidelines, recombinant DNA are molecules constructed outside of living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or molecules that result from their replication.

Regulated waste: liquid or semi-liquid blood or other potentially infectious materials and contaminated items that would release blood or other potentially infectious material in a liquid or semi-liquid state if compressed; items that are caked with dried blood or other potentially infectious materials and are capable of releasing these materials during handling; contaminated sharps; and pathological and microbiological wastes containing blood or other potentially infectious materials.

Research Laboratory: a workplace or a work area of a workplace that is used primarily for research, development, non–routine testing, or experimentation activity in which any high-risk agent is used by or under the direct supervision of a technically qualified individual.

Research Occupational Health Program (ROHP): The Boston University Research Occupational Health Program provides prevention, diagnosis, and treatment for work-related injuries and illnesses for the employees of Boston University in compliance with OSHA, CDC, and other regulatory requirements.

The Institutional Biosafety Committee requires that all investigators and their research personnel register with the Research Occupational Health Program (ROHP), by completing the Initial Health Questionnaire.

Select Agents: Biological agents and toxins that have the potential to pose a threat to public health and safety if used for bioterrorism purposes. The list includes over 80 bacteria, viruses, toxins, rickettsia, and fungi. The program is regulated by the Department of Health and Human Services (DHHS) and Department of Agriculture (USDA) under the Federal Regulation for Select Agents [42 CFR 73.0; 7 CFR 331; 9 CFR 121].

Sharps waste: any device having acute rigid corners, edges, or protuberances capable of cutting or piercing, including, but not limited to, all of the following:

• Hypodermic needles, syringes, blades, and needles with attached tubing
• Broken glass items, such as Pasteur pipettes and blood vials contaminated with other medical waste

Shipper: The shipper is the person who packages the subject material and signs the shipper’s declaration form. This person is responsible for the material to be classified, identified, packaged, marked and labeled, with all appropriate documentation included with the package. This individual is required to have shipping training, and notify the receiver regarding the planned shipment of high-risk material.

Shippers Declaration Form: The documentation that a high-risk material will be shipped. These documents will be maintained in accordance with all laws, regulations and BU policies including standards for the maintenance of original forms to be maintained by the shipper, the transporter and the receiver.

Subject Materials: A substance or material in a quantity and form that may pose a high level of risk to health, safety or property when received, transported and/or stored. These materials include, but are not limited to, toxic/infectious substances (including select agents), radioactive materials, chemicals, compressed gases, and any other materials that EHS deems a material that should be managed throughout its transport.

Tenant and Licensee Companies

• USDA/APHIS

Transgenic rodents: Rodents (typically mice or rats) in which the animal’s genome has been altered by stable introduction of recombinant or synthetic nucleic acid molecules, or nucleic acids derived therefrom into the germ-line.

Transporter: The transporter is the individual, operator or contracted service that obtains the package from the shipper, verifies it has been packaged correctly, and carries the package to the receiver.

Wild Type Strain: A strain found in nature or a standard strain.

Work Area: a defined space, or a room or rooms, or other area where infectious agents or substances are produced, stored, or used, and where employees are present in the course of their employment. A work area may include an entire workplace.

Workplace: an establishment or business of an employer at one geographic location at which work is performed and containing one or more work areas.