IBC Oversight

Biosafety levels categorize laboratory activities and facilities based on the level of risk posed by biological agents. These levels help in establishing appropriate containment measures to minimize the risk of exposure to laboratory personnel, the community, and the environment. There are four biosafety levels, each characterized by specific combinations of laboratory practices, safety equipment, and facilities tailored to the potential hazards posed by the agents being handled. These levels range from BL1 (minimal risk) to BL4 (highest containment), with each level imposing progressively stringent requirements for specific laboratory practices, safety equipment, and facilities. For example, BL1 facilities typically handle well-characterized agents not known to cause disease in healthy adults, while BL4 facilities are designed to handle dangerous pathogens requiring maximum containment measures.

Biosafety Level 1 (BL1):

BL1 facilities are suitable for handling agents that pose minimal risk to personnel and the environment. Agents are well-characterized, not known to cause disease in immunocompetent adult humans, and present minimal potential hazard to laboratory personnel and the environment. BSL-1 laboratories are not necessarily separated from the general traffic patterns in the building. Work is typically conducted on open benchtops using standard microbiological practices. Special containment equipment or facility design is not generally required but may be used as determined by appropriate risk assessment. Laboratory personnel receive specific training in the procedures conducted in the laboratory and are supervised by a scientist with training in microbiology or a related science.

Biosafety Level 2 (BL2): 

BL2 facilities are designed for handling agents associated with human disease and pose moderate hazards to personnel and the environment. These facilities incorporate additional safety measures such as controlled access, biological safety cabinets (BSCs) for working with aerosols, and enhanced waste management procedures. BSL-2 differs from BSL-1 primarily because: 1) laboratory personnel receive specific training in handling agents and are supervised by scientists competent in handling agents and associated procedures; 2) access to the laboratory is restricted when work is being conducted; and 3) all procedures in which infectious aerosols or splashes may be created are conducted in BSCs or other physical containment equipment.

UMassD works only with materials/agents classified as BSL2 or lower

Biosafety Level 3 (BL3):

BL3 facilities are required for handling agents that may cause serious or potentially lethal diseases through inhalation route of exposure. These facilities feature specialized engineering controls such as negative pressure rooms, double-door access systems, and dedicated exhaust systems to prevent the release of infectious aerosols. Applicable to clinical, diagnostic, teaching, research, or production facilities in which work is conducted with indigenous or exotic agents which may cause serious or potentially lethal disease as a result of exposure by inhalation. Personnel must receive specialized training in handling agents, adhere to strict decontamination procedures, and must be supervised by competent scientists who are experienced working with these agents. All procedures are conducted within biosafety cabinets or other physical containment devices and personnel must wear appropriate PPE.

Biosafety Level 4 (BL4):

BL4 facilities represent the highest level of containment and are reserved for handling dangerous and exotic agents that pose a high risk aerosol-transmitted laboratory infections and life-threatening diseases that are frequently fatal, agents for which there are no vaccines or treatments, or work with a related agent with unknown risk of trans­mission. Agents with a close or identical antigenic relationship to agents requiring BSL-4 containment are handled at this level until sufficient data are obtained to re-designate the level. Laboratory staff receive specific and thorough training in handling extremely hazardous infectious agents. Laboratory staff understand the primary and secondary containment functions of standard and special practices, containment equipment, and laboratory design characteristics. All laboratory staff and supervisors are competent in handling agents and procedures requiring BSL-4 containment. The laboratory supervisor controls access to the laboratory in accordance with institutional policies. These facilities employ the most stringent containment measures, including complete personal protective equipment (PPE) suits with supplied air, stringent entry and exit procedures, and highly controlled laboratory environments to prevent any possibility of escape of infectious agents. Only authorized persons are allowed to enter and work in the area and must follow stringent guidelines for safety.

Understanding the potential hazards posed by biological agents, the characteristics, and classifications of risk groups is crucial for implementing appropriate containment measures and ensuring the safety of laboratory personnel and the surrounding environment. Biological agents are categorized into four risk groups (RG) based on their pathogenicity to a healthy human adult. These risk groups provide a framework for assessing the potential risks associated with handling biological materials.  Assessments are based on the Risk Group (RG) of an agent, which determines the precautions needed to handle it safely.

Risk Group 1 (RG1):

RG1 agents pose minimal risk to laboratory personnel and the environment and are not associated with disease in healthy adult humans. They are unlikely to cause disease in healthy individuals and typically include well-characterized microorganisms with low pathogenicity. Examples of RG1 agents may include non-pathogenic bacteria and viruses commonly found in laboratory settings.

Risk Group 2 (RG2):

RG2 agents pose a moderate risk to laboratory personnel and the environment. They may cause mild to moderate disease in humans but are unlikely to spread rapidly or cause significant outbreaks. RG2 agents are associated with human disease, which is rarely serious and for which preventative or therapeutic interventions are often available. RG2 agents require appropriate containment measures and safety precautions, including personal protective equipment (PPE) and facility controls. Examples of RG2 agents may include certain bacteria, viruses, and fungi known to cause human disease, such as influenza viruses and Salmonella spp.

Risk Group 3 (RG3):

RG3 agents pose a significant risk to laboratory personnel and the environment. They may cause severe or potentially lethal disease in humans and have the potential for spread within the community and for which preventative or therapeutic interventions may be available (high individual risk but low community risk).  RG3 agents require stringent containment measures, including specialized facilities with controlled access, containment equipment, and enhanced biosafety practices. Examples of RG3 agents may include highly pathogenic bacteria, viruses, and parasites, such as Mycobacterium tuberculosis and Ebola virus.

Risk Group 4 (RG4):

RG4 agents pose the highest risk to laboratory personnel and the environment. They may cause severe or life-threatening disease in humans and have the potential for widespread transmission and significant public health impact and for which preventative or therapeutic interventions are not usually available (high individual risk and high community risk). RG4 agents require maximum containment measures, including high-level biosafety laboratories (BSL-4) with strict access controls, specialized engineering controls, and rigorous safety protocols. Examples of RG4 agents may include highly virulent viruses such as Ebola virus and Marburg virus.

Human etiologic agents, also known as pathogens, are classified into various hazard groups based on their potential risk to human health and safety. This classification system provides a framework for assessing the level of risk posed by different agents and implementing appropriate containment measures to mitigate potential hazards. The following is a summary of the hazard groups commonly used in biosafety and biosecurity practices:

Hazard Group 1 (HG1):  HG1 Agents pose minimal risk to human health. They are unlikely to cause disease in healthy individuals and do not typically spread from person to person.

Hazard Group 2 (HG2): HG2 Agents pose a moderate risk to human health. They may cause mild to moderate disease in humans, but the risk of transmission is limited. Proper handling and containment measures are required to prevent accidental exposure.

Hazard Group 3 (HG3): HG3 Agents pose a significant risk to human health. They may cause severe or potentially lethal disease in humans and have the potential for spread within the community. Enhanced containment measures are necessary to prevent exposure and minimize the risk of transmission.

Hazard Group 4 (HG4): HG4 Agents pose the highest risk to human health. They may cause severe or life-threatening disease in humans and have the potential for widespread transmission and significant public health impact. Maximum containment measures are required to prevent accidental exposure and contain outbreaks.

Involves research that presents minimal risk and does not fall under NIH Guidelines requiring higher levels of review. The risks are well-understood, and the materials used are generally considered safe for humans and the environment. Includes certain types of research using exempt quantities of recombinant DNA, non-hazardous biological agents, or materials that pose no significant risk to humans, animals, or the environment.

Examples:

• Recombinant DNA: Use of non-replicating recombinant DNA in E. coli K12 or other organisms recognized as safe (e.g., use of cloning vectors in strains of E. coli that are non-pathogenic).
• Bacterial cultures: Working with non-pathogenic bacterial strains (e.g., Lactobacillus acidophilus) for fermentation or probiotic research.
• Yeast or fungi: Experiments involving Saccharomyces cerevisiae (common yeast) in food science studies that are not intended to pose a biohazard risk.
• Environmental samples: Studies analyzing environmental samples (e.g., soil or water) that do not contain harmful biological agents and pose no risk of contamination.

Review Process: Exempt submissions are reviewed via Non-Committee Review by the IBC Chair, RO, and BSO. The IBC Chair may assign a designated reviewer to participate in the review if necessary. There is no requirement for a full committee review, once the reviewers agree the criteria of approval are met, and approval letter is issued.

Involves research that presents moderate-risk biohazardous materials or agents where the risks are well understood and manageable. Typically involves BSL-1 research, where proper containment and handling can mitigate risk.

Examples:

• BSL-1 organisms: Work with Risk Group 1 organisms such as Bacillus subtilisor Escherichia coli K12, which are known to be non-pathogenic under standard lab conditions.
• Inactivated viral vectors: Use of replication-incompetent viral vectors, such as adenovirus or lentivirus in cells, provided they don’t express harmful genes.
• Plasmid work: Work with plasmids expressing genes that are non-toxic or non-infectious in bacterial systems like E. coli or yeast.
• Human cell lines: Non-viral transfection of human cell lines (e.g., HEK293 cells) that are non-cancerous and do not pose a risk of human infection.
• Synthetic nucleic acids: Work with synthetic RNA that does not replicate or code for infectious agents or toxins.
• Minor amendments: Changes to the protocol that do not increase the risk level, such as adding new personnel, small changes to lab procedures or timeline, modifying non-biohazardous reagents. Minor amendments do not apply to changes in biosafety levels, biohazard management, or biocontainment measures. Minor amendments are NOT for changes in any of the following: approved management of biohazards, accidental exposure plans, changes in biosafety levels, changes in work location, or biocontainment and biosafety precautions.
• Annual Continuing Review: Ongoing research projects involving biohazards must undergo periodic review to ensure that safety protocols are still being followed and that there have been no significant changes. The PI must report the study’s status annually to the IBC, confirming:
• No incidents or noncompliance have occurred.
• No new amendments or changes to the protocol are required.
• Whether the study remains active or if closure is planned.

Review Process: The review is based on a predefined risk assessment and containment strategies, following NIH Guidelines and institutional biosafety policies. Expedited submissions are reviewed via Non-Committee Review by the IBC Chair, RO, and BSO. The IBC Chair may assign a designated reviewer to participate in the review if necessary. There is no requirement for a full committee review, once the reviewers agree the criteria of approval are met, and approval letter is issued. 

Research that has the potential to be misused in a way that poses significant risks to public health, agriculture, the environment, or national security. DURC typically involves experiments that could be used for harmful purposes beyond the scope of their intended research.

Examples:

• Pathogen enhancement: Experiments involving gain-of-function mutations in viruses like H5N1 (avian flu) or SARS-CoV-2 that could increase transmissibility or virulence.
• Toxin production: Research that enhances the production of botulinum toxin, or other select agents that could be misused for biological warfare or terrorism.
• Resistance mechanisms: Studies that involve engineering organisms with resistance to antibioticsor antiviral drugs in a manner that could be exploited to undermine public health.

Review Process: This is a specialized review that requires a higher level of scrutiny and may involve both the IBC and additional oversight from institutional or federal bodies. DURC protocols are reviewed with the potential for misuse in mind to ensure risk mitigation strategies, such as limiting dissemination of findings, are in place. Federal guidance and additional reporting to agencies like the NIH or CDC may be required. The protocol must be reviewed via Committee Review at a convened IBC meeting.

Full committee review is required for research that poses significant risks, involving hazardous biological agents, infectious organisms, recombinant DNA, or synthetic nucleic acid molecules which pose a potential for significant risks to human health, the environment, or safety concerns requiring stricter oversight. The research is typically conducted in BSL-2 containment environments. 

Examples:

• Risk Group 2 organisms: Research involving pathogens like Salmonella typhimurium, Staphylococcus aureus, or Herpes simplex virus, which can cause disease in humans.
• BSL-2 containment: Studies involving adenovirus or lentivirus for gene expression in human cells, where the vectors pose moderate risks but are unlikely to cause widespread harm.
• Animal research with rDNA: Experiments that involve generating or using transgenic animals or modifying the genome of animals using recombinant DNA or CRISPR techniques.
• In vivo studies with recombinant DNA: Animal studies where mice or rats are injected with recombinant adenovirus to study gene function or disease models, with a moderate risk of exposure to lab personnel.
• Human-derived materials: Experiments involving human blood, tissues, or primary cell cultures, which may potentially carry bloodborne pathogens such as hepatitis B (HBV) or HIV.
• Human gene therapy: Trials involving gene editing technologies such as CRISPR or viral vector delivery in human subjects, including treatments for genetic disorders (e.g., research on adeno-associated viruses (AAV) for gene delivery).
• Dual-use research: Projects involving organisms or toxins that could potentially be weaponized, such as anthrax (Bacillus anthracis) or the H5N1 influenza virus.
• CRISPR gene editing: Research involving CRISPR/Cas9 techniques to modify genes in human cell lines, which carries risks related to the potential off-target effects or unintended mutations.
• Major amendments: Significant changes to the protocol that increase risk, such as changing the organism used in research, increasing the biosafety level/containment, introducing new hazardous materials, or for changes in any of the approved: management of biohazards, accidental exposure plans, or work location.

Review Process: The review is based on a predefined risk assessment and containment strategies, following NIH Guidelines and institutional biosafety policies. The protocol must be reviewed via Committee Review at a convened IBC meeting. The full committee assesses risks, containment levels, adequacy of safety measures, training of personnel, and emergency response plans for accidental exposures. The IBC may request additional information or modifications before approval to ensure regulatory compliance.

Amendments:

Prior to implementing any changes or modifications that impact the approval category, risk, population, study funding, or Principal Investigator (PI), the PI must obtain IBC approval for the amendments.

Minor Amendments:

Minor amendments do not apply to changes in biosafety levels, biohazard management, or biocontainment measures and do not increase the risk to personnel, the public, or the environment. Examples include:

• Adding trained personnel to an approved project.
• Minor procedural changes that do not alter the risk profile.
• Addition of agents, vectors, or cell lines that require the same or lower biosafety levels.
• Adjustments in the experimental timeline.

Note: A minor amendment form must be submitted for small changes to an already approved registration before any changes can be made.  The designated reviewer assesses the changes, and if there are no objections from other IBC members, the amendment is approved. Documentation of the expedited review is recorded in the meeting minutes.

Major Amendments:

Major amendments involve significant changes to an approved protocol that may increase biosafety risks or require a higher level of containment and require a full committee review for the:

• Introduction of new biohazardous agents or recombinant DNA materials.
• Increase of the risk group classification of the biological agents.
• Substantial changes to the scope or design of the research that affect biosafety.
• Addition of a new facility that requires reevaluation of containment measures.

Note: The process for major amendments follows the full committee review procedure. These amendments require review during a convened meeting, with discussion focused on ensuring appropriate risk containment and compliance with biosafety standards.

Annual Continuation Reporting:

Annually, the PI is required to report to the IBC the study status; to confirm the research is still in compliance with biosafety standards, no new incidents, deviations, or noncompliance have occurred, no changes are required, and whether the study remains active, or study closure is planned. The IBC notifies the PI 60 days prior to the annual check-in deadline to ensure timely submission of the status report.

Continuation Post Expiration:

IBC registrations are approved for three years; the expiration date is included in the approval letters. PI’s are notified 60 days prior of the upcoming expiration date. PIs who wish to continue their research projects beyond the three-year term should plan to submit a new registration for review before the expiration date. Any active protocol approved by Committee Review must be reviewed via Committee Review to obtain approval for its continuation. In certain cases, a protocol that previously received approval via Committee Review can go through an Expedited Review if it meets one of the following conditions:

• All research-related activities involving biohazardous materials have been completed.
• The research remains active only for long-term data analysis without additional risks identified.

New Information, Unanticipated Problems, Incident Reports, and Risk Safety Assessments:

PIs must promptly report any new information, incident, risk/safety assessment, or unanticipated problems that may affect the risk to personnel or the environment to the IBC. This includes any findings that may impact ongoing research, or the welfare of personnel involved. The PI must submit a report detailing the nature of the new information or unanticipated problem, the potential impact on the research, and any proposed changes to the protocol. Provide a detailed account of the event should be included, documenting the date, time, location, individuals involved, and an evaluation of the associated risks and potential impacts on personnel, the environment, and ongoing research. This should assess whether the incident was accidental, anticipated, unanticipated, related to the research, or unrelated to the research. Documentation of how information about the incident was communicated to relevant stakeholders, including staff, the institutional biosafety committee, and Environmental Health and Safety (EHS), should also be provided. If noncompliance is reported, justification for why it was necessary for safety reasons, including any protocol deviations required to prevent harm or ensure safety, should be included. Outline the measures taken or proposed to address the incident, prevent recurrence, and ensure safety, along with plans for ongoing monitoring and assessment of the effectiveness of these actions. This section should also include documentation of any follow-up investigations or evaluations conducted after the incident to ensure compliance and safety.

Note: All submissions should include relevant documentation, outline revisions and/or new information within submission documents, include new vector maps, MSDS, reference publications, reports, etc.

Please report the following items to the IBC within 5 business days of discovery. If unsure, contact the IBC.

1. New Funding and Financial Conflicts of Interest
   • Types of Reports: New financial conflicts of interest or changes in funding affecting the study’s integrity.
   • IBC Review Process: Expedited or Committee Review to evaluate potential impacts on research objectivity and safety.
2. New or Increased Risk/Safety Issues and Protocol Deviations
   • Types of Reports: New information indicating increased or new risks, protocol violations or deviations that harm personnel or increase their risk, and participant complaints indicating new risks. Any changes significantly increasing the risk to personnel and affecting the research conduct, including deviations from the approved protocol.
   • IBC Review Process: Full Committee Review to evaluate the severity and impact of the risk or deviation on safety and study conduct.
3. Unexpected Harm Related to Research
   • Types of Reports: Harm that is unexpected based on previously reviewed risk information. This includes serious adverse effects on health or safety, life-threatening problems, or death associated with a procedure not previously identified.
   • IBC Review Process: Full Committee Review to evaluate the severity and relevance of the harm.
4. Compliance and Data Integrity Issues
   • Types of Reports: Noncompliance with federal regulations or IBC requirements, inspection audit reports, issues affecting the integrity or validity of research data, including potential falsification or manipulation.
   • IBC Review Process: Full Committee Review to evaluate the nature, severity, and impact of the compliance and data integrity issues.
5. External Reports
   • Types of Reports: Early suspension or termination of the study by the sponsor, investigator, or institution, findings from additional regulatory bodies, significant participant complaints related to study procedures or safety.
   • IBC Review Process: Full Committee Review to evaluate the circumstances, address additional regulatory findings, and assess the impact on participants.

The IBC cannot retrospectively approve research. Please do not begin non-exempt research without IBC approval. Approved IBC protocols that deviate from the policies, procedures, or stipulations of the IBC are subject to further inquiry by the IBC. The IBC may send a notice requesting the suspension of all research activities while the issue of noncompliance is reviewed, consistent with federal mandates. This initial notice will also include a rationale for the IBC's action. The IBC will investigate allegations of noncompliance.

Areas of Noncompliance IBC Inquiry Review:

• Category of Review: Determine if the study was approved via Exempt Review or Full Committee Review.
• Type and Nature: Identify whether the noncompliance is general, serious, or continuing.
• History of Noncompliance: Review the noncompliance history of the PI and any collaborators.
• Deviation and Implications: Assess specific deviations observed and evaluate how investigators deviated from the approved protocol or failed to adhere to IBC procedures. Consider the context of these deviations and their impact on research integrity.
• Reporting: Evaluate how and when the event was reported to the IBC, including the submission of final reports and corrective action plans.
• Corrective Actions: Assess actions taken to address and mitigate noncompliance, including necessary revisions to the protocol. Evaluate plans for training or re-training research staff on procedures and practices to prevent recurrence.
• Preventive Actions: Examine changes made to processes or systems designed to prevent similar issues in the future, including how feedback will be collected and addressed.

Noncompliance Process

Allegation:

1. Concerns about possible Noncompliance can be raised by RO, BSO, IBC Chairs, IBC members, investigators, subjects, or others. Concerns not raised by a DIEC should be forwarded to a DIEC for initial determination.
2. The RO may determine if the concern constitutes General Noncompliance or warrants further inquiry. Concerns determined to be greater than General Noncompliance are considered allegations and are forwarded to the Chair for review.

Allegations prompt investigations led by the IBC Chair, RO, BSO, and/or an EHS representative to gather information through:

• Unannounced visits to the laboratory or facility.
• Review of laboratory procedures, IBC registrations documents, and all other relevant lab/facility documents (including records pertaining to material purchases and research records);
• Interviews with the Principal Investigator (PI), laboratory personnel, and any other individual who might provide information.
• Consultation with experts in the area of research to make definitive, unbiased, and educated decisions regarding a potential violation.
• Assistance from other IBC members in collection of information.

Investigation:

1. RO and BSO conduct the Investigation, contacting relevant individuals for verification of facts.
2. Once sufficient information is available regarding the allegation, a report is prepared for committee review.
3. The Chair or convened IBC may accept, reject, or modify DIEC’s findings and recommendations report. Corrective actions may include changes to the research protocol, required training, research restrictions, subject notification, data destruction, publication disallowance, oversight monitoring, or protocol suspension/termination.
4. The Convened IBC, Chair, or RO can make a final determination, including severity and corrective actions, will be documented in the IBC meeting minutes.
5. A Final Report reflecting the IBC’s final determinations is sent to the IO. If Noncompliance is found, the Report is sent to Need to Know Individuals; if not, it is provided only to the Respondent.

Outcome:

1. If the Respondent disagrees with the Final Report, they may notify the IO, RO, and IBC Chair, to request an appeal citing reasons for disagreement within 30 days. The IBC Chair or RO can make the final decision, in consultation with the IO, as necessary.
2. If the PI agrees with the Final Report or after the IBC’s final decision, the DIEC or IBC Chair ensures the corrective and preventive action plan is implemented. If necessary, a notice of closure is sent to Need to Know Individuals. The IBC Chair will report to the full IBC a summary of the violation, review the information gathered, steps taken, and outcome at the next scheduled meeting.

Not for Cause Audits:

1. If Noncompliance is identified during a RO audit, RO determines the type of Noncompliance.
2. If not General Noncompliance, RO follows the same steps for investigation, reporting, and corrective actions as detailed above.

Notification to Regulatory Agencies or Sponsors:

The RO reports Serious or Continuing Noncompliance to the appropriate regulatory agencies and sponsors as required. This includes OSP and other relevant parties at the RO’s discretion.

Note: The IBC has the authority to address findings of serious or continuing noncompliance with the NIH Guidelines, the BMBL, University policies and procedures and other legal requirements via one or more of the following actions:

• Suspension or Termination of approval for use biohazardous material.
• Confiscation or Destruction of the biohazardous materials.
• Any other action necessary to protect the public and/or University, including restricting access to the laboratory in order to suspend activities.

Lapse in Approval

If IBC approval of a project expires, no activities involving the use of biological materials may occur. The Principal Investigator (PI) must report the lapse to the IBC and include:

1. An explanation of how and why the lapse occurred.
2. A corrective action plan to avoid future lapses.
3. Confirmation that no research activities took place during the lapse.
4. The timeline for when the lapse will be resolved, either through a Continuing Review application or Study Closure.
5. Confirmation that there are no pending issues/modifications, participant complaints/concerns, etc.
6. A statement about whether there have been prior lapses for this project.
7. Verification the lapse has been communicated to the sponsor, local site/IRB, DSMB, etc., if/when applicable.

If the PI of an IBC-approved study plans to leave the university, consider the following options:

1. Transfer to Another Institution: Submit a modification describing plans for transfer.
2. Change of PI at Current Institution: Identify a qualified individual to serve as PI at UMassD and submit a modification.
3. Data or Material Transfer: Execute an appropriate agreement before transferring any data or materials.

Regardless of how a study was approved (committee review or exempt review), closure is required in any of the following situations:

• The study was not initiated and will not be.
• The study was discontinued before completion.
• The IBC-approved time period has ended.
• All research-related activities are complete.
• The PI will no longer be affiliated with UMassD and does not plan to transfer the protocol.

The IBC may close a study without the principal investigator’s permission if:

• The principal investigator is no longer affiliated with UMassD, and no protocol transfer was arranged.
• The protocol has lapsed, and no extension or closure request was made.
• The IBC determines the protocol should be terminated due to issues like misrepresentation or ethical concerns.

Closing Process

Submit a closure report upon completion of the study before the study expiration date.

What to Do After Closing a Study

After closing a study, the research team must cease data collection and analysis of data. For additional data collection post-closure, submit a new registration to the IBC.