Biological Safety Manual

and

Exposure Control Plan

This resource developed by LabCentral for the Pagliuca Harvard Life Lab

Revision 2, Effective Mar 17, 2017

Page 2 of 19

Table of Contents 1.0 PURPOSE.............................................................................................................................3

2.0 SCOPE .................................................................................................................................3

3.0 PERMITTING........................................................................................................................4

4.0 ROLES AND RESPONSIBILITIES ..............................................................................................4

4.1 Life Lab ....................................................................................................................................... 4

4.2 Harvard Committee on Microbiological Safety (COMS) ............................................................ 5

4.3 Harvard EHS ............................................................................................................................... 5

4.4 Triumvirate Environmental (TEI) ............................................................................................... 6

4.5 Venture Principle Scientist(s)..................................................................................................... 6

4.6 Technical Research Staff ............................................................................................................ 7

4.7 Non-Technical Staff .................................................................................................................... 8

5.0 GOVERNANCE OF BIOLOGICAL RESEARCH PROJECTS ............................................................8

5.1 Applicant Screening ................................................................................................................... 8

5.2 Venture Teams ........................................................................................................................... 8

5.3 Project Registration Submittal and Review Process .................................................................. 9

6.0 BIOSAFETY PRINCIPLES ...................................................................................................... 10

7.0 HUMAN SOURCE MATERIALS ............................................................................................. 11

7.1 Bloodborne Pathogens ............................................................................................................ 11

7.2 Immortalized Human Cell Lines ............................................................................................... 12

7.3 Primary Human Cell Lines or Tissues ....................................................................................... 14

7.4 Human Derived Reagents ........................................................................................................ 14

7.5 Exposure Determination .......................................................................................................... 14

8.0 LABELING .......................................................................................................................... 14

9.0 MEDICAL SURVEILLANCE & VACCINATIONS ........................................................................ 15

9.1 Medical Surveillance and Consultation ................................................................................... 15

9.2 Hepatitis B and Other Vaccinations ......................................................................................... 15

9.3 Appropriate Disinfectants for use with Human-derived Materials ......................................... 16

10.0 EMERGENCY RESPONSE ..................................................................................................... 16

11.0 SELECT AGENTS ................................................................................................................. 16

12.0 REVISION HISTORY ............................................................................................................ 17

Page 3 of 19

1.0 PURPOSE

The Pagliuca Harvard Life Lab is committed to creating and maintaining a safe and healthy environment

for all who work in or visit our facility. This Biological Safety Manual and Exposure Control Plan has been

formulated in accordance with the recommendations from the National Institutes of Health (NIH) and

Centers for Disease Control (CDC). It outlines the policies and procedures for the handling of and research

involving biological materials, including recombinant DNA (rDNA) and human source materials. At the

present time, no biological agent requiring containment greater than Biosafety Level 2 (BL2), as outlined

by the NIH is permitted in the facility. This manual is intended for use as a supplement to the NIH

Guidelines for Research Involving rDNA Molecules and the CDC/NIH Biosafety in Microbiological and

Biomedical Laboratories (BMBL). These resources should be referred to should any questions or

clarifications be required for applicability to the work being proposed.

Copies of this manual are maintained in the following locations:

• Life Lab team office area in the Life Lab Safety Manual. This manual contains all the written plans

for general safety, lab safety, chemical hygiene and biological safety.

• Private lab on the 2nd floor in the Life Lab Safety Manual

• Co-working lab on the 2nd floor in the Life Lab Safety Manual

• Online in the member portal

This manual serves as both the written program and as a biosafety training document.

2.0 SCOPE

The provisions of the Biological Safety Manual and Exposure Control Plan apply to all personnel leasing or

working in the laboratory space at the Life Lab facility. This program also applies to contractors who might

be exposed to biological materials while at the Life Lab. All members of the Life Lab who are working with

biological agents/materials must read and be familiar with the contents of this manual, are expected to

follow the procedures outlined in this manual and actively participate in the facility environmental health

and safety program. The Life Lab encourages all members to report unsafe processes or conditions and

provide recommendations to improve the safety of the work environment at the Life Lab. The Biological

Safety Manual and Exposure Control Plan will be reviewed annually and amended as necessary based

Page 4 of 19

upon the feedback provided throughout the previous year and any new recommended changes to current

policies.

3.0 PERMITTING

The Life Lab has been authorized by Harvard University’s Committee on Microbiological Safety (COMS) to

hold an umbrella protocol for all work involving biological agents at the facility. The umbrella protocol is

a living document and will change as new projects at the Life Lab are submitted and approved. The list of

approved biological agents is maintained by the Life Lab Facility Biosafety Officer (BSO). Before

commencing research, all venture companies must register their projects with the Facility BSO and obtain

at least a preliminary pre-approval. Additional information on project registration can be found in Section

5.0 of this manual.

4.0 ROLES AND RESPONSIBILITIES

4.1 Life Lab

The Life Lab is responsible for ensuring that the handling of and research involving biological

agents/materials is carried out in a safe and efficient manner in compliance with the provisions of the NIH

Guidelines and the CDC/NIH BMBL practices. In order to provide for the safe conduct of rDNA and/or

biological research, the Life Lab has established policies to ensure compliance with federal, state and local

regulations. The Life Lab may establish additional procedures to assist researchers and employees in the

safe conduct of their work.

4.1.1 Principal Investigator (PI)

The PI for the Life Lab bears ultimate responsibility for ensuring that the research conducted in the facility

is in compliance with all training and other safety requirements imposed by COMS or by federal, state or

local legislation or regulation.

4.1.2 Institutional Biosafety Officer (BSO)

The Life Lab is responsible for appointing a BSO with appropriate expertise to serve as the primary liaison

between the Life Lab and COMS, ensuring that all research involving recombinant or synthetic nucleic acid

molecules or other hazardous biological materials are reviewed by COMS. This individual will be a

member of the Harvard EH&S biosafety program and will work closely with the Life Lab Facility Biosafety

Officer.

4.1.3 Life Lab Facility Biosafety Officer (BSO)

Page 5 of 19

The Life Lab Facility Biosafety Officer will be a full-time staff member at the Life Lab with appropriate

scientific expertise and who is fully aware of and oversees the day-to-day operations in the laboratory.

This person shall be responsible for:

• Reviewing all new project registration forms submitted by venture principal scientists until they

are in a completed state for submission to COMS

• Compiling all questions and comments stemming from COMS review and informing the principal

scientist (PS) to make the required corrections and/or provide the necessary information

• In collaboration with the Institutional BSO, determining the need for amendments to an approved

project and/or new project registrations based on information provided by the PS

• Reporting to the Institutional Biosafety Officer all significant problems with and violations of Life

Lab biosafety policies and procedures and all research-related accidents and illnesses of which

the BSO becomes aware

• Conducting periodic laboratory inspections to ensure standards are rigorously followed

• Ensuring that technical research staff have been trained adequately to comply with all written

plans and procedures in the case of accidental spills and personnel contamination

• Investigating research laboratory accidents

• Providing advice on laboratory security when needed; security measures can include such things

as locking up controlled substances and syringes and needles or implementing controlled access

to laboratory areas

• Providing technical advice to the PS on research safety procedures

4.2 Harvard Committee on Microbiological Safety (COMS)

Harvard University’s COMS serves as the Institutional Biosafety Committee (IBC) for Harvard as well as

Harvard-affiliated medical and research institutions. COMS is responsible for reviewing all research

projects involving recombinant or synthetic nucleic acid molecules as defined by the NIH Office of Science

Policy and the use of biological agents to be conducted at or sponsored by any of these institutions; no

such project may be commenced without COMS approval. For those interested in more information about

COMS, the COMS Policy Manual is available on line for review.

4.3 Harvard EHS

The Harvard Department of Environmental Health and Safety serves as the primary source of leadership

in anticipating environmental health and safety requirements and risks, and developing mitigation

Page 6 of 19

strategies to minimize impacts to the University’s people, academic and research enterprise,

infrastructure and operations.

4.4 Triumvirate Environmental (TEI)

TEI is the Environmental, Health and Safety consulting firm for the Life Lab. TEI is responsible for working

with the Life Lab to ensure that the handling of and research involving biological agents/materials are

compliant with the provisions of the NIH Guidelines and the CDC/NIH BMBL practices.

4.5 Venture Principle Scientist(s)

The principal scientist (PS) of each venture has primary responsibility for complying fully with the

requirements as set forth in this manual and ensuring that all the members of the venture are also in

compliance.

As part of this general responsibility, principal scientists must not initiate a research project involving

biological agents or rDNA without COMS approval if required per the NIH Guidelines and the classification

of the project in question. The PS must complete a Biological Project Registration and submit it to the

facility Biosafety Officer (BSO) for approval. If a modification is made to a project the PS should inform

the BSO before initiating the change so that a determination can be made on whether the change requires

an amendment or if a new project registration needs to be submitted to COMS.

The principal scientist is responsible for:

• Ensuring the safe conduct of the research on a day-to-day basis

• Reporting to the Facility BSO, as soon as possible, all significant problems with and violations of

the guidelines and all research-related accidents and illnesses

• Reporting to the BSO any proposed modifications or changes to the project prior to

implementation

• Reporting to the BSO any changes in health status of research personnel or illness which lasts four

days or longer

• Training laboratory personnel on the potential hazards of the biological agents with which they

are working and the appropriate safe work practices, techniques and equipment

• Knowing and understanding the approved emergency plans for dealing with accidental spills and

personnel contamination

• Complying with shipping requirements for recombinant DNA molecules, infectious agents and

microorganisms

Page 7 of 19

• Maintaining an inventory of biological agents and rDNA molecules in their possession

As part of the project submission process the PS should:

• Identify all biological materials and rDNA to be used in the duration of the project

• Make the initial determination of the required levels of physical and biological containment in

accordance with NIH and/or CDC guidelines

• Select appropriate microbiological practices and laboratory techniques to be used in the research

• Identify health and safety risks associated with the project

• Submit the initial project registration and subsequent changes to the BSO for COMS review and

approval

Once the protocol is approved by COMS, the PS should:

• Discuss and show research staff copies of the approved protocols and describe the potential

biohazards and the precautions to be taken

• Provide training in the appropriate safe practices and techniques and be sure that the research

staff knows what to do and how to deal with an accident or incident

• Be sure the research staff understands the reasons and provisions for any precautionary medical

practices advised or requested, such as vaccinations

During the conduct of approved research, the PS should:

• Supervise the performance of the research staff to ensure that the required safety practices and

techniques are employed

• Investigate any significant problems pertaining to the operation and implementation of

containment practices and procedures, report any problems, violations, or issues to the BSO

• Ensure the integrity of equipment used for physical containment and host-vector systems used

for biological containment (e.g., genotypic and phenotypic characteristics that reduce virulence,

pathogenicity, infectivity, or the ability to survive outside the laboratory or in the environment)

• Inform the BSO of any significant changes to the project including new biological materials or

procedures

4.6 Technical Research Staff

All laboratory personnel must be adequately trained prior to beginning any work with biological or

chemical material. General safety training will be provided by the TEI consultant. On an annual basis,

retraining sessions will be held to provide a review and summary of all safety procedures.

Page 8 of 19

Training for research personnel will include, but are not limited to:

• Emergency Action and Contingency Plan

• Laboratory Safety and Chemical Hygiene Plan

• Biological Safety and Exposure Control Plan

o Biological safety including rDNA research safety

o OSHA Bloodborne Pathogen training

o Waste management and decontamination/disinfection

Before research personnel can begin work they must:

• Attend all training classes related to the safety plans listed above

• Demonstrate working knowledge of all relevant safety practices, the research they will perform

and any potential hazards that may be involved. Technical research staff must obtain training for

specific laboratory procedures from their venture principal scientist.

4.7 Non-Technical Staff

All non-technical staff members are to be familiarized with the potential hazards associated with general

laboratory research. In general, all non-technical staff members must not enter the laboratory research

area unless properly supervised by researched personnel. Non-technical staff are required to attend EHS

training regarding the Life Lab’s Emergency Action and Contingency Plan and review the written plan

whenever changes are made.

5.0 GOVERNANCE OF BIOLOGICAL RESEARCH PROJECTS

In order to ensure that local and federal requirements for the use of rDNA and/or biological agents are

met, all research projects involving either rDNA or biological agents must be reviewed prior to initiation.

The Life Lab has implemented the following process for governance of all biological research projects.

5.1 Applicant Screening

Applicant ventures are required to complete a profile that identifies the anticipated biological hazards as

part of the screening process for Life Lab admittance. Profiles are reviewed by Life Lab team members

prior to acceptance into the Life Lab. This review provides a mechanism for early evaluation of potential

risks and ensures the facility has the appropriate containment facilities and equipment.

5.2 Venture Teams

Page 9 of 19

Upon acceptance into the Life Lab, applicant ventures are required to complete a Biological Research

Project Registration to describe the work to be conducted, techniques and materials to be used,

containment procedures and equipment, etc. This is required for all matriculating venture teams as well

as current venture teams who are considering new projects. Venture teams are required to file either an

amendment to their project registration or a new project registration if they change their procedures

and/or employ new vectors, cell lines etc. The type of filing (amendment or new) is dependent on the

scope of the change. Life Lab team members are available for consultation to help decide which form is

needed. Venture teams are required to purchase all biological and chemical agents through the Life Lab’s

procurement system to provide a mechanism for control over agents brought into the facility.

Student VIP teams are required to complete the same Biological Research Project Registration form;

however, these must be completed PRIOR to acceptance into the Life Lab.

5.3 Project Registration Submittal and Review Process

A summary flow chart of this process is located in Appendix I.

5.3.1 Project Registration Submission

Project registrations are submitted to the Life Lab Facility BSO for a review of completeness. If the

registration is incomplete or unclear, it will be sent back to the Principal Scientist for corrections. The

corrected submission is then ready for the review process.

5.3.2 Review Process

Project Registration work covered under the Life Lab COMS Protocol

• Projects that contain biological agents and rDNA materials that are already approved for use in

the Life Lab COMS umbrella protocol will be reviewed by the Life Lab Facility BSO and Triumvirate

Environmental (TEI) Consultant for administrative approval.

• If the Life Lab Facility BSO and TEI Consultant have questions or need additional information, the

form will be sent back to the PS for correction. All revisions made to the form must be submitted

for review through the facility BSO and TEI Consultant. This process is repeated until the project

is approved or rejected.

Project Registration work not covered under the Life Lab COMS Protocol

• Projects that contain biological agents and/or rDNA materials that are not approved for use in the

Life Lab COMS umbrella protocol may not commence until an amendment has been submitted

and approved by Harvard COMS.

Page 10 of 19

o If the newly proposed work describes use of biological materials falling outside the scope

of COMS, the Facility BSO will work with the PS to develop appropriate safety measures

as needed. Safety plans for these projects will be sent to the Institutional BSO when

finalized or if Institutional BSO input is needed.

• The Life Lab Facility BSO will submit an amendment to the COMS protocol which will then be

reviewed by the Institutional Biosafety Officer.

• If the Institutional BSO has questions or needs additional information, the amendment will be

sent back to the Life Lab Facility BSO. All revisions made to the amendment must be submitted

back for review through the Institutional BSO. This process is repeated until the amendment is

complete and ready for review by Harvard COMS.

• If no concerns are identified, the amendment will be given approval by Harvard COMS. NOTE: If

there are more questions to be answered or some concerns are identified, COMS may give some

stipulations that must be met to receive approval. If stipulations are set by the committee, the

Facility BSO and Institutional BSO will affirm that they are met before work commences. It is

extremely rare that a protocol is outright rejected from COMS, but there are certain categories of

experiments and certain agents that are simply not able to be worked with on the Harvard

campuses (i.e. select agent research).

• The Life Lab Facility BSO will then inform the PS that the project has been approved and that work

may commence.

Copies of all correspondence are maintained on file at the Life Lab.

6.0 BIOSAFETY PRINCIPLES

Biosafety, as defined by the CDC, is “the discipline addressing the safe handling and containment of

infectious microorganisms and hazardous biological materials.” This is accomplished through biological

risk assessment and the application of containment principles.

A biological risk assessment is determined by scrutinizing the hazards posed by the biological agents and

the associated laboratory activities. Pathogen hazards are categorized into four groups of ascending risk

(RG1 – RG4). The Risk Group is determined using three criteria:

• Pathogenicity, or the ability to cause disease in humans or animals

• Availability of medical countermeasure or prophylactic treatment for the associated disease

• Ability of the disease to spread

Page 11 of 19

The risk assessment also takes into consideration all aspects of the laboratory space that can increase the

risk of exposure to a pathogen.

Preventing exposure of laboratory workers to pathogens or the inadvertent escape of a pathogen from

the laboratory is achieved by applying layers of containment which are appropriate to the risk assessment.

Primary containment provides immediate protection to workers from exposure to chemical and biological

hazards. This includes biosafety cabinets, chemical fume hoods and other engineering devices used by

laboratory workers as well as personal protective equipment (PPE) such as gloves, lab coats and protective

eyewear. Secondary containment consists of architectural and mechanical design elements of a facility.

There are four containment or biosafety levels (BL1 – BL4); BL1 requiring the lowest level of primary and

secondary containment and BL4 requiring the greatest.

Another important element of any biosafety plan is training. This includes basic training on best practices

in the laboratory as well as specialized training on bloodborne pathogens for those laboratory workers

that may be exposed to human blood or human blood products.

Please refer to the Life Lab Biosafety Practices document for specific procedures on the use of

containment equipment and laboratory practices.

7.0 HUMAN SOURCE MATERIALS

7.1 Bloodborne Pathogens

The Occupational Safety and Health Administration (OSHA) created the Occupational Exposure to

Bloodborne Pathogens Standard, 29 CFR Part 1910.1030 to minimize or eliminate exposure to infectious

agents that may be present in human blood, tissues or certain body fluids. The Bloodborne Pathogens

Standard applies to all employers having employees that are “occupationally exposed” to human blood

or other potentially infectious materials (OPIM). An employee is considered occupationally exposed if

there is “reasonably anticipated skin, eye, mucous membrane, or parenteral contact with human blood

or other potentially infectious materials in the performance of an employee’s duties.” Other potentially

infectious materials include:

• Human cell or tissue cultures

• Organ cultures

• Any unfixed tissue or organ, other than intact skin, from a human being (living or dead)

• Human Immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis C virus (HCV)-

containing culture media or other solutions

Page 12 of 19

• Human body fluids, except urine, feces, saliva or tears unless visibly contaminated with blood

• Blood, organs, or other tissues from experimental animals infected with HIV, HBV, HCV or other

bloodborne pathogens

An individual is also considered occupationally exposed if they do not have direct contact with blood or

OPIM but use equipment that is used to process or store blood, OPIM, or bloodborne pathogens. All

occupationally exposed employees are required to attend a bloodborne pathogens training session prior

to beginning work and annually thereafter.

OSHA has determined that occupational exposure to human blood, tissues and body fluids poses a

significant health risk because they may contain bloodborne pathogens including, but not limited to:

• HIV

• HBV

• HCV

• Hepatitis D virus

• Human T-lymphotropic virus Type I

• Hemorrhagic Fever viruses

• Creutzfeldt-Jakob prions

The OSHA Bloodborne Pathogen Standard defines safety requirements for working with human blood and

other clinical materials, HIV, and the bloodborne hepatitis viruses. Those safety requirements, also known

as universal precautions are described in this Biological Safety Manual.

Materials other than those mentioned above which should also be handled within BL2 containment using

universal precautions are:

• Human derived immortalized (established) cell lines

• Primary human cell lines or tissue

• Human serum derived reagents

• Non-human primate blood, tissues and cells

7.2 Immortalized Human Cell Lines

An immortalized human cell line (also known as an established human cell line) is defined as in vitro or

animal passaged (e.g., nude mouse) cultures or human cells that fulfill traditional requirements of a cell

line designation. That is, the cells are immortalized cells transformed by spontaneous mutation, natural

Page 13 of 19

infection, or laboratory infection with an immortalizating agent such as Epstein-Barr virus (EBV). EBV is a

bloodborne pathogen.

Characterization of human cells, as defined by the Bloodborne Pathogens Standard, would include

screening of the cell lines for viruses characterized as bloodborne pathogens including HIV, hepatitis

viruses, and Epstein-Barr virus (EBV). Most cell lines are screened for human mycoplasmas, and are free

of bacterial and mycotic contaminants. Testing may include antigenic screening for viral or agent markers,

co-cultivation with various indicator cells that allow contaminants to grow, or using molecular biology

techniques to identify latent viruses capable of infecting humans. Cell lines that are procured from

commercial vendors or other sources, with certification that they are free of human bloodborne

pathogens, and which have been protected by the researcher from environmental contamination, may

be excluded from the federal OSHA Bloodborne Pathogens Standard. However, ALL human derived

materials must be registered with COMS. At that time, one may request that COMS allow for the tested

cell line to be excluded from Bloodborne Pathogen requirements such as training or use at BL2.

It should be noted that human cells or other transformed human cell lines are sometimes adulterated

with laboratory pathogens accidentally introduced by cultivation with other cell cultures, or physically

contaminated by other cell cultures handled in the same lab. In order to handle human cells, without

having to comply with the requirements of the Bloodborne Pathogens Standard, human cells should be

documented to be pure cells AND shown to be free of bloodborne pathogens by testing AND receive

approval from COMS. Due to the difficulty of fulfilling all of the above requirements, it is the Life Lab’s

general policy to handle all human source materials including cell lines according to the Bloodborne

Pathogen standards.

When cell cultures are known to contain an etiologic agent, oncogenic virus, or amphotropic packaging

system, the cell line must be classified at the same biosafety level that is recommended for the agent.

This is the same for all cell cultures purposely inoculated with an infectious agent. Hybridoma cell lines

are immortalized cell lines created by fusion of primary cells with a continuous cell line. In general,

primary cell cultures are less characterized than established/transformed/immortalized cell lines, and are

not typically tested for contaminating pathogens. The tumorigenic potential is a risk to consider with

immortalized cell lines.

The following must be handled at Biosafety Level 2, within a Class II Biosafety Cabinet (BSC):

Page 14 of 19

• All cell lines (primary and established) of human or primate origin. If cell lines are classified by

other organizations as downgraded to BL1, documentation indicating that the line is free of

bloodborne pathogens and COMS approval is required, as described above.

• All cell lines from tumor tissue or transformed by any oncogenic virus or tumor suppressor

• All cell lines exposed to or transformed by amphotropic packaging systems

• All human clinical material (such as samples of human tissues and fluids obtained after surgical

resection or autopsy)

• All hybridoma cell lines

• Unknown biological systems

7.3 Primary Human Cell Lines or Tissues

Primary human cell lines or tissues (referred to as “cell strains” by OSHA) are defined as cells propagated in

vitro from primary explants of human tissue or body fluids which have a finite lifetime (non-transformed)

in tissue culture for 20-70 passages. Primary human cells must be handled as potential biohazards unless

characterized by testing to be free of bloodborne pathogens and approved by COMS to be exempted from

the Standard’s requirements.

However, if such tissue explants or subsequent cultures are derived from human subjects known to carry

bloodborne pathogens, such as hepatitis viruses or human immunodeficiency viruses, or are deliberately

infected with bloodborne pathogens, they must be handled in accordance with the precautions noted in

the Bloodborne Pathogens Standard. Likewise, animal tissues, explants, or cell cultures known to be

contaminated by deliberate infection with HIV or hepatitis viruses are also subject to the Standard.

7.4 Human Derived Reagents

The Centers for Disease Control cautions that all human-serum-derived reagents used in the lab, such as

Human Serum Albumin (HSA), must be handled at BL2 levels with universal precautions because no test

method can offer complete assurance that laboratory specimens do not contain HIV, HBV, or other

infectious agents.

7.5 Exposure Determination

The OSHA Bloodborne Pathogens Standard requires that an exposure determination be performed in

laboratories where human source materials are used.

8.0 LABELING

Page 15 of 19

All areas and equipment that contain biohazards agents must be marked

with a biohazard warning label. It must be red or orange in color with the

universal biohazard symbol and lettering in black as illustrated.

The following are examples of biohazards and are required to be labeled

with a Universal Biohazard symbol:

• Human blood, blood products, bodily fluids, and tissues

• Biotechnology by-product or effluent from living organisms

• rDNA materials

• Biologic agents, some of which may harbor pathogenic agents

• Equipment which is used with any of the above

• Equipment in which any of the above are stored

• Waste receptacles including sharps containers, pails, and boxes

9.0 MEDICAL SURVEILLANCE & VACCINATIONS

9.1 Medical Surveillance and Consultation

The Life Lab maintains a service agreement with Mount Auburn Hospital in Cambridge, Massachusetts,

that members may use for medical surveillance and consultations. The Life Lab does not maintain medical

records for members. This is solely the responsibility of each venture as is payment for services.

Contact Information: Mount Auburn Hospital Occupational Health Services 725 Concord Ave, Suite 5100 Cambridge, MA 02138 617-354-0546

Ventures must offer medical consultation at no cost to their personnel under the following circumstances:

• Whenever an individual develops signs or symptoms associated with a hazardous chemical or

biological agent which the member may have been exposed to in the lab.

• Following a report of an exposure to human source material.

• Where chemical exposure monitoring reveals an exposure level routinely above OSHA’s Action

Level or Permissible Exposure Limit for an OSHA regulated substance which requires such

monitoring or medical surveillance.

• Whenever an event occurs such as a spill, leak, or explosion, which results in the likelihood of a

hazardous exposure to chemical or biological material.

9.2 Hepatitis B and Other Vaccinations

Page 16 of 19

The OSHA Bloodborne Pathogen Standard requires that all personnel with the potential for occupational

exposure to bloodborne pathogens and other human source potentially infectious materials be offered

the Hepatitis B vaccine and/or titer. The Life Lab offers the Hepatitis B vaccination series to all Life Lab

team members who have the potential for occupational exposure, and extend post-exposure evaluation

and follow-up to all personnel who have had an exposure incident. It is the responsibility of each venture

to provide the same offerings to their own members.

9.3 Appropriate Disinfectants for use with Human-derived Materials

OSHA requires the use of EPA-registered tuberculocidal disinfectants, diluted bleach solutions and EPA-

registered disinfectants that are labeled as effective against both HIV and HBV as well as Sterilants/High-

Level Disinfectants cleared by the FDA to be used to disinfect and clean items contaminated with human

material that may harbor bloodborne pathogens. Disinfectants must be used according to their label.

Note that 70% ethanol is NOT an appropriate disinfectant for use with human material as it is not highly

effective against HBV. Please refer to section 5.3 of the Biosafety Practices document for guidance on

identifying these disinfectants.

10.0 EMERGENCY RESPONSE

Emergencies shall be handled in accordance with the Life Lab Emergency Action and Contingency Plan.

The EACP details specific actions to be taken for reasonably foreseeable emergency situations including

but not limited to:

• Local Area or Facility evacuations

• Medical emergencies

• Fire and explosion

• Chemical/Biological spills

11.0 SELECT AGENTS

Select Agents are materials that have been identified by the U.S. Government as agents that have

potential use in biological terrorism or warfare. The Department of Health and Human Services (DHHS),

through the U.S. Centers for Disease Control and Prevention (CDC), and the Animal Plant Health Inspection

Service (APHIS), through the United States Department of Agriculture (USDA) regulate Select Agents in

the United States and its territories. Each agency has developed and will maintain a list of Select Agents,

including human, animal, and plant pathogens, high-risk toxins of biological origin, and prions. The current

list of Select Agents can be accessed at the CDC and USDA websites.

Page 17 of 19

A permit must be obtained from the CDC or APHIS before Select Agents may be possessed, shipped, or

received. In order to obtain a permit for Select Agents, the facility must be registered and create a Select

Agents program. This manual does not cover a Select Agents program. Harvard does not currently

maintain a Select Agent Program.

For more details on Select Agents go to http://www.cdc.gov/od/sap/. Contact the facility BSO before you

consider working with any agents identified as a select agent or toxin.

12.0 REVISION HISTORY

Change Reason Effective Date

• New document To outline the policies and procedures for the handling of and research involving biological materials, including recombinant DNA (rDNA) and human source materials

Feb 23, 2017

• Section 4.0, Roles & Responsibilities: rearranged numbered sections, added more text describing Institutional BSO and Facility BSO

• Section 5.0, Governance of Biological Research Projects: more text added regarding Institutional BSO and Harvard COMS

• Section 7.0, Human Source Materials: changed “cell strain” to “primary cell lines”, added text on what needs to be registered with COMS, added text regarding Life Lab’s general policy on handling of human source materials

• Added section 9.3

• Added text in Appendix II, Section III-F

• For clarification on defined roles

• For clarification on responsibilities

• “primary cell line” phrase more widely recognized and used by the research community; more clarity on material registration for COMS and Life Lab policies

• clarification on appropriate disinfectants for human-derived materials

• more clarity on material registration for COMS

Mar 17, 2017

Page 18 of 19

APPENDIX I. PROJECT REGISTRATION PROCESS FLOW CHART

Page 19 of 19

APPENDIX II. NIH GUIDELINE DEFINITIONS FOR IBC APPROVAL

Section III-A Experiments that require Institutional Biosafety Committee (IBC) approval, Recombinant DNA

Advisory Committee (RAC) review and NIH Director approval before initiation (e.g., deliberate

transfer of drug resistance to a microorganism that is not known to acquire it naturally, if such

acquisition could compromise the ability to control disease agents in human, animals or

agriculture)

Section III-B Experiments that require NIH Office of Biotechnology Activities (NIH/OBA) and IBC approval

before initiation (e.g., cloning of toxin molecules with a LD50 less than 100 ng/kg)

Section III-C Experiments that require IBC and Institutional Review Board (IRB) approvals and RAC review

before research participant enrollment (e.g., human gene transfer)

Section III-D Experiments that require IBC approval before initiation (e.g., recombinant and synthetic

nucleic acids in pathogenic microorganisms, viral vectors for gene transfer, gene transfer in

Risk Group 2 microorganisms)

Section III-E Experiments that require IBC notice simultaneous with initiation (e.g., recombinant and

synthetic nucleic acids in Risk Group 1 microorganisms or formulated into synthetic or

natural vehicles, experiments involving whole plants at BSL1-P)

Section III-F Exempt experiments (e.g., recombinant and synthetic DNA that is not in organisms or

viruses, DNA/RNA in microorganisms that are exempt under III-F)

NOTE: While exempt from federal oversight, research falling into Section III-F of the NIH

Guidelines must still be registered and approved by COMS