Policy for Institutional Biosafety

Introduction

William & Mary recognizes the importance of conducting a broad spectrum of investigative research as well as classroom and laboratory educational activities that require the use of recombinant DNA technology and etiologic agents. Cognizant that these activities may be accompanied by some risks, the university requires that the following activities be reviewed and approved by an Institutional Biosafety Committee (IBC) to ensure that they are conducted in a safe and appropriate manner:

Recombinant DNA technology, which is subject to the NIH Guidelines for Research Involving Recombinant DNA Molecules;
Agents infectious to humans and other animals;
Use of human tissues, fluids, or cell lines or primate tissues, fluids or cell lines;
Lab or field work on animals for which a documented and reasonable potential for transmission of zoonotic agents exists, e.g., wild-trapped rodents, birds, amphibians
Lab or field work with the intent to isolate or culture pathogens;
Research on biological agents that produce harmful toxins, where there is significant potential for human exposure.

Recombinant DNA technology must be in accordance with the current editions of the NIH Guidelines for Research Involving Recombinant DNA Molecules, the CDC/NIH Biosafety in Microbiological and Biomedical Laboratories, and the university's Bloodborne Pathogens Exposure Control Plan (doc). IBC members are instructed to take special care in identifying any protocols involving experiments of concern identified by the National Academies of Science report "Biotechnology in an Age of Terrorism" Adherence to this policy shall not exempt investigators employing recombinant DNA molecules or etiologic agents in their research from compliance with other applicable laws, regulations or policies (e.g. research with human subjects, vertebrate animals, or radioactive materials). The appropriate paperwork must also be filed through the Protocol and Compliance Management system with the Protection of Human Subjects Committee (PHSC), the Institutional Animal Care and Use Committee (IACUC), and the Institutional Radiation Safety Committee (IRSC).

The Institutional Biosafety Committee at William & Mary is not limited to the narrow regulations on recombinant DNA technology set forth by the NIH. Most universities have mandates to oversee broader biosafety issues, particularly projects pertaining to zoonotic and infectious disease agents, but also those dealing with other biohazardous agents such as algal toxins. In fact, the scope of many IBCs is to oversee any biological agents that can potentially harm humans, the environment, or agriculture. The IBC at William & Mary takes the stance that any research involving potentially harmful agents must be registered and approved by the university's IBC.

Definitions

Recombinant DNA molecules are defined as either (I) molecules that are constructed outside living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate inside a living cell, or (ii) DNA molecules that result from the replication of those described in (I). Synthetic DNA segments likely to yield a potentially harmful polynucleotide or polypeptide (e.g. a toxin or pharmacologically active agent) shall be considered as equivalent to their natural DNA counterpart. If the synthetic DNA segment is not expressed in vivo as a biologically active polynucleotide of polypeptide product, it is exempt from this policy.

Etiologic agents are defined as those biological agents, both pathogenic and non-pathogenic, known to cause disease in humans as well as selected animal agents that may pose potential risks if transmitted to humans.

Zoonotic diseases are diseases of animals that can be transmitted to humans. The IBC recognizes that there can be an inherent and probabilistically low risk of transmission of many diseases to humans from field-based studies. Further, many vertebrates possess pathogens of varying risk, with some more likely to be encountered than others, and some more pathogenic than others. Therefore, certain field studies should include safety protocols to limit exposure to potential agents, particularly when working with vertebrates and invertebrates that are known to harbor zoonoses or serve as vectors for disease agents. There may be cases where the risk of infection is extremely small, or where the risks of handling wild-trapped animals have changed (e.g., bird flu, Hanta virus). In these cases, the institutional biosafety officer can determine if registration is required. However, IBC registration is required for any field-based studies where tissues, including blood or hemolymph, are sampled for the isolation and culture of viral or bacterial agents. Additional guidelines for field-based studies are given below.

Applicability

This policy is applicable to all research, teaching, and outreach activities involving recombinant DNA or etiologic agents that are conducted at or sponsored by (or under the aegis of) William & Mary. No activity involving the construction or handling of recombinant DNA molecules or the use of etiologic agents shall be initiated without the review and approval of the appropriate registration documents by William & Mary Institutional Biosafety Committee.

Institutional Biosafety Committee

An Institutional Biosafety Committee (IBC) comprised of university faculty and staff appointed by the Provost and at least two outside community members shall fulfill the responsibilities described in this policy and in the Guidelines for Research Involving Recombinant DNA Molecules, Biosafety in Microbiological and Biomedical Laboratories, and the university's Bloodborne Pathogens Exposure Control Plan.

Committee Membership

The IBC members shall be selected so that they collectively have experience and expertise in recombinant DNA technology and biological organisms and the capability to assess the safety of such activities and any potential risk to public health or the environment. At least two members shall not be affiliated with William & Mary (apart from membership on the IBC) and shall represent the interest of the community area with respect to the health and protection of the environment. When possible, there shall be at least one member from each department/ unit conducting recombinant DNA research. The Vice Provost shall also be a member.

Meetings

The IBC shall meet as needed, but at least once per year. A schedule of meetings shall be publicly posted when feasible. Meetings will be open to the public consistent with protection of privacy and proprietary interests. A quorum for conducting business shall consist of 2/3 of the current members except that at least one member not affiliated with William & Mary (apart from serving the IBC) must be present. The meetings will follow recognized parliamentary procedure.

Reports

The IBC will report publicly to the W&M community concerning the performance of its assigned functions by making available a copy of the approved minutes of each IBC meeting. Copies may be obtained from the Provost's Office or from the Chair of the IBC.

Forms and Procedures

Each investigator/instructor using recombinant DNA molecules or biological agents as indicated above is required to submit the appropriate IBC form as described below. You must submit these forms using the Protocol and Compliance Management system.

Registration Document for Research/Teaching Involving Recombinant DNA: for those investigators/instructors employing recombinant DNA molecules and technology, including the construction and use of transgenic animals, and transfection of mammalian cell lines. Investigators conducting "exempt experiments" must still submit a registration from to the IBC. However, investigators completing this registration document need not complete an additional registration document for infectious agents for the same project.

Registration Document for Research/Teaching Involving Etiologic Agents: for those investigators/instructors employing biological agents in their research and teaching, but not involving recombinant DNA technology

Registration Document for Research/Teaching Involving Human Tissue or Body Fluids: for those investigators/instructors employing human tissue or body fluids, including saliva, urine, blood, or primary human cell cultures.

Registration Document for Research/Teaching Involving Wild-Caught or Random Source Animals or Animal Tissues: for those investigators/instructors employing animals that may carry zoonotic disease, or for those investigators/instructors employing biologically-derived chemicals..

In addition, any substantive changes in procedures or type of recombinant DNA molecules/etiologic agents should be reported to the IBC. This includes changes in key personnel, laboratories, or other modifications to the protocols. An annual renewal form must submitted each year for each approved registration. A new registration document must be completed every three years.

Functions and Responsibilities of the IBC

A. On behalf of William & Mary, the IBC shall review all proposals to assure compliance with this policy and the NIH Guidelines for Research Involving Recombinant DNA Molecules, the CDC Biosafety in Microbiological and Biomedical Laboratories, and the College's Bloodborne Pathogens Exposure Control Plan.

B. On behalf of William & Mary, the IBC shall conduct periodic self-studies of the effectiveness of university policy on biosafety and the implementation procedures, reporting the results to the provost and recommending any needed revisions. This will involve responsibility for:

Reviewing the registration submission for the appropriateness of biosafety procedures and assignment to the proper biosafety containment levels of experiments;
Reporting within 30 days to the university Environment, Health, & Safety Office and the Vice Provost identified problems with or violations of the guidelines and research-related accidents or illnesses; the IBC along with the Vice Provost, under the direction of the Provost, has responsibility for communication with external sponsoring and monitoring agencies;
Participating with the university Environment, Health, & Safety Office in the development of emergency plans to deal with accidental spills and personnel contamination resulting from research;
Insuring through periodic inspections that laboratory standards are rigorously followed.

Investigator's Responsibilities

The Principal Investigator is responsible for reviewing this policy and complying with its requirements. Specifically, he/she will:

A) File the appropriate Registration Document and an Annual Renewal form for each project and meet all the requirements of the NIH Guidelines for Research Involving Recombinant DNA Molecules, the CDC Biosafety in Microbiological and Biomedical Laboratories, and the university's Bloodborne Pathogens Exposure Control Plan.

B) Make available to laboratory staff and students copies of the registration documents and other protocols that describe potential biohazards and the specific precautions to be taken;

C) Provide appropriate instruction and training in practices and techniques necessary to ensure laboratory safety, as well as maintain training records for all personnel associated with protocol;

D) Supervise the laboratory staff to ensure that appropriate safety techniques and procedures are employed;

E) Report in writing to the IBC any significant problems pertaining to the operation and implementation of containment practices and procedures;

F) Take prompt corrective actions on all issues during periodic inspections and/or incident reports;

Guidelines for Field-based Studies

Research projects involving animals that are known vectors or reservoirs of zoonoses must be reviewed and authorized by the IACUC and approved by the IBC. Note that if you receive tissues from animals based on the field studies of other investigators, then you may not be required to submit IBC registration. However, tissues used in such studies should be properly disposed of per the university's Regulated Medical Waste Guidelines. Below is a list of animals where IBC registration may be required for field studies. The rule of thumb is that if there is any doubt, register the research. The process is neither long nor arduous.

Mammals can be excellent vectors for zoonotic agents; therefore most field studies on mammals will require IBC registration. Wild rodents are known to harbor a number of pathogens that can infect humans including Hanta virus, plague, Lyme disease, several rickettsiae and several viruses. Field studies on rodents must document precautions against zoonotic diseases. Most of these precautions entail personal protective equipment such as the use of gloves, smocks and minimal generation of aerosols. Field studies on large mammals should document precautions against rabies, tularemia, or other pathogens specific to the animals being studied. Laboratory or field work on primates requires IBC registration.

Birds can host a number of zoonotic agents with varying risks of infection. These include Chlamydia psittaci, several encephalitis viruses, West Nile virus, bird influenza and some enteric bacteria. Field studies on birds should document precautions against zoonotic diseases.

Most of these precautions will minimally entail personal protective equipment such as gloves, smocks and minimal generation of aerosols.

Amphibians harbor few zoonotic pathogens. However, turtles commonly carry Salmonella and there are documented cases of Salmonella in humans who have handled turtles without taking proper precautions. Such precautions include washing hands with anti-bacterial soap after handling amphibians or wearing gloves. The handling of poisonous amphibians or reptiles falls under OSHA regulations.

Fishes have few pathogens that can infect humans. However, fish can carry several bacteria that are known to cause secondary infections in humans: Aeromonas, Pseudomonas, Klebsiella, and Mycobacteria. In particular, several species of Mycobacteria are known to infect humans (fish handler’s disease); therefore, IBC registration is warranted when the research is focusing on fish diseases, particularly those causing lesions. If research is focused on gonad maturation, gut contents, morphometric data, then registration is not typically required. Use of personal protective equipment, such as disposable gloves, smocks, minimization of aerosols, etc., will help prevent contamination of skin surfaces. Thorough hand washing can reduce the probability of infection. Other zoonotic agents are transmitted by ingesting raw or undercooked fish, the eating of which are not generally included in scientific protocols. The handling of venomous or dangerous fishes falls under OSHA regulations.

Terrestrial invertebrates vary in their potential as risk agents. Biting flies, ticks and mites are known to carry zoonotic agents and some arachnids are venomous. Studies working specifically with these arthropods, particularly work based on vector-borne pathogens or venomous spiders, must be registered with IBC. Marine invertebrates pose little risk of infection. Vibrio infections can arise from the mishandling mollusks and crustaceans, but proper care and handling of these animals minimize these risks. Therefore IBC registration is not required for handling invertebrates where there is little known risk of zoonoses.

Other agents of concern include harmful algae, bacteria, cultures of other micro-organisms, and raw products derived from harmful organisms (e.g., venom, toxins, etc.). Registration is required where there is risk of exposure to aerosols generated in working with these organisms. Note that aerosols can be generated by centrifugation and aeration. Registration may be required for large-scale culture of toxic agents.

Guidelines for Disposal of IBC-Regulated Materials

The current College Institutional Biosafety Guidelines requires each investigator/instructor using recombinant DNA molecules or biological agents to submit an IBC protocol for the safe and appropriate handling of these biological materials from receipt of the materials at the start of the research activity through to disposal of biological waste at the end of the activity. Description of the means of disposal is an essential part of the IBC protocol. Investigators are required to define when their biological materials shall be discarded as well as the decontamination and disposal protocols they will follow for handling these materials.

There are several key principles that aid Investigators in making a determination for their disposal practices. First, the act of discarding determines when a material becomes a waste; any material being handled under an approved IBC protocol is not a waste until the investigator decides to discard the material. Second, because work performed under William & Mary’s Institutional Biosafety Committee-approved protocols contributes to the university’s general waste stream, IBC protocols must be compatible with the waste handling requirements defined in the university’s Regulated Medical Waste Management procedure (doc).

It is clear from the university’s Regulated Medical Waste definitions that defining “discarded” items as "Regulated Medical Waste" is determined by whether such discarded items are also "contaminated" by organisms likely to be pathogenic to healthy humans at the time of disposal. Such contamination is obviously dependent upon whether in the course of normal laboratory processing of research materials there is a total inactivation of all such organisms. If "organisms likely to be pathogenic to healthy humans" are discarded without total inactivation then these items are correctly termed "Regulated Medical Waste." However, if total inactivation occurs as part of the normal laboratory protocol then such items are not RMW.

Therefore, investigators may opt to discard laboratory biological materials in one of two ways:

Infectious and/or potentially biohazardous materials may be discarded as RMW to obviate the additional effort of inactivating such materials before disposal in the common waste stream. Investigators shall follow the waste handling guidelines prescribed in the university’s Regulated Medical Waste Management procedure.

a. Investigators must restrict the use of the term "RMW" to indicate the materials that will be contained in specially marked plastic bags (orange or red) and held in specially marked boxes until removal from the laboratory by the VIMS or College EH&S Office for disposal by a licensed vendor of such services.

b. If red or orange colored bags are employed for any purpose then the bag contents will always be considered RMW; once loaded these bags must be disposed of by a licensed RMW contractor.

c. All autoclave bags must be labeled with an initial and a date.
Investigators may establish an IBC-approved protocol to work at either Biosafety Level (BSL) 1 or 2, and inactivate all materials to be discarded, with exception of sharps, in a manner that renders the materials non-infectious & non-biohazardous prior to disposal. [For a definition of “sharps” refer to Section 3, item 6 of the RMW Management procedure] Electing this option requires the submission of a protocol that will specify all chemical and/or heat inactivation methods to be employed. These methods shall be consistent with accepted practices and/or the product’s Material Safety Data Sheet for inactivation by means of chemical and/or steam sterilization.

a) Investigators selecting this option must specifically detail how any infectious and/or potentially biohazardous materials will be inactivated before they are discarded.

b)All research materials to be inactivated under an IBC-approved protocol specific to the project must be discarded only in clear bags and without any identification that could be confused with RMW. Each bag must be labeled with initials and a date.

Additional Guidelines:

A protocol should include the names of ALL persons (including students and staff) who are to be approved to work with all aspects of infectious/biohazardous material.
As part of any BSL 1 or 2 protocol, all potentially infectious/biohazardous material should be so identified within the laboratory by some form of recognized hazard label that includes the name or initials of the investigator. This label must remain affixed to all material that is discarded as RMW. However, all biohazard labels affixed to infectious materials while in use in the laboratory must be removed or fully defaced before autoclaving and the subsequent discarding of these autoclaved materials as common waste.
Persons named on a specific IBC-approved protocol will be responsible for taking research materials to the autoclave room and then autoclaving in clear plastic bags prior to final disposal. No materials may be left unattended in the autoclave room except while the autoclave is cycling. Autoclaved materials must be promptly removed when the cycle is completed. It is strongly recommended that all investigators review the operation manual for the autoclave used in their specific protocol.
Biosafety Personal Protective Equipment Matrix (pdf).