University of California San Francisco Biological Safety Manual April 1, 2016 1
Table of Contents: Chapter 1 Introduction to Biosafety.... 4 Chapter 2 Biological Safety Program Administration..... 6 Chapter 3 Who Needs a Biological Use Authorization (BUA) Approval? 11 Chapter 4 The BUA Process.... 12 Chapter 5 Human Gene Transfer Research..... 14 Chapter 6 Laboratory Design and Biosafety Cabinets.... 17 Chapter 7 Medical (Biohazardous) Waste Management..... 19 Chapter 8 Responding to Emergencies Involving Biohazardous Material.... 26 Chapter 9 Biological Safety Training.. 28 Chapter 10 Animal Biosafety.. 29 Chapter 11 Shipping and Transport of Biohazardous Materials.... 30 Chapter 12 Importation and Exportation Permits for Biological Materials. 34 Chapter 13 Select Agent.... 38 Chapter 14 Working with Aerosol Transmissible Disease...... 41 Chapter 15 Health Surveillance Program.. 49 Chapter 16 Audits and Inspections..... 51 2
The purpose of this manual is to define the biological safety policies and procedures for the University of California, San Francisco (UCSF). These policies and procedures were designed to safeguard personnel and the environment from biologically hazardous materials and to comply with federal and state regulatory requirements without unduly intruding on research. All UCSF Principal Investigators (PIs) and laboratory workers must adhere to these biological safety policies and procedures in the conduct of their research and in the management of their laboratories. For information about specific biological safety programs or operations not covered in this manual, contact your Environment, Health and Safety Specialist (EHS Specialist), the Biosafety Officer (BSO) or Assistant Biosafety Officers (ABSOs), or the Institutional Biosafety Committee (IBC) office, at the UCSF Environment Health and Safety (EH&S). 3
Chapter 1 Introduction to Biological Safety The goals of the Biological Safety (or Biosafety) Program are to protect laboratory workers, the public and the environment from potentially hazardous biological materials. Compliance with State and Federal regulations is essential if experiments are to be done safely, although excessive interference would hinder research unnecessarily. The University of California, San Francisco (UCSF) Institutional Biosafety Committee (IBC) provides guidance in determining the use of biological safety precautions that effectively reduce or eliminate the risk of exposure to potentially hazardous biological materials used in research. The other essential goal of the Committee, and by extension, the Biosafety Officers (BSOs), is to protect the University from punitive sanctions by Federal or State agencies as a result of compliance failures on the part of the research community. It is a difficult balance to maintain, and full cooperation and dialog between the research community and the IBC is essential to successfully achieve this balance. Biological research laboratories are special work environments that pose potential exposure risks to infectious diseases, genetically modified organisms (GMOs) or toxins by persons working in these laboratories or entering them. There is a clear historical record of laboratory-acquired infections; more than 4,000 laboratory-acquired infections have been reported and many others have certainly occurred. Incidents such as a splash to mucous membranes, needle stick, contamination of open wounds or skin lesions, ingestion or inhalation of an aerosolized infectious agent or toxin have all produced laboratory-acquired disease. There are two documents that provide key guidance to the UCSF Biosafety Program. The CDC-NIH document Biosafety in Microbiological and Biomedical Laboratories 5th Edition (BMBL-US Government Printing Office, Washington D. C., December 2009) recommends a tiered system of laboratory practices for protection of laboratory workers, depending on anticipated risks of exposure to infectious agents and toxins. Agents themselves are assigned to Risk Groups (RGs) based upon the extent of hazard they pose to a healthy adult. Requirements for laboratory facilities and operations for working with these agents are divided into Biosafety Levels (BSLs). The criteria are cumulative; BSL2 criteria include all of the criteria for BSL1 adding additional criteria as listed. BSL3 is layered upon BSL1 and BSL2 and so on. There are also separate sets of criteria designed either for work without or with experimental animals, grouped under Biosafety Levels (BSL), and Animal Biosafety Levels (ABSL) 1, 2, 3 and 4. The second and largely dominant document that governs much of the research work at UCSF is the NIH document Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (March 2013). It is essential that Principal Investigators (PIs) understand that all recombinant genetic work, regardless of species, falls under this document. While there are categories of exempt experiments, it is critical that the PI file a Biological Use Authorization (BUA) with the IBC for all recombinant work. The 4
BSOs will review the BUA and determine if the work is exempt. Some of the exemption criteria are straightforward while others are not, and this area of regulation is rapidly changing. In addition, there are state and federal regulations that the Biosafety Program is responsible for enforcing. At the state level, the Bloodborne Pathogens standard, the California Medical Waste Regulations, and the Aerosol Transmissible Disease Standard are the regulations that impact the campus. At the Federal level, the Biosafety Program is responsible for assisting the campus in complying with the Select Agent Program, the Federal Department of Transportation shipping and packaging regulations governing the shipment of biohazardous materials, and the highly complex import and export regulations as well as other regulations that have more limited impact. The essential component of evaluating and controlling exposure to biohazardous materials is the process called Risk Assessment. The most straightforward component of risk is evaluating the possibility that a researcher could become infected with an agent they are handling. However, protection of the environment and community against an accidental release of biohazardous materials and/or genetically modified materials or animals is also essential. In order for the Biosafety Officers and the Institutional Biosafety Committee to do their analysis, researchers must provide complete and comprehensive information. It is therefore essential when completing applications, such as a Biological Use Authorization (BUA), for descriptions of the work and materials to be written so that a layperson can understand. This will be described in more detail in chapter 3. A comprehensive description of the Risk Assessment process from the BMBL may be found here: http://www.cdc.gov/biosafety/publications/bmbl5/bmbl5_sect_ii.pdf The tools used during risk assessment include identifying an agent s Risk Group, and determining the appropriate Biosafety Level (BSL) required for adequate containment. The characteristics of Risk Groups and BSLs are described in the tables at the end of the chapter. Note that Risk Groups are only based upon the potential for an agent causing disease in healthy adults, not children or those who may be at increased risk due to immunocompromised conditions. Also note that the Biosafety Level often corresponds to the Risk Group, but not always. There are many cases where an agent poses little or no risk to a person but could do serious harm to agriculture or the environment if released. The Biosafety Level will be higher than the risk group would indicate. The BSL may also be increased for working with large quantities of culture (greater than 10 liters) or if laboratory manipulations dictate higher containment conditions (i.e. generating aerosols). It is important to understand that the Risk Group for an agent is assigned by entities external to UCSF, such as the National Institutes of Health (NIH) or the World Health Organization (WHO). It is the practice of the UCSF IBC to use the most conservative reasonable RG assignment for an agent in their risk assessment. However, it is entirely the UCSF IBC s responsibility to assign the appropriate BSL for the work being done. Biosafety Information by Biosafety Level: Risk Groups Summary (http://www.ehs.ucsf.edu/risk-group-summary) Biosafety Level Summary (http://www.ehs.ucsf.edu/bio-safety-levels-summary#special%20prac) Based upon the CDC/NIH Document Biosafety in Microbiological and Biomedical Laboratories ( BMBL ), 5 th edition, December 2009. 5
Chapter 2 Biological Safety Program Administration The essential objectives set forth in the Biological Safety (Biosafety) Manual and associated biosafetyrelated trainings are: To protect University of California, San Francisco (UCSF) patients, students, and employees against unnecessary and potentially harmful exposures to biological materials. To protect the human and animal populations outside of our facilities from the release of any potentially hazardous agent whether wild-type or especially if genetically modified. To ensure compliance with international, national, state, and local regulations that impact biological research, thereby protecting both the researcher and the institution from harm. For these rules and procedures to be effective each involved person or administrative office must have their roles and responsibilities clearly defined. A. CHANCELLOR The Chancellor is ultimately responsible for assuring that comprehensive campus-wide programs are in place for the safe handling of all hazardous materials at UCSF. The Institutional Biological Safety Committee (IBC) and the Office of Environment Health and Safety (EH&S) have been charged with the planning and implementation of the campus Biological Safety Program whose purpose is to ensure the health and safety of all personnel working with biohazardous or infectious agents, toxins, and materials and agents containing recombinant DNA or other genetic alterations. B. UCSF BIOLOGICAL SAFETY COMMITTEE (IBC) Federal law requires the establishment of an Institutional Biosafety Committee (IBC) at institutions where recombinant biological materials are used in research. At UCSF, the IBC is appointed by the Vice Chancellor for Research and consists of a Chair, Vice Chair, and members selected to represent the UCSF faculty, staff, and public interests, and to provide expertise in a wide variety of biological disciplines. At least two community members with no UCSF affiliation (other than membership on the IBC) are required, and are responsible for representing the surrounding community s interests regarding health and environmental protection. Ex Officio members include the Director of EH&S, the Biosafety Officer (BSO), the Director of the Animal Care Facility, and the Public Health Officer, or their designated representative. The IBC membership represents collective expertise and research experience in recombinant DNA, infectious agents, biological toxins, and animal research which are applied to the 6
evaluation of appropriate safety measures needed for experiments that may pose potential risks to health or the environment. The IBC is also specifically authorized by the Chancellor to limit or suspend any research that is not in compliance with UCSF biosafety policies and procedures. The IBC advises and works with EH&S in administering the various aspects of the campus Biosafety Program. The IBC is responsible for 1) ensuring that research conducted at UCSF is in compliance with the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules ( Guidelines ); 2) drafting campus biosafety policies and procedures; and 3) reviewing individual research proposals for biosafety concerns. The IBC meets monthly to review proposals from faculty at all UCSF campuses and affiliated Institutes (Gladstone, Gallo, Howard Hughes Medical Institute, and others), and faculty members who work off-campus. Veterans Administration-funded projects are specifically excluded from the IBC's charge. The IBC does not oversee biosafety policies for the hospitals and clinics, but does provide consultation when requested. Biosafety policies for hospitals and clinics are the responsibility of the respective Hospital Epidemiology and Infection Control Committees. Principal Investigators (PIs) who wish to perform research using biological materials must submit a Biological Use Authorization (BUA) application to the IBC for approval prior to beginning work. The Committee generally reviews applications that involve work at Biosafety Level 2 or 3 and the BSO and Assistant Biosafety Officers (collectively BSOs ) review Biosafety Level 1 research applications. BSL 1 applications are usually considered exempt from committee review unless a BSO has specific concerns that warrant full Committee involvement, or if the work involves certain types of recombinant genetic work. IBC review includes an independent assessment of the containment levels required by the NIH Guidelines for the proposed research, an assessment of the laboratory facilities, procedures and practices, and a review of the training and expertise of personnel. While the IBC cannot alter the Risk Group of an organism, it is within the IBC s authority to raise or lower containment for the work involving the organism based upon a full risk assessment of the work being done. Recommendations for the biosafety level (BSL) of laboratory operation are often modified according to the number of infectious particles encountered in the project and the usual route of infection. C. ENVIRONMENT HEALTH AND SAFETY (EH&S) The Office of Environment Health and Safety (EH&S) administers the Biological Safety Program as well as other campus safety programs such as radiation and chemical safety. As designated by the Director of EH&S, the Biological Safety Officer is primarily responsible for implementing and overseeing the campus Biological Safety Program. 1. BIOSAFETY OFFICER (BSO) UCSF has one Biosafety Officer (BSO) and one or more Assistant Biosafety Officers (ABSOs). The BSO has overall responsibility for the operation of the UCSF Biosafety Program, and provides supervision to the ABSOs. In general the BSOs duties include, but are not necessarily limited to, providing technical advice to the IBC and researchers on laboratory containment and safety procedures, conducting pre-reviews of authorization applications and interacting with Principal Investigators to ensure that the applications are 7
complete and understandable, overseeing or conducting periodic inspections to ensure that laboratory standards are rigorously maintained, and developing emergency plans for handling spills and personnel contamination. The BSO regularly reports on the status of the Biological Safety Program to the IBC, particularly if any significant problems or violations of the NIH Guidelines or any research-related accidents or illnesses have occurred. The BSO is also responsible for overseeing all phases of operations for all BSL3 laboratories, and is the Responsible Official for Select Agents. The ABSOs review and approve Biosafety Level 1 applications and work closely with the Environment, Health and Safety Specialists on all aspects of the Biological Safety Program. One ABSO provides specialized safety consultations to the vivarium staff. 2. EH&S SPECIALISTS Environment, Health and Safety Specialists (EH&S Specialists) are the primary contact persons regarding all EH&S activities for their assigned departments. The EH&S Specialist is responsible for conducting laboratory inspections, reviewing proper operation of safety equipment such as biosafety cabinets and autoclaves, and ensuring that laboratory personnel are current on required trainings. EH&S Specialists also help researchers complete their Biological Use Authorization (BUA) application and maintain an accurate and up-to-date Biological Safety Logbook. 3. PUBLIC HEALTH OFFICER (PHO) The Public Health Officer (PHO) is an employee of EH&S who interacts with the Occupational Health Program and works closely with researchers to ensure that medical surveillance, such as screening and vaccinations, are completed. The PHO also ensures biohazardous material exposure reports are managed and investigated, as necessary. The PHO works with the BSOs and IBC to investigate laboratory exposures and laboratory-acquired infections, advises the IBC regarding new developments in regulatory medical surveillance programs, and is an ex officio member of the IBC. D. OCCUPATIONAL HEALTH PROGRAM (OHP) The Occupational Health Program (OHP) provides general occupational health services to all UCSF staff. The director of the OHP serves as an ex officio member of the IBC and provides recommendations for appropriate medical surveillance and preventive programs for personnel using biohazardous materials. E. DEPARTMENT CHAIR Each Department Chair is responsible for providing adequate support to researchers in their unit or department to ensure that appropriate facilities are available to contain and control biological hazards, as well as to enable PIs to comply with applicable regulations and campus policies. Chairs are also responsible for assuring that the PI and all personnel listed on a Biological Use Authorization (BUA) application have both technical ability and safety training that is commensurate with the proposed project, and that the project s design and monitoring methods meet UCSF safety standards. Department Chairs, or their designated safety representatives, are responsible for correcting work errors and 8
conditions that may result in personal injury, exposure to, or release of biohazardous agents or materials. F. PRINCIPAL INVESTIGATOR (PI) The Principal Investigator (PI) is directly and primarily responsible for the safe operation of their laboratory, and for compliance by all their laboratory personnel with all UCSF biosafety policies and procedures. The PI s knowledge and judgment are critical in assessing risks and appropriately applying campus biosafety guidelines. 1. THE PI MUST ASSURE THAT: they will not initiate research using infectious agents, human blood or tissues, toxins, or recombinant DNA (rdna) unless all the applicable requirements outlined in this manual are met. they will consult Chapter 1 s tables and the appropriate references (web links) to determine the appropriate Risk Group classification of the microorganisms to be used, and that they will use the prescribed microbiological practices and laboratory techniques required by the Biosafety Level assigned to their work by the IBC. they will report immediately to the BSO all violations of the policies and procedures and all significant research-related accidents (spills, needle-sticks, exposures, injuries, etc.) which result in overt or potential exposure to infectious materials, or their release into the environment, whether contained within the laboratory or not. they are prepared to implement methods for dealing with accidental spills and personnel contamination. appropriate permits required by the United States Department of Agriculture (USDA), the Centers for Disease Control (CDC), Food and Drug Administration (FDA), and any state or local permits for work with certain animal and plant pathogens are obtained prior to beginning work. they will follow all appropriate importation, exportation and interstate shipping requirements for certain biological materials. See Chapter 19. 2. PRIOR TO BEGINNING RESEARCH, THE PI SHALL: receive appropriate IBC or BSO approval for all research projects. determine, in consultation with the BSO (514-2824) and Public Health Officer (514-3531), the usefulness of serological screening, the requirements of medical surveillance, and the availability of vaccination for Risk Group 2 and 3 agents. They shall inform the laboratory staff of the reasons and provisions for any precautionary medical practices advised or requested, such as vaccination or antibody titers. Where appropriate, the hepatitis B vaccination series must be offered free of charge to the employee. The PI is responsible for ensuring that records of HBV immunizations and/or declination statements for his or her staff are sent to the Occupational Health Program for filing. The PI must not keep these documents themselves. communicate in writing to the IBC any protocol changes that modify the research procedures or alter the list of biohazards, upon which approval was originally based. Other modifications, such as changes in personnel or laboratory sites, should be submitted online via the Research Information Online (RIO) system. 9
assure that personnel working with infectious agents or biohazardous materials are appropriately trained so that they are aware of the hazards, and are proficient in the practices and techniques required for the safe handling of such materials. Instruction in proper laboratory procedures, bloodborne pathogens, Herpes B and Q-fever training is available through EH&S. For more information, contact the department s EHS Specialist. 3. DURING THE CONDUCT OF THE RESEARCH, THE PRINCIPAL INVESTIGATOR SHALL: appropriately supervise the performance of their staff to ensure that the required safety practices and techniques are employed. investigate and report in writing to the IBC via the BSO any significant biosafety problems pertaining to the pursuit of the research goals, specifically, new information which was not available at the time of the application. The PI is responsible for correcting any conditions that might expose their personnel or release biohazardous materials into the environment. implement the procedures prescribed for dealing with laboratory accidents. assure that the biological characteristics of the microorganisms used in experiments haven t undergone adverse change. Periodic assessment should include the purity and phenotype of the strain. Special restrictive characteristics such as attenuation or replication deficiency require regular surveillance. Strain verification should be performed periodically on all replicationdefective microorganisms. G. LABORATORY PERSONNEL Safety in activities involving biohazardous agents ultimately depends on the individual conducting these activities. Motivation and good judgment are essential in the protection of health and the environment. The NIH Guidelines are intended to help the institution, the IBC, EH&S, and the PI determine the safeguards that should be implemented. These guidelines will never be complete or final in that all conceivable experiments involving rdna and other biohazardous agents cannot be foreseen. Therefore, it is the responsibility of each individual employee to adhere to the intent of the NIH Guidelines as well as to specific procedures. Personnel who work with RG 1 agents must have standard training in microbiological practices to ensure proper handling of the agent. Those personnel working with RG 2 or 3 agents must also have specific training in handling pathogenic microorganisms, and those individuals working with Risk Group 3 agents must have specific training in handling potentially lethal agents. Annual Bloodborne Pathogen training is required for all UCSF employees with potential occupational exposure to HIV/HBV/bloodborne pathogens and Q-fever training is required for personnel working with sheep, goats or their tissue. Herpes B virus training is required for those working with Old World Primates, their tissues or body fluids. Immunocompromised persons should contact the Occupational Health Program, whose practitioners can provide medical advice regarding possible work restrictions. This includes individuals under systemic corticosteroid therapy, chemotherapy for malignancies, radiation therapy, and those who have certain diseases (e.g., lymphomas, leukemia, AIDS) which induce severe impairment of immune competence. 10
Researchers who are pregnant, or anticipate becoming pregnant are encouraged to contact the Occupational Health program. Amended work practices can be identified by OHP practitioners who can then guide the researcher and the PI towards establishing safe working conditions. Certain microbes such as Listeria monocytogenes, Toxoplasma gondii, LCMV, Rubella virus, cytomegalovirus, and vesicular stomatitis virus pose a specific hazard to pregnant women, who should carefully evaluate the risk of working with or near these agents. The Public Health Officer and OHP should also evaluate special hazards and exceptions (e.g., individuals vaccinated against rubella virus) so that appropriate guidance can be given to the individual and the PI. Chapter 3 Who Needs a Biological Use Authorization Approval? University of California, San Francisco (UCSF) Principal Investigators (PIs) planning to carry out research which may involve biological hazards should submit a Biological Use Authorization (BUA) application form to the Institutional Biosafety Committee (IBC) for review and approval. The BUA application is available electronically at Research Information Online (https://rio.ucsf.edu). Researchers using any of the following should complete and submit a BUA application form for review and approval (Orientation and Reference Guide for Online BUA Application in RIO): Recombinant DNA materials or technology Human source material (including established or primary cell lines, blood, body fluids, organs, and tissues) Infectious agents (including Risk Group 1 agents that are infectious to vertebrates other than humans). Toxins of biological origin Transgenic plants or animals in which the genome will be altered by stable introduction of recombinant DNA into the germ-line (e.g. making founder lines and breeding existing lines to create new genetic lines, but NOT including purchasing or maintaining already established lines) Human gene transfer Sheep or primates or their source material Wild caught animals Animals or their source material requiring permits to use or bring in to the State of California If you are uncertain whether your research falls into any of the above categories, contact the Biosafety Officer (BSO) at 514-2824. The IBC has delegated authority to the Biosafety Officer (BSO) to approve the following types of research without Committee review: Bloodborne pathogen only applications (e.g., human blood, body fluids, or cell lines, fixed human tissue). Work with human or some primate blood or tissues known to harbor pathogens may require full IBC approval. Infectious agent work limited entirely to RG1 agents 11
rdna work where hosts and vectors are restricted to RG1, or human cell lines are used as hosts, unless oncogenes or other toxic genes are inserted Toxin usage where the LD 50 value of the toxin >25 ug/kg (including non-hazardous subunits) Modifications to BUAs that are either administrative (adding rooms or staff), or involve adding any materials listed above, even if the overall BUA is designated for Committee review If you are working with potentially infectious agents, recombinant materials, or toxins and human subjects or experimental animals, IBC review is necessary in addition to review by the Committee on Human Research (CHR) and/or the Institutional Animal Care and Use Committee (IACUC), respectively. Note: The IACUC and the CHR do not consider biosafety issues during their respective reviews. PIs whose research comes under the governance of any of the following campus rules or governmental regulations are required to complete a BUA, and where applicable, maintain a medical surveillance program for laboratory employees: NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules Cal-OSHA Bloodborne Pathogens Standard Cal-OSHA Aerosol Transmissible Diseases Standard Cal-OSHA Special Orders for Q-Fever Medical Waste Management Act (generation of medical [red bag] or sharps waste) International, Federal, and State Transport, Import, or Export Regulations For additional information, call the Technical Committees Coordinator at 476-2198 or contact your Environment, Health and Safety Specialist (EH&S Specialist). For more detailed information about the BUA review process, see Chapter 4. Chapter 4 The Biological Use Authorization (BUA) Process New BUA applications and renewals are done online in RIO (https://rio.ucsf.edu). If you are new to UCSF, request a new RIO Account by completing the online form at the above link. Instructions for completing the online BUA are detailed in the Orientation and Reference Guide for Online BUA Application in RIO. A. NEW APPLICATION PI status is required to obtain a BUA. Request PI status for RIO by contacting the BSO at 514-2824 or via email at Peili.Zhu@ucsf.edu. You will be notified when you have PI status in RIO. To start a new BUA Application, log into RIO using the same username and password you use for MyAccess and click on Portfolio List. Populate your portfolio with locations, personnel, and equipment. To create your BUA application, scroll up to the Authorizations and Protocols section of your portfolio. Start a BUA 12
application using the Create New Application(s) link. Click the box for Biological Use Authorization (BUA) Application. Press the Create Application(s) button. B. RENEWALS BUAs must be renewed every three years, with the exception of BUAs covering work conducted at Biosafety Level 3, which are renewed annually. Renewal reminder notices are sent approximately 90 days prior to the expiration date of each application. If the PI does not respond within the prescribed period, the IBC will be notified and the BUA terminated. To renew your BUA, log into RIO using the same username and password as MyAccess and click on Portfolio List on the RIO Home Page. Find your portfolio and follow the Click Here link under Details to open the portfolio. Read the instructions and then scroll down to see the authorizations, personnel, locations and equipment that are listed in your portfolio. Check the contents of each list and update as needed. Scroll up to the Authorizations and Protocols section of your portfolio and read the instructions. Press Click Here to open the BUA you want to renew. Click the Create Renewal or Modification button and select the Renewal option. The renewal application will have the same BUXXXXX number, but with an -02, -03, etc. extender, depending on how many times the BUA has been renewed. Demographic information on your BUA application is on the Main page, i.e., type / sub-type, PI name, BUA title, PI department (or location), assigned EH&S Specialist, approval date (blank until approved), expiration date (of currently approved BUA), approval status (of BUA renewal application). C. MODIFICATIONS It is important that the IBC and EH&S maintain accurate records of all ongoing experiments utilizing biological materials. Therefore, PIs should submit a modification request for changes in personnel, research locations, biomaterials and/or experimental procedures which may impact the biosafety requirements. This modification must include a narrative describing proposed changes when adding biomaterials or procedures. To submit a modification, open up the BUA you wish to modify and press the Create Renewal or Modification button. Select the Modification option. D. BUA TERMINATION If a PI terminate a BUA, EH&S must be notified in writing via a Principal Investigator BUA Termination Form. This notification will ensure that the inspection, training and surveillance programs instituted for the BUA are appropriately included, that all research materials are accounted for, and that items which are no longer to be used are appropriately decontaminated and/or disposed. EH&S provides assistance in the disposal or transfer of any biological materials which are no longer needed and all biohazard warning signs will be removed from the facility. 13
Chapter 5 Instructions for Human Gene Transfer Research Submission to IBC at UCSF Human gene transfer is the process of transferring genetic material (DNA or RNA) into a person. At present, human gene transfer is experimental and is being studied to determine whether or not it can treat certain health problems by compensating for defective genes, producing a potentially therapeutic substance, or triggering the immune system to fight disease. Human gene transfer research falls under the federal NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guildelines). The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules specify practices for constructing and handling rdna molecules, organisms and viruses containing rdna molecules. For experiments involving human gene transfer, no research participant shall be enrolled until the Recombinant DNA Advisory Committee (RAC) review process has been completed and approvals obtained from the Institutional Biosafety Committee (IBC) (from the clinical trial site), the Institutional Review Board approval (IRB), and any additional applicable regulatory authorization(s). Please note that although the information below is extensive, PIs should not consider it to be a complete list of all requirements; please refer to the NIH Guidelines for additional information. It is the PI s responsibility to ensure that ALL regulations and requirements are met. Below are UCSF s procedures for assisting Principal Investigators (PIs) in complying with the NIH Guidelines. I. PRIOR IBC APPROVAL REQUIREMENTS: Submit a BUA application for IBC review and approval via the online system Research Information Online RIO (https://rio.ucsf.edu). Provide the following documents by uploading electronic copies to the BUA document library ('Documents' link in the left menu). Requirements Status 1 Completed Appendix M submitted to the NIH RAC Explain if not applicable 2 Copy of RAC Review and Relevant Correspondence with RAC If pending, provide date when submitted for RAC review. 3 Clinical Protocol Explain if not applicable 4 Investigator s Brochure Explain if not applicable 5 FDA IND Correspondence Explain if not applicable 6 Informed Consent Forms Must be site-specific II. POST IBC APPROVAL REQUIREMENTS 14
Biosafety Officer must conduct a site inspection III. CHANGES TO BUA BUA modification is required for: Serious Adverse Event (SAE) submission Changes in location Title change (in some instances) Changes to the investigational drug (at a minimum requires an amendment but may require a new BUA) IV. REPORTING REQUIREMENTS (POST IBC APPROVAL) A. If clinical trial is initiated at UCSF, the Principal Investigator(s) shall submit the following documentation to the IBC and NIH/OBA within 20-working days after enrollment of first trial participant: 1. copy of the informed consent document approved by the IRB; 2. copy of the protocol approved by the IBC and IRB; 3. copy of the final IBC approval from the clinical trial site; 4. copy of the final IRB approval; 5. applicable NIH grant number(s); 6. the FDA IND number; and 7. the date of the initiation of the trial. 8. brief written report that includes the following information: how the investigator(s) responded to each of the RAC s recommendations on the protocol (if applicable); and any modifications to the protocol as required by FDA B. Annual Reports: Although the BUA does not expire annually, the annual report is subject to verification requirements: 1) Within 60 days after the one year anniversary of the date on which the IND application went into effect, and after each subsequent anniversary until the trial is completed, the PI (or delegate) shall submit to the NIH/OBA and IBC the information set forth in the NIH recombinant DNA guidelines (see below) 2) To submit the report to the IBC, log on to RIO (https://rio.ucsf.edu). to access the BUA application. Upload the Annual Report to the BUA document library and provide a brief, non-technical summary of the study. 3) The following items must be included in each annual report: (a) Clinical Trial Information: A brief summary of the status of each trial in progress and each trial completed during the previous year. The summary must include the following information for each trial: 15
1. the title and purpose of the trial; 2. clinical site; 3. the Principal Investigator; 4. clinical protocol identifiers, including the NIH OBA protocol number, NIH grant number(s) (if applicable), and the FDA IND application number; 5. participant population; 6. the total number of participants planned for inclusion in the trial; the number entered into the trial to date; the number whose participation in the trial was completed; and the number who dropped out of the trial with a brief description of the reasons; 7. the status of the trial, i.e. open to accrual of subjects, closed but data collection ongoing, or fully completed, and 8. if the trial has been completed, a brief description of any study results. (b) Progress Report and Data Analysis. Information obtained during the previous year's clinical and non-clinical investigations, including: 1. a narrative or tabular summary showing the most frequent and most serious adverse experiences by body system; 2. a summary of all serious adverse events submitted during the past year; 3. a summary of serious adverse events that were expected or considered to have causes not associated with the use of the gene transfer product such as disease progression or concurrent medications; 4. if any deaths have occurred, the number of participants who died during participation in the investigation and causes of death; and 5. a brief description of any information obtained that is pertinent to an understanding of the gene transfer product s actions, including, for example, information about dose-response, information from controlled trials, and information about bioavailability. (c) A copy of the updated clinical protocol including a technical and non-technical abstract. C. Safety Reporting: 1) Principal Investigators must submit a written report clearly labeled as a Safety Report to the NIH/OBA and the IBC (via BUA amendment) in the following instances: a) Any SAE that is both unexpected and associated with the use of the gene transfer product (i.e., there is reasonable possibility that the event may have been caused by the use of the product; investigators should not await definitive proof of association before reporting such events); and Any SAE that is fatal or life-threatening, that is unexpected, and associated with the use of the gene transfer product must be reported to the NIH OBA as soon as possible, but not later than 7 calendar days after the sponsor s initial receipt of the information (i.e., at the same time the event must be reported to the FDA). Any SAE that is unexpected and associated with the use of the gene transfer product, but are not fatal or life-threatening, must be reported to the NIH OBA as soon as possible, but not later 16
than 15 calendar days after the sponsor s initial receipt of the information (i.e., at the same time the event must be reported to the FDA). 2) Safety Reporting: Content and Format a) The SAE report must include, but need not be limited to: 1. the date of the event; 2. designation of the report as an initial report or a follow-up report, identification of all safety reports previously filed for the clinical protocol concerning a similar adverse event, and an analysis of the significance of the adverse event in light of previous similar reports; 3. clinical site; 4. the Principal Investigator; 5. NIH Protocol number; 6. FDA s IND Application number; 7. vector type and subtype; 8. gene delivery method; 9. route of administration; 10. dosing schedule; 11. a complete description of the event; 12. relevant clinical observations; 13. relevant clinical history; 14. relevant tests that were or are planned to be conducted; 15. date of any treatment of the event; and 16. the suspected cause of the event. 3) The items above may be reported by using the NIH OBA s Adverse Event Reporting Template or other means provided that all of the above elements are specifically included. V. CONTACT INFORMATION EH&S Biosafety Staff: Peili Zhu Biosafety Officer (415) 514-2824 peili.zhu@ucsf.edu Jonathan Koolpe Assist. Biosafety Officer (415) 502-1799 jonathan.koolpe@ucsf.edu Mei-Chuan Huang Assist. Biosafety Officer (415) 476-2097 mei-chuan.huang@ucsf.edu Sean Umamoto Assist. Biosafety Officer (415) 514-2665 Sean.umamoto@ucsf.edu NIH/OBA Office of Biotechnology Activities 17
National Institutes of Health, MSC 7985 6705 Rockledge Drive, Suite 750 Bethesda, Maryland 20892-7985 E-mail: oba@od.nih.gov Fax: 301-496-9839 Chapter 6 Laboratory Design and Biosafety Cabinets Laboratory Design must follow: UC EH&S Laboratory Safety Design Guide UCSF Addendum to UC EH&S Laboratory Safety Design Guide BSO must attend Plans Review meetings for all new and/or renovation projects. Biosafety Cabinet Characteristics Comparison Biological Safety Cabinets (BSCs) are designed to provide personnel, environmental and product protection when appropriate practices and procedures are followed. Three kinds of BSCs, designated as Class I, II and III, have been developed to meet varying research and clinical needs. From Primary Containment for Biohazards, Selection, Installation and Use of Biological Safety Cabinets, 5 th edition, September 2009 Installation may require a special duct to the outside; an in-line charcoal filter; and a spark-proof, explosion-proof motor and other electrical components in the cabinet. Discharge of a Class I or Class II, A2 cabinet into a room should not occur if volatile chemicals are used. The chemical concentration in the cabinet should never approach the lower explosive limit (LEL) of any compound. 18
Chapter 7 Medical (Biohazardous) Waste Management Research with biological and in particular with biohazardous materials generate waste that cannot be discarded in the regular trash. At UCSF, the large majority of this waste is accumulated in red Medical Waste bags, which are picked up by EH&S to be transferred to the waste disposal vendor, and depending on the nature of the contents, are either autoclaved or incinerated. The storage and disposal procedures are described below. For A/BSL3 laboratories only, wastes are autoclaved out of the laboratories. The autoclaved waste is then picked up and transferred to the vendor for incineration. 19
Medical (Red Bag) Waste Accumulation Policy & Procedure Only red bags are legal in California, ALL other colors are prohibited. Anything contained in a red bag labeled Biohazardous MUST be managed as medical waste. Do NOT use red bags for storing non-waste or as an equipment cover. These may be picked up. All solid medical waste must be picked up by EH&S. For pick up at Parnassus, Mt. Zion, Mission Bay, Laurel Hts. call 476-0546 SFGH Call 206-8076. If you work in a Biosafety Level 1 (BSL1) laboratory Microbiological solid waste such as petri dishes can be discarded in regular trash, in closed clear or white bags to contain odors prior to pickup by janitorial staff. Drain dispose liquid waste if not mixed with chemicals or radioisotopes. Discard sharps in sharps containers. NOTE: Waste generated from Recombinant DNA procedures involving RG1 materials are disposed of as biohazardous waste. See detailed information here. The following types of BSL1 rdna waste are EXEMPT from the NIH Guidelines and can be disposed of as non-biohazardous waste (in regular trash), in closed clear or white bags to contain odors prior to pickup by janitorial staff. ** 1. BSL1 rdna waste which is not in organisms or viruses (e.g., DNA, RNA, oligos waste, PCR waste, Microarrays, etc.). 2. BSL1 rdna waste from experiments which use Escherichia coli K-12 host-vector systems. The system uses only non-conjugative plasmids as vectors (e.g., pbr322, pbr313) and does not contain conjugation proficient plasmids or generalized transducing phages. 3. BSL1 rdna waste from experiments involving Saccharomyces cerevisiae and Saccharomyces uvarum host-vector systems. 4. BSL1 rdna waste that contains less than one-half of any eukaryotic viral genome that is propagated and maintained in cells in tissue culture. If you work in a BSL2 or BSL3 laboratory Discarding Liquid Biohazardous Waste Decontaminate liquid biohazardous waste by mixing one volume of undiluted bleach with nine volumes of liquid biohazardous waste (final dilution of 1:10), and mix thoroughly but carefully to avoid any spill or aerosol. Allow to stand for 30 minutes (prion waste has other requirements; contact a BSO for more information). This can be drain-disposed if not mixed with chemical or radioactive material. Liquid biohazardous waste must be decontaminated. 20
* Examples of liquid biohazardous waste include: Risk Group 2 (RG2) or Risk Group 3 (RG3) vacuum trap contents, decanted tissue culture media, microbial cultures human or primate blood, serum, or other body fluids Discarding Solid Medical Waste: Pathological Waste is: All solid waste from BSL3 labs after autoclaving, human surgery specimens, tissue, or human body waste > 1 cubic inch but not needing mortuary disposal, animal tissues > 1 cubic inch, animal carcasses Biohazardous Waste is: Solid waste from BSL2 laboratories known or thought to be contaminated with RG2 agents such as: diagnostic specimens, sharps, cultures from human or animal specimens, RG2 bacterial or viral culture or spore production, live or attenuated vaccines used in research, fluid blood or blood products, or containers or equipment containing fluid, blood Segregate pathological and biohazardous wastes into separate clearly labeled containers. Medical Waste Container Labeling: Both liquid and solid medical waste must be labeled with the biohazard symbol and "Biohazard" on all sides and lid. Pathological waste containers must be labeled with Pathology Waste or PATH or for incineration on all sides and on the lid, in addition to the biohazard symbol. Bags containing medical waste must be inside a medical waste container with a tight-fitting lid at all times. The lid must be in place when container is not in active use. DO NOT store red bags containing waste on floors or carts. DO NOT overfill bags. Ensure that they are securely fastened for transport with no tearing or leaking. If needed, use double bags. What must NOT go into a red bag? Sharps such as needles, syringes, scalpels, razors or Pasteur pipettes (these must be placed in rigid sharps containers) Chemical or radioactive waste, or mixed waste (bio+chem, bio+rad, chem+rad). Contact your EH&S Specialist before creating any mixed-waste to ensure proper disposal. Uncontaminated waste, except in BSL3 laboratories. What laboratory waste must not be autoclaved? BSL1 & 2 labs should never autoclave sharps waste containers. 21
Never autoclave chemical or radioactive or mixed waste as these materials may become volatile in an autoclave. Autoclaved waste must not go into the trash except under special conditions. Contact your EHS Specialist to learn more. BSL3 and ABSL3 laboratories must autoclave out all wastes. Please see the description of steam autoclaving below and the Autoclave Quality Control Procedures at the end of this chapter. Sterilization and Disinfection There is an essential difference between the terms disinfection and sterilization. As the word implies, sterilization is the complete rendering of all viable materials non-viable. Disinfection is less broad or thorough. It is the sufficient reduction in quantity of organisms present to render them harmless. At the minimum, all infectious or biological materials, and all contaminated equipment or apparatus should be disinfected before being washed, stored or discarded. There are a number of alternative methods available to achieve sterilization and disinfection. The specific method used will depend on a number of parameters such as the agents, area surfaces, sensitivity of equipment to chemicals or temperature and the facility design. These guidelines are not intended to be a comprehensive listing of all potential methods or chemicals used. Contact the BSO or your EHS Specialist for specific recommendations. Steam Autoclaving The recommended method for sterilization of biohazardous material is steam autoclaving. Since treatment conditions to achieve sterility will vary in relation to the volume of materials treated, its contamination level, the moisture content, and other factors care should be exercised in using this method of sterilization. In general, it is recommended that the autoclave be operated at a temperature of 121 C and run for a minimum of 30 minutes. The use of steam autoclaves at UCSF for destroying waste is limited to work in BSL2* or BSL3 laboratories, or ABSL3 facilities. These autoclaves must meet stringent requirements for certification under the California Medical Waste Management Act for medical waste disposal. Even after autoclaving, waste from these autoclaves is disposed of as pathological waste, which is collected by EH&S and sent out for incineration. Biohazardous waste from BSL2 labs is also collected by EH&S for offsite autoclaving and disposal. See the Autoclave Quality Control Program at the end of this chapter for more information. For non-waste autoclaving, the recommendations of the manufacturer of a particular autoclave should be followed in order to provide an adequate pressure/temperature/time cycle to ensure sterilization. It is also recommended that plastic autoclaving bags with a color indicator be used to give a visual indication that the material is indeed sterile. This is especially important when highly potent biological agents are involved. The use of sterilization tape is required on all contaminated materials undergoing all types of sterilizations listed above. However, since these tapes are likely to be dislodged during the process, it is 22
also required that red medical waste bags are also capable of having lettering that states autoclaved or similar, that changes color, or appears after sterilization cycle is complete. This confirms that the surface of the bag met sterilization criteria. The following is a listing of adequate time and temperature for most common steam sterilizations using autoclaves. Laundry 250 F (121 C) for 30 minute with 15 minutes pre-vacuum of 27" Hg. Waste 250 F (121 C) for 1 hour with 15 minute pre-vacuum of 27" Hg. Glassware 250 F (121 C) for 1 hour with 15 minute of pre-vacuum of 27" Hg for a full rack of glassware. Ensure that glassware is in a secondary container of metal or heat-resistant plastic, so that any broken glass is kept from the chamber bottom. Do not place glassware directly on an autoclave rack. Liquids Liquid biological waste can usually be diluted with sufficient bleach (final dilution of 1:10) and allowed to stand for 30 minutes before being disposed down the drain. In instances where media or other non-waste liquids are sterilized, use 250 F (121 C) for 1 hour for gallon quantities of liquid. Liquids should not be treated using pre-vacuum, as this can cause the liquid to boil over. Vivarium Autoclaving Carcasses Animal carcasses are almost never autoclaved, they are disposed of as pathological waste for incineration. In rare cases where they are autoclaved, use 250 F (121 C), 30 minute minimum, no pre-vacuum. Time depends on volume, moisture and density, and is determined by trial. Bedding 250 F (121 C) for 30 minutes or more, with a pre-vacuum of 27 Hg., Time depends on volume, moisture and density and determined by trial. Gas Sterilization Gas sterilization is reserved for entire laboratory sterilization after a major contaminating spill, or for large pieces of equipment that cannot be rendered safe by other means. All laboratory gas sterilization is conducted by outside vendors with specialized equipment and training in order to meet strict safety and environmental requirements. LARC staff is specially trained to sterilize animal housing rooms, and these operations are done with oversight and monitoring by EH&S. Liquid Disinfection An alternative method to dry heat sterilization of re-usable (not waste) sharps, glass, etc. is the disinfection of the material using a chemical agent. The recommended method is to soak the sharps, glass, and other materials for a period of time in the liquid disinfectant. The period of time contact time is dependent upon the nature of the chemical, the amount of contamination, the type of base material (metal, plastic, glass), and the resistance of the organism(s) to disinfection by the chemical being used. 23
The most common liquids fall under one of the following categories: Quaternary Ammonium Compounds These can be acceptable as general use disinfectants to control vegetative bacterial and non-lipidcontaining viruses. However, they are not active against bacterial spores or many viruses at the compounds usual use concentration (1:750). The Institutional Biosafety Committee (IBC) must approve use of quaternary ammonium compounds. Phenolic Compounds These are recommended for killing of vegetative bacteria, including Mycobacterium tuberculosis, fungi and lipid-containing viruses, spores and non-lipid-containing viruses. However, they are toxic, and their use must be approved by the IBC. Chlorine Compounds These are recommended for virtually all disinfecting procedures provided the available chlorine needed is used. Low concentrations of available chlorine (about 500 ppm) can be used for cleaning environmental surfaces if no known contamination by infectious agents is present. Household bleach is the most common type used. A 1:10 dilution of household bleach will provide sufficient strength. Bleach is corrosive, and this must be considered when disinfecting certain materials. It may be necessary to follow a wipe down with bleach with another with clear water to prevent corrosion. Also, as a corrosive, bleach must be stored as a hazardous material. Iodophores Although these show poor activity against bacterial spores they can be used for general disinfection (75-150 ppm). They are effective against many vegetative bacteria and viruses. Because of the limited range of effectiveness, their use must be approved by the IBC. Alcohols In concentrations of 60% to 70% ethanol in water, ethanol solutions are very good general use disinfectants, however they exhibit no activity against bacterial spores. Ethanol disinfection has two significant concerns. Because these solutions evaporate rapidly, sufficient liquid must be used to ensure adequate contact time. This is at least 30 seconds for environmental surfaces, and could be more depending on the nature of the contamination. Also, these solutions are highly flammable. Their use in the presence of or proximity to heat sources is potentially very dangerous. Isopropyl alcohol is slightly less effective than ethanol. If used, the optimal concentration is 60% isopropyl alcohol in water. 24
Formaldehyde Solutions At a concentration of 8%, formalin exhibits good activity against vegetative bacteria, spores, and viruses. However, this is toxic, and its use must be approved by the IBC. Formaldehyde-Alcohol Solutions of 8% formalin in 70% alcohol are considered very good for disinfection purposes because of their effectiveness against vegetative bacteria, spores and viruses. However, they are toxic, and their use must be approved by the IBC. Due to the carcinogenic nature of formaldehyde the facility must have a specially designed ventilation system and is subject to air monitoring requirements. Contact EH&S if you intend to use this method. Activated Glutaraldehyde 2% solutions exhibit good activity against vegetative bacteria, spores and viruses. Their use, however, must be limited and controlled because of their toxic properties and hazards of damage to the eye. This material s use must be approved by the IBC. Ultraviolet Light Under very limited conditions of UV radiation intensity and exposure time, certain ultraviolet radiation will kill many kinds of microorganisms; its greatest effectiveness is against vegetative forms. Room-wide use of UV has been shown to be ineffective in reducing or eliminating airborne contamination. Use in biosafety cabinets is also discouraged because it is an inadequate substitute for surface disinfection. After surface disinfection that is done properly, additional methods such as UV are not necessary, and can lead to accidental injury if someone uses the cabinet without turning off the UV lights. The eyes and skin should not be exposed to direct or strongly reflecting UV radiation. Adequate eye and skin protection must be worn when working in an UV irradiated area. Ensure that specialty goggles or safety glasses with side shields that provide protection in the far ultraviolet light range are worn when working in a UV irradiated area. Face shields, caps, gloves, gowns, etc. will protect skin. Overexposure of eyes will result in a painful inflammation of the conjunctiva, cornea and iris. Symptoms will develop 3 to 12 hours following exposure and will disappear in a day or two. Long period of exposure to high intensity UV radiation may damage the eyes permanently. Exposure to the skin will produce erythema in 1 to 8 hours following exposure. UCSF Autoclave Quality Control Program Medical (Red Bag) Waste Policy & Procedures 25
Contact your EH&S Specialist to learn more. Chapter 8 Responding to Emergencies Involving Biohazardous Materials Biological Emergencies SPILLS In any spill scenario, the priority of actions is determined by the "PEP" rule - People, Environment, and Property. The highest priority is to provide aid to injured personnel and prevent spill area access to others. Next, action should be taken to prevent environmental damage if it can be done without endangering personnel. An example would be to prevent a radioactive biomaterial or a potent toxin from entering a sanitary drain by placing an absorbent in the flow path. Finally, action to prevent property damage should be taken if it can be done safely Small spills involving most biological materials used at UCSF may be handled by laboratory personnel. If a spill is large or if laboratory personnel are uncomfortable handling the spill on their own, call the UCSF emergency number to obtain help from EH&S: From Parnassus, Mt. Zion, Laurel Hts., Mission Bay: Call 9-911 From SFGH: Call 415-206-8522 Laboratory personnel must be prepared to clean up small spills of biological or biohazardous material. Keep basic clean up equipment on hand and ensure that all laboratory staff are trained to clean up spills. Researchers working with Risk Group 2 or 3 (RG2, RG3) materials should prepare fresh 1:10 bleach solutions weekly for routine decontamination. Clean up spills of non-biohazardous biological materials using steps 3-9 below Clean up Procedures: If someone is injured and contaminated, provide first aid assistance if possible and ask an uncontaminated co-worker to call 9-911 for medical assistance. Do not take a contaminated person to the emergency room unless told by emergency room staff to do so. If a person is contaminated but not injured, remove contaminated clothing and help the person use an emergency shower or eyewash as needed. Call 9-911 for medical guidance. If a biohazardous spill is in the open laboratory, alert people in the vicinity and evacuate the laboratory immediately. The last person out closes the doors. Do not re-enter for at least 30 minutes so aerosols can be cleared to minimize the risk of inhalation exposure. Do not spread 26
contamination beyond the laboratory by staying as close to the laboratory as possible, and disinfecting shoes. Proceed as follows: 1. Post signs, and keep personnel not involved in cleaning up the spill away from the area. 2. For RG2 agents: Wear disposable gloves, eye protection, and a lab coat. For RG3 agents: Wear a disposable gown, gloves, eye protection, shoe covers, and a respirator. Also contact the Biosafety Officer at 415-514-2824 for spills of RG3 agents. 3. Remove contaminated sharps from the spill using forceps or tongs, NOT your hands! 4. Cover the spill with paper towels or other absorbent material. Avoid making the spilled material splash or spray. 5. Pour a freshly prepared 1:10 dilution of household bleach around the edges of the spill and work inward to the center. Allow 20 minutes for the bleach to kill the organisms. 6. Use additional paper towels to wipe up the spill, working from the edges into the center. 7. After initial cleanup, flood the spill area with bleach and let stand for at least 20 minutes. 8. Use paper towels to absorb spill, then wipe-down with clean paper towels soaked with bleach. 9. Disinfect any equipment, walls, or other areas likely to have been splashed by the spill. 10. Discard paper towels into a red biohazard bag if used to clean up RG2 or RG3 materials. 11. Thoroughly wash your hands and any contaminated skin with soap and water. 12. Notify a Biosafety Officer at 415-514-2824 if the spill is large, involves RG3 materials, recombinant DNA materials, a toxin, or if an injury or inhalation exposure may have occurred. If a spill is found when opening a centrifuge, close the centrifuge as soon as possible, evacuate the laboratory immediately and do not re-enter for 30 minutes, then disinfect using steps 3-9 above. If the spill is found when opening a rotor or bucket, close the rotor and move it and its contents to a biosafety cabinet (BSC) before opening to disinfect using steps 3-9. Disinfect the centrifuge interior. If the spill is inside a BSC, evacuation is not necessary. Follow steps 3-9 and keep the BSC running for at least 15 minutes after the cleanup is done. Clean the spill tray below the work area and the trough below the air intake grill while the BSC is running. Exposure and Needlesticks Exposures to any biological material (whether resulting in injury or not) and on-the-job needlesticks must be reported to the 24 hour UCSF Occupational Health Exposure Hotline. In particular, it is very important that an individual who has been exposed to any substance potentially containing bloodborne pathogens call the Hotline immediately to receive advice on time-sensitive post-exposure prophylaxis. IMMEDIATELY REPORT ALL BIOLOGICAL EXPOSURES AND NEEDLESTICKS ALL UCSF LOCATIONS EXCEPT SAN FRANCISCO GENERAL HOSPITAL (SFGH): 24 HOUR EXPOSURE HOTLINE: 415-353-7842 (STIC) AT SFGH: 415-353-7842 (STIC) 27
Chapter 9 Biological Safety Training EH&S conducts training classes for the Campus Community on a regular basis. The classes meet the regulatory requirements mandated by OSHA and the California Department of Health Services. These cover general health and safety issues, and do not replace requirements for supervisors to train or make certain employees are trained in the specific hazards of their workplace. What Safety Training is Needed? (http://ehs.ucsf.edu/ehs-safety-trainings) Accessing the UC Learning Center safety trainings: https://learningcenter.ucsfmedicalcenter.org/default.aspx Animal Biosafety Level lll Training Biosafety Training, Bloodborne Pathogen Training Safe Shipping of Biohazards Laboratory Safety for Researchers Q-Fever Training Herpes-B Training 28
Chapter 10 Animal Biosafety Animal research is highly regulated, and UCSF is committed to full compliance with all regulatory agencies and oversight groups. Everyone involved in the use of animals in research at UCSF must receive the approval of the UCSF Institutional Animal Care and Use Committee (IACUC). A Biological Use Authorization application (BUA) to work with animals involving the use of rdna (including generation of, but not the purchase of transgenic animals) and/or infectious or transmissible agents must be submitted as an online BUA application to the IBC for review and approval, in addition to requiring approval from the IACUC. (Orientation and Reference Guide for Online BUA Application in RIO): For online BUA applications, applicants must fill in the Animal Involvement section available from the link https://rio.ucsf.edu. Applicants must describe the work involving animals and any hazards that UCSF Laboratory Animal Resource Center (LARC) staff may be exposed to, and how applicants will ensure that LARC staff are protected. Assistance may be available from LARC through the LARC Assistant Manager of Husbandry at 502-1242, or email marsha.potolo@ucsf.edu before completing the form. Animal biosafety levels are assigned by the IBC for each BUA involving animal use. Once approved, LARC must be contacted prior to initiation of the research to ensure that safe operating procedures will be established. For Animal Biosafety Level Criteria (ABSL1-4), please see the CDC/NIH document Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5 th edition, Section V, located here: (http://www.cdc.gov/biosafety/publications/bmbl5/). These requirements are also briefly summarized in the table in chapter 1 of this manual. Higher-risk, complicated, or unusual animal projects are assigned a Biosafety Considerations Meeting by the IBC and/or the biosafety officer (BSO). The meeting includes project-related scientists, animal facility staff, BSO, IACUC, and occupational health professionals. At the Biosafety Considerations Meeting, the PI describes the project, its goals, significance, and challenges. The BSO and all in attendance discuss the details of the project and conduct a risk assessment (including discussion of the possible routes of exposure of biohazardous materials to staff). Any special conditions designated by the IBC, applicable occupational health concerns, and medical surveillance are discussed in the meeting. The meeting continues until consensus is reached regarding research-related procedures, required equipment and PPE, waste disposal, animal care and use issues, and emergency response procedures, among other items. 29
Disposal of Biohazardous Animal Carcasses and Large Animal Parts Animal carcasses and body parts that are recognizable or greater than 1 cubic inch (or 2 cm) must be disposed of through the approved vendor under contract with UCSF, currently Stericycle. Biohazardous animal carcasses must be double bagged in red biohazard bags, transported in leak-proof containers and taken to freezers located in LARC for storage until vendor pick-up. Animal Procedures: Procedures for using Infectious Agents in Rodents at ABSL2 Facilities Procedures for using Risk Group 2 Viral Vectors in Rodents at the ABSL2 Viral Shedding Facility Procedures for using Toxins in Rodents Procedure for using Particularly Hazardous Chemicals (PHC) in Rodents Chapter 11 Packaging, Shipping and Transport of Biomedical / Biohazardous Materials 1. Packaging, Shipping, and Transport Federal (Department of Transportation, 49 CFR 171-175) and international agencies (ICAO (the branch of the United Nations that governs all international civil aviation matters), IATA (International Air Transport Association) have in place numerous regulations for shipping of dangerous goods by surface or air. Anyone packaging, handling, shipping or transporting hazardous materials must receive training in the general requirements of handling hazardous materials as well as function specific training for the specific task(s) performed. Training is required before performing any tasks associated with shipping hazardous materials and periodically thereafter. UCSF requires retraining every two years for anyone shipping biological agents since air transport is routinely involved. Nonconformance of these regulations can result in a fine and/or imprisonment. The online UCSF Safe Shipping Training can be found at the UC Learning Center website: https://learningcenter.ucsfmedicalcenter.org/default.aspx. All documentation related to shipping biomaterials must be retained for a minimum of 2 years. 2. Shipment of Category A infectious substances Category A infectious substances includes any Infectious substance which is transported in a form that, when exposure to it occurs, is capable of causing permanent disability, life-threatening or fatal disease in otherwise healthy humans or animals. Examples of Category A infectious substances designated by scientists at WHO and the U.S. Department of Health and Human Services (HHS) are listed in table below. 30
Table 3.6.D: Indicative Examples of Infectious Substances Included in Category A in Any Form Unless Otherwise Indicated (3.6.2.2.2.1) 31