Biosafety guidelines are a set of policies, rules, and procedures necessary to observe by personnel working in various facilities handling microbiological agents such as bacteria, viruses, parasites, fungi, prions, and other related agents and microbiological products. Institutions requiring strict adherence to these biosafety guidelines include clinical and microbiological laboratories, biomedical research facilities, teaching and training laboratories and other healthcare institutions (e.g., clinics, health centers, hospital facilities). These guidelines are intended to provide proper management and regulation of biosafety programs and practices implemented at all levels of the organization.
Essential components of the biosafety guidelines contain some or all the following, depending on the facility: biorisk assessment and identification; specific biosafety measures, which cover the code of practice, physical plant such as laboratory design and facilities, equipment acquisition and maintenance, medical surveillance, staff training, safe handling of chemicals, with fire, radiation and electricity safety, among others. Additional components may be included such as commissioning and certification guidelines for the facilities.
Biosafety guidelines must be made clear, practical and suitable for each facility and must be available for easy reference by all staff, must be reviewed, and updated regularly. While it provides guidance in the application of biosafety practices, this technical guide cannot solely ensure a safe working environment without the commitment of each person to adhere adequately to the biosafety guidelines at all times. Continuous research on biosafety can improve the development of future guidelines
History of Biosafety
A significant milestone on biosafety initially referred to as “microbiological safety” dates back to 1908 where Winslow described a new method of examination to count bacteria present in the air A survey reviewed by Meyer and Eddie in 1941 described laboratory-acquired brucellosis which also revealed that similar infections could pose a threat to non-laboratorians. Later in 1947, the NIH Building 7 had the first peacetime research laboratory especially tailored for microbiological safety. These historical landmarks and breakthroughs are just a few of the more studies which untied the importance and relevance of biosafety in healthcare and research institutions.
The principle and profession of biosafety have developed together with the history of the American Biological Safety Association (ABSA). As briefly described by the Federation of American Scientists, the first meeting was held in 1955 with the members of the military, as the focus addressed “The Role of Safety in the Biological Warfare Effort”. Succeeding meetings attendees included the US Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH), universities, laboratories, hospitals and representatives from the industries. From then, written regulations covered the shipment of biological agents, safety training and programs, with the development of biological safety level classification International issues on biosafety and studies on the individual or group of agents became the focus in the 1980s. At present, aside from studies focusing on specific biohazard levels of pathogens, new strategies were developed to enhance biorisk assessment capacities, biosecurity, and biocontainment measures including the regulation of biosafety through national and international policies. Other industries such as in agriculture and biotechnology are now considering biosafety applications.
Epidemiology of Laboratory-Acquired Infections (LAIs)
Laboratory-acquired infections (LAIs) were considered significant because of the high risk in the laboratory workforce relative to the public, although the exposure to infectious agents can be higher in other groups of healthcare workers. Sulkin and Pike in 1949 studied several works of literature and mail surveys with an attempt to evaluate the risk of infection associated with employment in a clinical or research laboratory. Follow-up studies and reviews led to the identification and description of hazards unique to these laboratories, which later formed a basis for the development of approaches to prevent the emergence of LAIs.
The incidence of laboratory-acquired infections varies among institutions conducting surveys to a specific or group of laboratories and facilities. Monitoring and evaluation of LAIs are still absent for many institutions which could be caused by the difficulties in the reporting schemes and lack of accurate data interpretation. For instance, reporting of LAI is not similar to the reporting of notifiable diseases which is highly regulated for each healthcare institution across countries as implemented by their ministries of health. Laboratory-acquired infections may not always manifest as a disease entity. An example would be a person infected with tuberculosis, who could have an infection with TB bacilli but with no signs and symptoms, thus, cannot be considered as TB disease.
No national and global recording and reporting of LAI is in place. Though LAI incidence is reported in several publications recently, the variables and the levels of measurement under study differ, hence, combination and comparison of such studies is not a simple task. However, the need for data collection for current LAIs should highlight the importance of improving biosafety which outweighs the above issues. LAI databases were then created to contain all recently published studies and to verify its relevant findings. While these address the need for acquiring new information, it will not replace the reporting schemes implemented by individual institutions.
In 2018, Siengsanan-Lamont and Blacksell presented the results of a rapid review of LAI studies within the Asia-Pacific. Studies from 1982 to 2016 included several agents, some of these include: Shigella flexneri (Australia), Mycobacterium tuberculosis (Japan), Rickettsia typhi (South Korea), SARS-CoV (Singapore, China, Taiwan), Dengue (South Korea, Australia) and Ralstonia picketti (Taiwan) to name a few. Regarding potential biorisks for zoonotic diseases, viruses predominate, followed by bacteria and parasites. The importance of biorisk assessment and management was also emphasized, including preventive practices. Strict biosafety measures are a must for these working environments to protect themselves and the community
All specimens collected from patients require the application of biosafety measures. It starts with the instructions provided by the healthcare worker to the patient. Clear statements with explanations and step-by-step procedures are necessary, especially for patients who will collect the specimen. Healthcare workers, including laboratory staff, should be well-oriented especially when they are to collect specimens directly from patients. Personal protective equipment (PPE) must be worn at all times during the specimen collection. Universal precautions must be applied accordingly.
Several procedures exist for collecting sterile and non-sterile sample specimens. Better strategies were developed recently to minimize hazards either during and after sending the specimens into the laboratory. For example, the use of the evacuated tube system (ETS) prevented the contact of the patient’s blood from the site of extraction to the phlebotomist and the external environment during venipuncture. This is much safer than the previous practice of manual transferring blood samples from the syringe to the tube. Sputum collected in a clear and transparent container will aid in efficient visualization and assessment of sputum quality which is safer than reopening the cap. These are examples where applying biosafety measures become crucial in the pre-analytical phase.
Clinical laboratory scientists (medical technologists) must perform laboratory procedures both accurately and safely. PPE must be worn out while inside the premises of the laboratory and throughout the diagnostic procedure. There is a proper sequence of donning (putting on) and doffing (removing) PPE as recommended by the US Centers for Disease Prevention and Control (CDC). Generally, donning starts with gowning, wearing a mask (or respirator), goggles (or face shield) and gloving. Doffing may be done by removing gloves, goggles, gowns, and mask followed by proper handwashing.
Pathogen-specific and risk-specific biosafety measures are shown to be more practical and cost-effective. For example, low and medium-risk procedures do not need a containment facility and infrastructure which are designed only for high-risk procedures. Safe handling and processing of specimens can be conducted in biological safety cabinets (BSC) to prevent inhalation of generated aerosols when performing a microbiological procedure. The purpose of using BSC must be well differentiated from using fume hoods, in which the latter is only necessary for handling chemicals and not for infectious microorganisms. When dealing with specimens, keep hands away from the face and should remain inside the cabinet. Unnecessary movements inside the BSC is prohibited to prevent changes in the flow of air. For instance, the crossing of arms during the laboratory procedure is inadvisable. Also, ensure to disinfect the BSC before use.
In procedures done in the absence of a BSC, a well-ventilated area must be secured and maintained before considering it as a bench work area. When gloves become heavily contaminated, wear new gloves. Do not reuse gloves in other procedures nor soiled masks or respirators. Molecular biology laboratories perform procedures that require the use of different rooms for sample preparation, DNA extraction, amplification and sequencing, thus, the need for additional biosafety measures.
Proper disposal of wastes is necessary to prevent disease transmission. Waste segregation must be appropriately employed (e.g., infectious and non-infectious waste). Waste disposal via burning may not be practical nowadays. Hence, alternative disposal mechanisms must be finalized and institutionalized in each healthcare institution. Environmental impact is always a consideration when making decisions for waste disposal. Treatment facilities (i.e., treatment plants) are used to remove contaminants before sewage gets released into the environment. Specific steps should be written on standard operating procedure manuals and work instructions intended for laboratory staff involved.
Recording and reporting procedures must be free from possible contamination and should of in a clean and dedicated space. Similarly, wearing gloves when encoding via a computer or when using the phone is forbidden.
Because of the complexity of the laboratory work, one must be well-trained and supervised to perform biosafety measures at work, while non-authorized personnel must have restricted access to the laboratory, especially when a diagnostic test is in process.
The development of biosafety guidelines is part of the overall quality management systems implementation. For newly established facilities, ensure biosafety before the start of operations. Workflow inside the laboratory must facilitate an efficient means for carrying out processes by the laboratorian. Activities involving dirty areas (e.g., a specimen receipt, sample preparation, etc.) should be kept separate from the clean areas (e.g., microscopy, use of automated instrumentation, recording of results, etc.). Procedures for laboratory workflow can be tested through observation and evaluation by a designated biosafety officer, laboratory supervisor or an independent consultant who can conduct monitoring activities and provide technical assistance.
For labs using BSC, a smoke pattern test using in-house or commercial testers may be regularly performed to assess for good airflow before use. Anemometers may be used to check for air velocity. BSC certification provided by a service professional must be secured before use and continually re-certified once a year.
Before performing any laboratory test, the provision of required training on biosafety to the laboratory workforce is vital, either as a focused training program or as part of the training curriculum for certain laboratory procedures. Laboratory managers, section heads and supervisors should receive biosafety training as well, including topics on biorisk management and biosafety program implementation. Effective supportive supervision of laboratory staff working in any facility is a key factor for the sustained implementation of quality laboratory services.
The integration of the monitoring of biosafety practices with monitoring of laboratory processes should proceed based on set criteria or standards. Certain indicators which indirectly assess the overall biosafety may include the presence of an updated procedure manual and work instructions, a list of trained staff with regular competency or proficiency tests, with regular quality control and maintenance of laboratory equipment. Regular medical consultation for staff can early detect the risk of infection. Moreover, the presence of laboratory signage such as a biohazard symbol to recommended sites of the facility, with a well-organized mechanism for disposal of wastes can significantly minimize the risk of accidents and incidents both inside and outside the laboratory. Laboratory accreditation and certification may also aid in ensuring that biosafety measures get implemented in accordance with the written guidelines.
Several factors impede the application of laboratory-related biosafety measures within the facility. These may include, but not limited to:
Biosafety guidelines are more likely to be poorly implemented in facilities because of:
Results of testing procedures done for biosafety checks must be recorded, consolidated and interpreted regularly (i.e., daily, weekly, monthly, quarterly, or as applicable). The results may show a trend that may signal a need either for equipment maintenance, or replacement. Frequent incidents associated with a particular process may demonstrate a need to have a review and modification of the procedure. Involved staff should willingly report accidents inside the laboratory. Laboratorian should not be reluctant to report such events as these may become a future source of infection. Baseline data and critical findings encountered relative to implementing biosafety guidelines can improve existing practices and limit biorisks from all personnel.
Ensuring quality and biologically safe work environment fosters good and effective delivery of laboratory and clinical services for patients. While performing complex laboratory procedures, staff can work with a certain level of confidence they won’t contract any infection or disease. The spread of infectious agents from facilities to other healthcare workers, patients and from the community is preventable with the application of biosafety practices.
Biosafety monitoring can be part of quality control measures and quality assurance programs in the laboratory or any healthcare institution. It must be an important component of competency tests for staff and must be an essential element of organizational plans and goals.
Biosafety, as implemented in laboratories and related facilities, supports the aims and principles of infection control, as implemented in hospitals and clinics. Likewise, adherence to biosafety guidelines takes a collaborative approach from all professionals including non-laboratory healthcare personnel. Respirator fit testing, for example, can be carried out at regular intervals (i.e., once a year), in partnership with the infection control committee (ICC) or an infection control nurse of a hospital facility. Production laboratories may seek the advice of laboratory staff in the application of biosafety measures when handling certain infectious agents or products. Clinicians may work with laboratory professionals, nurses, pharmacists, sanitary officers, among others, in coming up with organizational strategies as part of the healthcare-associated infection program in hospitals and medical facilities.
From its current scope, biosafety has expanded to research facilities such as in animal research. International conferences from various institutions still exist which concentrate on sharing of best practices and harmonization of biosafety guidelines at the regional, national and global scale. Biosafety has been an emerging concern for occupational health. Educational intervention on biosafety is highly essential so that staff can be fully equipped with the correct knowledge of biosafety principles and can be able to demonstrate or enhance proper biosafety skills for all healthcare workers. Therefore, the best practices for healthcare, research, and other institutions would always require a team commitment and cooperation to achieve a biologically “safe and secure” workplace and community.
|||Kimman TG,Smit E,Klein MR, Evidence-based biosafety: a review of the principles and effectiveness of microbiological containment measures. Clinical microbiology reviews. 2008 Jul; [PubMed PMID: 18625678]|
|||Winslow CE, A NEW METHOD OF ENUMERATING BACTERIA IN AIR. Science (New York, N.Y.). 1908 Jul 3; [PubMed PMID: 17834254]|
|||Yagupsky P,Baron EJ, Laboratory exposures to brucellae and implications for bioterrorism. Emerging infectious diseases. 2005 Aug; [PubMed PMID: 16102304]|
|||Bayot ML,Bhimji SS, Biohazard Levels 2018 Jan; [PubMed PMID: 30570972]|
|||SULKIN SE, Laboratory-acquired infections. Bacteriological reviews. 1961 Sep; [PubMed PMID: 13918299]|
|||Sewell DL, Laboratory-associated infections and biosafety. Clinical microbiology reviews. 1995 Jul; [PubMed PMID: 7553572]|
|||Siengsanan-Lamont J,Blacksell SD, A Review of Laboratory-Acquired Infections in the Asia-Pacific: Understanding Risk and the Need for Improved Biosafety for Veterinary and Zoonotic Diseases. Tropical medicine and infectious disease. 2018 Mar 26; [PubMed PMID: 30274433]|
|||Cornwell-Smith N, Personal protective equipment for employees. BMJ (Clinical research ed.). 1992 Aug 22; [PubMed PMID: 1392972]|
|||Hersi M,Stevens A,Quach P,Hamel C,Thavorn K,Garritty C,Skidmore B,Vallenas C,Norris SL,Egger M,Eremin S,Ferri M,Shindo N,Moher D, Effectiveness of Personal Protective Equipment for Healthcare Workers Caring for Patients with Filovirus Disease: A Rapid Review. PloS one. 2015; [PubMed PMID: 26451847]|
|||Broussard IM,Bhimji SS, Precautions, Universal 2018 Jan; [PubMed PMID: 29262198]|
|||Ialongo C,Bernardini S, Phlebotomy, a bridge between laboratory and patient. Biochemia medica. 2016; [PubMed PMID: 26981016]|
|||Fujii C,Ishii H,Takanishi A, Safe venepuncture techniques using a vacuum tube system. International journal of nursing practice. 2013 Sep; [PubMed PMID: 24090293]|
|||Karinja MN,Esterhuizen TM,Friedrich SO,Diacon AH, Sputum volume predicts sputum mycobacterial load during the first 2 weeks of antituberculosis treatment. Journal of clinical microbiology. 2015 Apr; [PubMed PMID: 25552362]|
|||Simundic AM,Lippi G, Preanalytical phase--a continuous challenge for laboratory professionals. Biochemia medica. 2012; [PubMed PMID: 22838180]|
|||Sewunet T,Kebede W,Wondafrash B,Workalemau B,Abebe G, Survey of safety practices among hospital laboratories in Oromia Regional State, Ethiopia. Ethiopian journal of health sciences. 2014 Oct; [PubMed PMID: 25489194]|
|||Kruse RH,Puckett WH,Richardson JH, Biological safety cabinetry. Clinical microbiology reviews. 1991 Apr; [PubMed PMID: 2070345]|
|||Beilby J, Diagnostic molecular biology. The Clinical biochemist. Reviews. 2006 Feb; [PubMed PMID: 16886042]|
|||Askarian M,Motazedian N,Palenik CJ, Clinical laboratory waste management in Shiraz, Iran. Waste management [PubMed PMID: 21987412]|
|||Singh Z,Bhalwar R,Jayaram J,Tilak VW, AN INTRODUCTION TO ESSENTIALS OF BIO-MEDICAL WASTE MANAGEMENT. Medical journal, Armed Forces India. 2001 Apr; [PubMed PMID: 27407320]|
|||Armbruster DA, Hazardous waste disposal and the clinical laboratory. Clinical laboratory management review : official publication of the Clinical Laboratory Management Association. 1990 May-Jun; [PubMed PMID: 10104718]|
|||Ezzelle J,Rodriguez-Chavez IR,Darden JM,Stirewalt M,Kunwar N,Hitchcock R,Walter T,D'Souza MP, Guidelines on good clinical laboratory practice: bridging operations between research and clinical research laboratories. Journal of pharmaceutical and biomedical analysis. 2008 Jan 7; [PubMed PMID: 18037599]|
|||Newsom SW, A test system for the biological safety cabinet. Journal of clinical pathology. 1974 Jul; [PubMed PMID: 4214380]|
|||Whistler T,Kaewpan A,Blacksell SD, A Biological Safety Cabinet Certification Program: Experiences in Southeast Asia. Applied biosafety : journal of the American Biological Safety Association. 2016 Sep; [PubMed PMID: 27721674]|
|||Heiby J, Quality assurance and supervision systems. Q.A. brief. 1998 Jun; [PubMed PMID: 12294098]|
|||Rim KT,Lim CH, Biologically hazardous agents at work and efforts to protect workers' health: a review of recent reports. Safety and health at work. 2014 Jun; [PubMed PMID: 25180133]|
|||Baldwin CL,Runkle RS, Biohazards symbol: development of a biological hazards warning signal. Science (New York, N.Y.). 1967 Oct 13; [PubMed PMID: 6053882]|
|||Karim N,Choe CK, Laboratory accidents--a matter of attitude. The Malaysian journal of pathology. 2000 Dec; [PubMed PMID: 16329540]|
|||Bennett A,Parks S, Microbial aerosol generation during laboratory accidents and subsequent risk assessment. Journal of applied microbiology. 2006 Apr; [PubMed PMID: 16553720]|
|||Mehta Y,Gupta A,Todi S,Myatra S,Samaddar DP,Patil V,Bhattacharya PK,Ramasubban S, Guidelines for prevention of hospital acquired infections. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2014 Mar; [PubMed PMID: 24701065]|
|||Murphy DC, Designing a respirator fit testing program. AAOHN journal : official journal of the American Association of Occupational Health Nurses. 1992 Nov; [PubMed PMID: 1489480]|
|||Or P,Chung J,Wong T, A novel approach to fit testing the N95 respirator in real time in a clinical setting. International journal of nursing practice. 2016 Feb; [PubMed PMID: 24828795]|
|||Collins DE,Reuter JD,Rush HG,Villano JS, Viral Vector Biosafety in Laboratory Animal Research. Comparative medicine. 2017 Jun 1; [PubMed PMID: 28662750]|
|||Thelaus J,Lindberg A,Thisted Lambertz S,Byström M,Forsman M,Lindmark H,Knutsson R,Båverud V,Bråve A,Jureen P,Lundin Zumpe A,Melefors Ö, Network Experiences from a Cross-Sector Biosafety Level-3 Laboratory Collaboration: A Swedish Forum for Biopreparedness Diagnostics. Health security. 2017 Jul/Aug; [PubMed PMID: 28805472]|
|||Bakanidze L,Imnadze P,Perkins D, Biosafety and biosecurity as essential pillars of international health security and cross-cutting elements of biological nonproliferation. BMC public health. 2010 Dec 3; [PubMed PMID: 21143822]|
|||Dyson MC,Carpenter CB,Colby LA, Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards. Comparative medicine. 2017 Jun 1; [PubMed PMID: 28662748]|
|||Ritterson R,Casagrande R, Basic Scholarship in Biosafety Is Critically Needed To Reduce Risk of Laboratory Accidents. mSphere. 2017 Mar-Apr; [PubMed PMID: 28405626]|
|||Jonsson CB,Cole KS,Roy CJ,Perlin DS,Byrne G, Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents. Journal of bioterrorism [PubMed PMID: 24900945]|
|||Emery RJ,Rios J,Patlovich SJ, Thinking Outside the Box: Biosafety's Role in Protecting Non-Laboratory Workers from Exposure to Infectious Disease. Applied biosafety : journal of the American Biological Safety Association. 2015 Sep 1; [PubMed PMID: 28966562]|