Introduction

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: bio-risk 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.[1]

Etiology and Epidemiology

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.[2] 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.[3] 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 concurrently through 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, and developing biological safety level classification.[4] 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 bio-risk assessment capacities, biosecurity, and biocontainment measures, including the regulation of biosafety through national and international policies. Other industries such as 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 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 developing approaches to prevent the emergence of LAIs.[5][6]

The incidence of laboratory-acquired infections varies among institutions conducting surveys to a specific or group of laboratories and facilities. The 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, it cannot be considered 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 their relevant findings. While these address the need for acquiring new information, they 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 bio-risks for zoonotic diseases, viruses predominate, followed by bacteria and parasites. The importance of bio-risk 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[7]

Specimen Requirements and Procedure

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.[8][9] Universal precautions must be applied accordingly.[10]

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.[11] This is much safer than the previous practice of manual transferring blood samples from the syringe to the tube.[12] 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.[13] These are examples where applying biosafety measures become crucial in the pre-analytical phase.[14]

Diagnostic Tests

Clinical laboratory scientists (medical technologists) must perform laboratory procedures both accurately and safely.[15] 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.[4] For example, low and medium-risk procedures do not need a containment facility and infrastructure 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.[16] 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.[17]

Proper disposal of wastes is necessary to prevent disease transmission.[18] 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.[19] 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.[20]

Recording and reporting procedures must be free from possible contamination and clean and dedicated space.[21] 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.

Testing Procedures

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, 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.[22][23]

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 also receive biosafety training, including topics covering bio-risk 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.[24]The integration of the monitoring of biosafety practices with monitoring of laboratory processes should proceed based on set criteria or standards. Certain indicators that indirectly assess the overall biosafety may include an updated procedure manual and work instructions, a list of trained staff with regular competency or proficiency tests, and regular quality control and laboratory equipment maintenance. 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 help ensure that biosafety measures are implemented according to the written guidelines.[25][26]

Interfering Factors

Several factors impede the application of laboratory-related biosafety measures within the facility. These may include, but not limited to:

• The absence of a technical document containing specific biosafety guidelines
• Poor biosafety skills (for example, on spills management) because of lack of training 
• The continuous presence of laboratory hazards and increased vulnerability due to poor execution of bio-risk assessment, reduction, and management activities
• Use of substandard laboratory supplies
• Poor equipment maintenance

Biosafety guidelines are more likely to be poorly implemented in facilities because of:

• Poorly written guidelines, including the adoption of generic, nonspecific procedures
• Unclear roles and responsibilities for each staff involved
• Lack of review and updating process of existing guide
• Poor dissemination and access to such guidelines

Results, Reporting, and Critical Findings

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 perform reviews and modify the procedure. Involved staff should willingly report accidents inside the laboratory. Laboratorians should not be reluctant to report such events as these may become a future source of infection.[27] Baseline data and critical findings encountered relative to implementing biosafety guidelines can improve existing practices and limit bio-risks from all personnel.[28]

Clinical Significance

Ensuring a 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 that they won’t contract any infection or disease. The spread of infectious agents from facilities to other healthcare workers, patients, and the community is preventable by applying biosafety practices.

Quality Control and Lab Safety

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.

Enhancing Healthcare Team Outcomes

As implemented in laboratories and related facilities, biosafety supports infection control aims and principles, as implemented in hospitals and clinics.[29] Likewise, adherence to biosafety guidelines takes a collaborative approach from all professionals, including non-laboratory healthcare personnel. For example, respirator fit testing 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.[30][31] 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.[32] International conferences from various institutions still exist, which concentrate on sharing best practices and harmonizing biosafety guidelines at the regional, national, and global scale.[33][34] Biosafety has been an emerging concern for occupational health.[35] 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.[36][37] 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.[38]