Introduction

Biosafety guidelines are a set of policies, rules, and procedures that personnel must follow in various facilities handling microbiological agents, such as bacteria, viruses, parasites, fungi, prions, and other related agents and microbiological products. Institutions that must strictly adhere to these biosafety guidelines include clinical and microbiological laboratories, biomedical research facilities, teaching and training laboratories, and other healthcare institutions such as clinics, health centers, and 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 include the following, depending on the facility—bio-risk assessment and identification; specific biosafety measures covering the code of practice and physical plant, such as laboratory design and facilities; equipment acquisition and maintenance; medical surveillance; staff training; safe handling of chemicals; and safety protocols for fire, radiation, and electricity, among others. Additional components may be included, such as commissioning and certification guidelines for the facilities.

Biosafety guidelines must be clear, practical, and suitable for each facility, ensuring they are accessible to all staff and regularly reviewed and updated. While this technical guide provides guidance on biosafety practices, a safe working environment requires the commitment of each person to consistently adhere to the biosafety guidelines. Ongoing research in biosafety can improve the development of future guidelines.[1]

Etiology and Epidemiology

History of Biosafety

A significant milestone in biosafety, initially referred to as microbiological safety, dates back to 1908 when Winslow described a new examination method to count bacteria in the air.[2] In 1941, a survey reviewed by Meyer and Eddie described laboratory-acquired brucellosis, highlighting the risk of similar infections for non-laboratory workers.[3] In 1947, the National Institutes of Health (NIH) Building 7 had the first peacetime research laboratory specially tailored for microbiological safety. These historical landmarks and breakthroughs are just a few studies that untied biosafety's importance and relevance in healthcare and research institutions.

The principles and professions 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 military members, as the focus addressed The Role of Safety in the Biological Warfare Effort. Succeeding meeting attendees included the United States Centers for Disease Control and Prevention (CDC) and the NIH, universities, laboratories, hospitals, and industry representatives. From then, written regulations covered the shipment of biological agents, safety training and programs, and the development of biological safety level classification.[4] International issues on biosafety and studies on the individual or group of agents became the focus in the 1980s. 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 biosafety regulation through national and international policies. Other industries, such as agriculture and biotechnology, are now considering biosafety applications. 

Epidemiology of Laboratory-Acquired Infections

Laboratory-acquired infections have historically been considered significant due to the high risk they pose to laboratory personnel compared to the general public. However, the exposure to infectious agents can be greater in other groups of healthcare workers. In 1949, Sulkin and Pike conducted a literature review and mailed surveys to evaluate the risk of infection associated with employment in clinical or research laboratories. Follow-up studies and reviews led to identifying and describing hazards unique to these laboratories, which later formed a basis for developing approaches to prevent the emergence of laboratory-acquired infections.[5][6]

The incidence of laboratory-acquired infections varies among institutions conducting surveys of a specific group of laboratories and facilities. However, many institutions still lack systematic monitoring and evaluation of LAIs, often due to challenges in reporting and interpreting data accurately. For instance, reporting laboratory-acquired infections is not similar to reporting 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. For example, a person infected with tuberculosis could have an infection with tuberculosis bacilli but with no signs and symptoms; thus, it cannot be considered a tuberculosis disease.

There is currently no system for recording and reporting laboratory-acquired infections on a national or global scale. Although the incidence of laboratory-acquired infections has been reported in several recent publications, the variables and the levels of measurement under study differ; hence, combining and comparing such studies is not a simple task. However, the need for data collection for current laboratory-acquired infections should highlight the importance of improving biosafety, which outweighs the above issues. Laboratory-acquired infection databases have been created to compile recent studies and verify relevant findings. Although these address the need to acquire new information, they do not replace the reporting schemes implemented by individual institutions.

In 2018, Siengsanan-Lamont and Blacksell presented the results of a rapid review of laboratory-acquired infection studies conducted in 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 pickettii (Taiwan). Regarding potential bio-risks for zoonotic diseases, viruses are the most prevalent, followed by bacteria and parasites. Bio-risk assessment and management were also emphasized, including preventive practices. Strict biosafety measures are essential in these working environments to protect laboratory personnel and the community.[7]

Specimen Requirements and Procedure

All specimens collected from patients require the application of biosafety measures, beginning with the instructions provided by healthcare workers to patients. Clear statements with explanations and step-by-step procedures are necessary, especially for patients who collect the specimen. Healthcare workers, including laboratory staff, should be well-oriented, especially when collecting 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]

There are several procedures for collecting sterile and non-sterile sample specimens, with improved strategies developed recently to minimize hazards during and after specimen transport to the laboratory. For example, using the evacuated tube system prevented the contact of the patient's blood from the site of extraction to the phlebotomist and the external environment during venipuncture.[11] This method is much safer than the previous practice of manually transferring blood samples from the syringe to the tube.[12] Sputum collected in a clear and transparent container aids in efficient visualization and assessment of sputum quality, which is safer than reopening the cap.[13] These examples highlight the importance of applying biosafety measures during the pre-analytical phase.[14]

Diagnostic Tests

Clinical laboratory scientists, also known as medical technologists, must perform laboratory procedures accurately and safely.[15] PPE must always be worn out while inside the laboratory and throughout the diagnostic procedure. There is a proper sequence of donning (putting on) and doffing (removing) PPE as recommended by the CDC. Generally, donning starts with gowning, followed by wearing a mask (or respirator), goggles (or face shield), and gloving. Doffing may be done by removing gloves, goggles, gowns, and masks, followed by proper handwashing. 

Pathogen- 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 to prevent inhalation of generated aerosols when performing a microbiological procedure.[16] The purpose of using biological safety cabinets 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 biological safety cabinets are prohibited to prevent changes in airflow. For instance, crossing arms during the laboratory procedure is inadvisable. In addition, the biological safety cabinets should be disinfected before use.In procedures without a biological safety cabinet, a well-ventilated area must be secured and maintained before being considered a bench work area. If gloves become heavily contaminated, new gloves should be worn. Gloves, soiled masks, or respirators must not be reused in other procedures. Molecular biology laboratories perform procedures that require using different rooms for sample preparation, DNA extraction, amplification, and sequencing; thus, additional biosafety measures are needed.[17]

Proper disposal of wastes is necessary to prevent disease transmission.[18] Waste segregation must be implemented appropriately to ensure that different types of waste, such as infectious and non-infectious materials, are handled and disposed of correctly. Waste disposal through 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, such as treatment plants, are used to remove contaminants before sewage is released into the environment. Specific steps must be documented in standard operating procedure manuals and work instructions for the laboratory staff involved.[20]

Recording and reporting procedures must be conducted in a clean, dedicated space free from contamination.[21] Similarly, wearing gloves when encoding through a computer or phone is forbidden. Due to the complexity of laboratory work, biosafety measures must be performed by well-trained and supervised personnel. In contrast, 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 implementation of overall quality management systems. For newly established facilities, ensuring biosafety is critical before operations begin. Workflow inside the laboratory must facilitate an efficient means for carrying out processes by the laboratorian. Activities involving dirty areas, such as specimen receipt and sample preparation, should be kept separate from clean areas, such as microscopy, automated instrumentation, and result recording. 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. A smoke pattern test using in-house or commercial tests may be regularly performed for biological safety cabinet labs to assess for good airflow before use. Anemometers may be used to check for air velocity. Biological safety cabinet 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, 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 bio-risk management and implementation of biosafety programs. Adequate 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 the 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 consultations with staff can detect the risk of infection early. Moreover, laboratory signage, such as a biohazard symbol to recommended sites of the facility, with a well-organized mechanism for the 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 factors may include, but are not limited to:

• The absence of a technical document containing specific biosafety guidelines
• Poor biosafety skills, such as spill management, due to insufficient 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 due to:

• 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

Testing procedure results for biosafety checks must be recorded, consolidated, and interpreted regularly, such as daily, weekly, monthly, or quarterly, 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 the effective delivery of laboratory and clinical services. When performing complex laboratory procedures, staff can work confidently, knowing they are protected from potential infections. Applying biosafety practices prevents the spread of infectious agents from facilities to other healthcare workers, patients, and the community.

Quality Control and Lab Safety

Biosafety monitoring should be part of quality control measures and quality assurance programs in the laboratory or any healthcare institution. Biosafety monitoring must also be an important component of staff competency tests and 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 in hospitals and clinics.[29] Likewise, adherence to biosafety guidelines takes a collaborative approach from all healthcare professionals, including non-laboratory healthcare personnel. For example, respirator fit testing can be carried out at regular intervals, for example, 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 laboratory staff's advice in applying biosafety measures when handling certain infectious agents or products. Clinicians may work with laboratory professionals, nurses, pharmacists, and sanitary officers, among others, to develop 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 animal research.[32] International conferences from various institutions still exist, concentrating on sharing best practices and harmonizing biosafety guidelines at the regional, national, and global scales.[33][34] Biosafety has been an emerging concern for occupational health.[35] Educational interventions are critical to ensure that staff stay equipped with the knowledge and skills to implement proper biosafety practices across healthcare sectors.[36][37] Therefore, the best practices for healthcare, research, and other institutions always require team commitment and cooperation to achieve a biologically safe and secure workplace and community.[38]