Wiping the Slate Clean—Assessing Clinical Laboratory Contamination Risk

Laboratory safety policies and procedures are essential for ensuring the wellbeing of our clinical laboratory workforce. Laboratory acquired infections can impact both employees and the general public (1, 2,), as is highlighted by previous multistate outbreaks of Salmonella (3,). Evaluation of laboratory acquired infection risk plays an important role in biosafety assessments, particularly in clinical microbiology (4, 5,). However, the risk of instrument or surface contamination in automated clinical laboratory environments is also important to consider. An important 2016 report by Bryan et al. demonstrated hepatitis B (HBV) and hepatitis C (HCV) viral nucleic acid contamination on components of a total laboratory automation (TLA) system (6,). This previous study was conducted to further understand laboratory risk associated with the challenge of routine specimen handling in the context of Ebola virus disease (7).

While the safety of our clinical laboratory workforce is essential, patient test results can also be adversely impacted if there is contamination or carryover caused by specimen handling, processing, or instrumentation. This is particularly important for analytes that have wide analytical measurement ranges or for which testing includes amplification steps. Microbiological culture methods and molecular diagnostic techniques are particularly vulnerable to specimen contamination or carryover.

Advances in instrumentation and analytical processing have led to commercially available automated platforms for both microbiology and molecular diagnostics. In these systems, contamination risk may be minimized through incorporation of engineering controls such as disposable pipette tips, plate sealing, and high-efficiency particulate air filtration. Connection of such systems into larger TLA solutions can bring additional operational efficiency (8), as has previously only been available for disciplines such as chemistry, hematology, and immunology. In such systems, what is the risk of specimen and/or instrument contamination and how should that risk be evaluated?

In this issue of Clinical Chemistry, a report by Farnsworth et al. (9) outlines such an assessment, where the authors evaluated the potential for surface contamination and viral nucleic acid carryover on automated chemistry and microbiology instruments. Gross contamination was assessed by applying a fluorescent marker to the exterior surface of primary blood collection tubes prior to specimen processing and then visualizing fluorescent transfer on instrument components, laboratory surfaces, and personnel through detection by ultraviolet light. Personal protective equipment (PPE) compliance was also assessed through direct observation. In an additional set of experiments, the investigators spiked specimens with a nonpathogenic virus (Bacteriophage MS2) to assess for carryover risk, as well as instrument and surface contamination. While these experiments did not demonstrate any carryover, instrument contamination, or surface contamination in the MS2 spiking studies, extensive transfer of fluorescence was observed on numerous laboratory and instrument surfaces. Noncompliance with hand hygiene and PPE policies was also observed.

Areas of particular concern in regards to specimen and/or surface contamination on automated instrumentation include shared processing steps (e.g., decapping, recapping, and centrifugation), specimen transportation through instrumentation that incorporates reusable pipettes or aerosol-generating procedures, and conveyance of uncapped specimens along an automated track that may or may not have external shielding. Conversely, it is possible that automation may standardize such procedures and therefore potentially reduce specimen contamination risk caused by manual handling. Priority routing of specimens through a TLA system (i.e., directing specimens intended for molecular diagnostics immediately to such instrumentation) may help to mitigate contamination risk. However, such strategies may also not fully reflect real-world practices and procedures, including shared decapping and centrifugation modules, specimen reloading, reroutes, and challenges in resolving definitive container identification (e.g., primary tubes versus aliquots). The responsibility for verifying that contamination risk is at an acceptably low level is likely a shared one, requiring input from the instrument vendor, automation provider, and clinical laboratory end-user.

The inability to detect instrument surface and/or component contamination by MS2 virus using spiked specimens was encouraging, although it contrasts with observations of the Bryan et al. report, which investigated instruments and automation from a different vendor, and in the context of HBV and HCV nucleic acid contamination (6). It is unclear whether these differences reflect incorporation of engineering controls such as track enclosures in newer generations of automation, or rather that some of the burden of HBV and HCV nucleic acid contamination in the previous study accumulated over a longer span of time and/or by the presence of high viral titers present in additional routine patient specimens. Examination for potential contamination by HBV and HCV nucleic acid on newer generations of instrumentation and automation could facilitate a more direct comparison of contamination risk.

Clinical laboratory accreditation programs typically include extensive requirements related to safety, facilities, PPE, and laboratory cleanliness. Safety requirements are included in the Clinical Laboratory Improvement Amendments standards regarding facilities (§493.1101) and laboratory director responsibilities (§493.1407 and §493.1445) (10,). Guidelines from the Centers for Disease Control and Prevention, the Clinical Laboratory Standards Institute, and the International Standards Organization (ISO) provide further information on developing and maintaining effective safety programs in laboratory and healthcare facilities (11–13,). Best practices regarding glove use in ISO 15190 note that “all telephones, doorknobs and handles, computer keyboards, […] etc. are considered contaminated unless these areas/items are protected by a barrier that allows for decontamination” (11,). Such communal objects—a term described in New York State Department of Health Clinical Laboratory Standards—present unique challenges for contamination spread in designated laboratory “dirty” areas, as the mitigation measures (hand washing and availability of disposable gloves) do not stop the spread of contaminants within the laboratory dirty area itself (14). Such objects are considered fomites (i.e., objects or materials that can potentially carry infection). In areas designated for automated clinical laboratory testing—where gloves are mandatory—communal objects are specifically meant to be used while wearing gloves. Activities involving specimen handling, instrument operation, and result review by paperwork or computer introduce opportunities for more wide-spread surface distribution, as was clearly demonstrated by the Farnsworth et al. fluorescence studies.

PPE policies and procedures can help mitigate the risk that surface contamination might lead to laboratory acquired infections, as PPE is removed when leaving such areas followed by thoroughly washing the hands with soap and water. Effectiveness, however, is only as good as compliance. The present study demonstrates that PPE use may be suboptimal—the authors should be commended for both conducting and reporting these important observations. Previous studies suggest that contributing factors to PPE noncompliance in healthcare settings may be multifactorial (15). The need for PPE and meticulous hand hygiene is further heightened in the setting of a global pandemic such as Coronavirus Disease 2019.

Laboratory contamination events, when they do occur, can be incredibly challenging to resolve. Additionally, safety policies designed primarily for microbial decontamination may be ineffective in addressing nonmicrobial contaminants (16,). Furthermore, dispersion of contaminants onto floors can result in tracking of substances into adjacent areas (i.e., “traffic transmission”) (16). Shared objects such as keyboards, computer mice, and laboratory telephones, as well as nonporous surfaces and sensitive electronics, can be exceedingly difficult to clean safely. Additionally, protocols for cleaning such surfaces may not typically be incorporated into laboratory policies and procedures. Defining responsibility for the full scope of housekeeping activities within a laboratory is essential for ensuring that key areas are not overlooked. Equally important is that these activities should be performed by individuals familiar with the laboratory environment, to help ensure the safety of all employees. In the long run, it is advantageous to declutter, reorganize, and maintain a space that is easier to clean (e.g., through Lean 5S events and similar activities), than to try cleaning and maintaining an otherwise suboptimal space.

How clean does a routine clinical laboratory setting really need to be? It should be clean enough to prevent risk of laboratory acquired infection, to prevent the spread of harmful substances to employees, to enable testing to be performed in an efficient and optimal manner, and to prevent the risk of carryover and specimen contamination that could lead to erroneous patient results. Cleanliness requirements may also vary across differing laboratory activities. Biohazard assessments help to address potential risk and identify appropriate mitigation strategies. Compliance with PPE policies and procedures is essential, and its importance should be highlighted in ongoing educational activities and communications as part of an active and engaged clinical laboratory safety culture.

Author Contributions

All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved.

Authors’ Disclosures or Potential Conflicts of Interest

Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:

Employment or Leadership

J.R. Genzen, University of Utah, ARUP Laboratories.

Consultant or Advisory Role

None declared.

Stock Ownership

None declared.

Honoraria

None declared.

Research Funding

None declared.

Expert Testimony

None declared.

Patents

None declared.

References

Nonstandard Abbreviations:

 
• HBV

  hepatitis B virus

 
• HCV

  hepatitis C virus

 
• TLA

  total laboratory automation

 
• PPE

  personal protective equipment

 
• ISO

  International Standards Organization