Writing a Reliable SOP for TB Drug Susceptibility Testing
A standard operating procedure for tuberculosis drug susceptibility testing (DST) translates technical requirements into consistent, repeatable laboratory practice. It should tell trained staff exactly what to do, what materials to use, how to recognize invalid results, and when to stop or escalate a procedure. A useful SOP is therefore more than a description of a test method: it is a controlled quality document that connects patient safety, laboratory safety, result interpretation, and reporting.
The document should match the testing platform, the laboratory’s scope of work, and the resources available at the testing site. Molecular assays, culture-based phenotypic DST, and line probe assays have different specimen requirements, controls, turnaround times, and interpretation rules. The SOP must identify the applicable method rather than combining several workflows into vague general instructions.
Within a quality management system, the procedure should be approved, version-controlled, reviewed at defined intervals, and supported by training records. Its content should also align with current national policy and authoritative technical guidance, since critical drug concentrations, resistance targets, and reporting terminology can change.
Define the purpose and scope
Begin by stating what the procedure covers. The scope might include testing of Mycobacterium tuberculosis complex isolates using a specified phenotypic method, or detection of genetic resistance to selected anti-tuberculosis medicines with a named molecular platform. Identify whether the procedure applies to sputum, cultured isolates, or both, and clarify which drugs and resistance mechanisms are included.
The purpose should explain how the test supports clinical and public health decisions. It can state that DST is performed to detect susceptibility or resistance, guide regimen selection, support surveillance, and identify results requiring referral or confirmatory testing. Avoid promising information that the method cannot provide. For example, a molecular assay that detects selected mutations should not be described as proving susceptibility to every drug.
List responsibilities by role. The section may assign specimen acceptance to accessioning staff, testing to authorized technologists, technical review to a senior scientist, and final authorization to a designated signatory. Include requirements for competency assessment, supervision, and access to current instructions. This makes accountability visible when an unexpected or critical result is identified.
Control specimens, safety, and workflow
A DST SOP must describe how specimens and cultures move through the facility without creating avoidable exposure or contamination risks. Specify work areas, containment requirements, personal protective equipment, disinfectants, spill response, waste treatment, and actions after an exposure. Procedures involving viable TB cultures should clearly distinguish activities performed in appropriate containment from steps that can occur in lower-risk areas.
Pre-analytical controls begin before the sample reaches the testing bench. Define acceptable containers, labeling requirements, minimum volume, storage limits, transport temperature, and documentation for leakage or delay. Laboratories receiving specimens from distant facilities can use remote TB transport guidance to connect the DST procedure with a dependable specimen referral process.
Describe accessioning in enough detail to prevent identity errors. Staff should compare the request form with the container, record collection and receipt times, assign a unique laboratory identifier, and document any rejection or conditional acceptance. A specimen should never enter testing solely because it arrived; the SOP needs objective acceptance criteria and a process for contacting the submitting facility when information is missing.
Build the technical procedure around decisions
The main procedure should be written in the order staff perform the work. Use numbered actions within the controlled SOP, even if the broader document uses paragraphs. State how to prepare reagents, verify instrument status, prepare the inoculum or reaction mix, load specimens and controls, operate the assay, and record raw observations. Include precise volumes, time limits, temperatures, incubation conditions, and permitted substitutions.
For molecular testing, identify cartridge or strip handling, nucleic acid preparation, internal controls, invalid-result rules, contamination precautions, and instrument checks. For culture-based DST, specify isolate purity checks, inoculum standardization, media or plate preparation, drug concentrations, incubation conditions, reading criteria, and the method for classifying growth. A procedure should refer to the exact manufacturer instructions or validated method version used by the laboratory.
Interpretation rules deserve their own subsection. Define susceptible, resistant, indeterminate, invalid, contaminated, and no-result categories. Explain how mixed resistance patterns, low-level resistance, discordant controls, or mutations with uncertain clinical significance are handled. Staff should know whether to repeat the test, request a new specimen, refer the isolate, report a qualified result, or withhold reporting until technical review is complete.
A clear decision path is especially important when results affect treatment quickly. The SOP should state which findings are urgent, who receives immediate notification, how the notification is documented, and when the result is released in the laboratory information system. Record the primary result, interpretation, reviewer, date, and any comments needed to explain limitations.
Link quality controls to each testing run
Quality control should demonstrate that the method worked for the specific run, not simply that the instrument was switched on. Identify positive, negative, internal, and growth controls as appropriate for the platform. State their expected outcomes and the conditions that invalidate a run. Include rules for control lot changes, reagent storage, expiration dates, and temperature monitoring.
For phenotypic DST, the SOP should explain how control growth is compared with drug-containing conditions and how borderline growth is treated. For molecular testing, it should state what each internal control verifies and how to respond when amplification, extraction, or assay controls fail. Control results must be recorded in a durable format that can be linked to patient results.
Quality indicators can reveal problems before a formal failure occurs. Track rejected specimens, contamination, invalid rates, amended reports, turnaround time, external quality assessment performance, and repeat testing. Trends should be reviewed by authorized personnel and connected to corrective and preventive action. A single acceptable run does not prove that the overall process remains stable.
The document should also explain equipment maintenance and calibration checks relevant to the assay. Include daily start-up checks, scheduled maintenance, temperature verification, software or firmware controls, and actions when equipment is out of service. If testing is referred elsewhere during an interruption, preserve chain-of-custody records and clearly identify the performing laboratory.
Organize records, reports, and document control
Specify every record generated by the procedure: request forms, accession logs, worksheets, instrument files, control results, temperature records, maintenance logs, referral records, and authorized reports. State where each record is stored, who may edit it, how corrections are made, and how long it is retained. Corrections should preserve the original entry, identify the person making the change, and include the date and reason.
The reporting section should use standardized language that clinicians and public health teams can understand. Include the patient or specimen identifier, test method, specimen or isolate type, drugs or resistance targets assessed, result, interpretation, date, and authorized signatory. Where the method has limits, include a concise comment explaining that a negative molecular result does not exclude resistance mechanisms outside the assay’s target range.
Define communication for critical or unexpected findings. A resistant result may require prompt telephone or electronic notification according to local policy, followed by a formal report. The SOP should identify the authorized contact, documentation requirements, read-back or acknowledgement expectations, and escalation route when the receiving clinician cannot be reached.
Document control prevents obsolete instructions from remaining at the bench. Include the SOP title, unique document number, version, effective date, review date, author, technical reviewer, approver, revision history, and controlled-copy locations. Withdraw superseded versions and retain them only according to the document retention policy.
| SOP component | What it should specify | Evidence of control |
|---|---|---|
| Specimen handling | Acceptance, labeling, transport, storage, and rejection criteria | Accession record and rejection log |
| Testing process | Reagents, equipment, steps, timings, and precautions | Completed worksheet or instrument record |
| Quality control | Control types, expected outcomes, and invalid-run actions | QC log linked to the run |
| Interpretation | Result categories, limitations, repeats, and referrals | Technical review record |
| Reporting | Required fields, critical notifications, and authorization | Final report and notification log |
| Document control | Version, approval, distribution, and review cycle | Master document register |
Verify competence and review performance
Before independent work begins, each staff member should receive training on the current SOP, related biosafety procedures, equipment operation, result interpretation, and documentation requirements. Competency assessment can include direct observation, examination of known samples, worksheet review, and evaluation of corrective actions. Retraining is needed after major procedural changes, prolonged absence, or repeated errors.
The laboratory should use internal audits and external quality assessment to test whether the written procedure is followed in practice. Check that staff use the current version, controls are acceptable, records are complete, equipment checks are performed, and reports contain the required information. The GLI resource provides quality checklists that can help laboratories organize assessments across personnel, equipment, documentation, safety, and continual improvement.
Review the SOP after an assay change, new drug recommendation, equipment replacement, quality incident, audit finding, or change in national policy. The review should involve technical staff who use the procedure, the quality officer, and the person responsible for clinical or public health communication. Record the decision even when no revision is required.
Practical safeguards for daily use
- Keep a controlled electronic or printed copy at every testing workstation.
- Use a pre-run checklist for specimen identity, reagent status, equipment readiness, and controls.
- Require independent technical review of resistant, invalid, discordant, or urgent results.
- Link corrective actions to a named person, completion date, verification step, and retained evidence.
- Monitor turnaround time and invalid or contamination rates at defined quality meetings.
A strong SOP becomes useful when staff can follow it during routine work and under pressure. Write in direct language, separate mandatory requirements from explanatory notes, define unfamiliar terms, and support complex steps with approved diagrams or photographs. Validate the completed procedure before implementation, authorize it through the laboratory’s quality system, and make its review part of normal DST operations. Download the current laboratory quality resources, adapt the procedure to your validated method and national requirements, train authorized staff, and place the approved version into controlled use.