TAL/LAL Reagent, as the core reagent for bacterial endotoxin detection, its quality and effectiveness directly affect the accuracy of detection results, and the shelf life of the reagent is an important indicator to ensure its performance. In daily laboratory operations, expired TAL/LAL Reagent is often encountered. Faced with this situation, whether expired TAL/LAL Reagent can continue to be used has become a problem that laboratory personnel need to carefully judge. From the perspectives of reagent performance, detection risks, and regulatory requirements, expired TAL/LAL Reagent is not recommended for continued use, for the following specific reasons:
I. Expiration Causes Decline in Reagent Performance Stability
The main active components of TAL/LAL Reagent are coagulation factors (such as Factor C, Factor B, prothrombin, etc.) in the hemocyte lysate of horseshoe crabs. These biologically active substances are extremely sensitive to storage time and conditions. Within the shelf life, manufacturers ensure that the reagent can maintain the specified sensitivity and specificity under the required storage conditions (usually refrigerated at 2-8°C) through strict stability tests. After the expiration date, even if the storage conditions are met, the biologically active components will gradually degrade, leading to decreased reagent sensitivity or changed specificity.
For example, expired TAL/LAL Reagent may fail to accurately identify low concentrations of endotoxins, resulting in false negative results; it may also cross-react with non-endotoxin substances due to denaturation of active components, leading to false positives. This instability in performance will make the detection results lose reference value and cannot reliably determine whether the endotoxin content in the sample meets the standards. In addition, excipients in the reagent (such as buffers, stabilizers, etc.) may also undergo chemical changes after expiration, further affecting the reaction system of the reagent and interfering with the detection process.
II. Reliability of Detection Results Cannot Be Guaranteed
Bacterial endotoxin detection is of great significance for quality control in the pharmaceutical, medical device and other fields, and the detection results directly determine whether products meet listing standards or clinical use requirements. Using expired TAL/LAL Reagent for detection will significantly reduce the reliability of results, mainly reflected in the following two aspects:
On the one hand, the sensitivity of expired reagents may deviate from the labeled value (λ), failing to meet the sensitivity requirements for detection methods specified in pharmacopoeias or industry standards. For example, a reagent originally with a sensitivity of 0.25 EU/mL may drop to 1.0 EU/mL after expiration, making it impossible to detect low concentrations of endotoxins actually present in the sample, resulting in unqualified products being misjudged as qualified, which poses serious safety hazards. On the other hand, the reaction kinetics of the reagent may change after expiration, such as prolonged gel formation time and weakened photometric signal, leading to poor experimental repeatability and large deviations in the detection results of samples from the same batch, which cannot pass methodological verification.
III. Violation of Regulatory and Quality System Requirements
In the field of quality control of pharmaceuticals and medical devices, detection processes must strictly comply with relevant regulations and standard operating procedures (SOPs), and the use of qualified reagents within their validity period is a basic prerequisite required by regulations. The United States Pharmacopeia (USP <85>), European Pharmacopoeia (EP 2.6.14) and other pharmacopoeias clearly stipulate that reagents used for endotoxin detection must meet quality standards and be used within their validity period.
Laboratory quality systems (such as GMP, ISO 17025) also put forward strict requirements for reagent management, including reagent procurement, storage, validity monitoring and other links. Using expired TAL/LAL Reagent is an irregular operation. Once discovered by regulatory authorities during inspections, it may face serious consequences such as invalidation of experimental results, product recalls, and qualification penalties. In addition, in detections involving product registration or clinical research, data obtained using expired reagents cannot be recognized, which will directly affect the progress and effectiveness of the project.
IV. Potential Costs and Risks Are Not Worthwhile
Some laboratory personnel may try to use expired TAL/LAL Reagent to save costs and verify its performance through sensitivity rechecks and other methods. However, although this approach seems to reduce short-term costs, it actually carries greater potential risks and hidden costs. First, the recheck experiment itself consumes consumables such as standard endotoxins and pyrogen-free water, and cannot fully simulate the complex sample matrix in actual detection. A qualified recheck does not mean that the reagent can play a stable role in all detection scenarios.
Second, if detection results are incorrect due to the use of expired reagents, it may lead to product rework, batch scrapping, market recalls and other problems, and the economic losses caused are far greater than the cost of the reagent itself. More seriously, if products with excessive endotoxins flow into the market, they may cause adverse reactions such as fever and shock in patients, leading to medical accidents and legal liabilities. Therefore, from the perspective of risk-benefit ratio, using expired TAL/LAL Reagent is not worthwhile.
Summary and Recommendations
After expiration, the biologically active components of TAL/LAL Reagent degrade and its performance stability decreases, which will lead to inaccurate and unreliable detection results. At the same time, it violates regulatory requirements and quality system specifications, posing huge quality risks and safety hazards. Therefore, expired TAL/LAL Reagent must not continue to be used for formal detection.
Laboratories should strengthen reagent management, establish a sound validity monitoring mechanism, regularly check the storage conditions and remaining validity period of reagents, and promptly dispose of expired reagents. Before detection, it is necessary to confirm that the TAL/LAL Reagent is within its validity period, and verify the reagent performance through positive controls, negative controls and other methods to ensure the accuracy and compliance of detection results, and fundamentally guarantee product quality and patient safety.
