For many years, the safety issues surrounding traditional Chinese medicine (TCM) injections have been a critical and challenging focus of drug regulation in China. Despite their irreplaceable role in safeguarding public health and responding to public health emergencies, TCM injections have been increasingly associated with safety concerns as clinical use expands. Major adverse drug reaction events, including anaphylactic shock and even fatalities, have triggered widespread public skepticism and regulatory scrutiny. This paper systematically explores the establishment of new strategies and methods for safety evaluation and control of TCM injections from four integrated dimensions: toxicity cognition, objective evaluation, mechanism analysis, and precise prevention and control. Regarding toxicity cognition, we propose for the first time that the key factor triggering rapid, difficult-to-prevent, and severe adverse reactions is the instantaneous, high-dose systemic exposure of TCM components following injection—especially intravenous injection—along with the entry of potential immunogenic substances into the bloodstream. Unlike oral administration, intravenous injection bypasses gastrointestinal barriers and hepatic first-pass effects, achieving nearly 100% bioavailability and causing dramatic increases in blood drug concentrations. Additionally, certain components with potential immunogenicity may enter the circulation, bind with plasma proteins to form haptens, and activate the immune system, thereby inducing allergic or pseudo-allergic reactions rarely observed with oral formulations. In terms of toxicity classification, we are the first to categorize TCM injection toxicity into direct type (intrinsic), idiosyncratic type, indirect type, and mixed type, based on clinical manifestations and pathological mechanisms. This novel framework moves beyond traditional crude descriptors that have long dominated TCM pharmacology. Accordingly, we construct precise risk prevention and control strategies tailored to each toxicity category, enabling targeted clinical interventions rather than generic regulatory approaches. For objective identification, we have created the “Integrated Evidence Chain Method” to shift causality assessment of serious adverse reactions from vague empirical exclusion to confirmation based on objective evidence. This method systematically excludes non-drug factors, Western medicine confounders, non-delivery-route-related risks, drug quality defects, and irrational medication practices through a stepwise evidentiary process, achieving scientific determination of causal relationships in complex clinical scenarios. Regarding re-evaluation strategies, we recommend emphasizing a safety-oriented approach: utilizing real-world studies to monitor serious adverse reactions while considering efficacy evaluation; employing the “Four-Quadrant” method for benefit-risk assessment; adding biological effect assays in quality control beyond merely detecting “6–8-9” components; incorporating syndrome-linked toxicology studies in preclinical evaluations; and establishing rational sequential medication time windows based on pharmacokinetic characteristics to avoid drug-drug interaction risks. Ultimately, this paper aims to propel TCM injection safety risk management from a reactive stance towards a scientific, proactive, and precise approach, providing theoretical foundations for sustainable development of this unique dosage form.
Zhao et al. (Mon,) studied this question.