Journal of Pharma and Drug Regulatory Affairs (e-ISSN:2582-3043)

A Regulatory Perspective on the Us and European Drug Master File (Dmf) Frameworks

2025-09-01T04:56:21+00:00

The Drug Master File (DMF) is an important part in making sure that drugs are safe, effective, and kept secret. This page gives a detailed comparison of the DMF regimes in the US and the EU. The article talks about the rules, submission processes, contents, and functions of each framework in the medication approval process. The Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) in the European Union, along with national competent agencies, have set up different but complementary ways to handle DMF. Global manufacturers who want to fulfil compliance standards in all areas must have a good awareness of various regulatory ideas. The final section of the manuscript gives pharmaceutical companies who want to make their regulatory submissions more consistent some useful advice.

Review: Diethylene Glycol and Ethylene Glycol Contamination in Pediatric Oral Liquid Medication: A Comprehensive Review of Outbreaks, Toxicity, Clinical Features, and Regulatory Failures

2025-12-29T06:44:46+00:00

Recent outbreaks of acute kidney injury (AKI) in pediatric populations have highlighted a critical global health threat linked to the contamination of oral liquid medications with industrial solvents such as diethylene glycol (DEG) and ethylene glycol (EG). These toxic adulterants, often substituted for pharmaceutical-grade excipients like glycerin or propylene glycol, have caused multiple mass poisoning events across low- and middle-income countries, including India, The Gambia, Uzbekistan, Nigeria, and Indonesia. The 2025 Coldrif cough syrup–associated fatalities in India represent the latest in a recurring pattern of manufacturing failures, inadequate regulatory oversight, and supply-chain vulnerabilities. Children are particularly susceptible due to immature metabolic pathways, low body weight, and reduced renal clearance, making even small exposures potentially lethal. Clinical manifestations typically begin with gastrointestinal and neurological symptoms, progressing within 24–72 hours to severe metabolic acidosis, elevated creatinine, oliguria or anuria, and biopsy-proven acute tubular necrosis. Toxicological analyses frequently reveal high concentrations of DEG and its metabolites. Investigations across outbreaks show that contaminated paracetamol syrups, multi-ingredient cough and cold formulations, teething mixtures, sedatives, and expectorants have repeatedly served as the sources of poisoning. Polypharmacy and the widespread over-the-counter availability of pediatric cough syrups further increase risk, despite limited evidence of therapeutic benefit. The recurring nature of these incidents underscores systemic gaps, including poor-quality excipient sourcing, lack of routine DEG/EG screening, weak laboratory infrastructure, and delayed pharmacovigilance responses. Strengthened regulatory enforcement, mandatory excipient testing, improved traceability, and global harmonization of safety standards are essential to prevent further tragedies. Clinicians and caregivers should exercise caution with pediatric liquid medications, especially multi-ingredient OTC products. This review synthesizes historical and recent evidence to provide an integrated understanding of DEG/EG-induced pediatric AKI, the mechanisms of toxicity, clinical features, risk factors, and regulatory challenges. Urgent, coordinated action is required to ensure the safety of pediatric medications worldwide.

Sustainable Innovation Through Green Toxicology: Principles, Methods and Applications

2025-12-29T07:27:55+00:00

Green toxicology is an emerging and transformative discipline that integrates the principles of toxicology, green chemistry, and sustainability to design safer chemicals and materials. Its core objective is to minimize human and environmental toxicity by embedding predictive toxicological assessment early in the chemical design process. By adopting a proactive rather than reactive approach, green toxicology employs advanced tools such as in vitro assays, in silico computational modeling, high-throughput screening (HTS), organs-on-chips, and adverse outcome pathways (AOPs) to evaluate potential hazards efficiently without relying on animal testing. This field emphasizes the “benign-by-design” concept, ensuring safety throughout a product’s life cycle—from synthesis and use to disposal. Industrial applications span pharmaceuticals, cosmetics, agrochemicals, and nanomaterials, where green toxicology supports innovation, regulatory compliance, and sustainable manufacturing. Despite its promise, challenges remain in the form of standardization of protocols, validation of predictive models, and regulatory acceptance of non-animal methods. Future directions involve integrating artificial intelligence (AI) and machine learning for enhanced predictive modeling, expanding green-by-design approaches in academia and industry, and aligning these innovations with the United Nations Sustainable Development Goals (SDGs). Overall, green toxicology represents a paradigm shift toward sustainable chemical design, advancing public health protection, ethical testing, and environmental preservation.

Sepsis Reimagined: The Immunometabolic and Microbiome Frontiers of Sepsis

2025-12-29T08:38:47+00:00

Sepsis is a life-threatening syndrome arising from a dysregulated host response to infection, culminating in organ dysfunction, circulatory collapse, and persistently high global mortality. Conventional management, including timely antibiotics, fluid resuscitation, and vasopressor support, targets infection control and hemodynamics but does not adequately address the deeper immune, metabolic, and microbiome disturbances that fundamentally drive sepsis progression. Growing evidence highlights the central roles of innate immune dysregulation, endothelial injury, mitochondrial dysfunction, and neuroimmune crosstalk in triggering multi-organ failure. The gut microbiome has emerged as a key regulator of host immunity, metabolism, and epithelial integrity. Its metabolites, especially short-chain fatty acids, promote immune homeostasis, while sepsis-induced dysbiosis exacerbates inflammation, increases gut permeability, and fuels systemic deterioration. Parallel research shows that immunometabolic reprogramming determines whether patients develop overwhelming hyperinflammation or profound immunoparalysis, emphasizing the need for precision-based therapeutic strategies. Emerging interventions, including mitochondria-targeted antioxidants, metabolic modulators, probiotics, synbiotics, fecal microbiota transplantation, postbiotics, and selective immunotherapies, demonstrate significant promise in preclinical studies. However, translation into consistent clinical benefit remains limited, underscoring the complexity of sepsis pathobiology. Integrating these mechanistic insights with clinical practice may support the development of personalized, immunometabolic, and microbiome-directed therapeutic approaches that complement conventional care. Such strategies aim to restore host homeostasis, improve organ recovery, and ultimately reduce sepsis-related morbidity and mortality.

Mentzer Index with RCDW as a High-Specificity Screening Tool for Differentiating Iron Deficiency Anemia from Beta-Thalassemia Trait

2025-12-29T08:59:52+00:00

Background: Differentiating iron deficiency anemia (IDA) from beta-thalassemia trait (BTT) remains challenging in clinical practice, often requiring expensive confirmatory tests. This study evaluated the diagnostic performance of the Mentzer Index combined with red cell distribution width (RDW) for discriminating between these conditions.

Methods: This cross-sectional diagnostic accuracy study enrolled 200 patients with microcytic anemia (MCV <80 fL), including 120 with confirmed IDA and 80 with BTT. Complete blood count parameters were analysed, and the Mentzer Index was calculated as MCV/RBC count. IDA diagnosis required ferritin <30-40 ng/mL and additional iron study abnormalities, while BTT required HbA₂ >3.5% by HPLC. Combined criteria defined IDA as Mentzer Index ≥13 AND RDW >15%, and BTT as Mentzer Index <13 AND RDW ≤15%. Diagnostic performance metrics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, were calculated.

Results: IDA patients demonstrated significantly higher Mentzer Index (16.7±2.3 vs 10.7±1.5, p<0.001) and RDW (18.4±2.1% vs 13.2±1.4%, p<0.001) compared to BTT patients. The Mentzer Index alone achieved 88.5% accuracy, 89.2% sensitivity, and 87.5% specificity. The combined approach significantly improved performance, achieving 93.5% accuracy, 91.7% sensitivity, and 96.3% specificity. Specificity increased by 8.8 percentage points, with the false positive rate reduced by 70% (from 12.5% to 3.7%). PPV improved from 91.5% to 97.3%.

Conclusion: Combining the Mentzer Index with RDW provides superior diagnostic accuracy for differentiating IDA from BTT, particularly improving specificity and reducing misclassification. This cost-effective screening approach using routine CBC parameters can correctly classify 93.5% of patients, potentially reducing unnecessary confirmatory testing by approximately 90% while maintaining high diagnostic confidence.