A simplified checklist for the visual inspection of finished pharmaceutical products: a way to empower frontline health workers in the fight against poor-quality medicines.

BACKGROUND: Substandard and falsified medicines, mainly prevalent in low and middle-income countries (LMICs), cause avoidable morbidity and mortality, and put at stake the performance of health systems. They may be prevented by an adequate implementation of pharmaceutical Quality Assurance (QA) guidelines, but unfortunately, most guidelines address upstream stakeholders and specialized staff in the supply chain. A multi-layered approach is needed, in order to empower the health workers at the point-of-care to proactively contribute to the fight against poor-quality medicines.Visual inspection is a simple technique, suitable for field screening. The findings of a survey conducted in the Democratic Republic of the Congo (DRC) suggested that it might be a fairly good (yet partial) predictor of poor-quality, when compared to full laboratory tests. METHODS AND RESULTS: Starting from the 68-questions checklist originally used in the survey in the DRC, we developed a simplified checklist, specifically designed to guide health workers at the point of care to rapidly identify suspect poor-quality medicines. We selected those medicines' attributes the assessment of which does not require technical expertise, or access to regulatory information. Attributes were categorized according to a 3-level risk scale, to guide decision-making on suspect poor-quality medicines, based on an informed risk assessment.The simplified checklist contains 26 binary questions (YES/NO), grouped into four themes: packaging, identification, traceability, and physical appearance. Each non-conformity corresponds to a level of risk for patients. The user is guided towards three possible actions: A) reasonably safe for dispensing; B) dispense with explanation; C) quarantine and make a risk-benefit evaluation before dispensing. CONCLUSION: The simplified checklist should now be implemented in real-life setting in LMICs. If proven useful in guiding health workers at the point-of-care to take rapid, transparent, patient-centred actions when facing a suspect poor-quality medicine, it could be further extended to address specific formulations. Digitalization for linkage with pharmacovigilance programs could also be considered.

Pharmaceutical compounding of orphan active ingredients in Belgium: how community and hospital pharmacists can address the needs of patients with rare diseases.

BACKGROUND: Pharmaceutical compounding of orphan active ingredients can offer cost-effective treatment to patients when no other drug product is available for a rare disease or during periods of drug product shortages. Additionally, it allows customized therapy for patients with rare diseases. However, standardized compounding formulas and procedures, and monographs are required to ensure the patients' safety. RESULTS: Standardized formulas and compounding procedures were developed for seven orphan active ingredients (L-arginine, sodium benzoate, sodium phenylbutyrate, L-carnitine, chenodesoxycholic acid, primaquine phosphate, pyridoxal phosphate) and one non-orphan molecule (sodium perchlorate) regularly compounded by hospital pharmacists for extemporaneous use. The stability of these formulations was evaluated over 3 months at refrigerated (5 °C) and standard storage conditions (25 °C/60%RH) using HPLC-based assays and a suitable shelf life was assigned to the formulations. Additionally, suitable analytical methods for quality control of formulations of pyridoxal phosphate and sodium perchlorate were developed as monographs for these components were not available in the European Pharmacopeia or United States Pharmacopeia. CONCLUSIONS: Availability of compounding formulas and protocols, as well as stability information, for orphan active ingredients can improve patients' access to treatment for rare diseases. Such data were collected for seven orphan active ingredients to treat patients with rare diseases when no other treatment is available. More efforts are needed to develop standardized formulas and compounding procedures for additional orphan active ingredients whose clinical efficacy is well-known but which are not available as products with a marketing authorization. Additionally, a legal framework at EU level is required to enable the full potential of pharmaceutical compounding for orphan active ingredients.

The potential role of quorum-sensing peptides in oncology.

Cancer is a leading cause of death worldwide, with a limited cure rate and late diagnosis for certain types of cancer (e.g. pancreatic cancer). As this disease presents an enormous challenge for scientists, new paradigms in oncology are needed to defeat this serious disease. Currently, several peptide drugs are investigated for their preventive, diagnostic and therapeutic properties in oncology, with already 15 peptide drugs marketed for cancer therapy. However, we suggest that quorum-sensing peptide agonists and antagonists can be used in oncology as well, resulting in a larger potential peptide space. This hypothesis is based on (1) the recent evidence of prokaryote-eukaryote signalling by the use of quorum-sensing signalling molecules, (2) the apoptotic phenomenon seen in bacteria, (3) the clear similarities between the bacterial quorum-sensing mechanisms and the metastatic process tumor cells initiate, (4) the multiple receptor targeting and (5) the possibility of pharmacologic manipulation of peptides, resulting in increased receptor targeting. Up till now, however, the use of quorum-sensing signalling peptides in oncology has not yet been investigated, despite the urgent need for new insights in oncology and the promising perspectives.