Quality testing of mifepristone and misoprostol in 11 countries.

OBJECTIVE: Previous studies have demonstrated quality concerns with misoprostol. Mifepristone, however, has not been extensively assessed for quality. Between 2020 and 2021, Concept Foundation and the International Planned Parenthood Federation conducted a study to determine the quality of these medical abortion drugs in low- and middle-income countries (LMIC). METHODS: The collection of batch samples of misoprostol and mifepristone was carried out by trained sampling agents in selected LMIC. Single drug packs and combipacks were sampled. A World Health Organization prequalified laboratory conducted testing method verifications and subsequent sample analysis. Tests included identification, assay, related substances, and content uniformity for misoprostol, and identification, assay, related substances, and dissolution for mifepristone. RESULTS: Samples were collected from Burkina Faso, Cambodia, Democratic Republic of Congo, India, Kyrgyzstan, Moldova, Nepal, Nigeria, Pakistan, Uganda and Vietnam. Sixty-four pooled batch samples were tested, consisting of 31 combipacks, 26 misoprostol-only and seven mifepristone-only products. Overall, 54.7% of samples were non-compliant with one or more of the specifications, representing 51.6% of combipack products, 57.1% of misoprostol tablets analyzed and 23.7% of mifepristone tablets. One falsified misoprostol-only product was found. CONCLUSION: The present study confirms that a significant problem still exists in relation to the quality of medical abortion drugs in LMIC. For misoprostol, our findings suggest that historical concerns around primary packaging may have been largely resolved but that manufacturing processes for both finished product and active pharmaceutical ingredient need to be improved. The present study also provides evidence of mifepristone quality issues.

Prepared omadacycline for injection: Nine-day stability and sterility in an elastomeric pump.

Objective: To investigate compatibility, stability, and microbiologic risk of omadacycline 1 mg/mL when prepared in an elastomeric infusion pump and stored under refrigeration for 9 days based upon requests for information from healthcare providers. Methods: Omadacycline was reconstituted to 1 mg/mL with sodium chloride 0.9% w/v or dextrose 5% w/v in SMARTeZ® elastomeric infusion pumps and refrigerated for up to 9 days. Samples were taken daily and tested for appearance, pH, osmolality, chemical composition, and particulate matter. For a microbial challenge study, the pumps were spiked with a challenge microorganism (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, or Aspergillus brasiliensis) and samples were plated daily for 9 days to assess microbial survival. Results: Appearance, pH, osmolality, percent label claim, and particulate matter results remained essentially unchanged for omadacycline solutions in either diluent over the 9-day study. No > 0.5-log day-to-day increases in the challenge-microorganism populations were measured in diluted omadacycline pumps or positive controls. With omadacycline, no growth was seen for S. aureus or E. coli in either diluent, nor for P. aeruginosa in dextrose 5% w/v. Reduction of C. albicans and A. brasiliensis populations over time was similar between omadacycline solutions and positive controls. Conclusion: After reconstitution, omadacycline for injection was stable and remained within specifications for use for up to 9 days when refrigerated.

An MRI evaluation of carpal tunnel dimensions in healthy wrists: Implications for carpal tunnel syndrome.

BACKGROUND: Deviated wrist postures and pinch grip use have been linked to the development of carpal tunnel syndrome and are likely related to the size and shape of the carpal tunnel. The purpose of this study was to quantify carpal tunnel dimensions with changes in wrist posture and pinch grip. METHODS: Eight healthy volunteers (4 male, 4 female) underwent magnetic resonance imaging of their dominant wrists under seven conditions which included: 30 degrees wrist extension, neutral and 30 degrees flexion (with and without a 10 N pinch force) and a fist with a neutral wrist. Cross-sectional area of the carpal tunnel and its contents were calculated at 3mm increments along the length of the tunnel and integrated to calculate volumes. Ratios were calculated between the contents of the tunnel to the tunnel itself for area and volume. FINDINGS: The use of a correction factor significantly reduced volume and distal carpal tunnel area in flexed and extended wrists. Carpal tunnel areas were largest in neutral and smallest at the distal end with wrist flexion. An extended wrist resulted in the smallest carpal tunnel and content volumes as well as the smallest carpal tunnel content volume to carpal tunnel volume ratios. While men had significantly larger areas and volumes than women for both the carpal tunnel and it contents, there were no differences in ratios between the contents and tunnel size. INTERPRETATION: A simple correction factor for non-perpendicular magnetic resonance images proved useful in relating volume changes to known pressure changes within the carpal tunnel. More inclusive and detailed evaluation of the carpal tunnel and its contents is required to fully understand mechanisms for median nerve compression in the carpal tunnel.