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.

A descriptive analysis of medical abortion commodity availability and pricing at retail outlets in 44 countries across four regions globally.

Pharmacies in low- and middle-income countries play an important role in increasing the availability of medical abortion to individuals for self-use. We aimed to document the costs to users of medical abortion products at outlets across geographies and understand the diversity of available products, primarily in low- and middle-income countries or in places where access to abortion is restricted. A descriptive analysis of price data was completed for identified medical abortion products at retail outlets visited in 44 countries from November 2017 to February 2018. Median prices and ranges are reported in $US for mifepristone 200 mg tablets, misoprostol 200 mcg tablets, and combipacks. Misoprostol, mifepristone, and combipacks were found in 44, 19, and 16 countries, respectively. Nearly two-thirds of products (321/508) required a prescription. The median price of misoprostol was $0.63 per tablet (range $0.09-$27.63) based on 304 price points. Mifepristone and combipacks had fewer price points available (n = 59 and n = 44, respectively). Median prices were $11.78 per mifepristone tablet (range $1.77-$37.83) and $11.18 per combipack (range $3.50-$35.86). Overall, prices were highest in Latin America and lowest in South/Southeast Asia. Only 11.5% (7/61) of the total unique misoprostol brands were quality-assured (i.e. approved by a stringent regulatory authority or pre-qualified by the World Health Organization), compared to 25.0% (4/16) of unique combipack products. There was wide variation in product pricing and availability across settings. The infrequent availability of mifepristone and combipacks, in addition to the limited availability of quality-assured medicines and high cost of abortion medications, are important factors affecting access to high-quality abortion care.

A cross-sectional analysis of mifepristone, misoprostol, and combination mifepristone-misoprostol package inserts obtained in 20 countries.

OBJECTIVES: To evaluate the characteristics, clinical information, and storage instructions contained in package inserts from medical abortion commodities collected in low- and middle-income countries. STUDY DESIGN: From November 2017 to February 2018 mifepristone, misoprostol, and combined mifepristone-misoprostol (combipack) products were collected to populate the Medical Abortion Commodities Database. We extracted stated indications for use, storage instructions, and date of last revision from each package insert obtained. For those inserts listing medical abortion as an indication, we also extracted eligibility criteria, recommended regimens, side effects, and contraindications. RESULTS: We identified 41 package inserts from 20 countries; 19 (46%) listed medical abortion as an indication including all 7 combipacks, all 7 mifepristone products, and 5/27 (19%) misoprostol products. Date of last insert revision ranged from 1991 to 2016. Gestational age limits for early medical abortion ranged from 49 days to "first trimester." Three (43%) mifepristone products recommended a 600 mg oral dose and two (29%) recommended regimens with gemeprost. Eighteen (67%) misoprostol and one (14%) combipack inserts recommended protection from moisture. CONCLUSIONS: The characteristics, clinical information, and storage instructions in medical abortion product package inserts from a variety of field settings in low- and middle-income countries included inadequate storage instructions and outdated gestational age limits and regimens. IMPLICATIONS: There is an urgent need to revisit approved inserts for medical abortion products in low- and middle-income countries to ensure information is accurate and reflects the current evidence base. Simultaneously, providing supplemental instructions targeted at users may fill some gaps. People have a right to accurate information to ensure a safe and effective medical abortion experience.

A randomized trial of face-to-face counselling versus telephone counselling versus bibliotherapy for occupational stress.

OBJECTIVE: The aim of the present study was to compare the effectiveness and acceptability of three interventions for occupational stress. METHODS/DESIGN: A total of 90 National Health Service employees were randomized to face-to-face counselling or telephone counselling or bibliotherapy. Outcomes were assessed at post-intervention and 4-month follow-up. Clinical Outcomes in Routine Evaluation (CORE), General Health Questionnaire (GHQ-12), and Perceived Stress Scale (PSS-10) were used to evaluate intervention outcomes. An intention-to-treat analyses was performed. RESULTS: Repeated measures analysis revealed significant time effects on all measures with the exception of CORE Risk. No significant group effects were detected on all outcome measures. No time by group significant interaction effects were detected on any of the outcome measures with the exception of CORE Functioning and GHQ total. With regard to acceptability of interventions, participants expressed a preference for face-to-face counselling over the other two modalities. CONCLUSIONS: Overall, it was concluded that the three intervention groups are equally effective. Given that bibliotherapy is the least costly of the three, results from the present study might be considered in relation to a stepped care approach to occupational stress management with bibliotherapy as the first line of intervention, followed by telephone and face-to-face counselling as required.