USP and MHLW-PMDA held a joint workshop on September 10-11, 2024 in Tokyo, Japan¹⁾. This workshop was organized by the United States Pharmacopeia (USP) in collaboration with Japan’s Ministry of Health, Labour, and Welfare (MHLW) and the Pharmaceuticals and Medical Devices Agency (PMDA). This workshop aimed to address critical issues in pharmaceutical quality and foster international collaboration between our two organizations and critical stakeholders. The workshop covered a range of topics, including the harmonization of standards with a specific focus on the inaugural pilot between USP and JP on the harmonization of a drug substance monograph and a drug product monograph, as well as on ICH Q2(R2)/Q14. Participants discussed advancements in quality testing, particularly for high-risk excipients like ethylene glycol and diethylene glycol, and shared insights on managing contamination issues. The event also explored the integration of emerging technologies such as quantitative nuclear magnetic resonance (qNMR) and the challenges associated with complex generics. Overall, the USP-MHLW/PMDA joint workshop underscored the commitment of both organizations to advancing public health through the development and harmonization of high-quality standards. By fostering collaboration and innovation, the workshop aimed to enhance the safety, efficacy, and accessibility of medicines globally.

Dry eye disease is an ocular disease in which the stability of tear fluid decreases, causing ocular discomfort and abnormal visual function as well as damage to the ocular surface. It has been reported that specific types of food ingredients can promote lachrymal secretion, which is expected to prevent and improve dry eye. Here, we evaluated the effects of a heat-killed form of Fructobacillus fructosus FMO-85, a species of fructophilic lactic acid bacteria (FLAB) that is derived from the digestive tract of honeybees, on lacrimal fluid secretion using a stress-induced dry eye mouse model. Male C57BL/6J mice were fed a 3% FLAB-mixed diet 3 weeks before stress loading. We observed that the tear fluid volume was decreased after stress loading, which was significantly improved by FLAB treatment after 7 and 11 days. Mechanistically, the mRNA levels of brain-derived neurotrophic factor (Bdnf), one of the important growth factors involved in lacrimal fluid secretion, isoform-2 and -6 were increased in the hippocampus of FLAB-treated mice. Furthermore, the plasma levels of an anti-inflammatory cytokine, interleukin-10 (IL-10), increased in the FLAB-treated mice. These results suggested that the ingredients contained in dried FLAB increase tear fluid volume by affecting the lacrimal secretion mechanism and the production of inhibitory cytokines. In conclusion, the decrease in tear fluid volume after stress loading was suppressed by FLAB intake. These results indicated that FLAB supplementation may be a useful strategy for the prevention and treatment of dry eye.

The Committee on Sick House Syndrome: Indoor Air Pollution, established by the Ministry of Health, Labour and Welfare of Japan, is reviewing indoor air quality guidelines. A comprehensive exposure assessment is essential for pollutants with revised guideline values or newly developed candidate pollutants, necessitating the development of standardized test methods for an accurate evaluation. However, the available test methods that have been provided as a standard test method (measurement manual) were introduced over 20 years ago. Its applicability to pollutants for which guideline values have been established since then had not been examined. Therefore, we established a test method for six compounds based on the current guideline values and three candidate compounds that underwent initial risk assessment. This method considered the new guideline values established after 2001 using solid-phase adsorption-thermal desorption-gas chromatography/mass spectrometry, as indicated in the measurement manual for volatile organic compounds. This method was validated at four institutions using samples at approximately 1/10^th the concentration of the current, revised, and newly proposed guideline values, as of 2017. Results revealed that the average recovery of the four laboratories ranged from 84.2 to 95.6%, the repeatability ranged from 0.43 to 16%, which was <20%, thereby effectively achieving the target evaluation criteria. Therefore, this method could be presented as a standard test method for nine volatile organic compounds.

To avoid harm caused by falsified medicines, we aimed to devise a method to identify falsified medicines in Japan using visual observation among medicines obtained from personal import agency websites, which are the main conduits through which falsified medicines are obtained. We recorded details regarding the information provided on personal import agency websites used to purchase medicines, the outer package received, the customs declaration description, and the product appearance for 212 samples of medicines obtained through personal import via the Internet. We investigated the relationship between each observed item and the rate of falsified medicines. We developed a classification and prediction model to identify falsified medicines using items that could be visually observed. The results showed that the rate of falsified medicines was significantly higher for websites that did not contain identifying information such as the name and address of the contact or import agency, as well as for products that did not contain the name and address of the manufacturer, indicating that these items may be useful in the identification of falsified medicines. In the prediction model constructed, we extracted features such as the country of dispatch and address of the import agency, and a prediction model was created to identify falsified medicines and websites selling these medicines. Careful observation of the identified features and use of our prediction model will help to prevent harm owing to the use of falsified medicines.

Bisulfite modification of cytosine residues is a widely used method for analyzing genomic DNA methylation. Despite its robustness, degradation of DNA during modification has hampered the application to the analysis of small amounts of DNA. We show that the addition of large volume bisulfite-treated heterogeneous DNA promotes the amplification of the targeted region in bisulfite-treated DNA by PCR. The addition of untreated DNA did not promote the amplification. The addition of large volume bisulfite-treated heterogeneous DNA neither promoted the amplification when untreated DNA was used as template. PCR products were detected when a ten thousandth of aliquot of bisulfite-treated 1 μg of human genomic DNA (0.1 ng) was used as template. This figure is equivalent to that of human genomic DNA derived from as little as 15 cells. This procedure permits the analysis of genomic DNA methylation when only limited numbers of cells are available.