WHO implementation workshop on guidelines on procedures and data requirements for changes to approved biotherapeutic products, Seoul, Republic of Korea, 25-26 June 2019.

The first global workshop on implementation of the WHO guidelines on procedures and data requirements for changes to approved biotherapeutic products adopted by the WHO Expert Committee in 2018 was held in June 2019. The workshop participants recognized that the principles based on sound science and the potential for risk, as described in the WHO Guidelines on post-approval changes, which constitute the global standard for product life-cycle management are providing clarity and helping national regulatory authorities in establishing guidance while improving time-lines for an efficient regulation of products. Consequently, the regulatory situation for post-approval changes and guideline implementation is changing but there is a disparity between different countries. While the guidelines are gradually being implemented in some countries and also being considered in other countries, the need for regional workshops and further training on post-approval changes was a common theme reiterated by many participants. Given the complexities relating to post-approval changes in different regions/countries, there was a clear understanding among all participants that an efficient approach for product life-cycle management at a national level is needed to ensure faster availability of high standard, safe and efficacious medicines to patients as per the World Health Assembly Resolution 67.21.

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A systematic review.

BACKGROUND: In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment. METHODS: The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023. RESULTS: Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion. CONCLUSION: By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A protocol for systematic review.

There is still unmet medical need in cancer treatment mainly due to drug resistance and adverse drug events. Therefore, the search for better drugs is essential. Computer-aided drug design (CADD) and discovery tools are useful to streamline the lengthy and costly drug development process. Anthraquinones are a group of naturally occurring compounds with unique scaffold that exert various biological properties including anticancer activities. This protocol describes a systematic review that provide insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment. It was prepared in accordance with the "Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 guidelines, and published in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904). Search strategies will be developed based on the combination of relevant keywords and executed in PubMed, Scopus, Web of Science and MedRxiv. Only original studies that employed CADD as primary tool in virtual screening for the purpose of designing or discovering anti-cancer drugs involving anthraquinone scaffold published in English language will be included. Two independent reviewers will be involved to screen and select the papers, extract the data and assess the risk of bias. Apart from exploring the trends and types of CADD methods used, the target proteins of these compounds in cancer treatment will also be revealed in this review. It is believed that the outcome of this study could be utilized to support the ongoing research in similar area with better quality and greater probability of success, consequently optimizing the resources in subsequent in vitro, in vivo, non-clinical and clinical development. It will also serve as an evidence based scientific guide for new research to design novel anthraquinone-derived drug with improved efficacy and safety profile for cancer treatment.

Regulatory challenges with biosimilars: an update from 20 countries.

The World Health Organization (WHO) issued guidelines for the regulatory evaluation of biosimilars in 2009 and has provided considerable effort toward helping member states implement the evaluation principles in the guidelines into their regulatory practices. Despite this effort, a recent WHO survey (conducted in 2019-2020) has revealed four main remaining challenges: unavailable/insufficient reference products in the country; lack of resources; problems with the quality of some biosimilars (and even more with noninnovator products); and difficulties with the practice of interchangeability and naming of biosimilars. The following have been identified as opportunities/solutions for regulatory authorities to deal with the existing challenges: (1) exchange of information on products with other regulatory authorities and accepting foreign licensed and sourced reference products, hence avoiding conducting unnecessary (duplicate) bridging studies; (2) use of a "reliance" concept and/or joint review for the assessment and approval of biosimilars; (3) review and reassessment of the products already approved before the establishment of a regulatory framework for biosimilar approval; and (4) setting appropriate regulatory oversight for good pharmacovigilance, which is essential for the identification of problems with products and establishing the safety and efficacy of interchangeability of biosimilars.

Drug administration errors in paediatric wards: a direct observation approach.

Paediatric patients are more vulnerable to drug administration errors due to a lack of appropriate drug dosages and strengths for use in this group of patients. Therefore, the aim of the present study was to determine the extent and types of drug administration errors in two paediatric wards and to identify measures to reduce such errors. A researcher was stationed in two paediatric wards of a teaching hospital to observe all drugs administered to paediatric inpatients in each of the ward, for 1 day in a week over ten consecutive weeks. All data were recorded in a data collection form and then compared with the actual drugs and dosages prescribed for the patients. Of the 857 drug administrations observed, 100 doses had errors, and this gave an error rate of 11.7% [95% confidence interval (CI) 9.5-13.9%]. If wrong time administration errors were excluded, the error rate reduced to 7.8% (95% CI 6.0-9.6%). The most common types of drug administration errors were incorrect time of administration (28.8%), followed by incorrect drug preparation (26%), omission errors (16.3%) and incorrect dose (11.5%). None of the errors observed were considered as potentially life threatening, although 40.4% could possibly cause patient harm. Drug administration errors are as common in paediatric wards in Malaysia as in other countries. Double-checking should be conducted, as this could reduce drug administration errors by about 20%, but collaborative efforts between all healthcare professionals are essential.

Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin.

Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.