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.

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.

The crosstalk between adenosine A2B receptor and insulin signalling in rat skeletal muscle cells.

Diabetes mellitus (DM) is a group of metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Insulin therapy might be affected by specific metabolic enzymes and transporters. There are conflicting reports in the literature on the role of adenosine receptor A2B (AR2B) in skeletal and cardiac muscle glucose metabolism. This study aims to find out if there is an association between AR2B and insulin signalling, especially the metabolic pathways (AKT-GSK). Differentiated L6 cell rat muscle cells were treated with insulin, adenosine agonist NECA, selective AR2B antagonist PSB 603 and combinations between these reagents, the expression of AKT2, GSK3α, and GSK3ß were measured by qPCR hydrolysis probe technique. Insulin increases AKT2, GSK3α and GSK3ß mRNA expression, while AR2B antagonist inhibits AKT2 GSK3α and GSK3ß mRNA expression and combining AR2B antagonist with insulin diminish insulin action and decrease AKT2 GSK3α and GSK3ß mRNA expression, which means a strong relationship between AR2B and insulin action. Furthermore AR2B agonist may be a good candidate as an anti-diabetic drug.