This issue of the GaBI Journal is being published as the global coronavirus 2 (SARS-CoV-2) pandemic is expanding rapidly in many areas of the world including in the United States of America, South America, Asia, and Africa. While there is no known effective vaccine or cure, preliminary results have suggested that some treatments approved for other diseases may shorten the duration of illness or decrease mortality. These include patent protected, e.g. remdesivir, and off-patent drugs, e.g. dexamethasone and anticoagulants. Human trials of both immuno- modulator drugs and dozens of vaccine candidates are either already under way or are planned to begin soon. What is clear is that the pandemic has exposed weaknesses in medical supply chains, traditional drug development processes, public health resources and political leadership in many countries. These weaknesses have resulted in shortages of personal protective supplies, medications, ventilators, hospital beds and personnel in both resource-rich and resource-poor countries. The need for access to quality generic and biosimilar therapeutic products may be more critical now than ever before and this need is likely to only increase once effective treatments, with or without an effective vaccine, are identified. Manuscripts in this issue of the GaBI Journal describe weaknesses in the systems currently being used globally for the development and approval of generic and biosimilar products in pre- pandemic times. The inadequacy of these systems will become even more evident as the effects of this pandemic grow. In addition, this is unlikely to be the last pandemic the world will face. The methods currently used are clearly inadequate in non-pandemic times. Public health and healthcare systems as well as governments will need to rapidly find ways to greatly improve how generic and patent protected drugs and vaccines are developed, tested, prescribed and administered if the mortality and morbidity caused by this pandemic are to be minimized.
In the Commentary, Professor Alain Astier describes the methods used to examine the higher order structure of proteins and explains why such an examination is important in the approval of biosimilar products. Much work remains to be done if these and other analytical methods can be made to better inform or possibly replace traditional clinical trials, but the pace of drug development must be improved if the challenges created by pandemics are to be overcome.
The first Review Article by Adjunct Associate Professor Sia Chong Hock et al. reviews the ‘global challenges in the manufacture, regulation and international harmonization of GMP and quality standards for biopharmaceuticals’. The review includes the biopharmaceutical industry and regulatory framework of the Association of South East Asian Nations (ASEAN). The authors explain that good manufacturing guidelines (GMP) in ASEAN are generally similar to other regions but point out that, ‘GMP alone does not address regulatory challenges such as the evaluation of biosimilarity, differing outlook on interchangeability and a growing occurrence of data integrity lapses’. The authors discuss the need, ‘for real-time monitoring and better predictive modelling’, to ‘improve and harmonize … standards’, and for, ‘better collaboration between key stakeholders’. The improvements needed suggest that the pace of product approval is unlikely to be adequate to deal with the challenges these (ASEAN) countries will face in dealing with future COVID-19 treatments.
The second Review Article by Dr Esteban Ortiz-Prado et al. discusses current trends in the South American biosimilar product market; including products they call biomimics, i.e. ‘copies of monoclonal antibodies and fusion proteins that have not demonstrated bioequivalence to their reference biologicals’. This article shows that the problems faced by countries in the ASEAN, as described in the previous article, are not at all unique and include: (a) the scarce information available regarding the Latin American biosimilars market in Latin America; (b) the relatively recent investment in the development of these drugs in Latin America; (c) the limited experience that the majority of countries in the region have in the production of biological drugs; and (d) and the need for robust guidelines and regulation regarding the development of biological medicines.
This overview suggests that Latin American as well as many other countries globally will face increasingly difficult challenges dealing with the current pandemic. Current trends suggest that these challenges require strong, public health oriented and science driven leadership.
Research News demonstrates that the need for improved use of biosimilars is not restricted to resource poor countries. Dr Kevin Klein reviews the results of a survey of ‘61 hospital pharmacists from 40 different National Health Service (NHS) Trusts (representing 23% of the 174 eligible NHS Trusts)’ in the UK which concluded, ‘that the Pharmacovigilance Legislation from 2012 to strengthen product identification for biologicals in adverse drug reactions (ADRs) reports has not yet achieved its objective. The traceability of biologicals in UK clinical practice is not always ensured, particularly for batch numbers’. The problems identified in the study reviewed suggest that a ‘robust pharmacovigilance system that allows for the timely identification of any manufacturing related safety issues’ with respect to biosimilars remains to be developed. The need for such a system is even more acute for products which are marketed after undergoing the much shorter, less extensive evaluations already underway for COVID-19 therapies.
The Legal paper by Professor Philip J Schneider and Mr Michael S Reilly, reviews in detail ‘the different approaches to biosimilar policy across the European continent, highlighting principles which can be applied to develop an efficient and sustainable biosimilar market’. The authors provide an extensive, well referenced summary of reports from the European Union, which has the longest and most extensive experience with the evaluation, approval and use of biosimilars. The authors suggest that, ‘European countries, with their large biosimilar markets and diverse healthcare systems, serve as valuable examples of different approaches to biosimilar policy’. The authors provide an extensive list of published, ‘studies, research papers and position statements’. Readers should find these data useful. The manuscript was funded by the Alliance for Safe Biologic Medicines (ASBM). The majority of the ASBM’s support comes from the pharmaceutical industry.
The last two Special Reports were written by GaBI Journal editors. The first Special Report presents the results of an Internet search for clinical trials evaluating trastuzumab biosimilars. Trastuzumab is a monoclonal antibody which has significantly improved survival in women with early and metastatic human epidermal growth factor receptor 2 positive (HER2+) breast cancer. The large number of studies/products identified illustrates how extensive biosimilar drug development can be for a product directed at a disease which is both highly prevalent in resource rich countries and often lethal. Similar or even more extensive work is underway for potential COVID-19 treatments and vaccines.
The second Special Report reviews the difference between the US and European Union in the time taken for biosimilar approval. It will be interesting to see whether recent changes in US regulations will close or reverse the historically shorter time to approval in the EU either for only COVID-19 treatments or for all generic and biosimilar products.
Generic and biosimilar products could both be more effectively and efficiently developed and marketed and result in improved human health and quality of life. Perhaps the death and disruption caused by the current pandemic will provide the incentives necessary to make this happen.
Professor Philip D Walson, MD
Editor-in-Chief, GaBI Journal
Disclosure of Conflict of Interest Statement is available upon request.
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