The first GaBI Journal issue of 2022 comes at a time of both hope and despair. While the COVID-19 pandemic continues to cause significant global morbidity and mortality; especially in resource poor countries, both the pace and direction of changes are beginning to produce some encouraging signs. Positive trends are in part the result of the continuing increase in our understanding of the virus itself, its treatment, and public health actions that are effective in limiting its spread. The availability of highly effective vaccines, antibodies, and antiviral medications have greatly limited infections and improved outcomes. Biological products, both innovator and biosimilar versions, as well as generic products are decreasing treatment costs and increasing the availability of effective treatments. Of special note is the increasing ability of resource-poor nations to produce their own versions of innovator products without patent constraints. Perhaps the most impressive example of this is, ‘The World’s COVID-19 Vaccine’ developed by the Texas Children’s Hospital at Baylor University and funding support of the Bill and Melinda Gates Foundation. This partnership has demonstrated that it is possible to overcome availability issues inherent in the for-profit pharmaceutical industry.
In contrast to the slowly improving outlook for the COVID-19 pandemic, the world is witnessing an increasing number of brutal hostilities both within (e.g. Syria, Libya, Mali, Ethiopia, and Yemen) and between nations that threaten human health. Especially dangerous examples include the invasion of sovereign nations by neighbouring countries (e.g. Georgia and Ukraine); that has produced a level of destruction and human suffering not seen in decades. These hostilities are causing untold suffering of innocent civilians, as well as of combatants. They have also blocked access to not only medicines, but also to medical treatment, hospitals, and health professionals. Global hostilities are depriving millions of people, including children, the disabled and the elderly of basic human needs. including shelter, food, and water, producing both medical and psychological damage that will consume health care and other resources for decades to come. Hopefully, future access to effective, reasonably priced generic and biosimilar products will help countries deal with these issues. This issue of the GaBI Journal contains articles that suggest some ways in which access to such products could be improved.
In a Letter to the Editor, Adjunct Professor Pekka Kurki reviews the history of switch studies done to approve EU marketing of biosimilars. The author concludes that such products should be made interchangeable with their reference products without the need for systematic clinical switch studies. The clinical evidence reviewed by Adjunct Professor Kurki includes 178 biosimilar clinical switch studies that failed to find any evidence of switch-related adverse effects, as well as recent reviews that also failed to find evidence of switch-related adverse effects. The author also cites the very limited power of such switch studies to identify or rule out rare adverse events and suggests that switch studies be replaced by pharmacovigilance and pharmaco-epidemiological studies instead. Readers, including those involved in the development of innovator products and those who simply disagree based on their own experience or their own review of the literature, are encouraged to submit letters presenting any alternative, supportive, or clarifying opinions.
The first Review Article was submitted by Drs Mihaela Buda, Olga Kolaj-Robin, and Emmanuelle Charton from the European Pharmacopoeia Department at the European Directorate for the Quality of Medicines & HealthCare (EDQM). Drs Buda et al., provides ‘an overview of strategies to overcome the challenges of elaborating monographs on biotherapeutics’. The opinions expressed in this article were based on discussions with various European stakeholders at scientific meetings, as well as on the experience of the authors in developing standards used to produce biosimilar pharmacopoeial monographs. The article should be very useful both for those who use or utilize the European or other pharmacopoeias. as well as for anyone unfamiliar with these useful publications.
The second Review Article by Adjunct Associate Professor Sia Chong Hock et al., from the National University of Singapore covers the timely topic of the challenges associated with the best-practices manufacture, storage, distribution, and regulation of both new and traditional vaccines. The COVID-19 pandemic has produced many examples of the problems remaining to be solved in, ‘the equitable distribution and availability of safe, efficacious, and good quality vaccines’ in a way that increases the efficient use of vaccines to prevent or mitigate the effects of infectious diseases and safeguard public health. The authors discuss how a lack of adequate controls of the manufacture, storage, distribution, and possibly regulation of vaccines contribute to, ‘the continued existence of poor-quality vaccines’ as well as costly waste and decreased efficacy of vaccines. The review should be useful for anyone involved in the testing, evaluation, procurement, or administration of vaccines and vaccination programmes.
The final Review Article by Dr Robert Janknegt and Ms Marloes Dankers, describe the System of Objectified Judgement Analysis (SOJA) and then explains how it was used at Dr Janknegt’s hospital in the Netherlands to provide clinicians with an objective, evidence-based method to evaluate which of the increasing number of competing, long-acting insulin products to prescribe for their diabetic patients. Criteria utilized in the SOJA included: effectiveness, safety, tolerability, and ease of use. Dr Janknegt explains that because application of these criteria to long-acting insulin products produced essentially identical scores, it was decided that acquisition cost and individual patient characteristics be used to determine the choice of formulary products. The article should be helpful for other hospitals when deciding on which long-acting insulins to include on their formularies. It is likely that the SOJA may also be useful to evaluate other medications. Comments are welcomed from readers who disagree with the use of the general approach described, or who want to discuss application of the SOJA to a different multisource product, as well as those familiar with different decision support systems.
The Opinion Article by Dr Pablo Matar raises an important issue concerning the possibility of, ‘loss of bioavailability over time’. Much has been written/claimed about how even minor changes in the manufacturing process can affect the qualities of a biological; whether an innovator or follow-on/biosimilar product. Less has been written about the fact that changes in manufacturing processes over time can also have important effects on originator products. Dr Matar points out that, ‘Current regulations do not require a given biosimilar to remain similar to its reference biological over time’ yet no post-marketing comparative bioavailability studies are required by regulators. Since any change in the manufacturing process can alter the final biological product, either of any two products deemed to be ‘biosimilar’ at one point in time are subject to divergent changes (‘drift, evolution and divergence’) that could result in later, undetected non-equivalence. To deal with this problem the author suggests: 1) pharmacovigilance systems should be strengthened; 2) interchangeability standards are needed to deal with this possibility; and 3) that harmonized regulatory definitions of comparability versus interchangeability need to be established. While the issues are clear, actual evidence-based recommendations for specific, proven effective changes needed in the regulatory approval or monitoring process were not well described. It is also not clear, to this reader at least, which (or even whether) pharmacovigilance programmes can reliably detect all clinically meaningful changes in biological product effects. The effects of manufacturing process changes over time need to be monitored for all innovator products, whether there are any approved biosimilar products available or not. Unfortunately, it is not clear which, if any, in vivo or in vitro methods, including those required by the US Food and Drug Administration (FDA) to declare interchangeability, are adequate to detect all clinically important differences in product performance. Reader comments on this complicated, important issue are encouraged.
I will close with my wishes for a more peaceful world with more equitable distribution of all resources needed for a long, rewarding, and healthy life for all peoples of the world.
Professor Philip D Walson, MD
Editor-in-Chief, GaBI Journal
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