The European framework for intellectual property rights for biological medicines

Introduction: The Pharmaceutical Strategy for Europe (2020) proposes actions related to intellectual property (IP) rights as a means of ensuring patients’ access to medicines. This review aims to describe and discuss the European IP framework and its impact on accessibility of biological medicines and makes some recommendations. Methods: A non-systematic literature review on IP for biological medicines was conducted. Data on authorizations and patent and exclusivity expiry dates of biological medicines obtained from the European Medicines Agency’s (EMA) website and literature was analysed quantitatively and qualitatively. Results: The analysis showed that as at end July 2021, 1,238 medicines were authorized in Europe, of which 332 (26.8%) were biological medicines. There were only 55 biosimilars for 17 unique biologicals. There is an increasing trend in biological authorizations but signifi cant delays in submission of applications for marketing authorization of biosimilars, with no signifi cant diff erences in the time for assessment for marketing authorization between originator biologicals and biosimilars. For some of the more recent biosimilars, applications for authorization were submitted prior to patent and exclusivity expiry. COVID vaccines confi rmed the impact of knowledge transfer on accessibility, especially when linked to joint procurement. Discussion: IP protects originator products and impacts the development of biosimilars. Strategies to improve competition in the EU biological market are discussed. Pricing policies alone do not increase biosimilar uptake since patients are switched to second generation products. Evergreening strategies might be abusing the IP framework, and together with trade secrets and disproportionate prices compared to R & D and manufacturing costs lead to an imbalance between market access and innovation. Conclusion: The European Pharmaceutical Strategy should focus on IP initiatives that support earlier authorization of biosimilars of new biologicals. Recommendations include knowledge sharing, simplifi cation of the regulatory framework and transparency of prices and R & D costs.

Extended stability of the trastuzumab biosimilar ABP 980 (KANJINTI™) in polyolefin bags and elastomeric devices

Study Objectives: To investigate the quality and in-use stability of the trastuzumab biosimilar ABP 980 (KANJINTI™) in both concentrated multi-dose bags and following dilution and extended storage in intravenous (IV) bags and elastomeric devices, to address the stability requirements of diff erent global pharmacy practices. Methods: The eff ect of extended refrigerated storage plus exposure to in-use temperature conditions on KANJINTI™ (trastuzumab) solutions was assessed using a range of stability-indicating analytical methods, including appearance, pH, SEC, nonreducing CGE, reducing-CGE, CZE, sub-visible particle counting and potency by a cell-based proliferation inhibition assay. Stability of reconstituted 21 mg/mL solution stored in multi-dose bags and diluted samples at 0.3 mg/mL, 0.8 mg/mL and 4 mg/ mL in 0.9% w/v NaCl solutions stored in IV bags and elastomeric devices was determined over diff erent storage durations. Forced degraded samples exposed to room temperature and natural daylight were used to demonstrate the stability-indicating abilities of the methods. Results: No signifi cant changes were observed in the appearance, pH, monomer concentration, purity, charge heterogeneity, sub-visible particle counts or bioactivity, regardless of initial concentration, container or storage duration. Discussion: There was no indication of signifi cant changes to the physicochemical stability or bioactivity of any of the solutions following extended storage when compared to the initial results acquired on the day of preparation. Conclusion: The data presented has demonstrated the physicochemical stability and bioactivity of a range of KANJINTI™ (trastuzumab) solutions when prepared using controlled and validated aseptic processes, stored protected from light for extended periods at 2°C–8°C and subjected to in-use temperatures. The stability demonstrated in multi-dose bags and elastomeric devices provides additional preparation options to address diff erent global pharmacy practices and requirements.

Biotechnological therapies and biosimilars for COVID-19: scarcities, poor regulation, and pharmaceutical black market: a case analysis in Ecuador

At the beginning of the COVID-19 pandemic, Ecuador was unprepared for the overwhelming number of COVID-19 cases. As the general population started to see the eff ects of the pandemic, unproven treatments and medications were sought by the population to try to ameliorate the impact of the pandemic. The growing demand for a cure, the fear of dying from COVID-19, and the lack of therapeutic rigour, pushed a signifi cant number of people to seek help outside the traditional healthcare system. Doctors, pharmacists, and patients started prescribing or selfmedicating pharmacological products that were later shown to be ineff ective, toxic or even contraindicated. In Ecuador, most people who developed the severe acute respiratory syndrome associated with infection by the coronavirus 2 (SARS-CoV-2) virus, which causes COVID-19, used antibiotics (azithromycin), antiparasitic medications (hydroxychloroquine or ivermectin), dangerous chemical products (chlorine dioxide) and in some cases, biological medicines, to try to cure or protect themselves from COVID-19. The growing demand for therapies that were unavailable, as well as the rise in misinformation, created the perfect scenario for the misuse of medicines and enabled the appearance of a rampant black market of unregistered biological products. In this manuscript, we describe the Ecuadorian experience in relation to the off -label use of biological and biosimilar products during the COVID-19 pandemic, the role of the pharmaceutical black market, and the lack of national regulations to avoid dangerous practices. To the best of our knowledge this is the fi rst report that has aimed to describe the unapproved and even illegal sale and use of biologicals, biosimilars and related products, with or without approved therapeutic indications in the treatment of COVID-19.

Fourth and final issue of GaBI Journal’s 10th volume

This issue of the GaBI Journal contains only a limited number of articles, but these include two scientifi c very data-rich articles and an interesting and important expose on the use and misuse of products to treat COVID-19 patients. All three articles have potentially major implications for the global struggle to deal with the current COVID-19 pandemic; either with respect to the proper use of biosimilar products to safely reduce COVID-19 related and non-related pharmaceutical expenditures, as well as to the effects of the pandemic on the criminal use and abuse of human and veterinary pharmaceuticals and other products, e.g. disinfectants.

Pharmacokinetics and bioequivalence of generic etoricoxib in healthy volunteers

Introduction/Study Objectives: A bioequivalence study was performed to compare the pharmacological profile of innovator etoricoxib (ETO) with a newly developed generic ETO, both in a 120 mg tablet formulation. A dissolution study was conducted to optimize the formulation process before evaluating physical changes in the active pharmaceutical ingredient and the formulated product. Methods: This was a randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, two-way crossover, truncated bioequivalence study involving a washout period of ten days. A total of 26 healthy male volunteers were recruited. The pharmacokinetic profile of the test formulation was compared with the reference formulation. Results/Discussion: The pharmacokinetic parameters of ETO were calculated based on the plasma drug concentration-time profile using non-compartmental analysis to determine its safety profile and tolerability. The Test/Reference (T/R) ratio of ETO was 104.36% (90% confidence interval (CI): 98.30%–110.80%) for area under curve (AUC)0-72 while the T/R ratio of maximum concentration (Cmax) was 101.39% (92.15%–111.56%). The 90% CI of the Cmax and AUC0-72 of ETO were within acceptable bioequivalence limits of 80%–125%. All values were within the predetermined limits of the Association of Southeast Asian Nation (ASEAN) bioequivalence guidelines. Conclusion: The test formulation was found to be bioequivalent with respect to the reference drug, according to ASEAN bioequivalence guidelines.

Biosimilar epoetin for cancer and chemotherapy-induced anaemia in the US

Biosimilars are biological drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety and efficacy. Biosimilar epoetin received US Food and Drug Administration (FDA) approval in 2018 [1]. The manufacturer received an FDA non-approval letter in 2017, despite receiving a favourable review by the FDA’s Oncologic Drugs Advisory Committee (ODAC) and an FDA non-approval letter in 2015 for an earlier formulation.

Microbiological, scientific and regulatory perspectives of hand sanitizers

Hand sanitizers are rub-on formulations for the purpose of inactivating microorganisms on the hands. With the recent COVID-19 pandemic, a surge in the manufacturing, sale and use of hand sanitizers is observed. However, the effectiveness and safety of hand sanitizers are not well understood by the public; thus, hand sanitizer usage may not confer adequate protection and may pose safety threats. Globally, the emergence of safety threats and inappropriate manufacturer claims also suggest that regulatory frameworks are insufficient in ensuring optimal effectiveness and safety standards for hand sanitizers. This paper presents an overview of the activity of antimicrobials as active ingredients in hand sanitizers and the principles of test methods to evaluate the effectiveness of hand sanitizers. Different antimicrobials confer different activities, rendering some more useful than others. There are also no specific compendial test for efficacy of hand sanitizers and the choice of test method is left to the discretion of manufacturers. It has also been reported that a significant number of hand sanitizers were improperly labelled or had inappropriate claims. Implementing a tighter regulatory framework, developing pharmacists’ knowledge and capabilities, raising consumer awareness and debunking common myths are some possible solutions to address the problems encountered.

Use of biologicals in dermatology – following the agreed path or going off-piste? A brief report

Introduction: Biological medicines are used to treat a range of conditions according to National Institute for Health and Care Excellence (NICE) technology appraisals. The annual drug treatment cost per patient per year varies depending on various factors, including newer or older biological, and availability of a biosimilar. Our biologicals pathway for dermatology (moderate or severe psoriasis) listed less expensive older biologicals (including biosimilars) early on in the treatment choices and more recently approved (and generally more expensive) choices lower down the pathway. Objective: We aimed to identify which biologicals or selective immunosuppressants were used first line in adult patients with moderate or severe psoriasis, and ascertain if the reasons for use of treatments other than adalimumab were in accordance with the locally agreed pathway. Methods: Medical records were reviewed for a sample of patients prescribed biologicals during late 2019 and early 2020. We identified patients who had commenced any treatment. Contact was made with lead dermatology nurses if needed. Results: There were 33 patients commenced on a biological – 17 had newly started biological therapy and 16 had switched from a prior biological therapy to a new therapy. Of the 17 new patients, two commenced apremilast (biological contraindicated), 10 commenced adalimumab, and five commenced other biologicals. Of these five who commenced other biologicals, two were on guselkumab, two on ustekinumab, and one on certolizumab. In all five instances there was a valid reason for not using adalimumab as first choice though this was not always explicit in the multidisciplinary team (MDT) documentation. Discussion: Though the number of psoriasis patients (17) newly starting a biological medicine was relatively small, it was reassuring that for five of these who commenced a subcutaneous biological other than adalimumab, there was a valid reason for this choice, though not always explicit in the MDT letter, which Dermatology will ensure is clear for future decisions. Hence going ‘off-piste’ was deemed justified. Conclusion: This very small-scale study found that the local guideline was followed with patients commencing treatments other than biosimilar adalimumab for valid reasons.

Reasons for patients’ generic drug switching at the pharmacy counter: a pilot study

Background: Drug switching describes switching between drug products with the same active substance. Drug switching occurs commonly in the Netherlands and mostly between generic drug products, however, the specific reasons for switching are incompletely understood. Methods: To document reasons for drug switches between products with the same active substance in the Netherlands. Results: In total, 207 drug switches were recorded. Most drug switches were caused by nationwide drug shortages (32%, n = 66) and the Dutch price-based tender system (23%, n = 47). Other reasons for switching included deals between pharmacists and wholesalers (12%, n = 25), distribution issues at wholesalers (11%, n = 22), and a financially favourable margin for pharmacists (11%, n = 21). Conclusion: This study indicates that drug shortages and the Dutch price-based tender system are likely to be major causes of drug switches in the Netherlands. However, other reasons, such as drug product distribution issues and local economic incentives, were also identified.

Latest features in GaBI Journal, 2021, Issue 3

This issue of GaBI Journal contains articles dealing with some very practical issues related to the evaluation, describing, and use of generic and biosimilar products. These issues include the uncertainty associated with extrapolating results of studies that used small, non-representative study populations, study sites, or product types. These problems are evident in the evaluation of three articles in this issue. Other articles illustrate difficulties evaluating published opinions without access to the original data upon which such opinions were based: the need to evaluate the possible effects of real or potential conflicts of interest; and the lack of consistent regulatory approaches to important, non-pharmaceutical chemicals.