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15 pages, 2370 KiB

Open AccessArticle

How Do Hospital Pharmacists Approach Substitution of Nanomedicines? Insights from a Qualitative Pilot Study and a Quantitative Market Research Analysis in Five European Countries

by Natalia Sofia, Stefan Mühlebach, Umberto M. Musazzi, Rani Khatib, José Manuel Martinez Sesmero, Hans-Peter Lipp, Jacqueline Surugue, Tiziana Di Francesco and Beat Flühmann

Pharmaceutics 2021, 13(7), 1010; https://doi.org/10.3390/pharmaceutics13071010 - 02 Jul 2021

Viewed by 2667

Abstract

We conducted research to assess hospital pharmacists’ familiarity with/interpretation of data requirements for the different regulatory approval frameworks and the impact of this on their approach to substitution in the formulary. The online questionnaire included a small molecule (acetylsalicylic acid—follow-ons approved via the [...] Read more.

We conducted research to assess hospital pharmacists’ familiarity with/interpretation of data requirements for the different regulatory approval frameworks and the impact of this on their approach to substitution in the formulary. The online questionnaire included a small molecule (acetylsalicylic acid—follow-ons approved via the generic pathway), two biologic drugs (insulin glargine and etanercept—follow-ons approved via the biosimilar pathway), a non-biologic complex drug (NBCD; glatiramer acetate—follow-ons approved via the hybrid pathway) and a nanomedicine, ferric carboxymaltose (no follow-ons approved as yet). The study was conducted in two phases: an initial qualitative pilot study with 30 participants, followed by a quantitative stage involving 201 pharmacists from five European countries. Most expected negligible safety/efficacy differences between reference and follow-on products. Head-to-head clinical data showing therapeutic equivalence as a prerequisite for reference product/follow-on substitution was perceived to be needed most for biologics (47%), followed by NBCDs (44%)/nanomedicines (39%) and small molecules (23%). Overall, 28% did not know the data requirements for follow-on approval via the hybrid pathway; 16% were familiar with this pathway, compared with 50% and 55% for the generic and biosimilar pathways, respectively. Overall, 19% of respondents thought the European Medicines Agency (EMA) was responsible for defining the substitutability of follow-ons. Education is required to increase hospital pharmacist’s knowledge of regulatory approval frameworks and their relevance to substitution practices. Full article

(This article belongs to the Special Issue Regulatory and Technological Aspects of New Drugs for Old Active Pharmaceutical Ingredients)

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12 pages, 958 KiB

Open AccessArticle

Uptake of Trastuzumab Biosimilars for the Treatment of HER2-Positive Breast Cancer: A Real-World Experience from a Cancer Center

by Michela Piezzo, Roberta D’Aniello, Ilaria Avallone, Bruno Barba, Daniela Cianniello, Stefania Cocco, Antonio D’Avino, Germira Di Gioia, Vincenzo Di Lauro, Giuseppina Fusco, Raffaele Piscitelli, Claudia von Arx, Michelino De Laurentiis and Piera Maiolino

Pharmaceutics 2021, 13(5), 684; https://doi.org/10.3390/pharmaceutics13050684 - 10 May 2021

Cited by 5 | Viewed by 2626

Abstract

Background: The introduction of trastuzumab biosimilars in clinical practice plays an important role in promoting the sustainability of healthcare systems. By contrast, the switching process can be challenging to the clinics. This survey describes the switching process at a National Cancer Institute over [...] Read more.

Background: The introduction of trastuzumab biosimilars in clinical practice plays an important role in promoting the sustainability of healthcare systems. By contrast, the switching process can be challenging to the clinics. This survey describes the switching process at a National Cancer Institute over a period of 2 years. Methods: Data regarding all trastuzumab-based regimens for breast cancer (BC) from 1 January 2019 and 31 December 2020 were extracted from both adverse drug reactions (ADRs) reporting systems and electronic systems involved in inventory management, prescribing, dispensing, and administration. Both patients under monotherapy and combination treatment regimens were included. There were no exclusion criteria. Results and Conclusions: Overall 354 patients received at least one trastuzumab-based regimen for a total of 493 lines of treatment and 5769 administrations. Biosimilar were used in 34.3% of trastuzumab-based treatments. No differences between biosimilars and reference drug have been observed in terms of ADRs. The effective cost-saving of the first 2 years is greater than EUR 800,000 and it is estimated to increase over time. Full article

(This article belongs to the Special Issue Regulatory and Technological Aspects of New Drugs for Old Active Pharmaceutical Ingredients)

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15 pages, 2493 KiB

Open AccessArticle

Medicine Shortages in Serbia: Pharmacists’ Standpoint and Potential Solutions for a Non-EU Country

by Nataša Jovanović Lješković, Aleksandra Jovanović Galović, Svetlana Stojkov, Nikola Jojić and Slobodan Gigov

Pharmaceutics 2021, 13(4), 448; https://doi.org/10.3390/pharmaceutics13040448 - 26 Mar 2021

Cited by 5 | Viewed by 2587

Abstract

Medicine shortages in Serbia have evidently been present for several decades, but literature data are scarce. The aim of our study was to get an insight on the present situation in Serbia, review the EU actions when managing shortages, and discern a set [...] Read more.

Medicine shortages in Serbia have evidently been present for several decades, but literature data are scarce. The aim of our study was to get an insight on the present situation in Serbia, review the EU actions when managing shortages, and discern a set of potential measures. A short survey was conducted among 500 pharmacists in public pharmacies, in 23 cities in Serbia. The survey questions addressed frequency of drug shortages, professional actions in the event of shortages, main consequences to patients and pharmacies, putative causes, and pivotal measures for the prevention/mitigation of drug shortages under current conditions. Moreover, a Panel of Experts was organized, whose suggestions and opinions were used to analyze the present situation and to form a set of potential solutions and effective measures to mitigate shortages of medicines. In-depth analysis of current Serbian legislation was conducted, with emphasis on specific steps to be made within the actual legal framework. Examples of good practice in the EU, applicable to a country such as Serbia, were examined. Our research showed that although Serbia is, in some aspects, behind EU countries regarding the approaches to overcome medicine shortages, progress can be made within short period of time, by specific well-targeted actions. Both patients and pharmacists would benefit from it. Full article

(This article belongs to the Special Issue Regulatory and Technological Aspects of New Drugs for Old Active Pharmaceutical Ingredients)

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21 pages, 924 KiB

Open AccessArticle

Surfactants, Nanomedicines and Nanocarriers: A Critical Evaluation on Clinical Trials

by Diego Alejandro Dri, Carlotta Marianecci, Maria Carafa, Elisa Gaucci and Donatella Gramaglia

Pharmaceutics 2021, 13(3), 381; https://doi.org/10.3390/pharmaceutics13030381 - 13 Mar 2021

Cited by 6 | Viewed by 2223

Abstract

Advances, perspectives and innovation in drug delivery have increased in recent years; however, there is limited information available regarding the actual presence of surfactants, nanomedicines and nanocarriers in investigational medicinal products submitted as part of a request for authorization of clinical trials, particularly [...] Read more.

Advances, perspectives and innovation in drug delivery have increased in recent years; however, there is limited information available regarding the actual presence of surfactants, nanomedicines and nanocarriers in investigational medicinal products submitted as part of a request for authorization of clinical trials, particularly for those authorized in the European Economic Area. We retrieve, analyze and report data available at the Clinical Trial Office of the Italian Medicines Agency (AIFA), increasing the transparency and availability of relevant information. An analysis of quality documentation submitted along with clinical trials authorized by the AIFA in 2018 was carried out, focusing on the key terms “surfactant”, “nanomedicine” and “nanocarrier”. Results suggest potential indications and inputs for further reflection and actions for regulators to actively and safely drive innovation from a regulatory perspective and to transpose upcoming evolution of clinical trials within a strong regulatory framework. Full article

(This article belongs to the Special Issue Regulatory and Technological Aspects of New Drugs for Old Active Pharmaceutical Ingredients)

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18 pages, 31058 KiB

Open AccessArticle

Orphan Designation and Cisplatin/Hyaluronan Complex in an Intracavitary Film for Malignant Mesothelioma

by Sabrina Banella, Eride Quarta, Paolo Colombo, Fabio Sonvico, Antonella Pagnoni, Fabrizio Bortolotti and Gaia Colombo

Pharmaceutics 2021, 13(3), 362; https://doi.org/10.3390/pharmaceutics13030362 - 09 Mar 2021

Cited by 3 | Viewed by 2178

Abstract

Pleural mesothelioma is a lung diffuse tumor, whose complete resection is unlikely. Consequently, metastases reappear where the primary tumor was removed. This paper illustrates the orphan medicine designation procedure of an intracavitary cisplatin film and related pharmaceutical development aspects requested by the European [...] Read more.

Pleural mesothelioma is a lung diffuse tumor, whose complete resection is unlikely. Consequently, metastases reappear where the primary tumor was removed. This paper illustrates the orphan medicine designation procedure of an intracavitary cisplatin film and related pharmaceutical development aspects requested by the European Medicines Agency (EMA) in its Scientific Advice. Since cisplatin pharmacokinetics from the implanted film in sheep resulted substantially modified compared to intravenous administration, the formation of a cisplatin/hyaluronan complex had been hypothesized. Here, the interaction between sodium hyaluronate (NaHA) and cisplatin (CisPt) was demonstrated. Size exclusion chromatography qualitatively evidenced the complex in the film-forming mixture, only showing the NaHA peak. Atomic absorption spectroscopy of the corresponding fraction revealed platinum, confirming the interaction. Reverse phase HPLC quantified about 5% free cisplatin in the film-forming mixture, indirectly meaning that 95% was complexed. Finally, a study of CisPt release from the film assessed how CisPt/NaHA complex affected drug availability. In water, a medium without chloride ions, there was no release and the film remained intact for 48 h and longer, whereas the placebo film dissolved in 15 min. In 0.9% NaCl medium, the film became more soluble, dissolving within 3–4 h. However, cisplatin release was still controlled by the existing complex in solution until chloride ions displaced it. While the film modified its dissolution with aging, CisPt release remained unaffected (90% released in 48 h). Full article

(This article belongs to the Special Issue Regulatory and Technological Aspects of New Drugs for Old Active Pharmaceutical Ingredients)

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16 pages, 1426 KiB

Open AccessArticle

The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA

by Ioana Gherghescu and M. Begoña Delgado-Charro

Pharmaceutics 2021, 13(1), 48; https://doi.org/10.3390/pharmaceutics13010048 - 31 Dec 2020

Cited by 36 | Viewed by 7754

Abstract

Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) [...] Read more.

Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) and Food and Drug Administration (FDA) repositories were searched to identify all biosimilar medicines approved before December 2019. Adalimumab biosimilars, and particularly their clinical evaluations, were used as a case study. In the past 13 years, the EMA has received 65 marketing authorization applications for biosimilar medicines with 55 approved biosimilars available in the EU market. Since the first biosimilar approval in 2015, the FDA has granted 26 approvals for biosimilars with only 11 being currently on the US market. Five adalimumab biosimilars have been approved in the EU and commercialized as eight different medicines through duplicate marketing authorizations. Whilst three of these are FDA-approved, the first adalimumab biosimilar will not be marketed in the US until 2023 due to Humira’s exclusivity period. The EU biosimilar market has developed faster than its US counterpart, as the latter is probably challenged by a series of patents and exclusivity periods protecting the bio-originator medicines, an issue addressed by the US’s latest ‘Biosimilar Action Plan’. Full article

(This article belongs to the Special Issue Regulatory and Technological Aspects of New Drugs for Old Active Pharmaceutical Ingredients)

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16 pages, 2851 KiB

Open AccessArticle

Cardiovascular Paediatric Medicines Development: Have Paediatric Investigation Plans Lost Heart?

by Bethany Faulkner and M. Begoña Delgado-Charro

Pharmaceutics 2020, 12(12), 1176; https://doi.org/10.3390/pharmaceutics12121176 - 02 Dec 2020

Cited by 4 | Viewed by 2460

Abstract

This work aimed to establish whether paediatric needs in cardiovascular diseases have been met by paediatric investigation plans (PIPs) produced since the development of the European Union Paediatric Regulation in 2007. The European Medicines Agency repository was searched for patterns in the development [...] Read more.

This work aimed to establish whether paediatric needs in cardiovascular diseases have been met by paediatric investigation plans (PIPs) produced since the development of the European Union Paediatric Regulation in 2007. The European Medicines Agency repository was searched for patterns in the development of paediatric medicines in general. Next, positive PIPs related to cardiovascular diseases were scrutinized for outcomes and compared to specific paediatric cardiovascular needs. In total, 1866 PIPs were identified with 12% corresponding to decisions taken for cardiovascular medicines. However, despite this therapeutic area having the greatest number of overall PIPs, only 14% of established needs in paediatric cardiovascular diseases were addressed by PIPs with positive decisions. Further, 71.9% of PIPs with decisions in cardiovascular disease corresponded to full waivers, so the product would not be studied in paediatrics. Despite the progress found in overall numbers of PIPs published, cardiovascular products are still commonly used off-label in paediatrics. Particularly, there is a need to develop products to treat heart failure and hypertension, two areas with clear unmet clinical needs in paediatrics. A case study on valsartan showed that industry, regulators, health technology assessment bodies, and prescribers should work together to reduce off-label use of paediatric cardiovascular diseases (CVD). Full article

(This article belongs to the Special Issue Regulatory and Technological Aspects of New Drugs for Old Active Pharmaceutical Ingredients)

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Review

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21 pages, 706 KiB

Open AccessReview

Drug Repurposing in the COVID-19 Era: Insights from Case Studies Showing Pharmaceutical Peculiarities

by Milo Gatti and Fabrizio De Ponti

Pharmaceutics 2021, 13(3), 302; https://doi.org/10.3390/pharmaceutics13030302 - 25 Feb 2021

Cited by 22 | Viewed by 3916

Abstract

COVID-19 may lead to severe respiratory distress syndrome and high risk of death in some patients. So far (January 2021), only the antiviral remdesivir has been approved, although no significant benefits in terms of mortality and clinical improvement were recently reported. In a [...] Read more.

COVID-19 may lead to severe respiratory distress syndrome and high risk of death in some patients. So far (January 2021), only the antiviral remdesivir has been approved, although no significant benefits in terms of mortality and clinical improvement were recently reported. In a setting where effective and safe treatments for COVID-19 are urgently needed, drug repurposing may take advantage of the fact that the safety profile of an agent is already well known and allows rapid investigation of the efficacy of potential treatments, at lower costs and with reduced risk of failure. Furthermore, novel pharmaceutical formulations of older agents (e.g., aerosolized administration of chloroquine/hydroxychloroquine, remdesivir, heparin, pirfenidone) have been tested in order to increase pulmonary delivery and/or antiviral effects of potentially active drugs, thus overcoming pharmacokinetic issues. In our review, we will highlight the importance of the drug repurposing strategy in the context of COVID-19, including regulatory and ethical aspects, with a specific focus on novel pharmaceutical formulations and routes of administration. Full article

(This article belongs to the Special Issue Regulatory and Technological Aspects of New Drugs for Old Active Pharmaceutical Ingredients)

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