Periodic Reporting for period 3 - RealHOPE (Real World Handling of Protein Drugs - Exploration, Evaluation and Education)
Reporting period: 2023-07-01 to 2024-06-30
During the last 20 years the number of protein drugs has increased substantially and have dramatically improved the lives of people with a range of diseases. However, ensuring the quality of protein drug products, particularly after manufacture, is far from easy. One drawback with these drugs is that their chemical and physical stability is considerably more complex than for small molecules. There are many things that can affect and compromise the safety and efficacy of the product. For example, handling of the proteins such as pumping of solutions (shear), interaction with primary packing material (adsorption) and temperature fluctuation are detrimental to product quality. Therefore, considerable effort has been made to identify triggers that reduce product quality for example during production and storage. However, only a few studies have focused on the effects of handling drug products in hospitals and by patients. Inappropriately handled protein drugs may lead to adverse effects, such as immunological reactions due to aggregation, and a need to discard prepared medications due to unintentional mishandling (if noticed) or e.g. visual aggregation. This leads to unnecessary patient suffering and increased cost for health care and medication.
The overall objective of RealHOPE is to aid the development of more robust protein drugs with increased safety profiles for patients or to improve the manual handling of drugs by medical professionals and patients. RealHOPE have partners from the whole value-chain: including pharmaceutical companies, logistics companies, pharmacies, and a patient organization. In combination with instrument- and app developers, and academic researchers from different fields, we will have the possibility to acquire a deep understanding of the whole life-chain of a protein drug, from production to when it reaches the patient.We will develop concrete and practical recommendations and tools for simulation of real-life events, mitigation of critical handling steps, and education to ensure careful handling by healthcare and pharmacy staff as well as patients.
The overall objective of RealHOPE is to aid the development of more robust protein drugs with increased safety profiles for patients or to improve the manual handling of drugs by medical professionals and patients. RealHOPE have partners from the whole value-chain: including pharmaceutical companies, logistics companies, pharmacies, and a patient organization. In combination with instrument- and app developers, and academic researchers from different fields, we will have the possibility to acquire a deep understanding of the whole life-chain of a protein drug, from production to when it reaches the patient.We will develop concrete and practical recommendations and tools for simulation of real-life events, mitigation of critical handling steps, and education to ensure careful handling by healthcare and pharmacy staff as well as patients.
The RealHOPE project has performed a literature review and stakeholder interviews to better understand the issues regarding handling of protein drugs by patients and professionals in the real world. The results of this exercise has been published to guide analytical study designs to better understand the impact of stressors encountered by protein drugs during their handling (https://doi.org/10.1016/j.xphs.2024.05.027 ). A study to better understand the real world handling of protein drugs by patients has been designed, approved and commenced in January 2024. The study is being undertaken by UNIVDUN and the results will inform and be compared with the simulation studies to highlight differences that can be addressed by the educational material. Real-world handling of protein drugs at hospitals and transport of compounded drugs has been performed and published (https://doi.org/10.1016/j.xphs.2023.05.003). Potential risks during handling at hospitals has been identified and mitigations suggested.
RealHOPE aim to simulate real-life events in laboratory setting under standardized conditions. To this end, we investigate how different stressors (e.g. shaking, dropping, injection, surface interactions, temperature excursions, and light) can influence the stability of monoclonal antibodies as well as small proteins such as insulin. The influence of light on the stability of monoclonal antibodies (e.g. Ipilimumab and Nivolumab) under various conditions, has been investigated. Shaking/temperature, light exposure dilution, were applied to observe the physicochemical and biological behaviour of the molecule. The results have been published in a paper (https://doi.org/10.1016/j.ejpb.2022.05.005). Furthermore, it has been found that light in combination with heat sterilised glucose give rise to increased risk of protein degradation through oxidative processes (doi.org/10.1016/j.ijpharm.2024.123926). Methodologies for use in laboratories are being set-up for studies in different scales, ranging from a few microlitres in miniaturised systems to millilitres in more conventional set-ups. Methods where real-life handling of protein drugs can be simulated in the laboratory environment, including injection, handling of filled syringes, and light exposure and additional simulation methods are under development. RealHOPE project has enabled Uppsala University Hospital to provide a clinical test bed for both robotic and manual preparation, including Closed System Transfer Devices (CSTDs), to EFPIA partners.
Stakeholder interviews have also been performed to identify the gaps in leaflet information of drugs and patients’ memories which helps to define the educational need by patients and professionals in the real-world handling of drugs. Based on these reports educational material has been developed. The educational module for nurses includes posters, pamphlets and videos with handling instructions and instructions on how to inform patients. The material will be made publicly available in at least 3 languages, English, Italian and Swedish. The educational material developed for academia and pharmacists is available on the platform CANVAS. Additionally, educational material for patients has been developed and this is available on the app platform ELSA.
RealHOPE aim to simulate real-life events in laboratory setting under standardized conditions. To this end, we investigate how different stressors (e.g. shaking, dropping, injection, surface interactions, temperature excursions, and light) can influence the stability of monoclonal antibodies as well as small proteins such as insulin. The influence of light on the stability of monoclonal antibodies (e.g. Ipilimumab and Nivolumab) under various conditions, has been investigated. Shaking/temperature, light exposure dilution, were applied to observe the physicochemical and biological behaviour of the molecule. The results have been published in a paper (https://doi.org/10.1016/j.ejpb.2022.05.005). Furthermore, it has been found that light in combination with heat sterilised glucose give rise to increased risk of protein degradation through oxidative processes (doi.org/10.1016/j.ijpharm.2024.123926). Methodologies for use in laboratories are being set-up for studies in different scales, ranging from a few microlitres in miniaturised systems to millilitres in more conventional set-ups. Methods where real-life handling of protein drugs can be simulated in the laboratory environment, including injection, handling of filled syringes, and light exposure and additional simulation methods are under development. RealHOPE project has enabled Uppsala University Hospital to provide a clinical test bed for both robotic and manual preparation, including Closed System Transfer Devices (CSTDs), to EFPIA partners.
Stakeholder interviews have also been performed to identify the gaps in leaflet information of drugs and patients’ memories which helps to define the educational need by patients and professionals in the real-world handling of drugs. Based on these reports educational material has been developed. The educational module for nurses includes posters, pamphlets and videos with handling instructions and instructions on how to inform patients. The material will be made publicly available in at least 3 languages, English, Italian and Swedish. The educational material developed for academia and pharmacists is available on the platform CANVAS. Additionally, educational material for patients has been developed and this is available on the app platform ELSA.
RealHOPE will study real-life handling of protein drugs using smart tag technologies. Different parameters, such as light, temperature and shock, will be logged and combined with protein characterization at different stages, as well as with information from EFPIA partners on their drugs in use. Statistical evaluation of the data will be used to identify patterns in handling that are linked to protein destabilization occurrence and type of protein degradation.
The study will also include interviews with personnel in hospital pharmacies, clinics, patients and care givers to understand current handling practice and what the desired handling instructions and limitations are. These insights will be used to design in-use mimicking stability protocols for future development and new formulations of protein drugs.
The collected data and interviews will form the basis for development of teaching materials directed towards different target groups: hospital pharmacists, nurses, patients, and care givers, as well as methods suited for simulation of real-world handling by patients, and handling in hospital pharmacy setting, respectively.
The study will also include interviews with personnel in hospital pharmacies, clinics, patients and care givers to understand current handling practice and what the desired handling instructions and limitations are. These insights will be used to design in-use mimicking stability protocols for future development and new formulations of protein drugs.
The collected data and interviews will form the basis for development of teaching materials directed towards different target groups: hospital pharmacists, nurses, patients, and care givers, as well as methods suited for simulation of real-world handling by patients, and handling in hospital pharmacy setting, respectively.