The second work package of RealHOPE project is called GOLD and will develop tools and methods for simulation of real-life events during drug product handling that mimic the effects on drug product quality. In their study, researchers Giorgia Miolo and Patrizia Polverino De Laureto, at University of Padova, exposed mAb samples to sunlight inside a solar box. The light doses were measured exactly inside this machine.
Hi Giorgia and Patrizia, what did you find out about how light affect protein drugs?
“The effects of light on mAbs depend on the individual structure of the protein. Chemical modification (oxidation, deamidation) of sensitive amino acids (Met, Cys, Trp, Tyr, Gln, Asn) and aggregation are exacerbated by light exposure.”
In your study, did you develop any methodology or anything else to deal with the sensitivity of protein drugs to light?
“Along side classical biophysical methods to characterize protein conformation and structure, we are applying high resolution mass spectrometry (HDX-MS) and surface tension approaches to find out more rapid and sensitive methods to detect the effect of light on protein samples.”
Will you go on to study light and its impact on protein drugs further?
“Our results are surprising since we are finding differences in the tested mAbs, therefore we are encouraged to proceed in these studies.”
How do you think your results will be received? Will they for example affect the way protein drugs are produced and managed?
“We hope our results will help health personnel (hospital pharmacists, nurses and physicians) as new guidelines for handling and administration of these therapeutic drugs during their real life. As examples of our findings, handling: glucose diluting solution can induce higher physico-chemical damage in the mAb under light exposure; manufacturing: light exacerbates mAb aggregation and fragmentation induced by low pH.”
Your latest article “Light exacerbates local and global effects induced by pH unfolding of Ipilimumab” was published in August 2024. What can we expect to read about in this latest article?
“The general aim of our study is to evaluate the effect of the light on the structure and the physical state of monoclonal antibodies. Since their primary structure and conformation have a great impact on the stability of the molecules under specific stressors, here we have underlined the importance to investigate them individually. Each therapeutic antibody should be analyzed to evidence the weak points on their structure and to elaborate a set of parameters and conditions for their safety and to improve the yield.”
What is new in this article compared to the other two?
“In this last study, we have evaluated the effect of light during the preparation of the drug in the final formulation. Indeed, to remove viruses a general procedure is applied consisting in exposing the protein to low pH. The combination of low pH (protein unfolding or partially unfolding) and accidental light irradiation may increase the occurrence of the modifications induced by light, which then may trigger protein misfolding and/or aggregation.
What challenges did you face during this latest study?
“Light appears as a minor risk factor for therapeutic mAb manufacturing, since in most cases the production and storage of biopharmaceutics are performed in light-protected conditions. However, the light-induced modifications are dangerous because they can trigger chain reactions that finally are critical for the administration of protein drugs and for the eventual immunogenic adverse effects on the patients. Therefore, it is extremely important to evidence these subtle protein modifications and a multiple technological approach is required.
How important was the RealHOPE collaboration for this last study?
RealHOPE provided an opportunity to meet researchers from pharmaceutical companies engaged in new drug research along with hospital workers as well as colleagues from other universities. Therefore, we better understood the issues revolving around life-saving drugs and thus addressed them in a comprehensive and synergistic way. It also gave us the chance to study these interesting molecules. Moreover, we could match the needs of hospital pharmacist non completely aware of the properties of mAbs and how important is to avoid light exposure during their administration.”
Light exacerbates local and global effects induced by pH unfolding of Ipilimumab
Latest comments