In the past two decades, protein pharmaceuticals have become the fastest growing class of therapeutics owing to their beneficial impacts on the treatment of severe and life-threatening conditions and diseases. Development and manufacturing of protein pharmaceuticals is, however, challenging and requires overcoming various manufacturing hurdles such as issues with the purity of the protein product. The safety and efficacy of protein pharmaceuticals depend on their purity. Impurities in marketed protein pharmaceuticals may be present due to limitations in manufacturing processes or may also be a result of degradation processes occurring not only during manufacturing, but also during long-term storage of the bulk drug substance and/or final drug product (DP). Impurities within therapeutic protein products can cause severe adverse drug reactions (ADRs) in patients, that may be acute, as is the case for infusion-induced anaphylaxis and pseudo-allergy responses, which may even result in patient death, or long-term like unwanted immunogenicity.
Physical aggregation and chemical degradation can occur throughout a protein product’s life history, and even modest environmental stresses can cause extensive damage. Development of effective upstream and downstream processes as well as robust formulations and filling processes are crucial for maintaining product quality, and hence, for the safety and efficacy of protein pharmaceuticals. The pharmaceutical industry has made great progress in improving bulk and DP manufacturing as well as storage and transportation conditions to minimise the level of degradation. However, there exists only low control over the many factors that may affect product quality after the protein pharmaceuticals are released and shipped. Routine handling or unintentional mishandling of therapeutic protein products may cause protein degradation that remains unnoticed but can potentially compromise the clinical safety and efficacy of the product. Storage of the DP outside the recommended condition ranges, use of incompatible supply and/or technology, careless handling of drug during preparation for administration and during delivery to patient are just a few examples of such (mis)handling. When it comes to handling of DP by patients, the social, cultural, logistical and environmental differences between different geographies and cultures can also impact the handling conditions.
There has been increasing expression of concern in the past decade regarding the significance of the post-production handling of protein pharmaceuticals. At the same time, studies revealed that the consequences of presence of impurities in DP can be severe. Potentially high likelihood and/or severity in consequences in combination with the low level of control over the processes by the industry make these concerns a significant risk that needs to be addressed in a public-private partnership that includes all relevant stakeholders.
The first objective of this topic is to improve the understanding of real-world stressful drug product handling steps and their effects on protein product quality.
The second objective of this topic is to use this understanding for development of guidelines and operating processes to improve the DP robustness and pharma processes, and to develop more efficient training.
Utilisation of technologic tools (video, webinar, online media and creative manuals) for development of novel training methods and materials is within the scope of the topic.Expected Impact:
Overall, the project is expected to lead to improvements in the safety and efficacy of protein drug therapies.
Deadline: 21 April 2020 17:00:00 Brussels time 21 April 2020 17:00:00 Brussels time