Trends in Light and Temperature Sensitivity Recommendations among Licensed Biotechnology Drug Products

Abstract

Purpose Inherent structural and functional properties of biotechnology-derived therapeutic biologics make them susceptible to light- and temperature-induced degradation and consequently can influence their quality. Photosensitivity of therapeutic proteins continues to be examined, but the commonalities and trends of storage conditions and information about light and temperature sensitivity among currently licensed therapeutic proteins has not been previously surveyed. Methods Using a comprehensive and relational database approach, we conducted a scientific survey of all licensed biotechnology-derived drug products with the goal of providing evidence-based information about recommended storage conditions of formulations sorted by light- and temperature-related attributes as described for each product at licensure. Results We report the prevalence of indications for light and temperature sensitivity in formulations categorized by their presentation type, number of doses, container type, dosage form and active molecule type. We also report the storage temperature range across formulations and diluents for reconstitution and dilution. Formulations with excipients that potentially facilitate light-induced and thermal degradation were also noted. Conclusions The result of our analysis indicates that light and temperature sensitivity are prevalent across therapeutic protein formulations. However, when a formulation is reconstituted or diluted, both light and temperature sensitivity are less clear. In addition, light and temperature sensitivity are more well defined in liquid formulations than lyophilized powder formulations, and more well defined in products manufactured in autoinjectors, prefilled-syringes, and pens than products in vials. Overall, our report provides a data-driven summary of storage conditions among therapeutic protein formulations to support the development of future biologic drug products.

Near UV and Visible Light-Induced Degradation of Bovine Serum Albumin and a Monoclonal Antibody Mediated by Citrate Buffer and Fe(III): Reduction vs Oxidation Pathways

“…5−12 In fact, the instructions for more than 80% of therapeutic protein formulations on the market require protection from light. 13 Pharmaceutical buffers are added to protein formulations to control the pH and improve protein stability and solubility. 14 Citrate buffer is one of the most commonly used pharmaceutical buffers in protein formulations.…”

“…The development of biopharmaceuticals has undergone substantial growth and advancement in the past decade, with a continuously increasing number of approvals and available biologic drugs on the market. − Protein therapeutics represent an important class of biopharmaceuticals to treat a variety of diseases, such as cancer, autoimmune diseases, and infections. , However, protein therapeutics can be subject to photodegradation during manufacturing, storage, and administration . Such photodegradation can lead to chemical modifications of amino acids, potentially causing protein aggregation and fragmentation, and compromising efficacy and safety. − In fact, the instructions for more than 80% of therapeutic protein formulations on the market require protection from light …”

Near UV and Visible Light Photodegradation in Solid Formulations: Generation of Carbon Dioxide Radical Anions from Citrate Buffer and Fe(III)

“…Therapeutic proteins play an important role in the treatment of a broad range of indications, either alone or in combination therapy. 1 At any stage during their development, the active pharmaceutical ingredient (API) may be exposed to light, potentially leading to light-induced degradation. 2,3 In 2013, Baertschi et al reported that the United States Pharmacopeia (USP) listed over 300 injectable products, of which 100 warn against light exposure.…”

“…3 In 2014, 312 light-sensitive injectables were reported, 4 while in 2023, 459 formulations were labeled with a "protect from light indication". 1 The European Pharmacopoeia reports over 250 drugs with photosensitivity that require protection from light. 5,6 Light-induced degradation can generate changes in the appearance of drug products, including discoloration, turbidity, or cloudiness, and lead to the formation of visible particles.…”

“…5,6 Light-induced degradation can generate changes in the appearance of drug products, including discoloration, turbidity, or cloudiness, and lead to the formation of visible particles. 1,7 This can indicate alteration of the API and/or excipients, and the formation of reactive products, potentially compromising the quality, safety, and efficacy of products. 1,7−10 Thus, it is crucial to control and monitor the stability of drug products by characterization of the physical and chemical degradation pathways.…”