An Industry Perspective on Forced Degradation Studies of Biopharmaceuticals: Survey Outcome and Recommendations

Abstract

The BioPhorum Development Group is an industry-wide consortium enabling networking and sharing of common practices for the development of biopharmaceuticals. Forced degradation studies (FDSs) are often used in biotherapeutic development to assess criticality of quality attributes and in comparability studies to ensure product manufacturing process consistency. To gain an understanding of current industry approaches for FDS, the BioPhorum Development GroupeForced Degradation Point Share group conducted an intercompany collaboration exercise, which included a benchmarking survey and group discussions around FDS of monoclonal antibodies. The results of this industry collaboration provide insights into the practicalities of these characterization studies and how they are being used to support the product lifecycle from innovation to marketed products. The survey requested feedback on the intended purpose, materials, conditions, number and length of time points used, and analytical techniques carried out to give a complete picture of the range of common industry practices. This article discusses the results of this global benchmarking survey across 12 companies and presents these as a guide to a common approach to FDS across the industry which can

Therapeutic Fc‐fusion proteins: Current analytical strategies

“…Halley et al. conducted an intercompany benchmarking survey and reported an overview of the common practices used to perform forced degradation studies [97]. Since Fc‐fusion proteins possess a large structural heterogeneity and complexity, no specific stress and no generic conditions could be advised.…”

“…There are many available options to perform forced degradation studies, such as different materials, conditions, number and duration of time points, as well as several analytical methods to evaluate the results of the applied stress. Halley et al conducted an intercompany benchmarking survey and reported an overview of the common practices used to perform forced degradation studies [97]. Since Fc-fusion proteins possess a large structural heterogeneity and complexity, no specific stress and no generic conditions could be advised.…”

“…Forced degradation studies allow the establishment of suitable stability indicating methods, i.e., methods able to detect specific degradations products. In addition, when performing forced degradation studies, the principle aim of the bio-pharmaceutical companies is to get valuable information about the degradation pathways (through the characterization of degradation products) and to highlight impurities which could also be defined as critical quality attributes (CQAs), as they can alter the product quality [96,97].…”

Importance of LCMS in Forced Degradation Studies for new Chemical Entities

“…To avoid further decomposition, the degraded sample is then neutralized using suitable acid, base, or buffering. [37][38] Drug substance of oxidative degradation involves a mechanism for the electron transfer to form reactive anions and cations. Hydrogen peroxide is widely used in forced degradation studies for the oxidation of drug substances but other oxidizing agents such as metal ions, oxygen, and radical initiators may also be used.…”

The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG)

“…Alternatively, Pikal et al noted that for FD Human Growth Hormone at 40 • C, there was a linear relationship between moisture content and aggregation rather than a bell-shaped distribution [14]. Guidelines for use when developing stressing strategies for biotechnology products have been published [15] and industrial stressing conditions have also been reviewed [16,17]. During long-term storage, the sugar excipient used in the formulation, moisture content and temperature can all affect the physical and chemical stability of FD cakes.…”