“Speed to milestone” – “Speed to Market” – “Speed to Patient” is the universal rally cry and well known for all BioPharmaceutical drug developers. Companies ranging from small Biotech to large Pharma are constantly driving to shorten development time and gain faster approval for their high quality, lifesaving therapies. Biologics, such as monoclonal antibodies, fusion proteins, and antibody drug conjugations, present unique and time-consuming challenges when balanced against our collective goal to accelerate development and regulatory approvals. Biologics add an extra level of complexity, whereby factors such as cell line and analytical development, biologic instability, scale up, and limited capacity may negatively impact time to market and budget outcomes.
Biologics are defined by their manufacturing process, which requires complete understanding through formal process characterization.1 Process characterization is an essential component of process validation and represents a critical area of importance, yet an opportunity in prompt milestone achievement. Process characterization provides an in-depth understanding of a drug product to establish effective process control strategies and it defines the critical product and process parameters for determining the proven acceptable ranges for efficient manufacturing.
Even a small change to the structure of a biologic during the manufacturing process can result in a significant impact on safety, efficacy and function. Something as simple as a deviation in pH, a temperature fluctuation, a variation in the method of thawing a vial or the switch to a different consumable supplier can affect a biopharmaceutical’s identity, purity or potency. By knowing in advance, the influence of different manufacturing events on a biologic and being able to provide supporting data to back up these occurrences through process characterization, the risk of manufacturing failures and regulatory time delays is significantly reduced.
Process characterization involves the determination of acceptable ranges for many hundreds of parameters to ensure manufacturing consistency by providing a thorough understanding of the process. One approach to the analysis of process characterization data is statistical in nature, yet this requires a significant amount of work and can dramatically extend timelines if the necessary expertise and equipment are not available in-house. Risk-based and failure-mode approaches are also feasible however the former can be limiting since it treats each possible source of failure in isolation, while the latter may be flawed if a potential failure mode is omitted
By establishing a platform approach to process characterization, which has supported the successful approval of several marketed biologics, AbbVie scientists ensure the entire process is robust, right first time, and results in a highly consistent product to facilitate efficient BLA filing. AbbVie’s five-step process below offers a thorough understanding of the biologic and process control strategies to help accelerate time to a robust and reliable commercial scale process.