Bringing Quality Forward Pays Off

With biologics filling the pipelines of life sciences companies more than ever, the biopharmaceutical industry needs to rethink its view of quality. Once primarily considered a focus in downstream drug development and manufacturing, quality now demands just as much attention in upstream discovery research.

The need to focus on quality during early biologics research stems in part from the complexity of biologics, but it also results from the increased regulatory scrutiny required when working with living organisms as source materials from early research through production of biologics.

Complexity of biologics
Biologics are often produced in cell lines, which are complex entities. Heterogeneous and even homogeneous populations are susceptible to somatic mutations and environmental stimulation, leading to changes in methylation states and, subsequently, expression. Cell line developers in discovery now need to have the necessary traceability, documentation and security in place to support handoff to process development. For example, a cell line developer in discovery may need to prove to the FDA that the biologic came from a single (mono) clonal cell line. The added complexity of development and manufacturing processes can often be mitigated by instituting quality processes in the early stages of biologics discovery. And it's a two-way street. The development of standard operating procedures for functional assays (e.g., example studies and cellbased assays) can often be optimized in early research, saving both time and money in later stages of development.

Increased regulatory scrutiny
The industry faces increased regulatory requirements for documenting the use of predictive analytics on vast data sets, combining knowledge from early -stage research, historical data from the public domain, preclinical experimentation, clinical trials data and even post-market analysis data. Many of the regulations imposed during biologics development and manufacturing require reports on processes that can be tested early in the product development lifecycle(e.g., reports covering biophysical characterization, post-translational modifications, aggregation propensity and other developability properties). Additionally, regulatory agencies require comparability studies from preclinical to clinical product development samples.

Quality by design in biopharma R & D
The concept of quality by design, postulating that quality cannot be inspected into products, but rather is created by processes along the end -toend development continuum, has become increasingly important for organizations committed to designing and developing successful therapeutics. Done well, quality by design works like a lever, enhancing good scientific practices and encouraging scientists to take the long view and not cut quality corners on the long road to releasing an approved therapeutic.

Quality by design is not a single event, but a series of events that constitute a planned journey aimed at accelerating high-quality products to market with lower cost and risk. Quality becomes something that the organization defines for itself and strives to achieve during every phase of product creation-from research through development to manufacturing (much like the near-constant retooling and reinvention of manufacturing processes in the automotive, semiconductor and electronics industries where the quality by design paradigm has been fully embraced).

The journey begins with the transition from paper to digital, which includes both the transfer of paper-based processes to 'glass' and the identification and adoption of information and process standards to harmonize data exchange. The completion of this step propels the organization down the path towards clean, traceable and tractable data, driving out human variability and improving data integrity. Automated laboratory systems speed execution by eliminating the need for scientists to manually document everything they execute. Vast, rich data sets can be mined and modeled to improve data -driven, predictive control. Most importantly, scientists gain improved scientific methodologies with better qualified workflows extending from the simplest research tasks to the most advanced planning of clinical trials.

Quality by design is a journey that takes time and careful planning across the research, development and manufacturing continuum, but the trip is worth it. The biopharma organization arrives at a much better understanding of the many interrelated product and process variables impacting quality and continuous product improvement. In an industry grappling with both scientific complexity and spiraling regulatory compliance costs, it's never too soon to focus on quality.