As published in Pharma's Almanac Q3 2016
The quality of pharmaceutical products is the top priority for both drug makers and regulators. To ensure consistent high product quality and improve the efficiency of manufacturing and regulation, the FDA introduced quality by design (QbD) to the pharmaceutical industry in its 2002 Pharmaceutical cGMP initiative, “Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach.”1
The QbD concept has been widely adopted as a standard of practice for manufacturers, including those in the automotive, semiconductor, electronics and chemical processing industries. Regulators have also embraced QbD as a means to modernize the regulation of pharmaceutical manufacturing and product quality through manufacturing science, based on methodologies proven across countless applications. From their standpoint, QbD-based processes hold great potential in creating the efficient, agile and flexible manufacturing systems required by biopharma to reliably deliver safe, effective high-quality drug products to patients in a secure supply chain.
Several advances in scale-down models have made great contributions to accelerating biopharmaceutical process development. Therapeutic biologics have gained considerable momentum in the past three decades by delivering superior clinical performance to common disorders (e.g., rheumatoid arthritis) and disease areas for which traditional small- molecule drugs have proven ineffective. Due to their inherent structural complexity, biologics production is strictly scrutinized from early development stages by regulatory agencies. Both biopharmaceutical manufacturers and regulators heavily emphasize developing science-based, consistent and robust manufacturing process to ensure quality, safety and efficacy of final biological products.
Gustavo Mahler, a 20-year biopharmaceutical industry vet, has just taken over the helm of CMC Biologics. From its small beginnings in 2001, the commercial manufacturer of therapeutic proteins now has more than 500 employees globally and operates facilities in Copenhagen, Denmark; Seattle, WA; and Berkeley, CA, from which it offers fully integrated biopharmaceutical process development and manufacturing services for clinical and commercially launched biological medicines.
Groomed over the course of a 15-year stay at Bayer in various manufacturing and general management positions in the U.S., Europe and Latin America, Mr. Mahler was heading up Bayer Healthcare’s biotechnology plant in Berkeley when he decided to join CMC Biologics in 2008, taking charge of the company’s Seattle facility. A couple years later in 2010 he took the post of chief operating and officer, which he held until taking over the chief executive role in January 2016.
Contract Pharma had the chance to talk with Mr. Mahler about his new position, plans for the company and the overall state of the market along with the trends and issues impacting it. —Tim Wright, Editor, Contract Pharma
As published in Pharma's Almanac Q1 2016
The vigorous growth of the biopharmaceutical market has boosted the demand for biopharmaceutical contract manufacturing services.1 Today, pharmaceutical and biotechnology companies outsource a broad spectrum of services from early stage drug development (e.g., cell line, process, analytical and formulation development) all the way to commercial-scale manufacturing. The outsourcing decision is often made by the need to expedite research and development, shorten the time to market, gain access to novel technologies and regulatory expertise and minimize risks, at competitive cost.
CMC Biologics remains vigilant in meeting customers’ growing demand for scalable biologics production. Its continued investment in technological advances, innovative facility designs and rapid facility expansions benefits customers and drives growth. CMC Biologics is dedicated to its customers’ focus to bring effective, safe medicines to patients quickly – improving lives.
From a CMO perspective, the traditional strategy behind process development has largely been to quickly identify target operational values that hit a primary quality target. This type of development strategy has been intended to generate at-scale product for clinical trials as fast as possible. The resultant operational ranges have traditionally been either very narrow because of lack of supporting experimental studies, or statistically derived with little to no data from experimental design to support the outer ranges. Timelines are often built without an opportunity to identify critical aspects of the process, perform range finding experiments, or optimize the process. Additionally, fears of making “process changes” within the clinical manufacturing phase have prevented many processes from being more robust and operationally friendly. The resultant Process Control Strategy becomes narrow and / or possibly at risk of consistent excursions outside of the acceptable ranges. As molecules progress through the clinical phase and begin gearing up for commercial submissions, the amount of development and characterization may increase and many experiments must be repeated, adding to timelines and cost. Thus, by not following a well-defined development plan up front, a Quality by Design (QbD) approach, there is a potential increased risk of delaying commercialization.