At the Biopharmaceutical Development & Production Week event in San Diego this week, David Chang, senior director of global biologics manufacturing science and technology for Roche/Genentech, outlined the fundamentals of the company’s global biologics network strategy. The company’s current primary areas of focus include:Building state of the art plants to ensure compliance and reliability. Roche/Genentech will retire all aging plants within the next five years, and start up new replacement drug substance (DS) and drug product (DP) plants within the next two to three years, he said. These new facilities include DS plants in Basel (CHO) and Singapore (CHO and e. coli), and DP plants in Kaiseraugst, Switzerland, and Hillsboro, Oregon.Balancing plant utilization for risk, cost, and agility. Roche produces some six metric tons of biologic drug substance per year (more than 110 batches), as well as seven million galenical units of drug product. Cross-licensing to ensure business continuity and flexibility.Leveraging CMOs for special technologies and flexibility. Blow-fill-seal, cartridge filling, and antibody drug conjugates are three areas of outsourcing, Chang said.An Emphasis on Tech TransferWith so much internal and external drug substance and product shifting, Roche/Genentech places a heavy burden on technology transfer operations. Starting in 2010, Change noted, the company has had 10 to 15 tech transfers per year, mainly from old plants to new ones. In 2012, it has a whopping 28 on its schedule.Fortunately, the company has more than 20 years of commercial biologics tech transfer experience and an excellent track record to fall back on, said Chang. He outlined the company’s standardized ten-step commercial tech transfer process:1. Data gathering2. Sourcing decision3. Initiation and planning4. Document tech transfer5. Technology and regulatory gap analysis and change control6. Analytical and quality transfer7. Production of batches8. Reports and change control authorization9. Registration10. LogisticsEach step is roughly two months, with the entire process comprising three years. The collective steps are consolidated into a Master Tech Transfer Plan.One way that Roche/Genentech has streamlined its tech transfer operations is via the Expanded Change Protocols (eCP) Approach. The approach is allowed by regulators as a form of a comparability protocol, Chang noted. An eCP is broad in scope, covering multiple products and multiple facilities; and leverages the company’s “knowledge and experience in defining comparability requirements for multiple products/facilities in a single comparability protocol.”An eCP must meet certain criteria. Recipient facilities must be licensed and recently inspected by FDA, and in good GMP standing. Meanwhile, the company must provide well established product and process understanding. “Streamlined but disciplined tech transfer greatly enhances the effectiveness of our manufacturing network optimization effort,” Chang concluded.
