Issue link: https://www.e-digitaleditions.com/i/1511466
14 BioPharm International ® Manufacturing and Facilities eBook 2023 www.biopharminternational.com T he oligonucleotide industry continues to grow at a rapid pace. Given the relatively small quantities of drug substance produced compared to, for example, products at an in- dustrial chemical manufacturing facility, one might assume only limited volumes of solvents would be re- quired. However, solid-phase oligonucleotide synthe- sis (SPOS) and downstream processing of oligos uses significant quantities of hazardous materials. It takes roughly 3000–7000 L of flammable liquids to produce 1 kg of drug substance. As oligo manufacturers scale up production from lab- scale to clinical and commercial scales to meet industry demand, they are likely to require volumes of hazard- ous materials that drive additional facility design con- siderations for code and regulatory compliance. Designing for hazardous materials in an oligo facility Manufacturing processes typically use a wide range of hazardous materials including flammable organic solvents, corrosives, and toxic compounds. As new processes and methodologies continue to emerge, ad- ditional materials with unique hazard challenges are constantly introduced into this repertoire. One must first comprehensively identify the hazard classifica- tions (Figure 1) and volumes of hazardous materials being used in a facility before code and regulatory im- plications can be understood. Design and construction of facilities housing haz- ardous materia l-intensive processing operations must adhere to codes and regulations adopted by their jurisdictions. In the United States and some other countries, this includes the International Build- ing Code (IBC) (1), the International Fire Code (IFC) (2), and NFPA 30: Flammable and Combustible Liquids Code (3). An exception to this is laboratory facilities that only use small volumes of hazardous materials for non-production chemical manipulations. These codes dictate the design of areas in which hazardous materials are used or stored as either control areas or Oligonucleotide Production Facilities Kyle Hubbard is process engineer at CRB; Bill Jarvis is senior fellow, Pharmaceutical Process, at CRB. As oligo manufacturers scale up production from lab-scale to clinical and commercial scales, they may require volumes of hazardous materials that drive additional facility design considerations. EDNURG - STOCK.ADOBE.COM