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www.biopharminternational.com Manufacturing and Facilities eBook 2023 BioPharm International ® 17 Facilities: OligOnucleOtides Ventilation H-occupancies require mechanical ventilation at a rate of not less than one cubic foot per square foot of f loor area, which often exceeds what is required if f lammable liquid quantities are maintained below the MAQ in each control area. Complex area supply and return systems may be required per code man- dates if the mechanical ventilation is required. Explosion control Explosion control in accordance with NFPA 68, NFPA 69, or NFPA 495 is required. Fire protection Automatic f ire detection systems and automatic s pr i n k ler s ys tem s w it h g reater capac it ies t h a n those in non-hazardous areas are required. Sprin- kler systems typically have higher densities of cov- erage, more sprinkler heads, more f low per head, and longer durations of operation. Areas may also require more fire extinguishers near hazardous material users and storage. Spill control and secondary containment Rooms, areas, or buildings must be provided with spill control and secondary containment. This typ- ically translates to integral specialty plumbing sys- tems. It can also include the addition of an exterior or remote spill containment tank to hold evacuated hazardous materials and contaminated firewater in the event of a fire. Egress ratings and distances Allowable lengths of exit paths from H-occupancies are limited by the building code. If those lengths are ex- ceeded, additional egress paths may be needed which must have fire-resistant construction. Emergency systems Mechanical ventilation, treatment systems, alarms, detec t ion , a nd ot her elec t r ica l ly operated l i fe- safet y systems must be provided with emergency or standby power. Process safety management Quantities of hazardous materials above 10,000 gal- lons in a given area require compliance with OSHA's Process Safety Management (PSM) requirements. This results in a range of complexities, including hazard analyses, more stringent operating procedures, more extensive personnel training, inspections, and more rigorous reporting. Facilities handling hazardous materials must per- form a hazard evaluation to determine if the quanti- ties and types of materials require control areas and/ or H-occupancies. A report of the hazardous material inventory, prepared by a qualified party, must be sub- mitted to retained for public record by the local building office or other applicable authority having jurisdiction. Processing scale and methodology impacts to facility design Code-compliant design of an oligo facility can have un- foreseen and costly consequences based on multiple fac- tors related to processing approaches. These factors have an impact on what must be considered when designing a facility and its necessary supporting infrastructure. The following are typical facility production ap- proaches that illustrate how process scale and method- ologies affect design. Base case: small-scale production of a short oligo For an initial production facility, such as a development lab, running at a small scale with a short chain oligo, the hazardous material inventory may remain under the MAQs. The batch scales for a typical length of oligo (e.g., 20-mer anti-sense oligo) tend to range from 0.1–2 mmol, which require benchtop equipment and a few liters of solvents per synthesis. The following is a typical small- scale production scheme: • Benchtop equipment is instruments for synthesis and downstream purification. • Limited number of processing lines per area. • Synthesizers each operating at one synthesis/day. • 30-day inventory of raw materials and weekly waste removal (Figure 2). Code implications Control areas can be implemented for storage and use of hazardous materials. An operational strategy to ensure code compliance is needed under this ap- proach. If material storage is not managed correctly, it may require H-occupancy. Increasing production with more processing lines As expanding business drives the need for more prod- ucts and/or more types of product, additional pro- cessing lines or increased numbers of batches per day may be needed. The following is a typical increased production scheme: • Expanded number of processing lines per area • 24/7 production, with each synthesizer perform- ing two syntheses/day • More frequent raw material supply and waste collection (Figure 3). Code implications An increased volume of hazardous material in use and waste stored could exceed MAQs and require H-occupancies and associated systems, such as spill containment tankage, exterior wall requirements, and egress accommodation.