Availability

Availability efficiency is the fraction of time that a piece of equipment, suite, or facility is in a condition to perform its intended function or simply the amount of time processing actually occurs.^18,19 There are six main states: 1) the unscheduled state (not planned to be used); 2) the unscheduled down state (not able to perform); 3) the scheduled down state (not planned to be available); 4) the engineering state (used to conduct equipment or process trials); 5) the standby state (not operated because of lack of personnel or support equipment); and 6) the productive state (performing as intended).²⁰

Availability is limited by: 1) equipment, process and facility shutdown, maintenance, or failures, which lead to the unscheduled state and both the scheduled and unscheduled down states, and 2) set up and adjustment which primarily lead to scheduled downtime.^3,5,16,18,21 The unscheduled state and scheduled down state includes planned maintenance, operational shutdowns, unworked shifts, and holidays. The unscheduled down state generally includes unplanned shutdowns, lack of demand, breakdowns, and operator unavailability.^16,18 Set up or adjustment losses occur when production of one product ends and equipment is adjusted to meet requirements of another product [such as changeovers, preventative maintenance, cleaning and sterilization, equipment or process trials (engineering runs), and qualification]. These changeover times can be greater than production runs, and in multiproduct bioprocessing facilities, they typically are substantially greater.¹⁹ Changeover is often a key improvement opportunity, with best-in-class companies achieving significant reductions through cross-training team members, implementing lean principles such as workplace organization, and developing quick changeover techniques.²²

Performance efficiency is the fraction of equipment uptime that the equipment is processing actual lots at theoretically efficient rates.¹⁸ Consequently, it reflects losses incurred by suboptimal operation, specifically the difference between design and actual speeds.²¹ Idling or minor stoppage and rate losses prevent achieving maximum speed because production is interrupted or slowed respectively by a temporary malfunction, lack of input because of poor raw material or intermediate stream quality, or insufficient personnel.^1,3,10,16 This category can be a catchall for unclassified or immeasurable losses.²³ In biopharmaceutical manufacturing, performance efficiency can reflect inefficiency from unexpected campaign starts and stops (e.g., in-process assay delays), or from longer than expected step processing times (such as slower than expected depth filtration).

Quality

Another factor is quality, defined as "right the first time it is done."¹⁹ Unacceptable quality includes yield losses (leading to scrap) and defects (leading to rework) caused by equipment malfunction and start up losses in which yields are lower during early stages of a new campaign before stabilization.^3,16,21 In biopharmaceutical manufacturing, quality losses include atypical events such as contamination, impurities, and incorrect documentation that often occur in initial batches for a new product campaign in a multipurpose facility.