Having a well-managed facility maintenance schedule can avoid lengthy shutdowns and lost revenues, says a regulatory expert.
During the Q2 2019 reporting season, Samsung BioLogics reported revenues of KRW 78.1 billion ($65 million) compared to KRQ 15.1 billion recorded in the previous quarter. The Korean contract manufacturing organization (CMO) attributed the 38% drop to the plant operation rate temporarily decreasing at its 152,000 L plant number 2 during the quarter due to “regular maintenance essential for biopharmaceutical manufacturing.”
According to the firm, such activity is typically held every two years, and comprises of “activities essential to optimize productivity and efficiency of the plant and consumable parts replacements [taking] place all at once.”
John Godshalk, a senior consultant at Biologics Consulting, told Bioprocess Insider maintenance schedules is one of many elements NDA holders look at during the due diligence of selecting a third-party manufacturer.
“Maintenance is an important regulatory concern and some CMOs do better at it than others. From a cost perspective, it is tempting to do deferred maintenance and save some moment but at some point it will catch up on you.”
He continued: “One plant we audited for a customer acquisition – though of course I can’t mention names – had deferred its facility maintenance by several years. It was really bad: holes in the building, frost build-up in the cryopreservation equipment, and obviously no maintenance had been done for a long time. When the company eventually bought it, they were forced to pay a lot of money and time to fix it up.”
|In December 2018 Avid Bioservices reported its facilities in California were shut down for periods of more than three weeks for planned sequential maintenance, resulting in a significant drop in revenue for the contract development and manufacturing organization’s (CDMO’s) second quarter FY19.
At the time Avid told us the shutdowns were internally planned with no consideration for FDA or requirements from FDA. “Despite the less frequent shutdowns by Avid/Peregrine in the past, the company has always had an exemplary regulatory record when it comes to FDA inspections so this is not a concern for the company,” a spokesperson said.
While there is no downside to the FDA knowing that a firm is staying on top of compliance issues, Avid said that it in no way drove the company’s maintenance strategy.
Planned maintenance, therefore, addresses such problems and helps ensure high standards. However, it means lost revenue as manufacturing lines, or even full facilities, are deliberately shutdown to allow repairs and upgrades to take place.
“Regulations are intentionally vague as the US FDA [Food and Drug Administration] do not want to inhibit creativity. Therefore, they call manufacturers to carry out ‘periodic maintenance,’ but what does this mean?”
GMP guidance documents shed some light on requirements, but do not spell out what a firm must do. For example, for finished pharmaceutical products the FDA demands that: “Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product,” and demands a firm has “maintenance and cleaning schedules,” but does not give more precise guidelines.
Each machine and each piece of equipment will have different requirements, said Godshalk, adding to the complexity. But however a firm chooses to address maintenance, it needs to keep well organized records for future regulatory audits, he stressed.
Utilization rates and single-use
Maintenance schedules are also a factor in capacity utilization rates of commercial facilities.
Commercial biomanufacturing plants and CMOs are often deemed to aim for a utilization rate of around 70-80%, rather than the full 100%. While the excess capacity is there to rapidly and proactively increase production if needed for a certain campaign, often the extra 20-30% is used to account for facility and equipment maintenance.
Godshalk noted the 20-30% buffer will also be used to ensure smooth changeovers between campaigns as wells as process performance qualification (PPQ) and engineering runs.
He also spoke of a shift to single-use systems in biomanufacturing. While facilities still need maintenance, equipment – by its single-use nature – will not require cleaning, never mind repairing, and a run-to-failure maintenance schedule can take place.
“There is a difference in complexity between single-use and stainless-steel plants,” he said. “Single-use does make maintenance easier.”