In this stage of biopharm manufacturing, innovations focus on the production line itself.
by Raymond E Peck, CEO of VxP Pharma
Each stage of biopharmaceutical manufacturing requires careful attention to detail. From upstream bioprocessing, to cell culturing (or fermentation), to downstream purification, even small errors can easily render an entire batch of product unusable, sometimes requiring an expensive reassessment of the entire processing chain.
The formulation and mixing of the active pharmaceutical agent (API) into its final liquid or lyophilized form, and sealing that final form within containers or delivery systems, comprises the fill/finish stage. Because fill/finish is the final, and ostensibly the simplest, stage of biopharm production, it tends to invite less innovation than the other stages.
Even so, contract manufacturing organizations (CMOs) are increasingly enhancing their capabilities in this area; if not in technical innovation, then certainly in terms of streamlining production efficiency and building more flexible capacities. Thus, despite the apparent lack of major innovations in fill/finish, this stage remains a significant focal point for improvements in the manufacturing process itself.
Here are several ways in which contract manufacturers are improving their abilities in the fill/finish stage.
CMOs are focused increasingly on eliminating fill/finish activities that don’t add value.
Throughout the fill/finish stage, components and materials can be used much more efficiently if they’re available and easy to use when needed, and arrive just in time so they don’t pile up in inventory. Even small hitches in this supply chain can slow down production and raise costs to a surprisingly significant degree. For example, parts that arrive too early or too late can create inventory-storage or restocking costs, which are often passed on to partners (or to the market).
On the other hand, a proactive policy of eliminating non-value-adding activities can reduce the overall costs involved in the fill/finish stage, and speed up each batch’s time-to-market while mitigating risks and keeping prices low. For instance, some facilities have eliminated the process of washing and depyrogenating containers from their production lines, ordering pre-sterilized ready-to-use (RTU) containers instead. Not only does this allow containers to move directly from the warehouse into active production; it also lowers risks involved in singulated component handling, by treating each nest of containers as a single object.
Small changes like these can have major impacts. When production staff are able to handle up to 100 containers as a single unit, they’re able to load an unload lyophilizing equipment up to three times more quickly. This improvement also eliminates the step of stoppering and crimping each container, enabling thousands of vials to be reliably sealed in a matter of seconds. And nests of pre-sterilized containers are only the beginning, as many CMOs are also turning to nested syringes and cartridges.
Innovations like these, along with reductions in the number of operators required to observe automated processes, have helped reduce bottlenecks, cut down on waste, and lower the incidence of unnecessary labor. In all these ways, forward-thinking contract manufacturers have increased their ability to focus on value-adding actions.
Many contract manufacturers are also working to increase their fill/finish flexibility.
One added bonus of adopting pre-packaged materials is the ability to standardize the fill/finish process, reducing the time required for changeovers between different setups from several days to a matter of hours. This means a single facility can fill and finish multiple drugs on the same production line, on the same day. Since biopharmaceutical drugs target highly specific populations, market demand often changes from one week to the next. This, flexibility is a crucial component of any CMO’s success in the biopharm sector.
By cross-training production workers, facilities can increase their flexibility even further. Hours invested in employee education, and in the development of clear instructions for each fill/finish process, pay off significantly when a production line has to quickly switch between one drug and another.
In a similar way, the addition of robotic automation has helped some CMOs introduce much greater flexibility to their fill/finish stage. Robots will reliably repeat the same actions until instructed to do otherwise; and those instructions can easily be changed with software updates. As an increasing number of CMOs move forward into a future where production demands are often unpredictable from one day to the next, this combination of reliability and flexibility has proven crucial for staying ahead of the competition.
Increased fill/finish efficiency and flexibility can equate to millions of dollars in savings.
Throughout every area of pharmaceutical manufacturing, shortages reduce revenue, weaken patient outcomes, and can even damage a brand’s reputation. Biopharm manufacturing is no exception. For this reason, most CMOs now practice demand-driven manufacturing, shaping just-in-time production flows around the latest demands from their development partners, as well as weekly market trends.
This practice has been shown to reduce inventory costs involved in production by as much as 30 percent; and to lower a facility’s operating expenses by as much as 20 percent, while reducing downtime and shortening the time-to-market for each batch of a drug. In a sector in which billions of capital is often tied up in the manufacture of a given drug, efficiency improvements on this level can equate to millions of dollars saved.
In view of these statistics, it’s easy to see why many CMOs are investing not technological innovations to the fill/finish stage, but in streamlining their production, increasing their flexibility, and strengthening their ability to focus on value-adding activities.
In addition to being a writer and speaker, Raymond E Peck is the Founder and CEO of VxP Pharma Services and VxP Biologics, both based in Indianapolis Indiana.