How to Mitigate Biopharmaceutical Manufacturing Risk with Proactive Redundancy Planning
If the past two years have taught us anything, it’s that we can never be too prepared for disruption. That is especially true in critical industries like biopharmaceutical manufacturing, where continuity and operational efficiency can have serious consequences for the patients who rely on the drugs you make.
This article is posted on our Science Snippets Blog
Redundancy planning is about addressing various places where things can go wrong. There are plenty of opportunities to introduce error into the biopharmaceutical manufacturing process—from your vendors and complex supply chains to the production floor and in transit. Companies prepared to thrive in uncertainty are the ones that have a redundant process available for each of these critical junctures.
Preparing for Disruptions at 3 Key Levels
2020 definitely was not the first time manufacturers experienced disruption. But before COVID-19, most of these issues were minor blips on a very large radar. Companies could overcome short-term issues with backup supplies, by temporarily switching to another manufacturer to get critical components like disconnectors, or by making minor adjustments in the manufacturing process.
In that generally stable industry environment, companies validated a process and stuck with it as long as it worked. Most didn’t think about if or when something might disrupt their entire operation. Today, every company knows the value of planning for uncertainty at every level, but especially in three key areas.
1: Supply Chain
The supply chain is a critical aspect of any biopharma manufacturing process. COVID-19 exposed several weaknesses in today’s highly connected global supply chain. There isn’t one simple answer to fix a very complex supply chain. However, as companies look toward the future one option to consider is working with an end-to-end (E2E) supplier that utilized a more diverse supply network to mitigate risks from the bottom up; raw material procurement to product delivery.
While E2E suppliers can still feel some of the crunch during a global shortage, they take the necessary steps to diversify their own vendors and suppliers to minimize the risks. A trusted partner can dramatically lower your exposure at the supply chain level.
2: Vendors
The next consideration is vendor volatility. Manufacturers that have a validated process with a single vendor’s products can quickly run into challenges if the vendor cannot manufacture those products. Switching to a new vendor requires revalidating all your data to prove regulatory compliance. This can put you several months—or even more than a year—behind schedule, especially if you have to start from scratch to locate a new vendor.
Companies that proactively plan for risk and build in redundancies often have more than one vendor for critical parts. They have validation data using parts from both vendors, and regularly order from both. A 70/30 split is common, with 70% of supplies coming from a primary vendor and 30% from a secondary vendor to maintain these relationships and be ready to shift as needed.
3: Manufacturing Site
Manufacturing site disruptions can take many forms, including:
- Equipment failure or damage
- Contamination
- Operator error
- Natural disasters
- Component damage
Building in redundancies at this level requires thinking about the entire process from start to finish. MSAT teams tasked with improving efficiency can take a holistic view of the process—identifying potential risks and finding ways to protect against them before they become an issue.
Real-World Example of Proactive Planning: Pfizer Case Study
Pfizer understands the risks in biopharmaceutical manufacturing, so several years ago they started proactively looking at ways to incorporate redundancies at each of these levels. This case study (co-authored by Christine Megarity, Senior Technical Scientist at Pfizer, and Bobbi Allen, Global Product Manager at Sartorius), walks through some of the steps Pfizer took to build redundancy in disconnection methods.
Examining the “status quo”
A common industry practice is to use silicone tubing in most applications, and TPE tubing only in places that require welding and sealing. Since silicone is not a thermoplastic, manufacturers must have appropriate sterile fittings at any connection/disconnection sites. If a sterile disconnector fails in the manufacturing process, it can render an entire batch of pharmaceuticals unusable. TPE tubing is more expensive, but it does come with the advantage of being flexible when you apply heat, so companies can create a heat seal and disconnect product from an assembly if necessary if the primary mechanism is no longer viable.
Adjusting for manufacturing-level risks
To mitigate this risk, Pfizer redesigned its assemblies to use TPE throughout, and added Clipster® disconnectors on all the lines. Clipster® is sterile, simple, and efficient for sealing and disconnecting the bags that takes about 10 seconds. But if the disconnector fails, the team can immediately switch to a thermal seal with the TPE lines. That takes much longer (about 2 minutes compared to 10 seconds for the Clipster® disconnection), so it’s only used as a backup.
Adjusting for supply chain and vendor-level risks
Pfizer also took the next step to protect against supplier and vendor risks by purchasing equivalent assemblies from two different manufacturers. They went through the process of validating each to make sure both could provide the sterility necessary to meet regulatory requirements. Now they can switch seamlessly between the two as needed without any disruption to their manufacturing timelines.
