Solving 4 Common Challenges in Final Sterile Filtration
The final fill process is the last step in biopharmaceutical manufacturing, and one of the most critical steps for ensuring patient safety.
This article is posted on our Sartorius Marketing Blog.
You already have upstream and downstream sterility controls that prevent bioreactor contamination and establish bioburden control. However, the final filtration step, immediately prior to the final fill process, presents another potential opportunity for contamination if your facility does not have the right equipment in place.
Common Challenges in Final Filtration
Most manufacturers use single-use sterile filtration, but this type of assembly comes with significant frustrations. These can negatively impact your ability to deliver effective products and get them to market as quickly as possible. These are the four most common issues that manufacturers must overcome with single-use sterile filtration.
1: Regulatory Issues (EU GMP Annex 1 and PUPSIT)
Dating back to 1998, the EU Guidelines to Good Manufacturing Practices: Medicinal Products for Human and Veterinary Use Annex 1 (often referred to as “Annex 1”) outlines how manufacturers must verify the integrity of a sterilizing grade filter before use and after sterilization, commonly referred to as pre-use, post-sterilization integrity test or PUPSIT. In comparison, the U.S. Food and Drug Administration (FDA) does not require pre-use, post-sterilization integrity testing (PUPSIT). However, companies that want to sell products in Europe or other global markets must comply with the regulatory mandates of those countries.
PUPSIT requires testing the sterilizing filter and assembly—including the filter housing and the support structure and connections—after you install the assembly and before you use it to filter the product.
The European Union included the requirement for PUPSIT in EU GMP guidelines because of a concern that sterilizing filters could have flaws that allow microbiological contaminants to pass through the filter. These flaws may go undetected in post-use integrity tests—something manufacturers refer to as “filter flaw masking.” The discovery of microbiological contaminants after shipment or consumption could have catastrophic consequences.
2: Long Design Phase & Delivery Times Increase Time-to-Market
It could take several months to design, prototype, and manufacture a customized filter transfer set (FTS) ready for your specific process. The vendor must qualify all components and connections used in the design of the FTS. Qualification provides assurance that the FTS will function as intended and meet all specified requirements, including PUPSIT requirements. For companies trying to push competitive products out to market, this long design phase and extended delivery time can put you at a competitive disadvantage.
3: Product Loss Risks
During the final fill step, the product going into your packaging is highly pure and has the highest value in terms of cost per mL. You must keep this product sterile the entire time to minimize the risk of product loss. Any product loss or contamination at this stage is extremely costly and its vital to ensure that any filter transfer set used provides optimal protection in these critical final steps.
4: Operator Inefficiencies and Errors
There are many designs for final filtration processes, with little or no standardization. Processes definitely vary between companies and can even vary within the same company for different production lines.
The steps for PUPSIT testing also vary from one design to the next, so operators must learn how to manipulate valves and flow paths, and make sure filters are properly wetted to reduce the risk of additional contamination in a highly sterilized system. Whenever there is a new operator—whether it’s someone filling in temporarily while your regular operator is out on leave, or a new hire—they must relearn all the protocols, increasing the risk of error. At this stage of production, even small errors can be very costly.
Finding a Solution for Final Fill Filtration Challenges
Fortunately, there is a solution to help you address these challenges. Sartorius offers pre-designed, PUPSIT-optimized, and highly standardized filter transfer sets for final filling (FTS FF). These FTS FF assemblies address all the frustrations of conventional single-use filtration in final fill processing.
Shorten Time-to-Market
A typical design phase and delivery timeline can take nine months or longer:
- Concept phase – 4 weeks
- Single-use design and quote – 4 weeks
- Prototypes – 12 weeks
- Single-use design adaptations – 2 weeks
- Design approval (including manufacturing documents) – 4 weeks
- Lead time for single-use assembly – 20 weeks
With our predesigned FTS FF, you can cut up to 80% of that time, moving from the initial concept to assembly in as little as nine weeks. With predesigned components, the concept, design and quote phases take as little as one week. There is no need for prototyping, design adaptations, or design approval, and all the manufacturing documentation is already complete. Assembly for predesigned components is also much faster, taking less than half the time of a typical process.
You will be ready to go with a fully compliant, highly standardized, and flexible FTS FF in a matter of weeks, not months.
Comply With All PUPSIT Regulations
The need for risk assessment is lower when you have a qualified, sterile, PUPSIT-ready design. All the components in the filter transfer set are prequalified for PUPSIT, including the tubing, connectors, and connections, reducing wait times and speeding time-to-market, giving you a competitive edge in global markets. You can perform the PUPSIT without breaking sterility using our industry-leading wetting protocols for all filter variants and sizes.
The entire FTS FF meets the highest regulatory standards, including:
- Biological safety
- TSE-BSE
- Endotoxin
- Subvisible particle
- Sterility
- Bacterial retention
Every part of our FTS FF is prequalified and ready to use right when it arrives. That includes the toolbox with released and tested components, tested installation and operation instruction, and qualified wetting protocol for all filter sizes and types. It also comes with transport and sterility validation.
Standardize Filtration and PUPSIT
Sartorius offers a standardized design that incorporates the same operating procedure for all filter and filter sizes. Operators only need to learn a single process and can safely and efficiently run final fill steps on any lines within your production facility. We also simplified the entire venting design and removed the need for the filter capsule vent valve operation to reduce the risk of error further.
Predesigned and Prevalidated to Fit Multiple Filter Sizes
We have multiple design options that accommodate several different filter sizes, including the option to interface with other filter brands if needed. Sartorius also offers a specialized stainless-steel holder designed to ensure optimal orientation of the filter transfer set, which minimizes product loss. Providing a ready-to-order holder eliminates the lengthy and resource-intensive development process of ordering custom holders.
Solve Your Final Fill Process Challenges with Sartorius
Find out more about our standardized, predesigned, flexible filter transfer set for final filling and learn how we can reduce your risks with an off-the-shelf solution that meets all PUPSIT requirements. Contact us to discuss your needs or request an onsite consultation today.