Kenneth Laderman, PhD. Director of Manufacturing, Eurofins Advantar Laboratories, Inc
Eurofins BioPharma Product Testing highlights how it helps clients in the bio/pharmaceutical industry overcome challenges in sterile fill finish manufacturing with a state-of-the-art robotic vial filler solution for high value, small batches of sterile GMP or GLP products for use in Phase I or Phase II clinical trials.
What challenges does the bio/pharma industry face with regard to sterile fill finish manufacturing?
The industry is rapidly changing with increased product complexity such as mAbs, mRNAs, AAVs and LNP formulations and is pushing for shorter development and rapid turnaround times. These changes can often introduce additional risks and errors into the sterile fill/finish process, resulting in production delays, additional costs, and safety concerns.
The FDA is also pushing the industry for less human intervention in aseptic processing. Human contact with the sterile product is the greatest risk for contamination in the aseptic process.
The advent of personalized medicines also brings challenges to manufacturing. The need to move from large batch production to small lots of complex medicines, which may have a patient population of one, will change how manufacturing and supply chain are structured.
As many clinical hospitals lack a traditional cleanroom, close collaboration with an established sterile fill finish manufacturer may become crucial. The need for speed and flexibility pertaining to the manufacturing process could become important to personalized medicines.
How is Eurofins BioPharma Product Testing helping Companies overcome these Challenges?
Our state-of-the-art, sterile fill finish solution helps eliminate human error and other associated risks when producing small batches (up to 3000 vials) of sterile GMP or GLP products for Toxicology Studies, Phase 1 and 2 trials. Our system fills vials for small batches of GMP product, processing units quickly with precise filling volumes.
The system we use is the Vanrx Microcell Vial Filler. It is a gloveless, closed, and completely robotic system designed to reduce human error, time, and contamination as the flow path is single use, and disposable.
What else can you tell us about your Company’s Sterile Fill Finish Services?
We perform compounding of batches in an ISO 8 clean room followed by ISO 5 single or dual sterile filtration using sterile, single use, closed filtration systems with aseptic connectors.
Our state-of-the-art vial filler is capable of handling multiple sizes of vials and producing multiple batches of various drug products on a single machine thereby providing maximum flexibility to clients.
The system utilizes pre-washed, depyrogenated, ready-to-use, sterile vials that at are nested in sets for rapid filling. The vial system allows for less moving parts thereby reducing the risk of down time due to broken conveyer system.
Because the system’s flow path from sterile bulk to the fill needle is 100% disposable, product never touches the fill equipment. As a result, we are able to switch support to different product types with multiple batches very quickly. The isolator environment, with vapor hydrogen peroxide decontamination, requires less cleaning time and the highest level of cleanliness.
What types of drug products are best suited for this type of sterile filling system?
While we can support large and small molecule products, including biologics, such as antibody solutions, gene therapy products, etc. Our system is ideally suited for high value products with minimum product hold up in the low-volume fill line and right-sized surge bags; non-destructive weight checks conserve vials.
It is ideal for personalized medicines (either multiple treatment variants or autologous treatments). Eurofins offers the agility to support these with the potential to make multiple batches of personalized medicines each day.
The system is also adaptable to BSL2 filling for gene therapy and biologic products needing additional isolation not provided by traditional filling lines.
Can you describe the clean room classification required and walk us through the Sterile Fill Finishing Process?
The Microcell Filler is an ISO-5 isolator that is set up in an ISO-8, Grade A clean room with HEPA filtration and laminar flows. The room is designed to be unidirectional with drug substance materials coming in one door and finished product out another.
As needed, the drug substance is concentrated and compounded in this suite. Once the bulk formulation is complete (pre-filtration samples may be taken), it is moved into the ISO-5 hood where it is sterile filtered through dual filters using a peristaltic pump into a 5-liter bag with aseptic connectors. From this point forward, the product is in a sealed environment. The bag may be sampled through a medicine port if post filtration, in-process testing is needed. The bag is then transferred to the Microcell where it is connected to the fill needle flow path using an aseptic connection.
The Microcell is loaded with ready-to-use vials and caps. The door is closed and will not be opened until the product is filled and capped. The system then performs a pressure leak test to ensure it is sealed. Once confirmed, the system begins a validated vapor phase hydrogen peroxide (VPHP) decontamination cycle. After the peroxide is removed by evaporation, the Microcell performs a fill weight check and then proceeds to filling. It automatically fills and caps the 300 vials loaded into the system. Once capped, the door is opened and the vials removed. Another set of 300 vials and caps are loaded followed by a pressure check and VPHP decontamination. This cycle repeats 10 times to fill 3000 vials. At the end of the fills, the Microcell generates a fill report that is attached to the Batch Record.
What are the benefits of working with Eurofins for early phase sterile fill finish manufacturing?
Because our manufacturing facility located in San Diego, CA is a small site with a wealth of experience in manufacturing with qualified QC personnel; we can complete sterile fill finish projects in less time than other CMOs or CDMOs.
Upon project initiation, we will immediately begin drafting testing and specification documents needed to release the drug substance and critical excipients. Our state of the art QC lab can handle any drug substance from small molecules to complex mRNAs. Once documents are approved and methods qualified, we move immediately to releasing the drug substance (no wasted time shipping materials to other analytical sites for testing). Additionally, we stock pre-qualified sterilizing filers, ready to use vials, stoppers, and caps- no time lost there! While raw material release is going on, we will be tailoring a master batch record based on the information we have gathered from the client. With the materials released and the mater batch record approved, we move immediately into filling the product. Other advantages in working with Eurfoins BioPharma Product Testing include:
- Minimal product loss as dead volumes are very low.
- Press-fit closures sealed within the isolator significantly reduces particles.
- Isolator technology and robotics eliminate human interaction with the sterilized product.
- Single-use flow paths reduce the scope of cleaning.
- RTU vials eliminates the need for washers, autoclaves, depyrogenators.
- Reduced tech transfer requirements and shorter project timelines.
What's the lead-time for sterile filling at Eurofins BioPharma Product Testing?
Currently, our lead-time is very favorable at 4 to 6 weeks to start a new project. Because the Microcell fill line was designed to use 100% single use components, we can rapidly turnover the suite. Minimal time is needed for cleaning between manufacturing campaigns.
How can our readers learn more about Eurofins BioPharma Product Testing’s sterile fill finish services?
You can learn more about our sterile fill finish support on our website: Eurofins.com/BPT or e-mail us at [email protected]
We also hosted a webinar on this topic earlier this year and a recording is available on our website: www.Eurofins.com/bptwebinars
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