Drug Substance Manufacturing

• Mabion offers clinical and commercial drug substance manufacturing of therapeutic proteins using mammalian and insect cell lines.
• We deliver international drug development projects, including biosimilars, innovative monoclonal therapies, vaccine antigens, and other recombinant proteins.
• Mabion offers cGMP-compliant manufacturing of biologic therapeutics at competitive price points.

Upstream Processing

At Mabion, we have experience working with a variety of cell lines, including mammalian and insect lines dating back to our inception in 2007. The Inoculum stage cell cultures are performed in 50 to 5000 mL flasks, while bioreactor cultures are performed at 50 – 5000 L scale.

Offering multiple technologies for cell culture (impellor driven stirred tank SUB or orbital shaken SUBs) and for cell harvest (single use depth filtration or single-use centrifugation) we can tailor the drug substance manufacturing process depending on the scale, product or process.

Our fit-for-purpose facility possesses all equipment necessary for end-to-end production of biologics, operated by well-qualified and experienced specialists. We can perform a seamless technology transfer, use the available process with or without additional adjustments or develop process de-novo, depending on the client’s needs.

Our upstream processing offer comprises:

1. Cell line development and optimization

• Development of mammalian and insect cell lines for the purpose of monoclonal antibody production. Our in-house experts focus on developing robust, high-performance cell lines tailored to your unique requirements.
• Cell lines are optimized to achieve optimal yields and desired product characteristics.

2. Media development and optimization

• Development of customized media and feed strategies to enhance cell growth, productivity, and product quality, while minimizing variability and optimizing the Cost of Goods (COGs).
• Point-of-use-preparation and storage of cell culture media and feeds.

3. Bioreactor operations

• 2 x 2000L stirred tank bioreactors (to be upgraded to 4 x 2000L stirred tank bioreactors) with a seed train consisting of 2 x 50L and 2 x 200L bioreactors that allows for smooth transition from lab-scale to large-scale drug substance manufacturing.
• 2 x 2500L orbital shaking bioreactors with independent seed trains, which can be used in a stepwise manner to obtain large product quantities for clinical testing or commercial use.
• Inoculum cell cultures in local A-class environments.
• Real-time monitoring and control systems ensure consistent process performance and quality.

Downstream Processing

Mabion offers a wide range of protein purification techniques. Our flexible downstream purification processes enable us to purify volumes from a single liter, all the way up to up to several thousand liters of active drug substance from a single batch. We have many years of experience working with both single-use and multi-use chromatographic systems, including affinity and ion-exchange chromatography in binding and non-binding modes.

We provide a comprehensive range of chromatographic column sizes with customizable resin options. Importantly, our facility contains extensive and flexible DSP areas, which can accommodate even the largest columns. We carry out downstream development to tailor purification conditions to the product.

Complementing the chromatography steps, Mabion has extensive experience developing the right viral inactivation and filtration steps, completing our compliant and efficient viral contamination control strategy.

Finally, in our post-viral filtration areas, we finalize the drug substance manufacturing process with a flexible ultra/diafiltration setup for concentration and buffer exchange into the formulation buffer and sterile filtration to ensure the absence of contaminants.

Should the desired process require it, Mabion has the capacity to prepare thousands of liters of buffers and solutions each day. We can prepare all necessary media and supplements for cell culturing in-house, providing our company with a significant advantage during the increasingly common logistical challenges. Nonetheless, we are also fully equipped for using ready-made buffers, feeds and media.

Our downstream processing portfolio includes:

1. Primary recovery

• Cell harvesting and separation from cells/culture medium via depth filtration and/or centrifugation

2. Protein purification and filtration

• Protein purification using various methods including:
  • Affinity chroatographies (incl. protein A)
  • Ion-exchange chromatography (incl. CEX and AEX)
  • Ultra/diafiltration
  • Nanofiltration and sterile filtration

3. Virus inactivation

• Viral inactivation following filtration and chromatographic purification, both for early- and late-stage projects.
• Custom formulation solutions designed to stabilize your protein during storage

4. Preparation and storage of buffers

• Preparation of optimal buffers to enhance recovery and yield of target proteins

5. Storage of the drug substance

• Storage of the prepared drug substance under controlled conditions, prior to further processing

Process Validation and Documentation

Due to the complex nature of biological products, the drug substance manufacturing process itself significantly impacts product quality, safety, and efficacy. Thus, understanding and controlling the manufacturing process is essential in ensuring that the biological product consistently meets its intended quality attributes.

With Mabion, you can rest assured that every aspect of drug substance manufacturing process validation is meticulously managed to ensure consistent quality and compliance. Modern process validation is a data-driven lifecycle approach, where validation activities are conducted throughout the product’s lifecycle, from development through commercial production.

During the early stages of product development, we gain an in-depth understanding of the forthcoming manufacturing process through process characterization studies which lead us to identify critical quality attributes (CQAs) and critical process parameters (CPPs). This knowledge forms the basis for process design and co-development. Comprehensive process characterization is one of the foundations necessary for a successful process performance qualification (PPQ) and commercial production.

The validation process continues through process qualification, where we demonstrate that the process delivers consistent results under commercial-scale batch manufacturing conditions. This includes complete validation of all analytical methods, qualification of equipment and facilities, validation of all critical raw materials, as well as PPQ to demonstrate that the process operates within the limits established during the process characterization studies. For PPQ studies, Mabion uses a 3+1 batches approach to ensure its successful completion.

Ongoing process verification ensures that the drug substance manufacturing process remains in full control during routine production. Regulatory agencies expect manufacturers to use this data to ensure that the process is fully controlled and continues to produce products that meet specifications.

Our comprehensive panel of services covers whole lifecycle of process validation:

1. Design and preliminary evaluation of manufacturing process

• The foundation of a successful biologics manufacturing process lies in its initial design and evaluation. Our process design and preliminary evaluation services focus on defining a manufacturing process that is not only scalable and efficient but also capable of delivering a biologic product that consistently meets quality and regulatory standards.

2. Risk assessment and process control strategy development

• Risk assessment is a critical component of process validation, focusing on identifying and mitigating potential risks that could impact product quality, safety, or efficacy. Systematic risk assessment and control strategy development services provided by Mabion ensure that your process is robust and compliant with industry standards.

3. Process performance qualification

• We design and execute a comprehensive Process Performance Qualification (PPQ) plan, performing qualification runs under commercial-scale conditions. These runs validate the repeatability and robustness of the process. Key process parameters are monitored closely to confirm that the process delivers consistent quality across multiple batches.

4. Ongoing verification via testing and manufacturing process review

• After the PPQ phase, we implement a continuous monitoring program to ensure the process remains in a state of control. Our Ongoing Process Verification (OPV) services include regular testing, analysis, and review of critical manufacturing data. We use statistical process control (SPC) tools to detect trends, shifts, or out-of-specification results early, allowing for proactive interventions.

5. Revalidation after introducing process changes

• Process revalidation is essential whenever significant changes are made to the manufacturing process, equipment, or materials. Our revalidation services ensure that these changes do not adversely impact product quality, safety, or efficacy.

6. Comprehensive process validation documentation

• Comprehensive and accurate documentation is critical to ensuring regulatory approval and maintaining a state of control throughout the product lifecycle. Our documentation services encompass all aspects of process validation, ensuring full compliance with relevant guidelines and requirements: preparation of risk assessment, Process control strategy, Validation Master Plans (VMP, PVMP), Validation Protocols and Reports, Ongoing Process Verification Plan.

Logistics and Supply

Following the completion of the drug substance manufacturing process, Mabion is equipped to store the produced active substances under refrigerated or frozen conditions, ensuring their stability and integrity. The finished products can be securely stored in our warehouses under a wide range of temperature conditions until they are ready for shipment. From here, we can ship the frozen drug substance to a final storage or processing site of your choice.

Our clients benefit from our well-equipped Logistics Unit with its own specialized fleet of vehicles. Mabion provides professional transportation services for pharmaceutical products, including materials related to drug substance manufacturing, under environmentally controlled conditions, eliminating the need to engage additional logistics companies.

We can distribute drug product to nearly every location within Europe, inside and outside of the EU. We have successfully shipped thousands of IMPs and over 25,000 lab samples across 11 countries. This expertise enables us to seamlessly coordinate the transportation of biopharmaceutical products and related materials for Phase I-III multinational and multicenter trials.