Therapeutic Proteins Downstream Purification Process Development

Protein downstream process development involves purification, isolation, and characterization of target products from complex biological matrices to ensure that the final product is safe, effective, and of high quality. With years of experience in providing satisfactory downstream process development solutions to each customer, CD Formulation's team of process experts will perform many unit operations and provide you with high-quality downstream process development services by adopting various protein purification and preparation technologies. Whether you are seeking downstream purification process development for small-scale, preclinical evaluation and proof-of-concept studies, or clinical or commercial-scale processes that comply with cGMP, our team of experts can provide you with customized solutions.

What is the Downstream Process?

Downstream processing (DSP) is a series of unit operations that occur after cell growth and expansion are complete and the production or synthesis of the drug substance or other ingredients is complete. Therapeutic protein downstream processing refers to the recovery and purification of the drug substance from its natural source (e.g., animal or bacterial cells). The main goal of downstream process development is to obtain a drug product with the desired purity, efficacy, and reasonable unit cost, which involves isolating the target protein from the mixture while removing any contaminants that may interfere with its intended use. This stage is a critical step to ensure that the drug candidate does not contain any impurities and obtains adequate yield from the extraction. The process includes isolation, purification, concentration, and formulation.

• Isolation: The target protein is separated from the mixture. This step is usually achieved by filtration, centrifugation, or precipitation.
• Purification: This involves the removal of contaminants such as other proteins, DNA, or viruses. This step is usually achieved by chromatography.
• Concentration: Increasing the concentration of the target protein to the desired level.
• Formulation: Stabilizing the protein for its intended use by adding stabilizers or adjusting the pH.

Fig.1 The flow of downstream process development for therapeutic protein. (CD Formulation)

Explore Our Therapeutic Proteins Downstream Purification Process Development Services

CD Formulation has extensive experience developing purification processes for multiple types of protein therapeutics, including recombinant proteins, monoclonal antibodies, enzymes, Fc-fusion proteins, bispecific antibodies, and antibody-drug conjugate products. Our advanced protein characterization capabilities enable critical structure-function studies as well as a variety of product-related impurities, including aggregates, improper modifications, truncated forms, and degradation product assessments.

Our downstream processing team offers a broad range of downstream protein purification process development services in a highly competitive manner. We employ integrated process development services to ensure that we provide you with a reproducible, scalable manufacturing process that accelerates your timeline and reduces risk in your development strategy.

Our downstream capabilities are flexible enough to align with the scale of the upstream process, allowing one upstream process (USP) batch to be purified in a single run without the need for batching.

Many of the protein downstream purification process development services we provide include:

• Apply quality by design (QbD) principles throughout the development process.
• Integrate process development and analytical method development to optimize downstream purification steps.
• Evaluate product biophysical and biochemical properties to guide downstream process development and optimization.
• Identify critical process parameters through failure mode and effects analysis (FMEA).
• Viral inactivation and clearance step development.
• Protein purification using various chromatographic techniques (from 1mL to 100mL).
• Protein concentration (normal and tangential flow filtration).
• Small-scale process characterization and scale-down validation studies.
• Harvesting (centrifugation, depth filtration) and cell disruption.
• Ultrafiltration and diafiltration.
• Purification process development.
• Isolation and solubilization of inclusion bodies and subsequent refolding of target protein.
• Large-scale process validation using AKTA Ready and AKTA Pilot.
• Process scale-up and technology transfer.
• Process characterization, process optimization, and process validation for late-stage clinical programs.

How Do We Develop Downstream Purification Processes for Protein?

Fig. 2 Therapeutic protein downstream purification process. (CD Formulation)

In downstream process development, our team of process experts always takes a holistic approach, viewing the entire therapeutic protein manufacturing process as a complex interaction of many factors at different stages of production. This holistic philosophy guarantees the development of reproducible, reliable, and efficient processes that meet all regulatory requirements.

We integrate QbD principles and provide development platforms in the following modular approach. You can choose a single or specific module or request the entire therapeutic protein process development package from bench to clinical process validation and optimization.

Protein Purification

In purification process development, we develop purification methods using preparative systems that have counterparts on an industrial scale and optimize existing purification methods.

Viral Inactivation and Removal

• We determine protein purity by capillary electrophoresis with UV-VIS and LIF detectors and measure molecular interactions using state-of-the-art SPR technology.
• We Use TCID50 assay to determine viral titers.

Protein Characterization

To demonstrate that the obtained product has appropriate quality characteristics, we perform a wide range of physicochemical and biological analyses to support the process development of protein products.

• We use modern high-performance liquid chromatography (HPLC, UHPLC) to assess key protein quality attributes (e.g. glycosylation profiles, aggregates).
• We use MS-based sequencing to determine amino acid sequences and post-translational modifications.

General Process for Protein Downstream Process Development

• First, we thoroughly assess the risks that may arise during process development and obtain as much information as possible about the product characteristics. During the assessment phase, our experts determine the product's critical quality indicators (CQAs) and critical process parameters (CPPs).
• Next, we develop a series of experimental designs to obtain the process design space.
• Finally, we will confirm the operating ranges of the critical process parameters through experiments and risk assessments.

Why Choose Us for Therapeutic Proteins Downstream Purification Process Development?

• Our team of experienced researchers and scientists have extensive knowledge and expertise in therapeutic proteins downstream purification process development. They are well-equipped to handle the complex nature of protein purification and ensure high-quality results.
• We offer a personalized and customized approach to downstream purification process development that is tailored to your specific needs and goals.
• We maintain strict quality control measures throughout the purification process to ensure the purity, potency, and bioactivity of the therapeutic proteins. Our rigorous quality assurance protocols guarantee reliable and consistent results.
• We work closely with our clients to optimize processes and minimize expenses.
• We adhere to industry standards and regulatory requirements to ensure compliance with all relevant guidelines and regulations.
• We provide flexible experimental options to meet the needs of different customers.

Publication

CD Formulation is dedicated to meeting your specific needs for protein purification process development and provides guiding regulatory requirements, process scale-up, and technology transfer, ensuring a seamless transition from development to manufacturing. Please don't hesitate to contact us if you are interested in our services. We look forward to cooperating with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.