Mammalian Biologics Development and Manufacturing Services

TECHNOLOGY TRANSFER

Manufacturing Risk Assessment

Our CMC experts, dedicated development and MSAT teams work with our clients to identify gaps and mitigate risks for process fitting and evaluate potential process improvements to help reduce clinical and commercial manufacturing cost via process efficiencies. Through our manufacturing risk assessment, we:

• Assess critical quality attributes (CQA) and potential critical process parameters (pCPP) via FMEA
• Introduce platform processes and next-generation analytical methods for streamlined, scalable production
• Recommend adjustments to process design and required analytical methods validation
• Mitigate risks related to supply and compatibility of raw materials with commercial manufacturing
• Deliver a summary report with action plan and recommended CMC and tech transfer strategy for early and late-phase projects

Proven Technology Transfer

Throughout the transfer process, we effectively balance the factors for success including:

• CQA, CPP and process ranges (NOR, PAR)
• Process comparability and consistency
• Process reproducibility
• Process and analytical panel robustness
• CQA monitoring via our Multi-Attribute Method (MAM) platform for a smoother tech transfer and regulatory pathway
• Robust quality management system and ALCOA principales for documentation
• Flawless project management, detailed Gantt charts and open, transparent communication

MANUFACTURING

Mammalian GMP Manufacturing

Our flexible facility and capacity for clinical and commercial-scale production supports global drug substance supply for monoclonal antibodies (mAb), mAbs for Antibody-Drug Conjugates (ADCs), and mAb-derived molecules such as bispecifics, antibody fragments and fusion proteins.

• Mobius^® single-use bioreactor platform
• Mid-scale manufacturing at 2,000 L
• Small-scale manufacturing at 200 L
• Strong Manufacturing, Science and Technology (MSAT) expertise
• Proven tech transfer

Commercial Manufacturing Readiness

Our process validation and MSAT teams have in-depth knowledge and scientific expertise of all aspects of upstream and downstream processing and validate the bioprocess for commercial-scale manufacturing.

• Risk assessment (FMEA) to define critical process parameters and process ranges (NOR, PAR)
• Scale-down model to gain process efficiencies before commercialization
• Pre-characterization before Process Design helps gain more data without impacting time to PPQ campaign
• Process characterization
• Robust control strategy (process, material, testing)
• Process Performance Qualification (PPQ)
• Resin lifetime study, resin reuse, mixing study and hold time study
• Continuous process verification
• BLA filing support
• Troubleshooting

REGULATORY SUPPORT

Tech Transfer Support

Our highly experienced regulatory experts are integral to each project, staying with it from the initial stages of the technology transfer through to scientific advice, regulatory filing and lifecycle management. We review and evaluate:

• Gap analysis & Chemistry, Manufacturing, and Controls (CMC) strategy
• Process control strategy
• Process changes post original
• Process and analytical methods fit-for-purpose
• GMP compliance
• Raw material origin
• Change notifications and regulatory impact

Scientific Advice

Review or author:

• Briefing books supporting meetings with Health Authorities (HA)
• Attendance of HA meetings upon request
• Responses to HA post submission

Regulatory Filing Support & Lifecycle Management

Review or author:

• CMC sections of regulatory dossier submissions(IND/IMPD & MMA/BLA)
• Information to the Common Technical Document (CTD) to build the CMC for the drug substances that will be submitted
• Support for post-approval changes
• Deviations and annual updates
• ROW continued filing support

Mammalian Analytical Packages

Our analytical packages support the entire product lifecycle, covering method development , transfer, optimization and analytical method validation. Our analytical experts consider our client’s program as a whole and ensure that each method is fit for purpose and compliant with local pharmacopeia and regulatory requirements. Several options are available for the development of the analytical panel:

An analytical package consisting of up-to-date, off-the-shelf techniques that assess content, purity, activity, and safety controls and includes platform methods such as ELISA, H/UPLC, qPCR, capillary electrophoresis, and glycan profile analysis can be leveraged. This templated, phase-appropriate strategy for monoclonal antibodies eliminates the time and expense of method development from scratch, while still allowing for flexibility.

For product-specific needs, methods can be custom-built by our analytical development team and transferred to our validation and QC labs. Our analytical capabilities includes methods such as binding assays (ELISA, SPR), enzymatic assays, SPR affinity & Kinetic (SPR), RP-U/HPLC, IEX-UPLC and others.

If a client has an existing set of analytical methods, they can be transferred as is, or optimized as part of the technology transfer process. This process may include adding or replacing current methods with state-of-the-art techniques to improve performance or throughput. Our high-throughput methods and equipment include OD HT microfluidic equipment, CE-SDS, cIEF, N-Glycan mapping using microfluidic, reverse CE-SDS by capillary, along with a pipetting robot for sample preparation.

Our analytical development team has extensive expertise in mass-spectrometry which clients can leverage for HCP characterization & quantification, peptide mapping, disulfide mapping, intact mass, and Multi-Attribute Method (MAM) platform to monitor post translational modifications and Critical Quality Attributes (CQA) in routine testing.

Multi-Attribute Method (MAM) Platform

Our MAM platform, based on liquid chromatography coupled to mass spectrometry (LC–MS), can be deployed to support biopharmaceutical companies at any stage, across process development, tech transfer and process validation. It’s a platform-based method that enables quality-by-design (QbD) and monitors product quality attributes (PQA) simultaneously, in one single assay.

It provides a consistent link between the process and the molecule PQAs, particularly important in process characterization studies, which aim at understanding the link between Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) to refine process ranges for commercial manufacturing.

Fine-tuned through deep scientific expertise and years of experience, our MAM platform offers the high specificity, precision, accuracy, and robustness needed to make it the perfect tool to reliably monitor Critical Quality Attributes (CQA) and comply to regulatory requirements for smoother BLA submissions.