Process optimization aims to increase process robustness and reduce production costs. The key focus areas includes: substitution of high-cost material, upstream titer enhancement, protein quality modulation, improvement of downstream recovery, quality optimization, and process robustness studies.
Process characterization (PC) refers to establishing a strategy of process control by purposely varying operational parameters to determine their effect on product quality attributes and process performance. PC normally starts in late Phase II or early Phase III.
The purposes of PC includes identification of critical process parameters (CPP) that impact critical quality attribute (CQA), determination of manufacturing operating ranges and acceptance criteria, and determination of interactions between process parameters and critical quality attributes.
Process validation (PV) refers to evaluating the process design to determine if it is capable of reproducible commercial manufacture, including design of the facility and qualification of the equipment and utilities & process performance qualification (PPQ).
The purposes of PV includes validation of process, identification of critical process parameters based on risk assessment, and Implementation of the proven control strategy .
Service Highlights
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Multidimensional Process Optimization
Enriched optimization experience with regulatory support for process changes
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Fast Process Characterization
PC completion in 4 months
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Global Quality System
100+ client audits globally
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Prompt Reply
E-mail response within one business day
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Favorable Unit Cost
2,000 L GMP manufacturing price <$100/g*
*DS unit price (a. Fed batch process in 2000L SUB, b. 7g/L, 70% yield, c. annual batch number≥ 20 batches), including FFS and material cost
Work Contents of Process Optimization
| Strategy | Time* | Cost Reduction |
|---|---|---|
| Substitution of high-cost material | 2 months | 10 – 20% |
| High density inoculation | 6 months | Up to 40% |
| Process parameters optimization | 6 months | Up to 40% |
| Clone change | 8 – 12 months | Up to 60% |
*When employing multiple process optimization strategies, several tasks are carried out in parallel, and the entire process optimization cycle is determined by the duration of the most time-consuming strategy.
Work Contents of Fast Process Characterization
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CPP/CQA Evaluation
- Data collection & risk assessment
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Upstream Process Characterization
- Scale-down model establishment and validation
- Design of experiments
- Worst-case condition confirmation
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Downstream Process Characterization
- Scale-down model establishment and validation
- Design of experiments
- Worst-case condition confirmation
ProBio offers 2 process characterization (PC) services: fast PC and standard PC, to meet the needs of various projects. Fast PC is appropriate for products with accelerated approval pathways or monoclonal/symmetrical bispecific antibodies in liquid formulation. Standard PC is appropriate for all products, particularly complex molecules such as proteins and asymmetric bispecific antibodies.
Works Contents of Process Validation
PPQ Relevant Validations
- 3 batches of commercial scale manufacturing
- DS/DP stability study
- Purification intermediate stability validation
- Validation of mixing effectiveness
- DS/DP transportation validation
- PPQ DS characterization
- EOPC/UPB/VC test
- Process related impurities study
Other Validations
- Cleaning validation
- Media/buffer shelf-life validation
- UF membrane/resin lifespan validation
- Post-sterilization material retention time validation
- Consumable/packaging material related validation
- Cell bank related validation
- HCP coverage test
- In-use compatibility study
