cGMP Process Development

Overview

Apart from process equipment and turnkey facilities, we offer process development services. These are to support clients' specific needs and requirements for cell culture process development and optimization.

Our capabilities includes developmental services from Upstream to downstream bioprocessing, analytical testing via process analytical technology (PAT) as well as chemistry, manufacturing, and controls (CMC) regulatory approval of your products.

With our in-depth understanding of the Asian market, we adopt a customisable approach in delivering sustainable risk-adjusted returns to our clients.

Upstream Processing Development Services

We are the industry’s leaders and expert in Upstream Processing (USP) development using our Tide Motion® bioreactors.

We support an integrated approach to service delivery to increase viral expression titer, multiplicity of infection (MOI), and increase cell viability at high-density cultures.

CelCradle X®
Semi-Automated
Harvester
(CCX-SAH)

TideXcell®
Harvesting System
(TXLHS)

Closed harvesting system for:
  • Biomass Expansion
  • Autologous/Allogeneic Cell Therapy
  • Intracellular Virus

TideXcell™
3,500 up to 5,000 L

Tide 2mm/s: 3,000 - 5,000 L (st. tanks)
Tide 6mm/s: 55,000 L

Large st. tank,scale for secreted virus production, viral vectors, cellular agriculture (optional edible scaffolds), or biosimilars/biobetters

TideXcell™
300 L

TideXcell™
100 L

TideXcell™
20 L

TideXcell™
2 L

CelCradle X®

with Semi-automated Harvester Esco standalone bioreactor. Single Bottle, Optional Docking to Isolator.

CelCradle® + CelShaker™

An ESCO standalone bioreactor using single bottle, equipped with semi-automated harvester.
optional docking to Isolator available as per request.

CelXrocker™

A laboratory Tide Motion shaker for process optimization of adherent cell culture.
~Seed from 20,000-60,000 cells/carrier

CHO library suits the expression of recombinant proteins, monoclonal antibodies, and biosimilars implemented with our proprietary bioreactors in a small footprint

Bioprocess optimization using Design-of-Experiments methodology in optimizing cultivations and unit operations

Animal component free media adapted to USP processes and lowering impurities

Robust proprietary technology platform that is scalable up to 5,000 liters capacity

Customizable and reprogrammable fed-batch, continuous, and perfusion mode(s) in hypoxia and/or anaerobic conditions

Downstream Processing Development Services

We integrate a Quality by Design (QbD) approach (based on ICH Q8-11), which is a global regulatory initiative designed to improve pharmaceutical development through the proactive blueprint of pharmaceutical manufacturing processes and controls to continually provide the intended product performance.

We offer a development platform in a modular approach, in which the customer can either choose a specific module or request for the entire process development package from bench to scale.

Process Development
  • Initial development with screening, selection and combination of downstream processing techniques to achieve the desired quality using a systematic development pathway within acceptable timelines
  • Identifying Quality attributes and Criticality assessment
Process Optimization

Optimization of the developed process aiming at:

  • Reducing process waste high recoveries
  • Establishing optimal conditions for the process variables using statistical tools to design and analyze data (DoE approach)
Process Scale up

Optimization of the developed process aiming at:

  • Process platform developed at lab scale will be scaled up to pilot scale
  • Demonstration of Process reproducibility and Consistency assessment
Process Characterization and Design Space Establishment
  • Comprises risk assessments for the identification of potential Critical Process Parameters (pCPPs), statistically designed experimental studies (DoE) along with studies evaluating the correlation of unit operations
  • Outcome of the studies is the categorization of process parameters in conformity with their criticality i.e. Critical Process Parameters and Non-Critical Process Parameters and the definition of appropriate acceptable ranges of operation
  • The process and product knowledge gained in these studies can lead to the approval of a Design Space
  • Additionally, the information gained in these studies are used to define the ‘impact’ which the manufacturing process can have on the variability of the CQAs, which is used to define the testing and monitoring strategy.
Downstream Process Train Design

On completion of the development activity, our bioengineers will propose the most feasible downstream processing systems tailored for your project requirement.

Note:

  • DSP development is not limiting to single-use concentrators or chromatography or microfluidics-size exclusion methods.
  • We advise clients to seek our advice and value-added services in conjunction to USP development.
Access to bioprocess expertise with dedicated scientist(s)
optimize extensive

Filtration Services

Applications where the harvested cells are the final product, tangential flow filtration (TFF) combined with a clarification step will consolidate the final downstream platform.

  1. Applications where the final product are biological, such as:
    • Extracellular Vesicles (EVs) / Exosomes
    • Viruses as Intermediate Products (CAR-T)
    • Protein Purification
  2. Applications where the final product are synthetic nanoparticles such as:
    • Biocompatible Polymer Particles
    • Liposomes
    • Polysaccharides

  • Number cells/ml: Recovery yields of as much as 87% depending on the product-of interest
  • Nanoparticles/ml: Recovery yields that enable the production of nanoparticles in concentrations required to meet biological outcomes in clinical studies
  • Identity, Potency, Morphology: Cell viability and proliferation as much as 98%
  • Purity: Removal of protein impurities and microcarriers to meet quality attributes for final product

Preparative Chromatography

  • Affinity Chromatography (e.g. antibody, specific group, tagged group)
  • Ion Exchange Chromatography
  • Multimodal Column Chromatography
  • Hydrophobic Interaction Chromatography
  • Reverse Phase Chromatography
  • Size Exclusion Chromatography

  • Optimization of process variables using Design of Experiment (DoE) analysis
  • Process development for the production of biologics (e.g. viral vaccines, recombinant proteins, viruses, VLPs, antibodies)
  • Scale-up and scale down of the bioprocessing platform from laboratory to industrial scale
  • Access to bioprocess expertise with dedicated scientist(s)
optimize extensive

cGMP COMPLIANCE

  • Our scientists are trained on the cGMP guidelines for industry issued by FDA.
  • Data integrity forms an important component ensuring completeness, consistency, and accuracy of data generated in our laboratory.
  • All the instruments used are 21 CFR Part 11 compliant.

DOCUMENTATION

Esco offers complete documentation of the development services including:

  • Protocols
    • Process Protocols
    • Scale up protocol
    • Process Characterization Protocol
    • Technology Transfer document
  • Reports
    • Development summary report
    • Scale up report
    • Risk assessment report
    • Process characterization report