Antibody Production

In recent years, the increasing number of therapeutic monoclonal antibody (mAb) candidates under preclinical and clinical development have required new flexible, efficient, and economic opportunities for GMP production of therapeutic antibody candidates. Small-scale batch production of test samples for late preclinical GLP animal studies or for phase-1 and phase-2 clinical studies is often not appropriate for large-scale manufacturing facilities in the industry. The Fraunhofer IZI, founded in 2005, investigates and develops solutions to such specific problems at the interfaces of medicine, life sciences and engineering.

Since January 2017 the newly constructed GMP antibody production facility of the department of Therapy Validation has been completely qualified. Our facility has a size of 180 m² and involves all clean room classes from D to A. The use of single-use equipment and materials enables an easy adaption to new process requirements. The GMP facility can be used for different contract manufacturing processes for preclinical and clinical (Phase 1/2) test samples as well as for process or instrument validation projects under consideration of special customer requests. The standard equipment can be easily broadened for new products.

In summary the main advantages are:

  • high flexibility
  • easy switch to different products
  • fast implementation of technology changes
  • customized production
  • ideal batch size for preclinical and early clinical trials
  • possibility to obtain ready-to-use GMP-compliant products by the integrated sample filling

 

Future projects could include:

  • transferring promising biopharmaceutical candidate from research to clinical development
  • designing a user-specific process with single-use materials
  • GMP-compliant production of e.g. human monoclonal antibodies in 200-L scale

Certificate

 

GMP antibody manufacturing – Our service for your antibody

Production of a monoclonal antibody for therapeutic use for the prevention of Graft-versus-Host-Disease (GvHD)

The aim of the project is the GMP-compliant production of a monoclonal antibody for the clinical trial for the prevention of Graft-versus-Host-Disease (GvHD) in allogeneic stem cell transplantation.

The project includes the following work packages:

  • Production of the master cell bank, its characterization and quality control
  • Process development of the upstream and downstream process
  • Formulation Development
  • Production of GMP-compliant batches for the preclinical and clinical trial
  • Establishment and validation of the approval-relevant analysis for quality control including in-process controls, as well as structural analyses and stability investigations including stress tests and long-term investigations
  • Contribution to the Investigational Medicinal Product Dossier (IMPD)

  • Single-use concept up to 200 L batch volumes using different scaled bioreactor systems (stirred tank reactor, RM bioreactor)
  • Control, monitoring and data acquisition of processes via a SCADA software (BioPAT® MFCS/win)
  • Production and characterization of cell banks (MCB / WCB)
  • Process development and optimization including scale-up in the upstream and downstream areas
  • Manufacturing of preclinical batches and clinical investigational medicinal products
  • Aseptic filling in glass vials (formats 5, 10, 20 ml)
  • Validation of aseptic filling (media fill) according to the requirements of Annex 1, EU GMP Guidelines
  • Evidence of virus safety according to EMEA / CHMP / BWP / 398498/2005
  • Proof of the integrity of sterile filters according to Annex 1 EU GMP Guidelines

  • Development and establishment of analytical methods
  • Validation of release-related methods
  • Development and validation of potency assays (e.g. ELISA)
  • Determination of visible particles according to Ph. Eur. 2.9.20
  • Determination of the tightness of rubber stoppers for containers according to Ph. Eur., Chapter 3.2.9 (self-sealing)
  • Spectrophotometric quantification and evaluation of the purity of proteins, DNA / RNA
  • Measurement of protein stability and aggregation (Prometheus NT.48, NanoTemper Technologies GmbH)
  • External order analysis with qualified and audited partner laboratories

  • Modular clean room facility approx. 180 m² clean room area, classified according to EU GMP Guidelines, Annex 1 (clean room classes A, B, C, D)
  • Permanent monitoring of the clean room system via a pharmaceutical monitoring system
  • Production rooms allow the processing of various process steps (upstream / downstream / bulk / bottling) due to the different cleanroom classes
     

Qualified equipment for production

  • CO2 incubators with integrated rotary shaker
  • Positive pressure isolator
  • Bioreactors BIOSTAT® RM20|50 and BIOSTAT® STR200
  • Various liquid handling devices for media production, upstream and downstream:
    • FlexAct® COM
    • BioWelder® Total Containment for sterile tube welding
    • BioSealer® for sterile tubing separation
    • Various pumps (pinch, diaphragm pumps)
  • Cleanroom-class transfer ports Biosafe® 110 Monolever Port
  • Chromatography unit ÄKTA™ pilot
  • Ultra- / Diafiltration unit SARTOFLOW® Advanced
  • Semiautomatic filling line (formats: 5 ml, 10 ml, 20 ml)
     

Qualified equipment for quality control

  • NucleoCounter® NC-200 ™ for automatic cell count and viability determination
  • ELISA reader Tecan Infinite M1000 PRO
  • NanoDrop 2000
  • Test device according to the specifications of Ph. Eur. 2.9.20 for the test for particle contamination (visible particles)
  • Refrigerators and freezers as well as incubators with temperature recording and monitoring via a monitoring system
  • Leak tester according to Ph. Eur. chapter 3.2.9

  • Hoffmann M. Erfahrungen aus dem Aufbau und der Nutzung einer SU-basierten Smale-Scale-Produktionsanlage für klinische Prüfpräparate. 10. Konferenz Single-Use Disposables "Einsatz von Single-Use Equipment in der Biopharma- und Sterilproduktion", December 5, 2018, Heidelberg.

 

 

GMP antibody manufacturing – Our service for your antibody

 

Fraunhofer IZI Services for Antibodies

Fraunhofer IZI provides GMP Antibody Manufacturing Services with Sartorius Stedim Biotech single-use technologies