PROCESS VALIDATION

We apply expertise and international regulations to your validation studies

Objective of Process Validation

Since end-product testing is of limited utility, the manufacturing process is critical regarding the complicity of biotechnology derived products.

The objective of process validation is to ensure product quality, in terms of safety and efficacy, and that products are being consistently produced and controlled to the quality standard appropriate to their intended use and as required by regulatory authorities for GMP release (21 CFR 211.100 and 21 CFR 211.110).

Bioprocessing

Currently biopharmaceuticals are being developed to fight against cancer, autoimmune disorders, infectious diseases and several other medical conditions.

Biopharmaceuticals or biosimilars are proteins, mainly derived from living organisms or systems by using recombinant DNA technology. Recombinant proteins are then produced by cell expression systems.

The basic science behind all biopharmaceuticals is the use of recombinant DNA technology. The cell consists of cell membrane, nucleus and cytoplasm. The nucleus contains the genic information in form of the so-called DNA.

Within the nucleus, the DNA replication, transcription, and RNA processing takes place. The translation, the final stage of gene expression is localized to the cytoplasm.

Genes, which are short DNA segments, code for proteins or have other regulatory cell functions. The cell activates only those genes required to produce specific proteins.

The interactions between the proteins control all the processes within an organism. Nowadays, it is possible to identify the exact genetic sequences that control the production of these proteins and pinpoint the exact functions of specific genes.

These genes are then isolated and duplicated on a large scale to produce the desired protein, which is then extracted, purified and used for the production of the biopharmaceutical item, as they have come to be known.

Regulation and control

Proteins can be 100 to 1000 times larger than synthetic small molecules.

Due to their large size and complex structure biopharmaceutical production entails complex manufacturing processes. They are highly sensitive to modification during and after production.

Therefore, biopharmaceuticals are different from chemically synthesized molecules in molecular size, three-dimensional shape, and process specific impurities. The formulation of the final product is distinct in terms of excipients, bioactivity and stability.

The manufacturing process can affect many parameters, including amino-acid structure, side chains, post-translational processing and tertiary and quaternary structure. Changes could have a profound effect on protein function.

Inconsistencies during manufacturing can lead to inter-batch variations and inconsistency of efficacy. Regarding the manufacture of  biopharmaceuticals, the control of quality, safety and efficacy especially in terms of “batch to batch” consistency is more complex and sophisticated.

Bioprocess Engineering

The main objective of bioprocess engineering is to design optimal cell culture conditions and bioreactor process parameters to achieve high yields of desired protein with high quality attributes.

Recombinant products are manufactured in mammalian cell cultures, yeast cells or bacteria. Proliferation-controlled production processes consist of an expansion phase followed by a production phase. To optimize cultivation several method strategies have been developed.

 

For effective bioprocessing advances have been made in the various area of bioprocessing:

 

  • Process Analytical Technologies (PAT)
  • Quality by Design
  • Cell line engineering
  • Recombinant DNA technology

Our Expertise

Expertise in upstream and downstream operations will be offered product and process specific. Through serval strategies, different process-dependent parameters can be evaluated and optimized. Critical in-process controls, tests used and the extent of testing are to be identified.

Also, strong ability in identifying critical product attributes and linking them to critical process parameters, defining in-process specifications, establishing a sampling plan as well as acceptance criteria, will be applied to your validation studies.

On-site Services

  • Validating process operations
  • Contributing to upstream and downstream operations
  • Developing cell line engineering from research to GMP manufactoring
  • Applying microbiology and hygiene concepts
  • Applying Annex 1
  • Validating aseptic processes

Your Benefits:

  • Contributing to cGMP compliant quality standards
  • Contributing to aseptic processing of APIs
  • Proven expertise with bioprocessing of Immunotherapeutics
  • Supporting product specifications
  • Supporting marketing and clinical trial authorization

Definition of Process Validation

Process Validation is the documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or API meeting its predetermined specifications and quality attributes (ICH Q7).