Process Validation Services
Definition “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).
Objective of process validation
Because end-product testing is of limited utility, the manufacturing process is discerning regarding the complicity of biotechnolocial-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 genetic information in form of the so-called DNA. Proteins are made within the cytoplasm. So how do we get from the nucleus to the cytoplasm? The process is called the “protein biosynthesis”. It starts within the nucleus with the transcription of DNA into mRNA. The mRNA now serves as a template for the protein synthesis and moves to the cytoplasm. Here are the ribosomes, where the final protein is synthesized.
Genes, containing the genetic information in form of DNA sequences code for proteins or have other regulatory cell functions. The cell activates only those genes, required to produce specific proteins. Nowadays, it is possible to identify the genetic sequences that control the production of these proteins. 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 of biological products
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 produced by living organism (e.g. 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 process strategies have been developed.
For effective bioprocessing advances have been made in the various area of bioprocessing:
- Process Analytical Technologies (PAT)
- Quality by Design (QbD)
- Cell line engineering
- Recombinant DNA technology
