FDA Definitions
Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.
About Process Validation
Process validation applies to drugs such as biological or biotechnological-derived medicinal products and drug substances (active pharmaceutical ingredients). The strategy to process validation should be laid down in a process validation plan.
Specifications, validation parameters and the associated acceptance criteria should be specified and justified based on the evaluation of the risk assessment in which critical quality attributes are linked to critical process parameters.
Current scientific knowledge and the accumulated data collected during drug and preclinical development, quality control and manufacturing processes should be included to the validation studies.
Objective of Process Validation
Process validation verifies that the manufacturing process is under control and operates within defined specifications, validation parameters and the associated acceptance criteria. Process validation contributes to confidence in product and process quality and ensures compliance with GMP to receive the manufacturing authorization.
Audits and Inspections
Regulatory authorities have the authority and responsibility to inspect and evaluate process validation. The manufacturer is in charge to perform and implement process validation. The European Medicines Agency (EMA) represents a Guideline on Process Validation.
Bioprocessing
Currently biopharmaceuticals and immunotherapies are being developed to fight against cancer, autoimmune disorders, infectious diseases and several other medical conditions.
Biopharmaceuticals 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 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.
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 characteristics.
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
Product Characterization of Biotechnological Products
The objective of product characterization is to contribute to a better knowledge of product-biology and structure-function relationships. The biological product is characterized by its biological, physico- and immunochemical properties, and by purity and impurities. The assessment of the biological properties, however, plays a major role in establishing a characterization profile. In defining the critical product quality, these properties add quality characteristics and support product safety. Analyses are mandatory regulatory GMP requirements for release and marketing authorization according to ICH Q6B.
Specifications of Biotechnological Products
Considering the complexity of biopharmaceuticals and that full product characterization is rather difficult to achieve specifications are part of quality control. Specifications are critical quality characteristics proposed and justified by the manufacturer. The objective of specifications is to ensure product and process quality in terms of consistency and compliance to good manufacturing practices (GMP). Specifications include data of product characterization studies, drug development and preclinical studies, clinical data and analytical procedures.
Key Benefits
We offer expertise in upstream and downstream operations, product and process specific. We contribute to critical in-process controls, validation parameters and their respective acceptance criteria, tests used and the extent of testing.