Process Validation Studies for Biologicals
FDA’s Definitions on Process Validation
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.
General Principles and Practices
Why Process Validation Studies?
- Process validation studies verify that the manufacturing process is under control and operates within defined specifications. Process validation contributes to confidence in product and process quality and ensures compliance with GMP to receive the manufacturing authorization.
- Validation studies apply to drugs, biologicals, drug substances, or active pharmaceutical ingredients. The strategy to process validation should be laid down in a process validation plan.
- 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.
Product Characterization
- 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.
- However, the assessment of biological properties plays a major role in establishing a characterization profile. When defining critical product quality, these properties add quality characteristics and support product safety.
- Product characterization analysis are mandatory GMP requirements for release and marketing authorization according to ICH Q6B.
Risk Assessment and Lifecycle Approach
- The risk assessment identifies and provides scientific knowledge about potential quality risks. Quality risks associated with biotechnological-derived products are highly dependent on the manufacturing process, the protein itself and the manufacturing facility and environment.
- The assessment shall follow the impact of potential risks in terms of critical process parameters (CPPs) and critical quality attributes (CQAs) and applies over the product and process lifecycle.
About Bioprocessing of Biological Products
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.
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.
Summary
- Specifications, validation parameters and the acceptance criteria represent the core element of your validation studies.
- Specifications must be established before process validation is performed.
- When establishing specifications, expertise from drug development, drug manufacturing and quality control should be incorporated into validation and qualification processes.
Hands-on Experience
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.
