GMP Requirements for Bioassay Validation
Bioassays Definitions
A bioassay is a test procedure used to determine the biological activity and to verify the mode of action of a protein or advanced therapy medicinal product (ATMP), by using a biological substrate e.g. living cells, or target receptors.
About Bioassays
Due to the complexity of biopharmaceuticals and their complex manufacturing process, bioassays are one of the most challenging parts of your quality control program. Heterogeneity is a key issue and impact the product quality in terms of batch-to-batch consistency.
Given these circumstances the evaluation of the biological activity belongs to one of the most challenging analyses within your bioassay procedures in terms of batch release and for commercial distribution of drug products.
Types of Bioassays
Cell-based Assays
Cell-based bioassay using cell lines, derived from tumors, immortalized cells or created by cell line engineering, to study the cellular response to the protein of interest. The cellular response depends on the mode of action of the desired protein.
Such responses include cell proliferation assays, apoptosis assays, or antibody-dependent cellular cytotoxicity assays (ADCC).
Potency Assays (Relative Potency)
The objective of potency assays is the determination of the relative potency, in which the biological activity of an analyte is analyzed by comparing the dose-response curve to the activity of a reference standard material.
ADCC Assays
Antibody-dependent cellular cytotoxicity assays
Assays for Drug Screening and Target Validation
Drug receptor interactions play an important role like drug delivery, tumor metastasis, and immune response. Assay development has become a powerful tool for drug screening and target validation studies as part of drug discovery and drug development.
Florescence Activated Cell Sorting (FACS)
Florescence activated cell sorting (FACS) and flow cytometry analysis are widely used for cell-based assays, potency or ADCC assays, to determine the biological activity and the mode of action of biological products or ATMPs.
GMP Compliance
Compliance with Good Manufacturing Practice (GMP) states that medicinal products must be manufactured under specified quality standards. Compliance with GMP is a mandatory regulatory GMP requirement for all medicinal products to obtain the manufacturing authorization.
Compliance with GMP aims to ensure that the product, the manufacturing process, and the manufacturing facilities meet applicable requirements to ensure the continued safety, purity and potency of the product.
A potency assay is required due to the complexity and heterogeneity of biologicals and biotechnological-derived medicinal products.
FDA and CBER
- Potency Tests for Cellular and Gene Therapy Products
- Cell and Gene Therapy Products
- Cell and Gene Therapy Guidance
United States Pharmacopeia (USP)
- USP <1032>: Design and Development of Biological Assays
- USP <1033>: Biological Assay Validation
- USP <1034>: Analysis of Biological Assays
- USP <111> : Design and Analysis of Biological Assays