GMP Compliance Services and Expertise – Biological and ATMP manufacturing
“The holder of a manufacturing authorization must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the marketing authorization (MA) and do not place patients at risk due to inadequate safety, quality or efficacy”.(Quote EudraLex Vol. 4)
Manufacturing Authorization
Manufacturer of medicines for human or veterinary use, are subject to regulatory GMP requirements with regulatory authorities such as the U.S. Food & Drug Administration (FDA) or European Medicines Agency (EMA). They are legally obliged to comply with GMP.
Manufacturing, distribution and marketing require a marketing authorization (MA). The “Manufacturing Authorization Holder” (MAH) is responsible for the performance of a biotechnological-derived medicinal product.
About GMP Compliance
Compliance with Good Manufacturing Practice (GMP) states that medicinal products must be manufactured under specified quality standards to ensure the product’s safety, efficacy and quality.
Compliance with GMP is mandatory for all medicinal products to receive the manufacturing authorization and applies over the product life cycle.
FDA statutory and regulatory GMP requirements
Federal Food, Drug, and Cosmetic Act (FDC Act)
The regulatory basis for Good Manufacturing Practice (GMP) is the Federal Food, Drug, and Cosmetic Act (FDC Act). The GMP requirements are codified by the FDA of the Code of Federal Regulations (CFR) Title 21 Food and Drugs parts 210 and 211:
CFR Title 21 Part 211 – Current good manufacturing practice for finished pharmaceuticals
GMP Compliance for Biologicals and Medicinal Products
Why do we need GMP regulation?
Medicinal products are intended to cure, relieve or prevent diseases, but they also have the potential to be unsafe or harmful. Compliance with GMP verifies that the product, the manufacturing process, the manufacturing facilities and the manufacturing environment (e.g. documentation, sanitation, personal, etc.) meet applicable requirements to ensure the continued safety, purity and potency over the product’s life cycle.
What are biopharmaceuticals?
Currently biopharmaceuticals are being developed to fight against cancer, autoimmune disorders, infectious diseases and several other medical conditions. Biopharmaceuticals are (mostly) proteins, mainly derived from living systems such as microorganism, animal cell, or plant cell by using recombinant DNA technology.
Why are biopharmaceuticals unique and different?
Proteins can be 100 to 1000 times larger than chemically synthetized 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.
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.
Therefore, biopharmaceuticals are different from synthetic small molecules in terms of molecular size, three-dimensional shape, and process specific impurities. The formulation of the final product is distinct in terms of excipients, bioactivity and stability.
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 demanding.
The responsibility of the regulatory authorities, as part of their review, is to inspect the manufacturing process and the manufacturer’s control strategy for these product variations.
GMP Regulations for Biological Products
Product Safety
- Microbial agents
- Tumorgenicity
- Pyrogenicity
Product Characterization
- Identity
- Purity
- Impurities
- Potency
- Quantity
Manufacturing
- Process Control
- Validation Program
- Qualification Program
- Quality Control Tracking
- Quality Assurance Tracking
We are contributing to regulatory requirements for GMP release of samples according to customer’s needs.
License Application
Biologics License Applications (BLA)
Biological products subject to the PHS Act are licensed under the section 351 of the PHS Act. The regulatory requirement for the BLA is defined in Code of Federal Regulations CFR Title 21 Part 601 Licensing.
The requirements are that the product, the manufacturing process, and the manufacturing facilities meet applicable quality standards to ensure the continued safety, purity and potency of the product.
A potency assay is required due to the complexity and heterogeneity of biotechnological-derived medicinal products.
