Therapeutic mAbs & Proteins

Cygnus Technologies products are used in the development and manufacturing of all types of biological drugs. These include monoclonal antibodies (mAbs) and recombinant proteins.

The FDA began approving therapeutic monoclonal antibodies (mAbs) in 1986. Since then 79 therapeutic mAbs have been approved by FDA and are currently on the market [1].  Around the world, at least 570 therapeutic mAbs have been studied in clinical trials by commercial companies [2]. Uses for monoclonal antibodies include: cancer, rheumatoid arthritis, multiple sclerosis, cardiovascular disease, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, psoriasis, transplant rejection, and other conditions [1].

The majority of mAbs are produced by a method using cultured cells such as CHO cells. Alternative eukaryotic cell lines, such as yeast, are also used for mAb production.

When biological drugs are produced using recombinant technology, the result is a mixture of the desired drug and unwanted impurities. Host cell proteins (HCPs) constitute a major group of process-related impurities for biologic drugs produced using cell culture technology, as they are naturally expressed with the recombinant drug product. When present in the administered product even at low levels, HCPs can induce an undesired immune response, interfere with drug efficacy, or affect drug stability. Thus, HCPs remain a critical quality attribute (CQA) for bioprocess development and must be adequately removed during the downstream purification process. Other process-related impurities that must be removed and quantified to ensure biotherapeutic safety are purification resin leachates, such as Protein A, growth media additives and host cell DNA [3,4].

Companies that make biological drugs must report the levels of HCPs in their products. Regulators require that HCP level in biological drugs is below 100 ppm. Ideally, companies should continuously monitor levels of HCPs in their drugs. This helps ensure their purification methods are consistent.

Cygnus encourages companies to aim to identify and quantify HCPs in their products as accurately as possible. Immunoassays such as ELISA (enzyme-linked immunosorbent assay) is the gold standard method for product monitoring and release testing for HCPs. Cygnus offers many sensitive and specific ELISAs used to determine the presence of HCPs and other impurities in biological drug products.

Other process-related impurities include purification resin leachates such as Protein A or Protein L, other affinity ligands, growth media additives, and host cell DNA. 

[1] The Antibody Society. In: Approved antibodies. Jun 27, 2019 

[2] Kaplon H, Reichert JM. Antibodies to watch in 2019. MAbs. 2019;11:219–38.

[3] ICH Q11 “Development and Manufacture of Drug Substances (Chemical Entities Biotechnological/Biological Entities)”, 2012

[4] ICH Q6B “Test Procedures and Acceptance Criteria for Biotechnological/Biological Products”, 1999