During the development of a drug product CMC tests are established and specifications determined for the manufactured drug product and drug substance. The drug product and drug substance must be characterized, process controls must be established and stability must be determined. Specifications for purity and potency are requirements. Raw materials using in the manufacturing process will also need similar specifications. For large molecules, MSD can be used for many of these CMC requirements.
Areas in which MSD can be used for release testing include:
Potency
Many different study designs could be established to determine the potency of a biological product. Potency assays could be a simple binding assays or a more complicated such as a custom cell based assay. Potency assays must be able to quantitate the biological activity of all functional domains of the protein therapeutic. MSD can aid in many study designs for potency testing.
Identity
The identity of the drug product must be able to be tested. Many different analytical methods can be used to prove the identity of drug product and drug substance. MSD can be one of the many tools used to establish the identity of drug product or drug substance.
Host Cell Protein Content
During production host cell proteins can contaminate the product and specifications for host cell proteins must be established. Each batch of product should be tested for host cell proteins which can be done using MSD.
Isotyping
Antibody therapeutics should have their class and subclass determined. There are five main isotypes of antibodies, IgM, IgD, IgG, IgE and IgA. These five isotypes all have very different properties and functions. Monoclonal antibodies of the wrong isotype would behave very differently and therefore could have detrimental effects on a patient if the product is allowed to enter the market. MSD is one of several analytical tools that can be used to determine the isotype of antibody therapeutics.
Protein A
Protein A binds to the Fc region of antibodies and therefore is commonly used for purifying antibody therapeutics from other host cell proteins. Protein A affinity columns are an excellent way to purify mAbs but Protein A contaminants have been shown to cause harmful affects to both animals and humans. MSD can be used to identify and quantitate Protein A contaminants.
MSD Development at PBL
Pacific BioLabs has performed CMC method development and validation for biopharmaceuticals for over a decade. Contact PBL for all your analytical and bioanalytical method development and validation work, including MSD.