With the growing number of biological products advancing to the market, the demand for thorough characterization has been increasing. Unlike traditional small molecule drugs, biological products are inherently heterogeneous; thus small differences in the molecular structure or low levels of impurities can dramatically change efficacy, immunogenicity or toxicity. Development activities related to biological products are covered by ICH guidelines. Of particular importance are the guidelines relating to quality [1,2], specifications , stability [4,5], comparability [6,7,8], and method validation [9,10,11].
The quality guidance directs inclusion of analytical methods for control of API as well as adventitious agents. It also specifies that the physicochemical and biological properties of biomolecules be defined, especially as they relate to manufacturing. Acceptance criteria are also recommended.
The guidance on specifications indicates that identity test(s) should be highly specific for the drug substance or drug product and should be based on unique aspects of its molecular structure and/or other specific properties. More than one test (physicochemical, biological, and/or immunochemical) may be necessary to establish identity. Physicochemical characterization generally includes determination of the composition, physical properties, and primary structure of the desired biological product. In some cases, information regarding higher-order structure may be obtained by appropriate physicochemical methodologies. The purity and impurities of biological products are usually estimated by a combination of methods (e.g., HPLC, UPLC, and electrophoresis).
Stability tests are needed, especially for protein and peptide drugs due to their structural complexity and instability. The most common chemical degradation mechanisms for peptides and proteins are deamidation and oxidation. The guidance on stability of peptides and proteins recommends tests of both chemical stability and biological activity.
- Guidance for Industry. M4Q: The CTD — Quality. ICH, August 2001.
- Guidance for Industry: QUALITY CONSIDERATIONS IN DEMONSTRATING BIOSIMILARITY OF A THERAPEUTIC PROTEIN PRODUCT TO A REFERENCE PRODUCT. Biosimilarity. April 2015.
- SPECIFICATIONS: TEST PROCEDURES AND ACCEPTANCE CRITERIA FOR BIOTECHNOLOGICAL/BIOLOGICAL PRODUCTS. ICH Harmonised Tripartite Guideline. Q6B, Current Step 4 version, March 1999.
- STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS. ICH Q1A(R2), revision 2, November 2003.
- QUALITY OF BIOTECHNOLOGICAL PRODUCTS: STABILITY TESTING OF BIOTECHNOLOGICAL/BIOLOGICAL PRODUCTS. ICH Harmonised Tripartite Guideline. Q5C, July 1996.
- COMPARABILITY OF BIOTECHNOLOGICAL/BIOLOGICAL PRODUCTS SUBJECT TO CHANGES IN THEIR MANUFACTURING PROCESS. ICH Harmonised Tripartite Guideline. Q5E, June 2005.
- Guidance for Industry: SCIENTIFIC CONSIDERATIONS IN DEMONSTRATING BIOSIMILARITY TO A REFERENCE PRODUCT. Biosimilarity. April 2015.
- Guidance for Industry (Draft Guidance): COMPARABILITY PROTOCOLS FOR HUMAN DRUGS AND BIOLOGICS:CHEMISTRY, MANUFACTURING, AND CONTROLS INFORMATION. PHARMACEUTICAL QUALITY/CMC. Revision 1. April 2016.
- VALIDATION OF ANALYTICAL PROCEDURES: TEXT AND METHODOLOGY. ICH Harmonised Tripartite Guideline. Q2(R1), Current Step 4 version, November 2005.
- Guidance for Industry: BIOANALYTICAL METHOD VALIDATION. Biotherapeutics. Revision 1, September 2013.
- Guidance for Industry: ANALYTICAL PROCEDURES AND METHODS VALIDATION FOR DRUGS AND BIOLOGICS. Pharmaceutical Quality/CMC. July 2015.