The Eight-Points Model of Analytical Development
The U.S. FDA current Good Manufacturing Procedures for drugs (CGMP, Title 21 of the Code of Federal Regulations, Parts 210 and 211) states that all pharmaceutical products must be analyzed for “identity, strength, quality, and purity.”
Many analytical development scientists in biotechnology consider these precepts too vague to serve as effective guidelines for biopharmaceutical analysis. When one of the authors (TJP) was working in the biopharmaceutical industry, he developed the following “eight points” model to guide analytical development for any new macromolecule he and his staff encountered.
Several successful regulatory filings attest to the adequacy of the model.
According to the model, assays should be developed and validated to address each of the following points:
CE can be used directly for all the points except, perhaps, numbers 4 and 8, which are usually addressed using biological and microbiological assays (supplemental CE activity assays may, however, sometimes be validated against biological assays).
Use of Capillary Electrophoresis to Assess the Identity of Proteins and Peptides
The purpose of an identity assay is to provide scientific proof that the contents of a container correspond, qualitatively, to what is claimed on that container’s label. Until the identity is established, all other analytical concerns are secondary. Because of this central role, proof of identity is usually approached by a summation of evidence from several assays. In addition, using multiple structural determination methods ensures that products are thoroughly characterized as well as adequately identified. For proteins, commonly used identity assays include specific activity, amino acid composition and sequence, and assessment of such physicochemical parameters as molecular weight and isoelectric point.
A list of assays commonly used to establish the identity of a biopharmaceutical protein is mentioned below.
There are several CE techniques that readily lend themselves to providing evidence of a protein’s identity. These include:…