Qualitätssicherung synthetischer Peptidwirkstoffe Empfehlungen der Deutschen Pharmazeutischen Gesellschaft (DPhG) Peptides and proteins in comparison to other groups of active ingredients show peculiarities with respect to their structure elements, their structure principle and their methods of manufacture. The resulting particular chemical and physicochemical properties require special measures of quality assurance as well as a product specific consideration in the establishment of standards for single test criteria.
The recommendations on hand drawn up by the section Drug Control/Pharmaceutical Analytics of the German Pharmaceutical Society (DPhG) cosponsered by the Special Interest Group âQuality of Pharmaceuticalsâ of the International Pharmaceutical Federation (FIP) exclusively concern synthetic peptide drugs and form a guidance for their quality assurance in drug development as well as for the evaluation of quality documents in drug registration. Simultaneously they may be regarded as a scientific base for the creation of regulatory standards. The recommendation extend to in process controls during the peptide synthesis, the quality control of its ingredients and synthetic aids, to the structure elucidation as well as to the chemical and physico-chemical characterisation and to the establishment of specification for the routine control of peptide drugs with consideration of toxicological aspects for definition of limits. Peculiarities in the quality assurance within the peptide synthesis in comparison to other active ingredients result from the high purity claim for the used amino acids and their derivates, respectively, particularly with regard to their chiral purity, from special synthesis aids (e.g. characterisation of polymers for the solid phase synthesis) as well as from the claim for the characterisation of key intermediates. The varied possibilities of by- and degradation reactions during the manufacture and storage of peptides and their dosage forms as epimerisation, Ã -isomerisation, hydrolytic cleavage of peptide bonds, desamidation, oxidation of sulfur containing amino acids, d- and oligomerisation cause a complex potential spectrum of related impurities. Their adequate limitation requires an ambitious analytics including the application of the total available spectrum of special instrumental methods.
The establishment of adequate specifications and test methods for the routine control of peptides must product specifically take place with consideration of extensive investigations during the development phase. Proposals for the toxicological qualification of concentration limits of impurities orientating at the principles of the ICH notes for guidance for synthetic active ingredients and their dosage forms, respectively, are presented. However, these notes for guidance as explicity emphasized in their preamble cannot be fully applied for peptide drugs and their drug products. This is particularly valid for the there defined identification limits for organic impurities. |
