Pharmaceutical compositions are in general suitable for administration to a subject, the subject being an animal or a human. Many pharmaceutical compositions are available that are either manufactured or purified by processes in which proteins or peptides are involved, or are based on protein and/or polypeptide and/or peptide or amino-acid compositions, including compositions with amino-acid derivatives. Important categories of nowadays pharmaceutical compositions comprising a protein or a proteinaceous compound as an active substance include, but are not limited to hormones, enzymes, vaccines and antigens, cytokines and antibodies. In addition to the above-mentioned proteinaceous pharmaceutical compositions, a large number of pharmaceutical compositions are manufactured with the help of a production and/or purification step comprising proteins. For example, many pharmaceutical compositions comprise one or more proteins as a stabilizing agent.
Safety aspects are of great concern with any pharmaceutical composition. Drug stability during production and storage, and after administering to the body, attracts much effort during development of new active compounds, and thereafter. Market withdrawals of initially successful pharmaceutical compositions are sometimes necessary because of the occurrence of unforeseen and undesired side effects. For example: plasma, erythropoietin, insulin, antibodies, aprotinin, albumin, thrombopoietin, interferon α, factor VIII, have all caused unwanted side effects after administration in individuals. These examples underline that continuous improvement of the current safety testing methodologies is necessary to reduce the risk for unforeseen, unwanted and/or deleterious side effects after administering pharmaceutical compositions to a human or animal.
Health problems related to the use of pharmaceutical compositions are, for example, related to the fields of hematology, fibrinolysis and immunology. An incomplete list of observed side-effects after administration of pharmaceutical compositions comprises, for example, fever, anaphylactic responses, (auto)immune responses, disturbance of hemostasis, inflammation, fibrinolytic problems, including sepsis and disseminated intravascular coagulation (DIC), which can be fatal. Side effects can be caused by either an alteration of a protein or a proteinaceous compound present in the pharmaceutical composition, or by added diluents or carrier substances of the pharmaceutical composition. A proteinaceous compound in this specification means any compound which comprises a peptide, polypeptide, or protein, and/or altered or degraded forms thereof. Alteration of the proteinaceous compound of a pharmaceutical composition comprises, for example, denaturation, multimerization, proteolysis, acetylation, glycation, oxidation or unfolding of proteins.