[Therapeutic antibodies: importance of galenics for efficacy and safety].
Monoclonal antibodies and their derivatives such as antibody fragments, immunoconjugates and Fc fusions, represent the majority of therapeutic proteins in clinical development. Recent successes of such molecules in cancer and in the treatment of autoimmune diseases found a great hope in biotherapeutics. The progress in genetic engineering and in analytical development allowed the production of increasingly humanized antibodies, and thus less immunogenic. However the use of such molecules in therapeutics would not be possible without a good comprehension of their degradation pathways and therefore the development of formulations and manufacturing processes ensuring them a good stability along their production, shipment, storage and administration. The present review summarizes the key degradation pathways of monoclonal antibodies and the formulation approaches allowing a satisfactory shelf-life, ensuring both efficiency and safety of such biomedicines.
Manache
Lucie
L
Sanofi-Aventis R&D, Laboratoire de développement de formulation-biotech, département des sciences pharmaceutiques, 13, quai Jules Guesde, 94403, Vitry-sur-Seine, France.
Dulieu
Claire
C
Boussif
Otmane
O
D000577:Amides / Q000737:chemistry; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D018796:Immunoconjugates / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010084:Oxidation-Reduction; D011489:Protein Denaturation
D000577:Amides; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D004304:Dosage Forms; D018796:Immunoconjugates