Building better drugs: developing and regulating engineered therapeutic proteins.
Most native proteins do not make optimal drugs and thus a second- and third-generation of therapeutic proteins, which have been engineered to improve product attributes or to enhance process characteristics, are rapidly becoming the norm. There has been unprecedented progress, during the past decade, in the development of platform technologies that further these ends. Although the advantages of engineered therapeutic proteins are considerable, the alterations can affect the safety and efficacy of the drugs. We discuss both the key technological innovations with respect to engineered therapeutic proteins and advancements in the underlying basic science. The latter would permit the design of science-based criteria for the prediction and assessment of potential risks and the development of appropriate risk management plans. This in turn holds promise for more predictable criteria for the licensure of a class of products that are extremely challenging to develop but represent an increasingly important component of modern medical practice.
Laboratory of Hemostasis, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. Electronic address: chava.kimchi-sarfaty@fda.hhs.gov.
Chava
C
Kimchi-Sarfaty
Tal
T
Schiller
Nobuko
N
Hamasaki-Katagiri
Mansoor A
MA
Khan
Chen
C
Yanover
Zuben E
ZE
Sauna
D000818:Animals; D015195:Drug Design; D006801:Humans; D015202:Protein Engineering / Q000379:methods*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use
D011994:Recombinant Proteins
drug development; drug safety; immunogenicity; quality by design; risk mitigation