Managing uncertainty: a perspective on risk pertaining to product quality attributes as they bear on immunogenicity of therapeutic proteins.
The critical question addressed in this paper regards how industry and regulatory agencies should manage the risk of adverse events to patients posed by product quality attributes for which a preponderance of evidence from clinical and/or non-clinical studies supports it as a risk, but for which the probability of clinical adverse events arising from the attribute is uncertain. We here provide our perspective on the principles that can be applied to determine the need for and the manner in which to control quality attributes when their impact on safety and/or efficacy is suspected, but uncertain. As an example, we use the risk of immune responses to protein therapeutics posed by sub-visible protein particulates in therapeutic proteins.
Division of Therapeutic Proteins, Center for Drug Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892, USA. amy.rosenberg@fda.hhs.gov
Amy S
AS
Rosenberg
Daniela
D
Verthelyi
Barry W
BW
Cherney
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001688:Biological Products / Q000009:adverse effects* / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011336:Probability; D011506:Proteins / Q000009:adverse effects* / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D011786:Quality Control; D012306:Risk; D035501:Uncertainty; D014614:Vaccines, Synthetic / Q000009:adverse effects* / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use
D001688:Biological Products; D011506:Proteins; D014614:Vaccines, Synthetic