Wednesday, June 2, 2010

Proteomic Discovery, Development, Clinical Submission - From Peptides to Biomarkers

Among new, emerging discoveries, personalized medicine, combination products, delivery systems, translational medicine is the discovery of peptide biomarkers, proteomics. Biomarker discovery is a dynamic area of R&D which is born from natural, native physiological and pathological processes in biological systems. The field of biomarker discovery and development - identification, classification, R&D, clinical development phase, transition and validation is currently under debate. A number of groups such as NIH, National Institute of Health Biomarker Definitions Working Group, Divisions at FDA and other regulatory agencies worldwide are in the process of establishing set criteria for proteomic biomarker development.

There are 3 types of Biomarkers:
  • Prognostic: capable of providing information on clinical outcome at the time of diagnosis, independent of therapy
  • Predictive: capable of providing information on the likelihood of response to a given therapeutic modality
  • Screening: capable of providing information on clinical diagnosis in the general population.

The developmental phases are commonly categorized as Discovery, Transition and Validation.

Estimated timelines for the development of a proteomic biomarker (total duration = 48 months) is provided in months:

  • Discovery 14
  • Prototype Assay Development 5
  • Pre-Validation of Assay 5
  • Assay Development 7
  • Clinical Validation 17.
  • Clinical Validation includes, 5 phases of development - preclinical, Phase 1,2,3,4.
  • The number of samples that must be collected and tested from discovery through validation into application and implementation increase in size in late phase development. Preclinical, POC, Proof of Concept samples collected and tested are usually small in number in discovery = 10, reaching hundreds in the validation stage, transitioning to thousands by the time of application to FDA and implementation.

Regardless of the type, a biomarker must demonstrate, under routine implementation methodologies and conditions of use how the marker impacts clinical management of a patient with life-threatening or terminal disease, either by improving patient outcome or QoL, Quality of Life or by lowering cost and time of patient care.

The quality, accuracy, reproducibility, consistency and integrity of data must be of high level and must be quality controlled, processed and assured. Quality management plans, SOPs, WIs, GCP, GLP, GMP and otherwise must be developed and meet compliance quality standards. All plans, procedures and processes must be developed in accordance with FDA regulatory requirements, guidance and guidelines for the year of the application/implementation.,

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