While the term ‘biomarker’ is relatively new, the concept is millennia old. However, with the introduction of new technologies to discover potential biomarkers comes the need to assess their utility and veracity for any given use. This is particularly true for the use of biomarkers to support regulatory decisions in medical product development. Hence the US Food and Drug Administration has developed processes for the qualification of biomarkers and other medical product development tools, processes that are underscored by recent legislation (i.e. the 21st Century Cures Act). In addition to these qualification processes, diagnostic tests that measure a biomarker may follow a process for regulatory decision through the processes that evaluate companion diagnostics. This mini-review provides an overview of these processes and their role in pharmaceutical development and clinical use.
Impact statement
This work summarizes very recent developments in the US FDA’s biomarker qualification program. Furthermore, it contrasts biomarker qualification with companion diagnostic evaluation. As such, it will be highly informative for researches considering taking a biomarker discovery farther along the road to validation.
KarpetskyTPHumphreyRLLevyCC.Influence of renal insufficiency on levels of serum ribonuclease in patients with multiple myeloma.J Natl Cancer Inst1977;
58:875–80
3.
21st Century Cures Act, Pub. L. No. 114–255, Stat. 130 (13 December 2016)
4.
Family Smoking Prevention and Tobacco Control Act, Pub. L. No. 111-31, Stat. 123 (22 June 2009)
5.
FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) resource. Maryland, 2016. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27010052 (accessed 24 October 2017)
6.
DewsI.Biomarkers are not new. In: BleavinsMRCariniCJurima-RometMRahbariaR (eds) Biomarkers in drug development.
Hoboken, NJ:
John Wiley & Sons, 2010, pp.3–14
7.
AllenJP.The art of medicine in ancient Egypt.
New York:
Metropolitan Museum of Art, 2005
8.
BoothJ.A short history of blood pressure measurement.Proc R Soc Med1977;
70:793–9
9.
ColeyNG.Early blood chemistry in Britain and France.Clin Chem2001;
47:2166–78
10.
SinghABhatTSharmaO. Clinical biochemistry of hepatotoxicity. J Clin Toxicol2011;
S4:001
11.
SchultePA.A conceptual framework for the validation and use of biologic markers.Environ Res1989;
48:129–44
12.
BleavinsMRCariniCJurima-RometMRahbariR, eds. Biomarkers in drug development: a handbook of practice, application, and strategy. 1st ed. Hoboken, NJ: Wiley & Sons, 2010
GoodsaidFFruehF.Biomarker qualification pilot process at the US Food and Drug Administration.AAPS J2007;
9:E105–8
23.
GoodsaidFFruehF.Process map proposal for the validation of genomic biomarkers.Pharmacogenomics2006;
7:773–82
24.
GoodsaidFFruehFMattesW.The predictive safety testing consortium: a synthesis of the goals, challenges and accomplishments of the critical path.Drug Discov Today Technol2007;
4:47–50
25.
SistareFDDieterleFTrothSHolderDJGerholdDAndrews-CleavengerDBaerWBettonGBounousDCarlKCollinsNGoeringPGoodsaidFGuYZGuilpinVHarpurEHassanAJacobson-KramDKasperPLaurieDLimaBSMaciulaitisRMattesWMaurerGObertLAOzerJPapaluca-AmatiMPhillipsJAPinchesMSchipperMJThompsonKLVamvakasSVidalJMVonderscherJWalkerEWebbCYuY.Towards consensus practices to qualify safety biomarkers for use in early drug development.Nat Biotechnol2010;
28:446–54
26.
DieterleFSistareFGoodsaidFPapalucaMOzerJSWebbCPBaerWSenagoreASchipperMJVonderscherJSultanaSGerholdDLPhillipsJAMaurerGCarlKLaurieDHarpurESoneeMEnnulatDHolderDAndrews-CleavengerDGuYZThompsonKLGoeringPLVidalJMAbadieEMaciulaitisRJacobson-KramDDefeliceAFHausnerEABlankMThompsonAHarlowPThrockmortonDXiaoSXuNTaylorWVamvakasSFlamionBLimaBSKasperPPasanenMPrasadKTrothSBounousDRobinson-GravattDBettonGDavisMAAkundaJMcDuffieJESuterLObertLGuffroyMPinchesMJayadevSBlommeEABeushausenSABarlowVGCollinsNWaringJHonorDSnookSLeeJRossiPWalkerEMattesW.Renal biomarker qualification submission: a dialog between the FDA-EMEA and predictive safety testing consortium.Nat Biotechnol2010;
28:455–62
27.
MattesWBWalkerEGAbadieESistareFDVonderscherJWoodcockJWoosleyRL.Research at the interface of industry, academia and regulatory science.Nat Biotechnol2010;
28:432–3
28.
HarpurEEnnulatDHoffmanDBettonGGautierJCRiefkeBBounousDSchusterKBeushausenSGuffroyMShawMLockEPettitS.Biological qualification of biomarkers of chemical-induced renal toxicity in two strains of male rat.Toxicol Sci2011;
122:235–52
29.
EngleSKJordanWHPrittMLChiangAYDavisMAZimmermannJLRudmannDGHeinz-TahenyKMIrizarryARYamamotoYMendelDSchultzeAECornwellPDWatsonDE.Qualification of cardiac troponin I concentration in mouse serum using isoproterenol and implementation in pharmacology studies to accelerate drug development.Toxicol Pathol2009;
37:617–28
30.
AmurSLaVangeLZinehIBuckman-GarnerSWoodcockJ.Biomarker qualification: toward a multiple stakeholder framework for biomarker development, regulatory acceptance, and utilization.Clin Pharmacol Ther2015;
98:34–46
31.
ParekhABuckman-GarnerSMcCuneSONeillRGeanacopoulosMAmurSClingmanCBarrattRRoccaMHillsIWoodcockJ.Catalyzing the critical path initiative: FDA’s progress in drug development activities.Clin Pharmacol Ther2015;
97:221–33
32.
US FDA. Guidance for industry and FDA staff: qualification process for drug development tools. In: HHS (ed) Federal Register, 2014, pp.83100–2
33.
US FDA. Qualification of medical device development tools guidance for industry, tool developers, and Food and Drug Administration staff. In: HHS (ed) Federal Register, 2017, pp.37456–8
34.
LeeJWDevanarayanVBarrettYCWeinerRAllinsonJFountainSKellerSWeinrybIGreenMDuanLRogersJAMillhamRO’BrienPJSailstadJKhanMRayCWagnerJA.Fit-for-purpose method development and validation for successful biomarker measurement.Pharm Res2006;
23:312–28
35.
US FDA. Patient-reported outcome measures: use in medical product development to support labeling claims. In: HHS (ed) Federal Register, 2009, pp.65132–3
36.
US FDA. In vitro companion diagnostic devices. In: HHS (ed) Federal Register, 2014, pp.45813–4
37.
US FDA. Enrichment strategies for clinical trials to support approval of human drugs and biological products. In: HHS (ed) Federal Register, 2012, pp.74670–1
EnzmannHMeyerRBroichK.The new EU regulation on in vitro diagnostics: potential issues at the interface of medicines and companion diagnostics.Biomark Med2016;
10:1261–8
40.
US FDA. Pharmacogenomic data submissions. In: HHS (ed) Federal Register, 2005, pp.14698–9
41.
US FDA. Pharmacogenetic tests and genetic tests for heritable markers. In: HHS (ed) Federal Register, 2007, pp.33765–6
42.
US FDA. In vitro diagnostic multivariate index assays. In: HHS (ed) Federal Register, 2007, pp.41081–3
43.
US FDA. Distribution of in vitro diagnostic products labeled for research use only or investigational use only. In: HHS (ed) Federal Register, 2013, pp.70306–7
44.
US FDA. Framework for regulatory oversight of laboratory developed tests (LDTs). In: HHS (ed) Federal Register, 2014, pp.59776–9
