The Rise of Personalized Medicine:

Implications for the IVD Industry

Linda D. Bentley, Esq.

MassMEDIC Diagnostics Industry UpdateMarch 31, 2009

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Personalized Medicine

The use of patient-specific information to tailor products and therapies that will increase the likelihood of a favorable outcome for that patient. Involves the use of biomarkers which may be associated with genes, proteins or metabolic pathways. Potential benefits include: • Earlier detection of disease• Information about likelihood to develop disease• Identification of therapies• Prediction of response to treatment

– Effectiveness– Appropriate dose– Adverse events

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Stephen Smith.  (2009, March 3). MGH to use genetics to personalize cancer care. Boston Globe, p. A.1. 

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In Vitro Diagnostics• Offered by clinical laboratories as testing service

– CLIA (Clinical Laboratory Improvement Amendments of 1988) certified laboratory

– Customers are physicians and other laboratories– Most not currently subject to FDA clearance or approval

• Sold as test kits– Customers are other laboratories– Regulated by FDA as medical devices requiring 510(k)

clearance, PMA approval or De Novo Classification • Device means an instrument, apparatus, in vitro reagent or

other similar or related article intended for use in the diagnosis of disease or other condition or the cure, mitigation, treatment or prevention of disease and does not achieve primary purposes through chemical action within or on body and not metabolized.

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FDA Regulatory Pathways

• Established– 510(k) Premarket notification

• Show that product is substantially equivalent to predicate device• Could require nonclinical and clinical studies• Some diagnostic tests used in conjunction with drug follow 510(k)

route while others will require PMA– 510(k) - UGT1A1 gene assay (Camptosar) but PMA for HER2/neu

(Herceptin)– Premarket Approval Application (PMA)

• Generally required of IVDs with higher risk• Safe and effective for intended use, i.e., clinical study• May involve advisory committee review

– De Novo Classification• No predicate device so automatic Class III/PMA• Permits low/moderate risk device to by-pass PMA, e.g.,

MammaPrint

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Laboratory Developed Tests• Formerly known as “home brews”• FDA asserted authority, but historically exercised

enforcement discretion and didn’t regulate• “New” FDA interest in some of these tests

– Warning letters• Who developed and validated test?

– Proposed draft guidance• In Vitro Diagnostic Multivariate Index Assay (IVDMIA)

– Utilizes algorithm, involves multiple markers or requires explanation of test result

• CLIA– Applies to all clinical laboratories that perform diagnostic

tests– Analytical validity versus clinical validity

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Potential for ChangeFDA• FDA’s newly appointed Senior Genomics Advisor in

Office of Chief Scientist– Dr. Elizabeth Mansfield has worked in FDA’s OIVD and in

industry• Critical Path Initiative - new tools for product evaluation

– Biomarker assessments to correlate the presence of genes or proteins and likely response to medication

– Guidance for the pharmaceutical industry on co-development of drugs and diagnostic tests.

• Collaboration with NIH and other research institutions in applied research efforts to study the genetic basis of drug-related toxicities.

• Medco partnership (PBM)

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Potential for Change (cont.)

External efforts to change FDA regulatory process

• Proposals in Congress to subject all IVDs to FDA review or approval

• Citizen petition – Genentech (12/5/08) asked that all IVDs be actively

regulated by FDA– AdvaMed (3/27/09) submitted proposal on “Risk-Based

Regulation of Diagnostics”

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Potential for Change (cont.)

Others - Governmental and Private• Secretary’s Advisory Committee on Genetics, Health

and Society (SAGCHS) – Chartered in 2002 to provide advice to Secretary of HHS– Issued report May 2008 on potential of

pharmacogenomics http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf

• The Personalized Medicine Coalition– A broad spectrum of academic, industry, patient,

provider and payer communities seeking to advance the understanding and adoption of personalized medicine. www.personalizedmedicinecoalition.org

• Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group

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Challenges

• Early Stage– Few products on market - tests not widely adopted, e.g.,

FDA-cleared test for 2 gene variants and warfarin– Need to access accuracy and predictive value

• FDA has incorporated pharmacogenetic information in somedrug labeling, but clinical usefulness of most tests still unknown

• Reimbursement uncertain• Current coding not conducive to innovative test development• Payers not convinced of usefulness• May not support cost of developing tests

• Needs robust health information technology

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Challenges (cont.)

• Economic Incentives for co-development– Decreased market for certain drugs – Faster drug approvals

• FDA Guidance on genomics and drug development– More post-marketing surveillance

• Education and training

• Ethical, social and legal issues

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Linda D. Bentley, Esq.Member

Mintz Levin Cohn Ferris Glovsky and Popeo, P.C.One Financial Center

Boston, MA 02111ph: (617) 348-1784

LDBentley@mintz.comwww.mintz.com