The Rise of Personalized Medicine: Implications for the IVD Industry

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The Rise of Personalized MedicineImplications
for the IVD Industry

• Linda D. Bentley, Esq.

MassMEDIC Diagnostics Industry Update March 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 didnt
  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 Change

• FDA
• FDAs newly appointed Senior Genomics Advisor in
  Office of Chief Scientist
• Dr. Elizabeth Mansfield has worked in FDAs 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
• Secretarys 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 some
• drug 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 02111
• ph [phone]
• LDBentley_at_mintz.com
• www.mintz.com