# Presentation: 931183

## REGULATORY CHALLENGES FOR In Vitro DIAGNOSTICS

- Joseph L. Hackett, Ph.D.
- Associate Director
- Office of In Vitro Diagnostic
-    Device Evaluation and Safety
- Center for Devices and
-    Radiological Health
- Food and Drug Administration

## SUBMISSIONS

**510(K)**
**PMA (Premarket Approval)**
**IDE  (Investigational Device Exemption)**
**Pre-IDE**

## Regulatory Classes

**Class I    General Controls**
**Class II   Standards**
**Class III  Premarket Approval**

## (Section) 510(k)

**Substantially Equivalent to a marketed device**
**Compared to device marketed in U.S. or to a regulation**
**90 Days**
**Internal Review**

## SUBSTANTIAL EQUIVALENCY

**Class I  and  Class II**
**“****Me too”**
**Cleared to market**

## PMA

**Not Substantially Equivalent to a marketed device**
**180 Days**
**External Panel Review Open Meeting**
**Safe and Effective on own merits**
**Summary Safety & Effectiveness**
**Pass Manufacturing inspection**
**Approval order to market**

## FDA Review Limitations

**Paper Review**
**Not Outcome Oriented**
**Not Cost Oriented**
**Not Directed at Social Issues**
**Not Directed at Practice of Medicine**

## IDE

**Objectives**
**Protocol**
**Description of Device**
**Manufacturing Information**
**Investigator’s Agreement**
**Informed Consent**
**30 Days**

## Pre-IDE

**Sponsor seeks FDA advice on proposal or protocol**
**Usually no IDE; informal agreement on development of 510(k) or PMA**
**Before study starts**
**Acceptable for gathering and analyzing required data**
**No guarantee**

## Review Items

**Inter and Intra-laboratory Reproducibility**
**Analytical Sensitivity and Specificity**
**Clinical Sensitivity and Specificity**
**Predictive Values**
**Intended Use**

## Challenges to Regulatory Process

**Problems in Analytical Studies**
**Problems in Feasibility Studies**
**Problems in Clinical Studies**

## Problems in Clinical Studies

**Numbers studied**
**Sites**
**Inclusion/exclusion Criteria**
**Bias in Data Collection**

## Numbers Studied

**Sometimes a Problem**
**Retrospective Data**
**Banked Data**
**Foreign Data**
**Labeling**

## RETROSPECTIVE SAMPLE CHALLENGE

**Informed Consent**
**Stability**
**Set protocol ?**
**Tissues**
**how read (consistency)**
**only large tumors?**

## Microarray KEY ISSUES

**Efficiently Review In A Timely Manner**
**Reproducibility**
**Develop Expertise**
**Lack Of Standardization **
**Data Mining (Bioinformatics)**
**Different Platforms/Genes**
**Manufacturing Controls**

##  Conventional vs. Genomics

**Genomic**
**10, 100, 1000 or more/sample?**
**firms: most have little experience**
**firms: most don’t understand GMPs**
**Conventional**
**1 result/sample**
**firms: experience with FDA**
**firms understand GMPs**

## Microarrays – Learning Mode

**36 Months – 50 Presentations**
**Industry - 33**
**Academia - 3**
**Government **
**NIH   - 4**
**FDA  - 4**

## EXPERTISE

**Continued Presentations**
**More Dialogue/Outreach**
**PhRMA Round Table**
**NCCLS**
**Office “Omics” Working Group**
**CDER Working Group**

## POTENTIAL SUBMISSIONS

**Drug Resistance/Toxicity**
**Cancer **
**Infectious Diseases**
**Genetic Diseases**
**Point Of Care**
**Proteomics**

## Related Documents

**Mock Submissions**
**CDRH**
**Safe Harbor **
**CDER (concept)**

## Increased Interaction

**Product Reviews**
**Development of Standards**
**Development of Guidance**
**Development of Policies**

## Guidances

**Product Specific - OTC Drugs of Abuse, Hepatitis, Rapid ASTs**
**General - Quality Control, calibrators, Point of care**
**Statistical/labeling**

## Guidance

_**[http://www.fda.gov/cdrh/ode/tumor821.html](http://www.fda.gov/cdrh/ode/tumor821.html)**_

## Roundtables

**IVD**
**Professional**
**Pharmacogenomics**
**Therapeutic Drug Management**

## Baltimore DO -- 1995

**Ice breaker with industry**
**Facilitator**
**Improve communications**

## Participants

**FDA – review and compliance**
**FDA -- field**
**Industry trade groups**

## Objectives

**Up-date industry**
**Up-date FDA**
**Look for collaborative projects**

## WORKSHOP

**2002 Workshop on Pharmacogenetics Pharmacogenomics in Drug Development and Regulatory Decision-Making**
**May 16-17, 2002**

## WORKSHOP

**Sponsored by the FDA, and companies represented  on the Pharmaceutical Research and Manufacturers of America (PhRMA), Preclinical Safety Committee (DruSafe), and the Pharmaceutical Working Group (PWG)**

##  Genomic Testing and Data Quality

**How will FDA look at data?**
**No data, can’t predict**
**Give FDA all or some of the data?**
**All microarray data  should be submitted on lead compounds at IND stage**
**FDA be “transparent” on how uses data**

## 1. Genomic Testing and Data Quality

**Data being generated, not submitted to FDA for lead compounds**
**Expression data useful, but for drug discovery; not diagnostic test?**
**Analysis approach non-uniform**
**When data pivotal, strive for exact measure of every analyte**

## Clinical Trial Safety and Efficacy

**We need to continue to have these open discussions and dialogues between scientists and regulatory bodies.**

## Core Mission

**Promote Public Health**
**Apply Good Science**
**Evolving Program**
**Relevant, Focused, Safe and Effective**

## Five F’s

**Friendly**
**Fair**
**Finalize Decisions**
**Follow-up**
**Flexible**

## Contacts

**JLH@CDRH.FDA.GOV**
**301-594-3084**
**http://www.fda.gov**
_**[http://www.fda.gov/cdrh/index.html](http://www.fda.gov/cdrh/index.html)**_
**http://drsmg5082927/cdrh/oivd/index.html**