# Presentation: 733017

## Update 2003: FDA and CLIA 

**Clara A. Sliva, MT(ASCP), MPA**
**Acting CLIA Coordinator**
**FDA**

- IVD Roundtable 510(k) Workshop
- April 22, 2003

## Surviving CLIA

**CLIA Overview**
**    ****--Something OLD**
**    ****--Something NEW**
**Key Features**
**Who are the players**
**FDA and CLIA **
**CLIA regulations**
**What is categorization**
**What requires categorization**
**What is not regulated under CLIA**

## Surviving CLIA

**How FDA categorizes tests **
**   ****-CDRH**
**   ****-CBER**
**“****Automatic” categorizations**
**Specific requests for categorizations**
**Categorization letter; CLIA website**
**Where do you go for help**

## What is CLIA?

**Clinical Laboratory Improvement Amendments of 1988 (CLIA)**
**Enacted as result of  reports of inaccurate test results from Pap smears**
**Questions were raised about how labs functioned and what quality control procedures existed**

## CLIA’88 - President Reagan- 10/31/1988
Social Security Act
Labs receiving Medicare funds must be CLIA-certified. 
All clinical labs must be CLIA-certified to test human specimens 
Notice Proposed Rule 1990/60,000 comments
Final Rule 2/28/1992
Final QC Rule 1/24/03

**Social Security Act**
**Labs receiving Medicare funds must be CLIA-certified. **
**All clinical labs must be CLIA-certified to test human specimens **
**Notice Proposed Rule 1990/60,000 comments**
**Final Rule 2/28/1992**
**Final QC Rule 1/24/03**

**CLIA ‘88**

## Highlights Final QC Rule

**Removes FDA’s review of manufacturers' QC instructions for compliance with CLIA  **
**Sets QC standards for nonwaived testing. **
**Reduces QC frequency in most of the subspecialties**
**Merges moderate & high complexity QC requirements  **
**Uses plain language  **

## Highlights 

**Reorganizes to mimic the flow of a specimen through the lab. **
**Studies show most lab errors are pre-analytical**
**Requires mod. complexity labs to validate a test once before use**
**Ensures the test works accurately before pts. tested. **
**Onus on laboratory**
**CMS drafting inspector guidelines**

##  Who are the Players?

**Centers for Medicare and Medicaid Services (formerly HCFA) oversees CLIA **
**Authority for regulation and policy**
**CLIA self-funded **
**User fees from regulated labs**
**CMS pays FDA to categorize commercially marketed tests **
**CDC categorizes lab procedures**
**    ****-Provider performed microscopy**
**    ****-Gram stain **

## CMS 

**Reimbursement**
**CLIA certificate**
**HIPAA – Privacy Act**
**CLIA regulations, lab sends report to authorized person **
**CLIA defines as individual authorized under State law to order tests or receive test results, or both.**
**HIPAA-- patient requests their records from a lab,   results should be sent to them.**

## CMS CLIA Contact

**Kathy Todd, CMS  **_**[ktodd@cms.hhs.gov](mailto:ktodd@cms.hhs.gov)**_
**Phone: 410.786.3385 **
** ****Fax: 410.786.1224**

## OIVD’s CLIA Players

**Renita Hoard, CSO**
**Dr. Joe Hackett, founding father**
**Don St. Pierre, Deputy Director**
**Dr. Steve Gutman, Director **
**CLIA team – represents OIVD**
**CBER devices – Clara**
**CBER waiver tests- Clara,  lead reviewer, OIVD CLIA team**

## Key Features

**Standards based on complexity of testing, not the laboratory site**
**The key to understanding categorization;  **
**   ****-the analyst/operator**
**   ****-how complex it is for the analyst to run the test**

## FDA and CLIA

**1992 CLIA regulations**
**FDA responsible for complexity categorization**
**1993-94 FDA categorized >900 tests**
**1994 CDC delegated responsibility**
**Resources, funding issues **

## FDA and CLIA

**Impetus for change**
**Manufacturers**
**Congress**
**“****Confusion and duplication of effort”**
**CDC, CMS, FDA consensus**
**Interagency agreement 2/27/99**
**Tri-agency team – CMS, CDC, FDA**

## What Regulations Govern Categorization

**42 CFR 493.17, categorization of specific laboratory tests by level of complexity**
**Moderate, high**
**7 Criteria **

## Moderate, High

_**42 CFR 493.17**_
**Knowledge**
**Training and experience**
**Characteristics of operational Steps**
**Calibration, QC, PT materials**
**Troubleshooting, Maintenance**
**Interpretation and judgment**

## Moderate, High

_**42 CFR 493.17**_
**7 criteria scored as 1, 2, or 3**
**Score of 1 = minimum **
**Score of 3 = specialized**
**Total scores of 12 or less = moderate**
**13 or higher = high **
**e.g. PCR = high complexity**

## Categorization Regulations

_**42 CFR 493.15 (c)**_**  **
**Lists the 9 generic test groups **
**Categorized by regulation**
**Automatically waived **
**But still requires categorization notification letter from FDA**
**Requires posting categorization on website**

## Generic 9

_**493.15 (c)**_
**- dipstick and tablet reagent urinalysis**
**fecal occult blood**
**ovulation tests**
**urine pregnancy tests**
**erythrocyte sedimentation rate****	**
**hemoglobin (copper sulfate)**
**blood glucose devices (FDA-cleared for OTC use)**
**spun microhematocrit**
**hemoglobin single analyte  instruments (1993**)
**     **

## Most Common Waived Tests

**Urine pregnancy – 34%**
**All other tests – 20%**
**Blood glucose (OTC) – 18%**
**Urine dipstick/tablet chemistries-19%**
**Ovulation tests – 5%**
**Fecal occult blood – 4%**

## Categorization Regulations

**CMS and PHS Sept 13, 1995 Notice of Proposed Rulemaking**
**Clarified statutory criteria for obtaining waiver **
**Guidelines list the criteria**
**Final rule pending**
**CMS leads tri-agency team**

## CMS/PHS Waiver Criteria

**Defined simplicity, low risk**
**Defined accuracy as comparison to reference materials, methods**
**Precision field studies in hands of lay user**
**Flex studies, different environments**
**Studies distinct from FDA premarket review**

## Categorization Regulations

**Food and Drug Modernization Act Nov. 21, 1997**
**clarifies tests cleared for **_**over-the-counter**_** are **_**automatically**_** waived.**
**But still requires categorization notification letter from FDA**
**Requires posting categorization on website**

## OTC

**Growing number of OTC tests **
**   ****-drugs of abuse**
**   ****-cholesterol, HDL chol**
**   ****-vaginal ph**
**   ****-microalbumin**
**   ****-FSH, qual.**
**   ****-HgbA1C**
**   ****-fern test, saliva.**
**   ****-semen, male fertility**

## Prescription Home Use

**Prescription home use is an Rx device physician instructs patient to use in home **
** ****FDA devices are OTC or Rx**
**Any device used in the home that is not OTC**
**Examples – prothrombin time, hemoglobin A1c**

## What is Categorization?

**Process of assigning new **_**commercially marketed**_** tests to one of 3 CLIA categories: ***waived, moderate, high*
**The key to understanding categorization;  the ***analyst/operator*** and the ***complexity*** of  testing**
**Regulations that govern categorization**

## What Requires Categorization

**Categorization applies to all laboratory test systems  on materials derived from the human body conducted for the purpose of diagnosis, prevention or treatment, or assessment of  the health**

## What Requires Categorization

**Plain Language  **
_**Commercially marketed**_** test systems that produce a result**
**This includes 510(k) exempt tests **

##  Not Categorized

_**Produce no test result**_
**Quality Control**
**Calibrators**
**Test tubes**
**Collection kits**
**    ****--drugs of abuse**
**    ****--Hepatitis C, HIV**

##  Not Categorized 

_**Not currently regulated under CLIA**_
**Non-invasive (laser hematocrit)**
**Breath tests    (h. pylori, alcohol)**
**Drugs of abuse – Workplace**
**Monitoring devices (Minimed)**

## How FDA Categorizes

**Center for Devices and Radiological Health**
**Center for Biologics Evaluation and Research**

## CDRH Categorizes

**Pre-amendment **
**510(k) exempt tests**
**New Premarket Notification 510(k) **
**   ****e.g. special 510(k)s**
**New Premarket Approvals (original, supplements)**

## CDRH Categorizes

**New Humanitarian Device Exemptions (original, supplement)**
**510(k) add-to-files**
**   ****-Replacement reagents **
**   ****-Manufacturer name change  **
**   ****-Relabel **
**Previously uncategorized test systems **

## Automatic Categorizations

**Manufacturer submits premarket submission to Document Mail Center **
**Categorization performed in conjunction with product review**
**CLIA notification accompanies clearance, approval order or follows shortly after**

## Automatic Categorization, Replacement Reagents

*Well characterized lab analyzers for use by laboratory professionals.*
*Previously cleared instruments and reagents, when a claim is made for a new reagent/instrument combination.*
*Introduction of new instrument family members of a previously cleared instrument family.*

## Automatic Categorization

**Replacement reagent**
*Replacement reagents require a package insert with the new instrument/reagent combination*
**CLIA notification follows shortly after**

## Categorization by Request

**Change in company name**
**Additional trade name**
**Modification?**
**Not previously categorized**
**   ****-defaults to high complexity**

## Categorization by Request

**Submit new labeling to FDA**
**Document Mail Center, HFZ-401, 9200 Corporate Blvd., Rockville, MD 20850**
**“****For CLIA Categorization Only”**
**Reference original 510(k) number**
**CLIA categorization performed**
**Notification letter to manufacturer**
**Categorization posted on website**

## Categorization by Request

**Exempt from 510(k), CLIA required**
**Submit new labeling to FDA’s DMC**
**“****For CLIA Categorization Only” **
**OIVD assigns “X” document number**

## Categorization by Request

**“****X” number accessible through CLIA database**
**CLIA categorization performed**
**CLIA letter issued **
**Categorization posted on CLIA website**

## Categorization by Request

**Waiver via CMS/PHS 1995 Criteria**
**Test cleared or approved to apply for waiver through process**
**FDA approves waiver protocol **
**Waiver studies begin**
**Timeframe depends on queue**

## CBER:

**Manufacturer submits request for product review to CBER**
**When test is cleared, approved, licensed CBER sends test instructions to Clara Sliva**
**CBER test logged into CDRH CLIA database using CBER document number: BK, BP, BLA, PL**

## Rapid HIV Waiver

**Manufacturer submits waiver application to CDRH**
**CBER reviewer consults**
**CMS consults**
**CDRH issues letter **
**CDRH posts categorization on CLIA website  **

## Categorization Notification Letter

**FDA’s document number is the key**
**“****k001111” – new 510(k) CDRH**
**“****BLA002222 – new BLA CBER**
**“****k001111/A1” – new trade name **
**complexity**
**test system name  **
**analyte name**

## Categorization Notification Letter

**Call – don’t be shy**
**No letter 3 weeks after clearance**
**Incorrect letter**
**Website updates monthly**

##  FDA’s CLIA Workload  

**10/1//02 – 4/18/03**
**1,125 categorized**
**912 - moderate **
**87 - high**
**126 - waived**

## >1,125 Tests Categorized

## FDA’s CLIA Website

_**[http://www.fda.gov/cdrh/clia/](http://www.fda.gov/cdrh/clia/)**_
**“****Government Google” for current CLIA information**
**Lists all waived analytes and tests**
**Links to CMS, CDC websites**
**CLIA database**

## CLIA Database

_**[http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCLIA/search.cfm](http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCLIA/search.cfm)**_
**Contains all commercially marketed tests categorized by CDC and FDA**
**Several ways to search**

## Search CLIA Database

**Search for CLIA records by**
**   ****-test system name**
**   ****-specialty/subspecialty**
**   ****-analyte**
**   ****-document number**
**   ****-qualifier (reagent application)**
**    ****e.g. SLIVA Analyzer/St. Pierre reagent**
**   ****-effective date**
**   ****-complexity**

## Tips

**You may enter the entire test name**
**But most successful if you enter the first word or two**
**Or just the first few letters**
**e.g. first few letters of manufacturer name **

## Mastering the CLIA Database

**Manufacturer Test System**
**Qualifier**
**Analyte **
**Document Number **
**Complexity  **
**Analyte **
**Specialty**
**Effective Date***** (mm/dd/yyyy) ***
**Sort  *****one***** or a***** combination***** of the values and select Search:  **

## Publication of Categorizations

**Monthly on FDA’s CLIA Home Page**
**Federal Register Notice, interval to be determined **

## What We Have Learned

**Multiple stakeholders **
**Labs **
**Providers**
**Patients**
**Manufacturers**
**Government**

## Over 31,000 Categorizations

**Laboratory Inspectors, Laboratories, Manufacturers, and Other Stakeholders**
**Want to Know **

## CLIA INFORMATION 

**Clara A.R. Sliva**
**http://www.fda.gov/cdrh/clia**
**clia@cdrh.fda.gov**
**phone (301) 827-0496**
**fax (301)827-1401**
**   **