# Presentation: 733016

## FDA’s CLIA Complexity Process

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

- IVD Roundtable 510(k) Workshop
- April 23, 2002

## Expected Outcomes

**What is CLIA ’88**
**Key Features**
**Who are the players**
**FDA and CLIA **
**CLIA regulations**
**What is categorization**
**What requires categorization**
**What is not regulated under CLIA**

## Expected Outcomes

**How FDA categorizes tests **
**   ****-CDRH**
**   ****-CBER**
**“****Automatic” categorizations**
**Specific requests for categorizations**
**Categorization notifications: letter, internet**
**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**

## What is CLIA

**Comprehensive plan to improve the quality of  labs**
**1987 = 12,000/200,000 labs regulated**
**2002 = 170,000 labs **

**Notes:**
Walt Bogdanich, Wall Street Journal award Pulitzer Prize in 1988 for series of articles published about “shoddy” lab practices in the US.

## Who are the Players

**Centers for Medicare and Medicaid Services (formerly HCFA) oversees CLIA **
**CLIA self-funded **
**User fees from regulated labs**

**Notes:**
For example, CMS in conjunction with CDC publishes regulations

## Who are the Players

**CMS pays FDA for CLIA categorization commercially marketed tests **
**CDC categorizes lab procedures**
**    ****--Provider performed microscopy**
**    ****--Gram stain **

## DCLD’s Players

**Lisa King**
**Renita Hoard **
**Dr. Joe Hackett**
**Dr. Steve Gutman**
**CLIA team represents all Branches**
**    **

## Key Features

**Standards based on complexity of**
**   ****testing, NOT lab site**
**How complex it is for the analyst to run the test**
**   ****-e.g. training, knowledge, interpretation**

## 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, HCFA, FDA consensus**
**Interagency agreement 2/27/99**
**HCFA, CDC, FDA = CLIA partners**

**Notes:**
DEJAVU

## 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 < = moderate**
**13 or > = high **
**e.g. PCR = high complexity**

## Categorization Regulations

**42 CFR 493.15 (c)  9 generic tests  **
**Categorized by regulation**
**Automatically waived **
**But still requires review and notification 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%**

**Notes:**
80% all waived tests waived by regulation

## 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**

**Notes:**
Proposed regulation

## CMS/PHS Waiver Criteria

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

## Categorization Regulations

**Food and Drug Modernization Act Nov. 21, 1997**
**Clarifies OTC tests **_**automatically**_** waived.**
**But still requires categorization notification letter from FDA**
**Requires posting categorization on website**

**Notes:**
Tests that are not categorized default to a high complexity rating

## OTC

**Growing number  OTC tests**
**   ****-drugs of abuse**
**   ****-cholesterol**
**   ****-vaginal ph**
**   ****-microalbumin**
**   ****-follicle stimulating hormone**

## 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**

## 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**

**Notes:**
Regulatory speak

## What Requires Categorization

**Plain Language:  **
_**Commercially marketed**_** tests  produce a result**

##  Not Categorized

_**Produce no test result**_
**Quality Control**
**Calibrators**
**Collection kits**
**    ****--drugs of abuse**
**    ****--hepatitis C**

##  Not Categorized 

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

## How FDA Categorizes

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

## CDRH Categorizes

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

## 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 in conjunction with product review**
**CLIA notification accompanies clearance, approval order or follows shortly after**

## Automatic Categorization, Replacement Reagents

**Well characterized  analyzers for use by lab professionals.**
**Previously cleared analyzers and reagents**
**Claim is made for a new reagent/analyzer combination.**
**New analyzer family members of a previously cleared analyzer family.**

**Notes:**
Replacement reagents – least burdensome approach to 510(k) review; 

## Automatic Categorization

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

## Categorization by Request

**Change in company name**
**   ****-e.g. Now GWB, formerly WJC**
**Relabel**
**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**

**Notes:**
Categorization by request also applies to PMAs. These could be submitted as an amendment

## Categorization by Request

**Exempt from 510(k), CLIA required**
**Submit new labeling to FDA**
**“****For CLIA Categorization Only” **
** ****Cite regulation, product code**

## Categorization by Request

**DCLD assigns “X” document number**
**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**

## 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, BL, PL**

## CBER

**CBER reviewer consults on categorization **
**Notification letter issued by CDRH**
**Categorization posted on CLIA website  **

## Categorization Notification Letter

**FDA’s document number is the key**
**“****k001111” – new 510(k) CDRH**
**“****BL002222 – new BLA CBER**
**“****k001111/A1” – new trade name **
**complexity**
**test system name  **
**analyte name**

##  FDA’s CLIA Workload  

** ****- 1/18/00 – 4/22/02**
** ****- 3,642 categorized**
** ****- 3,121 - moderate **
** ****- 521 - high**
** ****- 301 - waived**

## >3,121 Tests Categorized

## Benefits

**Streamlined administrative process**
**One stop agency for marketing and categorization**
**Reviewer familiar with the products**
**Categorization, no impediment to clearance or approval **
**Improved turn around time, decision**

## 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/Dr. Gutman 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:  **

**Notes:**
Plug for Dave Racine, Ian Barber (Internet), Sam Harris, Candy Cheung (Computer Support)

## 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 28,600 Categorizations

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

**Notes:**
We now have over 27000 categorizations that are of interest to the clinical laboratory community and those that have an interest in these laboratories 

## CLIA INFORMATION 

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