PART IV

**[ANALYTICAL]{.underline}**

**A. [ANALYZING LABORATORIES]{.underline}**

> The district will make all the necessary arrangements for proper
> handling of samples with the following designated testing facilities:
>
> [TYPES OF DEVICES]{.underline} [ANALYZING LABORATORIES]{.underline}

All General Medical Devices Winchester Engineering and Analytical Center

(WEAC)

109 Holton Street

Winchester, Massachusetts 01890-1197

Radioimmunoassay WEAC

All Other In Vitro Micro---WEAC

> Diagnostic Devices Chem---WEAC
>
> [Testing for sterility of finished devices,]{.underline} WEAC
>
> [package integrity, bioburden,]{.underline}
>
> [and endotoxins]{.underline}:

[Testing of biological indicators]{.underline}: WEAC

> See PART VI regarding those persons designated as contacts for WEAC
> and specific products.
>
> SPECIAL NOTE: For all other devices and questions concerning sampling
> of devices and laboratory capabilities, contact Division of Field
> Science (DFS), HFC-140, (301) 827-7605.

**B. [ANALYSES TO BE CONDUCTED]{.underline}**

> Sample collection and analysis will be determined on a case-by-case
> basis through consideration of inspectional findings, compliance and
> scientific capabilities and expertise. Full collaboration between
> investigations and analytical personnel is essential. See Part III, A,
> 4 for additional information.

**C. [METHODOLOGY]{.underline}**

1\. [Testing Finished Device Samples for Sterility]{.underline}

a\. Visually examine each unit to ascertain that its packaging is
intact. Report all defects observed by describing the size, type and
location of the defects. Units with defective packaging need not be
examined for sterility.

b\. Finished device samples are to be tested in accordance with the
requirements of USP 24 methodology for Sterility Tests. **Reference the
FDA Sterility Analytical Manual for guidance on applying the USP
methods.**

c\. Device samples are to consist of 132 units, as follows:

30 units tested in Soybean-Casein Digest Broth

30 units tested in Fluid Thioglycollate Broth

60 units for re-test, if required under USP methodology

10 units for bacteriostasis/fungistasis testing

2 units for system control

When 132 units are not available because of lot size or cost, follow the
USP 24 recommendations for the minimum number of articles to be tested
in each media, as follows:

Number of Articles Number of Articles

[in the Batch]{.underline} [to be tested]{.underline}

Not more than 100 articles 10% or 4 articles,

whichever is greater

More than 100, but not more 10 articles

500 articles

More than 500 articles 2% or 20 articles

> Note that the USP permits the division of articles into equal portions
> for addition to each of the specified media when the contents of the
> article are of sufficient quantity (see USP 24 to determine what is a
> sufficient quantity).
>
> NOTE: For the purposes of this compliance program, the "articles"
> referred to in the USP may be interpreted as devices.

d\. Positive subsamples

Check cultures for growth daily and begin qualitative analysis of growth
immediately upon detection of growth. Follow subculturing procedures in
the Sterility Analytical Manual. Continue to incubate growth vessels
after subculture for full term analysis to detect slow growing bacteria
and molds. For each subsample found to be non-sterile, prepare a pure
culture of each contaminant.

All isolates from sterility tests must be maintained until otherwise
notified by CDRH or for one year.

2\. [Presterilization Microbial Contamination (Bioburden)]{.underline}

Bioburden testing is to be performed in accordance with the guidance
provided in ISO 11737-1, Sterilization of medical devices -
Microbiological methods - Part I: Estimation of population of
microorganisms on products. The methodology used for estimating the
bioburden is to be validated. Twenty units are to be tested.

3\. [Analysis of Biological Indicators]{.underline}

Test 40 biological indicators according to USP 24 using sterilization
conditions specified on the indicator label. \"Survival time and kill
time\" and \"Resistance performance tests\" are to be used. 80
additional biological indicators may be required if either performance
test fails. Under some conditions, the D-Value may also be determined.
That determination requires a minimum of 45 biological indicators. These
determinations will be performed according to the claims of the
manufacturer of the indicator or inoculated product. Pertinent test
specifics will be required.

4\. [Analysis of Packaging Defects]{.underline}

> Perform a visual, non-destructive, inspection of the package noting
> the existence and location of seal or material defects. Normally 20
> packaged devices will be collected for analysis. Further testing is to
> be performed using consensus standards such as those identified in the
> Part VI.A.1 references for the American Society for Testing and
> Materials (ASTM). Selection of the test will depend on the materials
> and construction of the package, and on the nature of the noted or
> suspected problem.

5.  [Analysis of Endotoxins]{.underline}

Samples will be analyzed using the Bacterial Endotoxins Test found in
USP 24 and the Sterility Analytical Manual. Ten units are required for
endotoxin testing.