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**INTERNATIONAL FORMULA COUNCIL**

***Formerly the Enteral Nutrition Council and Infant Formula Council***

**5775-G Peachtree-Dunwoody Road, Suite 500 • Atlanta, Georgia 30342**

**(404) 252-3663 • Fax (404) 252-0774 • E-mail: ifc@kellencompany.com**

#  **ATTACHMENT D**

# 

# Via E-mail and Federal Express

June 27, 2003

Dr. Christine Taylor, HFS-800

Food and Drug Administration

CFSAN, CPK1/4C096

5100 Paint Branch Parkway

College Park, MD 20740-3835

Dear Dr. Taylor:

In March 2003, FDA charged its Food Advisory Committee, Subcommittee on
Contaminants and Natural Toxicants, to address intervention strategies
that can be used in infant formula manufacturing processes and plants to
reduce the risk of *Enterobacter sakazakii (E. sakazakii)*. The
Subcommittee made the following recommendation: "Intervention
strategies, which reduce bacterial presence in powdered infant formula,
should be used in manufacturing processes and plants. These include, but
are not limited to, prerequisite programs to assure the microbial
quality of raw materials, hygienic design and maintenance of equipment,
hygienic zoning in plant design, and continuous use and improvement of
HACCP programs and their verification."

We earlier advised you that we would be providing information we believe
will be of assistance regarding issues related to *E. sakazakii* and
powdered infant formula. On this note, attached for your review, is a
document developed by the infant formula industry\* addressing *E.
sakazakii* with respect to good manufacturing practices entitled
"Proposed Discussion Points on Powdered Infant Formula Good
Manufacturing Practices." The industry brings forth for discussion those
Prerequisite Programs (PrPs) and procedures for powdered infant formula
where significant enhancement may have been achieved since the 1996
Proposed Rule: Current Good Manufacturing Practices, Quality Control
Procedures, Quality Factors, Notification Requirements, and Record and
Reports, for the Production of Infant Formula (i.e. 21 CFR Parts 106 and
107). We look forward to discussing this document with you when we meet.

For your further information, the industry is currently working on two
additional documents addressing *E. sakazakii* with respect to
microbiological testing and sampling of powdered infant formula, and
special products. We believe this information will be of further
assistance to you and we will be pleased to provide it as soon as it is
available.

Sincerely,

### Robert C. Gelardi Mardi K. Mountford

## 

## Robert C. Gelardi Mardi K. Mountford

## President Executive Director

\* Note: United States infant formula manufacturers are Bristol-Myers
Squibb, Mead Johnson Nutritionals; Nestlé USA, Nutrition Division;
Abbott Laboratories, Ross Products Division; Solus Products; and Wyeth
Nutrition.

cc: Dr. Sue Anderson (w/attachment)

Brian Somers " "

Dr. Don Zink " "

Dr. Bob Buchanan " "

International Formula Council

5775 Peachtree Dunwoody Road

Bldg. G, Suite 500

Atlanta, GA 30342

Phone: (404) 252-3663 Fax: (404) 252-0774

Proposed Discussion Points on Powdered Infant

# Formula Good Manufacturing Practices

## Introduction

It is clear from the 1996 Proposed Rule: Current Good Manufacturing
Practice, Quality Control Procedures, Quality Factors, Notification
Requirements, and Records and Reports, for the Production of **Infant**
**Formula,** (i.e. 21 CFR Parts 106 and 107) -- as well as from industry
comments on that Proposed Rule -- that there is a general awareness of
the need for control procedures (i.e. HACCP and Prerequisite Programs)
to prevent adulteration of in-process and finished products with
biological, chemical or physical hazards in addition to
formulation/nutrition related hazards. It is also generally understood
that, since powdered infant formula is a food, the basic GMPs required
for food manufacture represent a minimum threshold requirement.

The proposed control procedures brought forward here for further
discussion with the FDA will focus on those Prerequisite Programs (PrPs)
and procedures relevant to powdered infant formula where significant
enhancement may have been achieved since 1996, or areas where procedures
still need to be developed to adequately provide:

-   Controls to prevent adulteration caused by workers (Sec. 106.10
    a-c).

-   Controls to prevent adulteration caused by facilities (Sec.106.20
    a-i).

-   Controls to prevent adulteration caused by use of equipment or
    utensils that are of inappropriate design, installation, etc. (Sec.
    106.30 a, f).

-   Controls to prevent adulteration caused by ingredients, containers,
    and closures (Sec. 106.40 d).

Prerequisite Programs and procedures relative to \"controls to prevent
adulteration by microorganisms (i.e. finished product monitoring)\" will
be addressed by a separate industry proposal.

**[Discussion Points]{.underline}**

1.  **Controls to prevent adulteration caused by workers (Sec. 106.10
    a-c)**

> Beyond the norm for industry Personnel GMPs, the following enhanced
> practices or components of PrPs may provide an extra measure of
> protection against recontamination by biological, chemical, and
> physical hazards of in-process and finished product materials:

-   Dedication of outer garments including footwear for use in High
    Hygiene areas. *High Hygiene areas will be defined as those areas
    where infant powder is exposed to the environment in its final form
    as it is processed, conveyed, stored, or filled into primary
    packaging.* The effectiveness of this practice can be further
    enhanced by the use of specially designed anterooms/airlock where
    outer garments and footwear can be changed while moving from one
    hygiene level zone to another. Facilities for hand disinfection may
    also be provided. (See Hygienic Zoning below.)

-   Inclusion of strict hygienic procedures, for outer garments, tools,
    and utensils which may come in contact with the food contact
    surfaces, in personnel practices particularly for maintenance and
    line workers required to make line interventions due to process
    stoppage for any number of reasons.

-   Enhancement of practices for all contractors\' performing work
    within the factory, equivalent to those required for factory
    personnel.

2.  **Controls to prevent adulteration caused by facilities (Sec.106.20
    a-i).**

> Beyond the norm for industry Facility GMPs, the following enhanced
> practices or components of PrPs may provide an extra measure of
> protection against recontamination by microbiological hazards of
> in-process and finished product materials:

-   Physical segregation of different unit operations or activities
    including the use of physical barriers (i.e. Hygienic Zoning) in
    regards to hygiene levels (i.e. High, Medium, and Base GMP for
    example).

    -   High Level areas are where processed products are exposed and
        vulnerable to process environmental influences for
        recontamination. Enhanced microbial environmental control
        practices with verification required. Dry cleaning practices are
        also normally required for such designated areas.

    -   Medium Level areas are where experience should demonstrate that
        sensitivity of the product stream is reduced from that described
        for High Hygiene zones. Typically, process line may be enclosed
        and risk of recontamination is lower. Microbial environmental
        control practices with verification are still required. Dry and
        wet cleaning or controlled wet cleaning practices may be
        employed.

    -   Base GMP Level areas would represent general facility area such
        as warehousing, maintenance, personnel traffic areas and do not
        require the same level of control or verification as the High
        and Medium Level zoned areas.

-   Physical separation including, but not limited to, hygienic
    engineering design to accomplish segregation of:

    -   Wet and dry manufacturing processes.

    -   Wet and dry cleaning and Sanitary Standard Operating Procedures
        (SSOPs).

    -   Raw materials handling and finished goods handling activities.

    -   Processing, packaging and general warehousing areas.

    -   Filtered ambient air and non-filtered air process environments.

-   Zoning to provide control over personnel, equipment, and materials
    traffic as well as circulation of ambient air (i.e. treated/filtered
    versus non-treated/filtered) and makeup air for treated/filtered
    process air. Details of the manufacturing line layout and equipment
    installation must complement the concept of zoning.

-   Use and management of water within the manufacturing process and
    environment to provide for strict control and minimization wherever
    possible to reduce the risk of microbial proliferation. This control
    should be addressed in PrPs related to SSOPs and facility hygienic
    design.

3.  **Controls to prevent adulteration caused by use of equipment or
    utensils that are of**

**inappropriate design, installation, etc. (Sec. 106.30 a, f)**

> Beyond the norm for industry Equipment GMPs, the following enhanced
> practices or components of PrPs may provide an extra measure of
> protection against recontamination by microbiological hazards of
> in-process and finished product materials:

-   Hygienic design for all processing equipment, tools, utensils, etc.
    to assure cleanability and the elimination of hollow body components
    that may provide micro-niches for microbial proliferation.

-   Hygienic design of processing equipment to eliminate water to the
    extent possible from the process (e.g., steam condensate, condensate
    from coolers, spray dryer exhaust water scrubbers). Dehumidification
    of cooling and transport air will also contribute to the elimination
    of moisture.

-   Hygienic design of processing equipment to assure use of process
    water/agglomerator rewet water of highest microbiological and
    chemical quality.

-   Design of processes to minimize the addition of ingredients to the
    process stream post-heat treatment to avoid post-process
    contamination. Assure appropriate PrPs for any ingredients that are
    added after heat treatment.

-   Explore the design of possible manufacturing operations to provide
    dedicated equipment for products where allergens may be of concern.
    Allow for longer and drier process runs and further reduction of the
    need for wet cleanup.

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-   Continue use of improved cleaning SSOPs and equipment to assure
    adequate cleaning and appropriate control of residual moisture. Work
    with vendors should continue in order to develop equipment with
    improved sanitary design and enhanced efficacy of
    cleaning/sanitizing tools, chemicals, and practices.

4\. **Controls to prevent adulteration caused by ingredients,
containers, and closures (Sec.**

**106.40 d)**

Beyond the norm for industry Ingredient, Packaging, and Closure GMPs,
the following enhanced practices or components of PrPs may provide an
extra measure of protection against recontamination by microbiological
hazards of in-process and finished product materials:

-   Implementation and maintenance of a strict ingredient supplier
    quality assurance program for all raw materials suppliers deemed
    sensitive or critical (particularly for dry mix operations). The
    industry as a whole may benefit from a collaboration in this area
    due to the limited number of qualified suppliers for common
    ingredients such as milk derivatives (e.g. whey and casein powders)
    and soy derivatives (e.g. isolated soy proteins, soy protein
    concentrates) to name a few.