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Implementation of FDAs

Current Good Manufacturing

Practices for DietarySupplements

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Current Good Manufacturing

Practices (CGMPs) for DietarySupplements

This final rule establishes the minimum

CGMPs to manufacturing, packing,labeling, or holding dietary supplements

to ensure the quality of the dietary

supplement.

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CGMPs

The final rule is organized into 16subparts that focus on specific aspects

of the manufacturing process or

addressing specific issues.

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CGMPs

General Provisions

SubpartA

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Who is Subject to this Part?

111.1

Manufacture, package, label or hold a dietarysupplement.

Package, label or distribute manufactured byanother firm.

Sell in bulk to a distributor

Imported or offered for import

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Definitions

111.3Actual Yield Batch Batch Number,

Lot Number,

Control Number

Component Contact Surface

Ingredient In-Process

Material

Lot Microorganisms Must

Pest Physical plant Product complaint Quality Quality Control

Quality control

Personnel

Representative

sample

Reprocessing Reserve Sample Sanitize

Theoretical yield Water activity We You

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Other Statutory Provisions and

Regulations?111.5

In addition to these regulations, youmust comply with other applicable

statutory provisions and regulations

related to dietary supplements.

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CGMPs

Personnel

Subpart B

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Personnel

Subpart B

Establish and follow written

procedures Microbial contamination

Qualified employees

Supervisor requirements

Record Keeping

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CGMPs

Physical Plant and Grounds

Subpart C

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Sanitation Requirements

Establish and follow writtenprocedures

Design and Construction requirements

Record Keeping

Physical Plant and Grounds

Subpart C

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CGMPs

Equipment and Utensils

Subpart D

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Establish and follow written procedures

Requirements Automated, Mechanical, Electrical

Record Keeping


Subpart D

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CGMPs

Production and Process

Controls

Subpart E

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Implement a system of production andprocess controls

Design requirements

Quality Control Operations

Specifications

Responsibility of Specifications


ControlsSubpart E

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Are Specifications met

What to do if specifications are not met

Representative samples

Reserve sample requirements

Material reviews and disposition decisions


ControlsSubpart E

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Requirements to Treatments, In-process Adjustments and

Reprocessing

Record Keeping


ControlsSubpart E

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CGMPs

Control Requirements forQuality Control

Subpart F

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Establish and follow written proceduresfor the quality control operations unit.

What Quality Control Personnel must do

Quality control for Laboratory operations

Material review and disposition decisions

Controls Requirements for

Quality ControlSubpart F

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Quality control for equipment, instruments and controls

Quality control for components, packaging and labelsbefore use

Quality control for master manufacturing record, batchrecord and manufacturing operations.

Quality control for Packaging and Labeling operations.



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Quality control for returned dietarysupplements

Quality control for Product Complaints

Record Keeping



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CGMPs

Requirements for Components,Packaging and Labeling

Subpart G

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Establish and follow written procedures

Requirements to components

Requirements to packaging and labels received

Requirements to products received for

packaging or labeling Requirements for rejected packaging and

labeling.

Requirements for Components,

Packaging, LabelingSubpart G

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CGMPs

Master Manufacturing Record

Subpart H

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Prepare and follow a written master

manufacturing record for each unique

formulation of dietary supplement

What the master record must include

Master Manufacturing Record

Subpart H

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CGMPs

Batch Production Record

Subpart I

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A batch production record must be

established every time youmanufacture a batch

Batch production record must include:

Batch Production Record

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CGMPs

Batch Laboratory Operations

Subpart J

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Requirements for

Laboratory Operations

Establish and follow written

procedures

Use adequate laboratory facilities

Requirements for Laboratory

control processes Methods for testing and

examination

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CGMPs

Manufacturing Operations

Subpart K

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Establish and follow written procedures for

manufacturing operations

Ensure product specifications are consistent Adequate sanitation principles

Prevent contamination

Appropriate disposition of rejected orunsuitable dietary supplements

Manufacturing Operations

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CGMPs

Requirements for Packaging andLabeling Operations

Subpart L

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You must establish and follow written

procedures for packaging and labelingoperations

Condition of packaging will ensure quality of

dietary supplements Requirements for filling, assembling

packaging, labeling and related procedures

Requirements for Packaging

and Labeling Operations

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Requirements for repackaging and

relabeling

Packaged and labeled supplements

rejected for distribution

Record Keeping

Requirements for Packaging

and Labeling Operations

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CGMPs

Holding and Distributing

Subpart M

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Establish and follow written procedures for holding

and distributing operations

Requirements to hold components, supplements,packaging and labels

Requirements for in-process materials

Requirements for reserve samples

Distribution requirements to protect against

contamination and deterioration

Holding and Distributing

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CGMPs

Returned Dietary Supplement

Subpart N

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Establish and follow written procedures under this

subpart

Identify and quarantine returned dietarysupplements

Destroy and suitably dispose of dietary

supplements

Salvaging a returned dietary supplement

Requirements for reprocessed dietary supplements

Returned Dietary Supplements

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Investigation of manufacturing

processes and other batches

Record Keeping

Returned Dietary Supplements

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CGMPs

Product ComplaintsSubpart O

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You must establish and follow written

procedures to fulfill the requirements of

this subpart

Review and investigation of product

complaints

Record Keeping

Product Complaints

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CGMPs

Record and RecordkeepingSubpart P

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Recordkeeping requirements

Records that must be madeavailable to FDA

Records and Recordkeeping

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Petition to Request Exemption from 100 Percent Identity

Testing of Dietary Ingredients

Interim Final Rule (IFR)

72 FR 34959 June 25, 2007

Ref: Current Good Manufacturing Practice in

Manufacturing, Packaging, Labeling or Holding

Operations for Dietary Supplements

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IFR

Requirement for 100 percent identity testing of

dietary ingredients is found at Subpart E

Requirement to Establish a Production and

Process Control System, 111.75 What must

you do to determine whether specifications are

met? in the CGMP final rule.

111.75(a)(1) Before you a component youmust: (1) Conduct at least one appropriate test

or examination to verify the identity of any

component that is a dietary ingredient.

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This identity testing requirement applies

to a manufacturer who:

purchases a dietary ingredient from adietary ingredient supplier

manufactures its own dietary

ingredient for use in the manufactureof its dietary supplement.

IFR

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IFR

FDA will consider, on a case-by-case basis, a

manufacturers conclusion, supported by

appropriate data and information in the petition

submission, that it has developed a system that it

would implement as a sound, consistent means

of establishing, with no material diminution of

assurance compared to the assurance provided

by 100 percent identity testing, the identity of the

dietary ingredient before use.

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IFR

The petition needs to set forth, at minimum:

Scientific Rationale for requested

exemption Supporting Data and information

Documenting and careful analysis of any

variability or errors in incoming product

Alternative testing proposal

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IFR

Under this IFR, firms will be granted

exemption from the requirement of 100

percent identity testing only when a manufacturer petitions the agency

under 10.30 and

the agency grants such anexemption.

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IFR

10.30 (21 CFR 10.30), the citizen

petition process requires your petition to

include: The action requested (i.e., a request

for an exemption from the

requirements of 111.75(a)(1)(i));A statement of grounds;

A section on environmental impact,

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A statement certifying that, to the best of your

knowledge and belief, your petition includes all

information and views on which the petition

relies, and that it includes representative data

and information known to you which are

unfavorable to the petition.

Identify any information in the petition that is

confidential commercial or trade secret

information

Should segregate such information from other

information in your petition.

IFR

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IFR

Note: FDA may Take into account other

data and information that we may

havefor example, from othermanufacturers who use the same

supplierin order to reduce the 100

percent identity testing requirementsapplicable to the particular dietary

ingredient from the particular supplier.

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Confidential or trade secret information in

a petition is not available for public

disclosure, however this would notpreclude the agency from considering

information, such as that about a particular

suppliers reliability, when it considers

whether to grant or deny other petitions forexemption from 100 percent identity

testing from other manufacturers.

IFR

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IFR

FDA has no preconceived notions of what would

constitute a successful petition. As we gain

experience in this area:

FDA will issue guidance on the information andtype of data it recommends be included in the

citizen petition.

The guidance will include our recommendations

about the type of information that a manufacturercould obtain about each supplier that it intends to

use for the ingredient and its specifications that

would assist us in evaluating the petition.

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IFR

The approval of an exemption

petition will be only for the dietary

ingredient(s) and supplier(s),requested in the petition.

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Manufacturers may use one petition to request an

exemption from 100 percent identity testing for one or

more dietary ingredients and one or more suppliers;

The petition needs to provide data and informationthat are specific to each dietary ingredient and

each supplier.

If the manufacturer changes dietary ingredient(s)

or supplier(s), or any other combination thereof,FDAs approval would not apply to the particular

changed dietary ingredient

IFR

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IFR

If the petition is granted, 111.75(a)(1)(i) would require

the manufacturer to implement the system identified in the

petition.

scientific method developed by the manufacturer identity may include physical characteristics (such as

crystal or powder), state of hydration, or part of the

plant (roots or leaves). The term identity would

include the manufacturers specification (s) that would

identify the attributes a supplier must meet.demonstrating that less than 100 percent identity

testing did not materially diminish assurance that the

dietary ingredient is the correct dietary ingredient.

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The manufacturer would be responsible

for documenting the tests and

examinations for the dietary ingredientunder the terms specified by FDA when

the petition is granted, and must make

and keep such records under 111.325(21 CFR 111.325).

IFR

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IFR

Firm requesting petition must also maintain

records of FDA action on the petition

If verification testing conducted by themanufacturer under the approved petition

results in failure of any component which is a

dietary ingredient to meet its identity

specification (s), the FDA approval for thatdietary ingredient and supplier would no

longer be in effect.

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IFR

Manufacturer would return to 100

percent identity testing until it can

re-petition FDA for a new exemption,and that re-petition is approved.

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Current DSGMPs

Inspections of Dietary Supplement firms:

There are a variety of firms of different

sizes and performing different activities

that will be subject to the new regulations.

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General Provisions

Applying new definitions during an inspection:

finished product, component and ingredient

Verifying if a component:

is an approved dietary ingredient, a new

dietary ingredient, a food substance or in

another category such as GRAS substance

or approved colors.

P l

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Personnel

Personnel requirements

Similar to what firms should already be doing

while preparing foods, including dietary

supplements

Procedures must be in writing and firms will

have to demonstrate they have trained their

employees in the procedures, that the

procedures are implemented and that they

are followed.

Ph i l Pl t & G d

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Physical Plant & Grounds

Sanitation - written procedures will

be in place for all sanitation and pestcontrol activities.

Records that demonstrate that water

used as an ingredient is safe andsanitary

Ph i l Pl t & G d

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Physical Plant & Grounds

Physical Plant requirements areas

identified for receiving, in-process andholding activities among others.

Look at what system the firm has in

place for keeping track of the

requirements under this part.


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Calibration - procedures and records of calibration

and preventive maintenance.

pH meters, thermometers, chart recorders,

scales

Keep in mind that many digital thermometers cannot

be adjusted; therefore calibration can only be

verified.

The records of this part will need to be reviewed by

Quality Personnel

Backup storage of Electronic records.

Production and Process Control

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Production and Process Control

Master Manufacturing record

written, implemented and followed.

Requirements of subparts E through L of this

part must be reviewed and approved by qualitycontrol personnel.

Items that need to be reviewed and approved there

should be a signature indicating the review and

approval.

Words that will be an important part of inspections

are: Specifications - Quality Identity Purity

Strength - Composition

Current DSGMPs

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Current DSGMPs

Investigators will be looking at new

procedures, new records, new datasheets.

Ask questions to your Investigator or

Consumer Safety Officer

Dont wait until the last minute.

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Monika Samtani

Moderator

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Janice Oliver

Deputy Director, CFSAN

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Vasilios H. Frankos, Ph.D.Dir., Division of Dietary Supplements

CFSAN

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Brad WilliamsSpecial Asst. to Division Director

Division of Dietary Supplements

CFSAN

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Sara Dent Acosta, MS, MPH

Consumer Safety OfficerLOS-DO, FDA

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Implementation of Current Good

Manufacturing Practices forDietary Supplements

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Sub Parts A - C

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Sub Parts D - P

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Interim Final Rule

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Inspections and

Other Considerations

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Moderator:

Monika Samtani

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Panelists/Presenters:

Dr. Vasilios Frankos

Brad Williams

Sara Dent Acosta

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Writer:

Angela Pope, MBA

Consumer Safety Officer

FDA/CFSAN/ONLDS

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Technical Assistance:Dr. Robert Moore, PhD

Dr. Kenneth Taylor, PhDConstance Hardy

Linda Webb

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In case of Trouble:Check with your IT

department.If unsuccessful, call:

1-888-626-8730

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Phone Bridge:1-888-469-1348

Access code:

5428315

Produced at the

FDA TV Studios, Division of Communication Media

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Producer/DirectorGlenn Scimonelli

Assistant Director

Barbara Ann Richards

Audio

Rodney Ladson

Floor Director

Rick Markley

Cameras

Stan Rose

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Stan Rose

Patty Edwards

Marty Martin

Stefan Monica

Lighting Director

Jim Sweeny

Graphics/IT Support

Dave Bailey

Videotape

Barry Goldstein

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Barry Goldstein

Phone/Fax/Email

Mike Sobola

PowerPoint

Kenton Frederic

Teleprompter

Jeannie Vinson

Makeup

Kim Foley

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Engineering Services

Jon Fleetwood

Contract Video Specialists

Division Director

Dr. Robert McCleary

dscgmps9

Documents