Implementation of FDA’s

Current Good Manufacturing

Practices for Dietary
Supplements

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 Current Good Manufacturing
Practices (CGMP’s) for Dietary
Supplements

This final rule establishes the minimum

CGMP’s to manufacturing, packing,
labeling, or holding dietary supplements
to ensure the quality of the dietary
supplement.

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 CGMP’s

The final rule is organized into 16

subparts that focus on specific aspects
of the manufacturing process or
addressing specific issues.

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 CGMP’s

General Provisions
Subpart A

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 Who is Subject to this Part?
§111.1
• Manufacture, package, label or hold a dietary
supplement.

• Package, label or distribute manufactured by

another firm.

• Sell in bulk to a distributor

• Imported or offered for import

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Other Statutory Provisions and
Regulations?
§111.5
In addition to these regulations, you
must comply with other applicable
statutory provisions and regulations
related to dietary supplements.

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CGMP’s
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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 CGMP’s

Physical Plant and Grounds

Subpart C

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 Physical Plant and Grounds
Subpart C
 Sanitation Requirements
 Establish and follow written
procedures
 Design and Construction requirements
 Record Keeping

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 CGMP’s

Equipment and Utensils

Subpart D

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 Equipment and Utensils
Subpart D
 Establish and follow written procedures
 Requirements
 Automated, Mechanical, Electrical
 Record Keeping

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 CGMP’s
Production and Process
Controls
Subpart E

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 Production and Process
Controls
Subpart E
 Implement a system of production and
process controls
 Design requirements
 Quality Control Operations
 Specifications
 Responsibility of Specifications

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 Production and Process
Controls
Subpart E
 Are Specifications met
 What to do if specifications are not met
 Representative samples
 Reserve sample requirements
 Material reviews and disposition decisions

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 Production and Process
Controls
Subpart E
 Requirements to Treatments, In-
process Adjustments and
Reprocessing
 Record Keeping

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 CGMP’s

Control Requirements for

Quality Control
Subpart F

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 Controls Requirements for
Quality Control
Subpart F
 Establish and follow written procedures
for the quality control operations unit.
 What Quality Control Personnel must do
 Quality control for Laboratory operations
 Material review and disposition decisions

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 Controls Requirements for
Quality Control
Subpart F
 Quality control for equipment, instruments and controls

 Quality control for components, packaging and labels

before use

 Quality control for master manufacturing record, batch

record and manufacturing operations.

 Quality control for Packaging and Labeling operations.

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 Controls Requirements for
Quality Control
Subpart F
 Quality control for returned dietary
supplements
 Quality control for Product Complaints
 Record Keeping

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 CGMP’s

Requirements for Components,

Packaging and Labeling
Subpart G

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 Requirements for Components,
Packaging, Labeling
Subpart G

 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.

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 CGMP’s

Master Manufacturing Record

Subpart H

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Master Manufacturing Record
Subpart H

 Prepare and follow a written master

manufacturing record for each unique
formulation of dietary supplement
 What the master record must include

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 CGMP’s
Batch Production Record
Subpart I

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 Batch Production Record

 A batch production record must be

established every time you
manufacture a batch
 Batch production record must include:

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 CGMP’s
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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 CGMP’s
Manufacturing Operations
Subpart K

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 Manufacturing Operations

 Establish and follow written procedures for

manufacturing operations
 Ensure product specifications are consistent
 Adequate sanitation principles
 Prevent contamination
 Appropriate disposition of rejected or
unsuitable dietary supplements

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 CGMP’s
Requirements for Packaging and
Labeling Operations
Subpart L

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 Requirements for Packaging
and Labeling Operations

 You must establish and follow written

procedures for packaging and labeling
operations
 Condition of packaging will ensure quality of
dietary supplements
 Requirements for filling, assembling
packaging, labeling and related procedures

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 Requirements for Packaging
and Labeling Operations

 Requirements for repackaging and

relabeling
 Packaged and labeled supplements
rejected for distribution
 Record Keeping

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 CGMP’s
Holding and Distributing
Subpart M

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 Holding and Distributing

 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

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 CGMP’s
Returned Dietary Supplement
Subpart N

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Returned Dietary Supplements

 Establish and follow written procedures under this

subpart
 Identify and quarantine returned dietary
supplements
 Destroy and suitably dispose of dietary
supplements
 Salvaging a returned dietary supplement
 Requirements for reprocessed dietary supplements

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Returned Dietary Supplements

 Investigation of manufacturing
processes and other batches
 Record Keeping

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 CGMP’s
Product Complaints
Subpart O

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 Product Complaints

 You must establish and follow written

procedures to fulfill the requirements of
this subpart
 Review and investigation of product
complaints
 Record Keeping

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 CGMP’s
Record and Recordkeeping
Subpart P

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 Records and Recordkeeping

 Recordkeeping requirements
 Records that must be made
available to FDA

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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 you
must: (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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 IFR

• This identity testing requirement applies

to a manufacturer who:
– purchases a dietary ingredient from a
dietary ingredient supplier
– manufactures its own dietary
ingredient for use in the manufacture
of its dietary supplement.

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 IFR

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

manufacturer’s 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 an
exemption.

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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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 IFR
– 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.

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 IFR

• Note: FDA may Take into account other

data and information that we may
have—for example, from other
manufacturers who use the same
supplier—in order to reduce the 100
percent identity testing requirements
applicable to the particular dietary
ingredient from the particular supplier.

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 IFR

• Confidential or trade secret information in

a petition is not available for public
disclosure, however this would not
preclude the agency from considering
information, such as that about a particular
supplier’s reliability, when it considers
whether to grant or deny other petitions for
exemption from 100 percent identity
testing from other manufacturers.
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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 and
type of data it recommends be included in the
citizen petition.
• The guidance will include our recommendations
about the type of information that a manufacturer
could 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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 IFR
• 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 information
that are specific to each dietary ingredient and
each supplier.
– If the manufacturer changes dietary ingredient(s)
or supplier(s), or any other combination thereof,
FDA’s approval would not apply to the particular
changed dietary ingredient

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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 manufacturer’s 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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 IFR

• The manufacturer would be responsible

for documenting the tests and
examinations for the dietary ingredient
under the terms specified by FDA when
the petition is granted, and must make
and keep such records under § 111.325
(21 CFR 111.325).

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 IFR
• Firm requesting petition must also maintain
records of FDA action on the petition

• If verification testing conducted by the

manufacturer 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 that
dietary 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 DSGMP’s

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.

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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.

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 Physical Plant & Grounds

• Sanitation - written procedures will

be in place for all sanitation and pest
control activities.
• Records that demonstrate that water
used as an ingredient is “safe and
sanitary”

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 Physical Plant & Grounds

• Physical Plant requirements – areas

identified for receiving, in-process and
holding 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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 Equipment and Utensils

• 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.

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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 quality
control 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

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 Current DSGMP’s

• Investigators will be looking at new

procedures, new records, new data
sheets.
• Ask questions to your Investigator or
Consumer Safety Officer
• Don’t 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 Williams
Special Asst. to Division Director
Division of Dietary Supplements
CFSAN

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Sara Dent Acosta, MS, MPH
Consumer Safety Officer
LOS-DO, FDA

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Implementation of Current Good
Manufacturing Practices for
Dietary 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, PhD
Constance Hardy
Linda Webb

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