# Presentation: 573652

##   Implementation of FDA’s Current Good Manufacturing Practices for Dietary Supplements

**  ****Implementation of FDA’s Current Good Manufacturing Practices for Dietary Supplements**

## 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.

## CGMP’s

- The final rule is organized into 16 subparts that focus on specific aspects of the manufacturing process or addressing specific issues.

## CGMP’s

**General Provisions**
**Subpart**** ****A**

## 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

## Definitions   §  111.3 

| Actual 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  |  |

## 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**.**

## CGMP’s

**Personnel**
**Subpart B**

## Personnel Subpart B

- Establish and follow written procedures
- Microbial contamination
- Qualified employees
- Supervisor requirements
- Record Keeping

## CGMP’s

**Physical Plant and Grounds**
**Subpart C**

## Sanitation Requirements 
Establish and follow written procedures
Design and Construction requirements
Record Keeping

- Establish and follow written procedures
- Design and Construction requirements
- Record Keeping

**Physical Plant and Grounds****Subpart C**

## CGMP’s

**Equipment and Utensils**
**Subpart D**

## Establish and follow written procedures
Requirements
Automated, Mechanical, Electrical
Record Keeping

- Requirements
- Automated, Mechanical, Electrical
- Record Keeping

**Equipment and Utensils**** Subpart D**

## CGMP’s

**Production and Process Controls**
**Subpart E**

## Implement a system of production and process controls
Design requirements
Quality Control Operations
Specifications
Responsibility of Specifications 

- Design requirements
- Quality Control Operations
- Specifications
- Responsibility of Specifications

**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

- What to do if specifications are not met
- Representative samples
- Reserve sample requirements
- Material reviews and disposition decisions

**Production and Process Controls****Subpart E**

## Requirements to Treatments, In-process Adjustments and Reprocessing
Record Keeping

- Record Keeping

**Production and Process Controls****Subpart E**

## CGMP’s

**Control 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

- What Quality Control Personnel must do
- Quality control for Laboratory operations
- Material review and disposition decisions

** ****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.

- 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.

** ****Controls Requirements for****Quality Control ****  Subpart F**

## Quality control for returned dietary supplements
Quality control for Product Complaints
Record Keeping

- Quality control for Product Complaints
- Record Keeping

** ****Controls Requirements for Quality Control ****  Subpart F**

## CGMP’s

**Requirements for Components, Packaging and 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.

- 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, Labeling ****  Subpart G**

## CGMP’s

**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

- What the master record must include

**Master Manufacturing Record ****  Subpart H**

## CGMP’s

**Batch Production Record **
**Subpart I**

## A batch production record must be established every time you manufacture a batch
Batch production record must include:

- Batch production record must include:

**Batch Production Record **

## CGMP’s

**Batch Laboratory Operations **
**Subpart J**

## Requirements forLaboratory Operations

- Establish and follow written procedures
- Use adequate laboratory facilities
- Requirements for Laboratory control processes
- Methods for testing and examination

## CGMP’s

**Manufacturing Operations**
**Subpart K**

## 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

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

**Manufacturing Operations**

## CGMP’s

**Requirements for Packaging and Labeling Operations**
**Subpart L**

## 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

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

**Requirements for Packaging and Labeling Operations**

## Requirements for repackaging and relabeling
Packaged and labeled supplements rejected for distribution
Record Keeping	

- Packaged and labeled supplements rejected for distribution
- Record Keeping

**Requirements for Packaging and Labeling Operations**

## CGMP’s

**Holding and Distributing**
**Subpart M**

## 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

- 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**

## CGMP’s

**Returned Dietary Supplement**
**Subpart N**

## 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

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

**Returned Dietary Supplements**

## Investigation of manufacturing processes and other batches
Record Keeping

- Record Keeping

**Returned Dietary Supplements**

## CGMP’s

**Product Complaints**
**Subpart O**

## You must establish and follow written procedures to fulfill the requirements of this subpart
Review and investigation of product complaints
Record Keeping

- Review and investigation of product complaints
- Record Keeping

**Product Complaints**

## CGMP’s

**Record and Recordkeeping**
**Subpart P**

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

- Records that must be made available to FDA

**Records and Recordkeeping**

## 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

## 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.

## 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. 

-  purchases a dietary ingredient from a dietary ingredient supplier
- manufactures its own dietary ingredient for use in the manufacture of its dietary supplement.

**IFR**

## 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**.**

## 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

## 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.** **

## 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,

## 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.

- 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**

## 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.

## 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.

**IFR**

## 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.

## IFR

- The approval of an exemption petition will be only for the dietary ingredient(s) and supplier(s), requested in the petition.

## 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

- 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

**IFR**

## 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.

## 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).

**IFR**

## 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.

## 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.

## 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.

## 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.

## 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.

## 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”

## 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.

## 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.

## 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

## 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.

## Monika Samtani
Moderator

- Moderator

## Janice Oliver
Deputy Director, CFSAN

- Deputy Director, CFSAN

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

- Dir., Division of Dietary Supplements
-  CFSAN

## Brad Williams
Special Asst. to Division Director
Division of Dietary Supplements
 CFSAN

- Special Asst. to Division Director
- Division of Dietary Supplements
-  CFSAN

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

- Consumer Safety Officer
- LOS-DO, FDA

## Implementation of Current Good Manufacturing Practices for Dietary Supplements

## Sub Parts A - C

## Sub Parts D - P

## Interim Final Rule

## Inspections and 
Other Considerations

- Other Considerations

## Moderator:
Monika Samtani

- Monika Samtani

## Panelists/Presenters:
Dr. Vasilios Frankos
Brad Williams
Sara Dent Acosta

- Dr. Vasilios Frankos
- Brad Williams
- Sara Dent Acosta

## Writer:
Angela Pope, MBA
Consumer Safety Officer
FDA/CFSAN/ONLDS

- Angela Pope, MBA
- Consumer Safety Officer
- FDA/CFSAN/ONLDS

## Technical Assistance:
Dr. Robert Moore, PhD
Dr. Kenneth Taylor, PhD
Constance Hardy
Linda Webb

- Dr. Robert Moore, PhD
- Dr. Kenneth Taylor, PhD
- Constance Hardy
- Linda Webb

## In case of Trouble:
Check with your IT department.
If unsuccessful, call:
1-888-626-8730

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## Produced at the
FDA TV Studios, Division of Communication Media

Producer/Director
Glenn Scimonelli

Assistant Director 
Barbara Ann Richards

Audio
Rodney Ladson

Floor Director
Rick Markley

- FDA TV Studios, Division of Communication Media
- Producer/Director
- Glenn Scimonelli
- Assistant Director
- Barbara Ann Richards
- Audio
- Rodney Ladson
- Floor Director
- Rick Markley

## Cameras
Stan Rose
Patty Edwards
Marty Martin
Stefan Monica

Lighting Director
Jim Sweeny

Graphics/IT Support
Dave Bailey

- Stan Rose
- Patty Edwards
- Marty Martin
- Stefan Monica
- Lighting Director
- Jim Sweeny
- Graphics/IT Support
- Dave Bailey

## Videotape
Barry Goldstein 

Phone/Fax/Email
Mike Sobola

PowerPoint
Kenton Frederic

Teleprompter
Jeannie Vinson

Makeup
Kim Foley

- Barry Goldstein
- Phone/Fax/Email
- Mike Sobola
- PowerPoint
- Kenton Frederic
- Teleprompter
- Jeannie Vinson
- Makeup
- Kim Foley

## Engineering Services
Jon Fleetwood
Contract Video Specialists

Division Director
Dr. Robert McCleary

- Jon Fleetwood
- Contract Video Specialists
- Division Director
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