Implementation of FDAs Current Good Manufacturing Practices for Dietary Supplements

Current Good Manufacturing Practices (CGMPs) for Dietary Supplements

This final rule establishes the minimum CGMPs to manufacturing, packing, labeling, or holding dietary supplements to ensure the quality of the dietary supplement.

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

CGMPs
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

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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.

CGMPs
Personnel Subpart B

Personnel Subpart B
Establish and follow written procedures Microbial contamination Qualified employees Supervisor requirements Record Keeping

CGMPs
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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CGMPs
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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CGMPs
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, Inprocess Adjustments and Reprocessing Record Keeping

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CGMPs
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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CGMPs
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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CGMPs
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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CGMPs
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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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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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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CGMPs
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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CGMPs
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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CGMPs
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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CGMPs
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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CGMPs
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 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 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 havefor example, from other manufacturers who use the same supplierin 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 suppliers 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, FDAs 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 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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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 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.

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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 DSGMPs
Investigators will be looking at new procedures, new records, new data sheets. 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 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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