InstantGMP Compliance Series for Dietary Supplements

Improving Specifications

Electronic cGMP Manufacturing Execution System

GMP Problems - Specifications

• Common citation in FDA Warning Letters

• Failure to set specifications for each component and for final product– Identity

– Purity

– Strength

– Composition

Electronic cGMP Manufacturing Execution System

GMP Problems - Specifications

• Specifications have to be set and met

• Failure to make or met specifications can lead to regulatory action such as an injunction

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Electronic cGMP Manufacturing Execution System

Why Specifications are Important

• Ensures you can verify identity, purity, strength and composition of final product

• Identify specs ensures you have the right ingredients in the product

• Strength allows calculation of precisely how much to add to a batch

• Purity specs keep contaminants from adulterating a batch

Electronic cGMP Manufacturing Execution System

Specifications Needed For:

• Components• In-process production• Labels and packaging• Finished batch of dietary supplement• Product you receive from a supplier for packaging

and labeling• Packaging and labeling for the finished dietary

supplement

Electronic cGMP Manufacturing Execution System

Specifications Parts:

• Test - Measurement of a quality attribute such as potency or water content

• Method - The procedure by which the quality attribute is measured

• Limit - The acceptable range for the attribute• Other Requirements

– Safety and Handling– Sampling Instructions

Electronic cGMP Manufacturing Execution System

Component Specifications

• Identity for each component of a dietary supplement

• A salt in a vitamin and mineral supplement may include the physical characteristics of the solid such as color and the state of hydration

• Identity of a botanical may include the part of the plant (e.g., roots or leaves), the color, and whether the part of the plant is in a native state or has been ground.

Electronic cGMP Manufacturing Execution System

Component Specifications

• Component specifications must ensure purity, strength, and composition of final product

• Limits for types of contamination that may adulterate or may lead to adulteration of the finished batch

Electronic cGMP Manufacturing Execution System

Vitamin and Minerals ID

• Specifications might include:– Identification– Assay– Appearance– Odor– Solubility– Melting Point– Loss on Drying or Residue on Ignition– Heavy Metals– Organic Volatile Impurities

Electronic cGMP Manufacturing Execution System

Botanicals ID

• Identity of a botanical may include:– The part of the plant (e.g., roots or leaves) to be used

– Color

– Odor

• Whether the part of the plant is in a native state or has been ground up

• Characteristics that differentiate botanical from related species

Electronic cGMP Manufacturing Execution System

In-Process Specifications

• Needed for any point where control in the manufacturing process ensures quality, for example:– Heating steps– Cooling steps– Specific sanitation procedures to protect product– Points where cross-contamination might occur– Where environmental hygiene is necessary

Electronic cGMP Manufacturing Execution System

Final Product Specifications

• Required for Dietary Supplements– Identity– Purity– Strength– Composition

• Limits on contaminates that may adulterate the final product

• May exempt spec if no scientifically valid method is available

Electronic cGMP Manufacturing Execution System

Preventing Adulteration

• Prevent adulteration by taking precautions during manufacturing

• Eliminate possible microbial contamination from raw materials

• Clean and/or sanitize critical equipment• Test components and equipment• Use established specifications and tests• Limit the contaminates that could be introduced

into the batch

Electronic cGMP Manufacturing Execution System

Specifications: Packaging/Labeling Firms

• Firms who perform labeling operations must establish specifications

• Ensure product received is adequately identified

• Set specs for packaging that may be in contact with dietary supplements

• Ensure product is consistent with purchase order

Electronic cGMP Manufacturing Execution System

Some Specs Not Needed

• Dissolution• Disintegration• Bioavailability• Premature to impose requirements in areas where

science is still evolving• Aesthetic appearance of dietary supplement• Various constituents that are normally present in a

natural product

Electronic cGMP Manufacturing Execution System

Exempted Specifications

• Specifications are exempted if you show that:– The spec selected is not able to verify that the control

system is producing a dietary supplement that is within that spec

– There is no scientifically valid method for testing or examining the exempted product spec at the finished batch stage

– You document why other information, such as component and in-process testing, will show the spec is met without finished batch testing for that spec

Specification List Example

Electronic cGMP Manufacturing Execution System

InstantGMP™ - makes specifications easy!

• Web-based manufacturing execution system

• Includes specification system with version control for GMP manufacturing

• Uses built-in quality procedures to check and control GMP compliance

• Provides opportunities for more flexibility, visibility and productivity

InstantGMP™

Find more presentation and videos on GMP Compliance for Dietary

Supplements in the Resource Center at

www.InstantGMP.com