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