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21 CFR Part 111 - GMP for Dietary Supplement Manufactures
21 CFR Part 111 is a set of rules issued by the U.S. Food and Drug Administration (FDA) that explains how dietary supplements must be made, packaged, labeled, and stored for sale in the United States.
These rules help ensure that dietary supplements are safe, high in quality, and accurately labeled. Following these requirements is important for manufacturers and exporters to avoid FDA penalties and to build trust with consumers.
21 CFR Part 111, often referred to as the Dietary Supplement Current Good Manufacturing Practice (cGMP) rule, is a comprehensive set of regulations that governs the manufacturing, packaging, labelling, and holding of dietary supplements.
Exclusions: 21 CFR Part 111 does not cover dietary supplement advertising or claims (medicinal claims), which fall under the FTC or Drugs
Importance of 21 CFR Part 111
Compliance with 21 CFR Part 111 is essential for dietary supplement manufacturers for several reasons including the following
⊕ Compliance is a legal requirement in the USA. Failure to comply can result in regulatory action
⊕ Strict implementation helps preventing contamination, adulteration, and misbranding.
⊕ Compliance helps to ensure that dietary supplements are manufactured with consistent quality.
⊕ Improve market access by demonstrating that manufacturer is committed to quality and safety.
⊕ Compliance can enhance a manufacturer’s reputation and build consumer trust.
Key Areas Covered by 21 CFR Part 111
| Key Area | What It Covers (Simple Explanation) | 21 CFR Part 111 Reference |
|---|---|---|
| Personnel | Employees must be trained, supervised, and follow hygiene practices to prevent contamination. | 111.8 – 111.12 |
| Physical Plant & Grounds | Facilities must be clean, well-designed, maintained, and protected from pests. | 111.15 – 111.23 |
| Equipment & Utensils | Equipment must be suitable, cleaned, maintained, and calibrated regularly. | 111.25 – 111.35 |
| Raw Materials | Suppliers must be approved, and incoming materials checked for quality and safety. | 111.70 – 111.75 |
| Manufacturing Operations | Manufacturing must follow written procedures with proper controls and batch records. | 111.55 – 111.65 111.255 – 111.260 |
| Packaging & Labeling | Packaging must protect the product and labels must be accurate and compliant. | 111.403 – 111.415 |
| Holding & Distribution | Products must be stored and distributed under suitable conditions with records. | 111.455 – 111.475 |
| Quality Control | A Quality Control unit ensures GMP compliance, testing, and product release. | 111.65 – 111.127 |
| Returned Products | Returned supplements must be evaluated before reuse or disposal. | 111.503 – 111.535 |
| Product Complaints | Complaints must be documented, investigated, and corrected if needed. | 111.553 – 111.570 |
| Records & Documentation | All GMP activities must be documented and records retained for FDA review. | 111.605 – 111.630 |
21 CFR Part 111 Implementation Timeline
Implementing 21 CFR Part 111 typically takes 3 to 4 months, depending on the size and complexity of the manufacturing operations. The actual timeline can vary based on several factors, including the type and number of dietary supplement products manufactured at the facility, the total shop-floor area, and the overall layout of the production and storage spaces.
Additional considerations include the technical skills and GMP awareness of employees, the condition and suitability of equipment and utensils, the effectiveness of the air handling and ventilation systems, and the adequacy of waste disposal and sanitation practices.
A well-prepared facility with trained personnel and established processes can achieve compliance faster, while facilities requiring infrastructure upgrades or extensive training may need additional time.
21 CFR Part 111 Documentation Requirements
| Document Type | Purpose |
|---|---|
| Quality Manual | Defines the company’s quality policy, responsibilities, and commitment to dietary supplement CGMP compliance. |
| Mandatory Procedures | FDA-required written procedures covering quality control, production, packaging, labeling, complaints, and returns. |
| Standard Operating Procedures (SOPs) | Step-by-step instructions for routine GMP activities such as manufacturing, cleaning, calibration, sanitation, and training. |
| Validation Protocols & Records | Evidence that processes, cleaning methods, test methods, and systems perform consistently as intended. |
| Batch Manufacturing Records | Detailed records documenting raw materials, processing steps, in-process checks, deviations, and batch release. |
| Quality Plans | Documents outlining quality objectives, risk management activities, audits, and continuous improvement plans. |
| Specifications & Test Reports | Defined acceptance criteria and laboratory results verifying identity, purity, strength, and composition. |
| Training Records | Proof that personnel are trained in CGMP requirements and job-specific responsibilities. |
| Stability Records | Stability study data supporting shelf life, expiry dates, and storage conditions. |
| Complaint & Return Records | Documentation of product complaints, investigations, corrective actions, and returned product evaluations. |
Consequences of 21 CFR Part 111 Non-Compliance during FDA Onsite Inspection
⚠ Consequences of 21 CFR Part 111 Non-Compliance
Failure to comply with 21 CFR Part 111 during an FDA onsite inspection can result in serious regulatory and commercial consequences for dietary supplement manufacturers.
- FDA Warning Letters and regulatory citations
- Mandatory product recalls and market withdrawals
- Product seizures, financial penalties, or legal enforcement actions
- Damage to brand reputation and loss of consumer trust
- Supply chain disruptions and delayed U.S. market access
- Loss of distributor and customer confidence
Why Choose I3CGlobal for USFDA Pre and Post -Inspection Support?
Our GMP compliance services for dietary supplement manufacturers are designed to help you meet 21 CFR Part 111 requirements with confidence. We support you through gap assessments, CGMP documentation, SOP development, employee training, mock FDA inspections, and inspection readiness programs. With our hands-on regulatory expertise, we help you identify risks early, close compliance gaps, and face FDA inspections with assurance, ensuring uninterrupted access to the U.S. market and long-term regulatory compliance.
Generally, the FDA informs the owner or operator of the registered facility about the inspection at least two months in advance. Following the intimation, manufacturers and the regulatory team will be in a hurry to make everything align with 21 CFR 111 requirements.
21 CFR Part 111 Consultants – Implementation & Support Service Fee
Implementation Services
Complete 21 CFR Part 111 CGMP implementation including gap assessment, documentation, SOPs, and compliance support.
Final fees depend on product type, shop-floor area, number of employees, facility layout, and process complexity.
Pre-FDA Inspection Support
Onsite or remote pre-inspection readiness support, mock audits, documentation review, and employee preparedness.
Travel and accommodation costs are charged on actuals.
Post-Inspection (FDA 483 Closure)
Expert support for preparing 483 response, root-cause analysis, CAPA development, and observation closure.
Fees are based on the number and complexity of observations issued.
Our 21 CFR Part 111 consultants are strategically located in Germany, India, Portugal, UK and the USA, enabling efficient onsite support for global dietary supplement manufacturers.
The I3CGLOBAL team has successfully supported hundreds of companies across the globe in this gesture by providing excellent 21 CFR Part 111 implementation support and or Pre and Post FDA inspection support