A brief introduction
21 CFR Part 111 was created by the US Food and Drug Administration (FDA) and was first published in 2007. It provides current good manufacturing practices (cGMP) for the manufacturing, packaging, labeling and holding operations for dietary supplements. Adherence to 21 CFR Part 111 means that supplements meet safety and quality standards, protecting consumers from substandard, and potentially harmful, products.
The foundation stone of supplement safety lies in cGMP and 21 CFR Part 111 is the mandatory rulebook that governs manufacturing process. The ‘c’ in cGMP is of the utmost importance – the regulation is frequently updated so companies must stay up to date on cGMP.
Quality, quality, quality
The word “quality” underpins all of cGMP – to ensure a supplement meets all of its specifications and is of excellent quality, quality has to be built into the process from the very beginning.
Quality control is of the utmost importance at every step of the manufacturing process, and this is carried out in a number of ways;
- Setting Specifications – the standards that lay out the requirements for all raw materials and final products in terms of potency, composition and more.
- Monitoring – checking all manufacturing procedures are being adhered to
- Testing – both raw materials and the final product must be tested and verified to ensure that what is said on the label, is what is in the container
- Labeling Accuracy – verifying that labels are truthful and not misleading regarding the contents and certifications of the supplement
What does 21 CFR Part 111 cover?
21 CFR Part 111 is organized into subparts covering many aspects, some of which include:
- Personnel – all staff must be qualified through education, training and experience to perform duties required of them
- Equipment – all machinery equipment must be easy to clean and regularly maintained to prevent contamination or the provision of incorrect results (e.g. all scales must be calibrated accurately)
- Production and process controls – written procedures for all operations, such as the master manufacturing record and a batch production record for each specific batch that is created
- Specifications – created by a Quality team that details the standards for components, raw materials and finished products. These will include specifications regarding potency, identity and composition.
- Manufacturing operations – ensuring that every procedural step of the manufacturing process is properly documented and verified showing who carried out which step, when and how.
- Components, packaging and labels – identity testing of all lots of components before use and verification of packaging and labels
Ensuring adherence to 21 CFR Part 111
The FDA checks that relevant manufacturers adhere to the provisions laid out in 21 CFR Part 111 by way of unannounced inspections of manufacturing facilities. Inspections can include a review of manufacturing operations, review of labeling and claims verification, and a review of the sampling of raw materials and finished products.
In the case that a manufacturer is found to be in violation of the standards they will be issued observations, known as a Form 483. This form lists the auditors’ observations and acts as a signal to the company to act to address them.
The manufacturer is expected to respond to and address any observations listed in form 483 before their next inspection. Following the inspection, the FDA reviews the 483 alongside the detailed inspection report and will ultimately decide whether further enforcement action is warranted, such as a warning letter.