Dietary Supplement GMP Lessons

The warning letter covers manufacturing equipment flaws, theoretical yields, incomplete 483 responses, missing product specifications, and other issues. Fun reminders of the importance of GMP compliance.

First, the manufacturing equipment flaws. Here, FDA notes that the seams inside a hopper were not smooth, creating an environment that could lead to issues or the introduction of pathogens. In my earlier career, I helped run contract manufacturing for 14 years and have seen how small issues in equipment, such as cracks or improper coating, can create issues over time. Here, FDA notes that there is a major allergen, wheat bran, in the seams, possibly creating serious allergenic contamination issues.

From warning letter. “You failed to ensure equipment and utensils you use have seams that are smoothly bonded or maintained to minimize accumulation of dirt, filth, organic material, particles of components or dietary supplements, or any other extraneous materials or contaminants. … The hopper was observed to have an accumulation of dietary supplement residue in the seams of the equipment. Furthermore … is a product that contains the allergen wheat bran and you manufacture products that do not contain this ingredient on shared equipment.

Asa comments on incomplete 483 responses. In many cases, companies can address 483s before they become a warning letter. Here, the company made corrections but didn’t show their work, which is a very basic but important reminder on how to properly respond to a 483.

FDA warning letter. “We have reviewed your response to the FDA Form 483… In your response, you stated that you reviewed and made corrections to your sanitation procedures and logs and retrained staff. You also stated that you implemented … sanitation inspections and conduct reviews of your cleaning logs. Your response is not sufficient in that you did not submit any evidence of corrective and preventive actions by providing copies of your updated cleaning SOPs or photos indicating that the hopper used in manufacture of your dietary supplement products has seams that are smoothly bonded to prevent accumulation of dirt, filth, organic material, particles of components or dietary supplements, or any other extraneous materials or contaminants, and that your cleaning and sanitizing procedures are effective.”

Asa Comments on theoretical yield: It helps manufacturers identify potential issues before they reach the next phase of manufacturing. For example, if the yield is too high or too low, it may signal that too much or too little of an ingredient was added, product was lost during manufacturing, or something in the batch record needs review.

From warning letter. “Specifically, your master manufacturing record … failed to include the following required elements of 21 CFR 111.210: A statement of theoretical yield of a manufactured dietary supplement expected at each point, step, or stage of the manufacturing process where control is needed to ensure the quality of the dietary supplement, and the expected yield when you finish manufacturing the dietary supplement, including the maximum and minimum percentages of theoretical yield beyond which a deviation investigation of a batch is necessary and material review is conducted and disposition decision is made”

Read the warning letter.