Incomplete Batch Records & Ingredient Specifications

Ensure 483 responses are complete

This letter is a great reminder of the basics of Good Manufacturing Practices, starting with developing specifications to ensure the ingredients and products are correct and not contaminated with microbials or heavy metals.

FDA inspected this company in January and February last year, and they provided 483 responses over the next couple of months. The findings during the inspection and the incomplete 483 responses led to this warning letter.

Ingredient Heavy Metal Specifications:

From warning letter. “You did not provide any heavy metal or microbial test specifications for your Acetyl-glutathione component.”

Batch Production Record (BPR) Issues:

From warning letter “A statement of the actual yield and a statement of the percentage of theoretical yield at appropriate phases of processing (21 CFR 111.260(f)).”

Asa comments: This is important to identify whether ingredients were added correctly. For example, a lower-than-expected yield could signify missing ingredients or low capsule fill weight.

From warning letter. “Documentation, at the date and time of performance, of labeling operations (21 CFR 111.260(k))”

Asa comments: This is essential to verifying when processes were conducted, which can help identify issues before the product is released to the public.

From warning letter. “An actual or representative label, or a cross-reference to the physical location of the actual or representative label used in production (21 CFR 111.260(k)(2))”

Asa comments: Batch production records are recipes built in conjunction with the product label. Cross-referencing the label is a key part of ensuring the formula and label match.

Master Manufacturing Record (MMR) Size: 

Each formula size should be its own MMR.

From warning letter. “The MMR you provided in your April 8, 2024, response….not specific to a unique formulation of a dietary supplement and is not specific to batch size.

Incomplete 483 Responses: 

The bizarre thing about the warning letter is that it could have been prevented.

From warning letter. “Your response dated April 8, 2024, includes a document titled Returned Product Procedure. However, the procedure does not address the requirement for quality control to conduct a material review and make a disposition decision, as required by 21 CFR 111.510. The procedure states that the food safety officer will perform these activities.”

Here is another reference to an incomplete 483 response. “Your current finished product specification sheet for your Acetyl-glutathione product lists the test method as N/A.”

Quality Must Investigate To Prevent Bigger Potential Issues: 

The following section of the warning letter speaks to a core principle of GMPs: if there is a safety issue due to a product return, the company is required to ensure the return is not related to a problem that affects other batches. This does not need to be complicated, but it should be part of a product complaint or product return SOP.

From warning letter related to the Returned Products Procedure. “Furthermore, the procedure also does not address the requirement that if the reason for a dietary supplement being returned implicates other batches, you must conduct an investigation of the manufacturing processes and each of those other batches to determine compliance with specifications.”

There’s a lot more in this warning letter.