GMP Issues

There are so many important GMP lessons in this warning letter. Let’s see what we can learn.

Botanical identification methods:  When developing botanical specifications, ensuring they are complete is essential. In the warning letter, the company apparently did not add crucial aspects of specifications.

• From warning letter. “None of these components have a listed specification target, range, reference, or test method.”

Incomplete 483 responses: When responding to 483s, it is important to follow through. Here, FDA cites the company for seemingly not providing the promised information.

• From FDA: “We have reviewed your response dated November 10, 2023. In your response you state you will create specifications for raw materials and that you estimate it will take approximately 90 days. You did not provide any documentation of your specifications, so we cannot evaluate the implementation.”

Internal audits are a good best practice but are generally not required unless an SOP states this. In this warning letter, the company is cited for not following its own SOP. The lesson here is ensuring SOPs are developed with the entire company’s capabilities in mind, as SOP requirements can paint a company into a compliance corner.

• From warning letter. “You did not conduct periodic Good Manufacturing (GMP) internal audits of the entire plant with documented corrective actions, as required by your SOP... An internal audit has not been conducted since 2022."

Master Manufacturing Records (MMRs) are the “recipe and directions” for making products. When I was in manufacturing, I would describe the MMR as this: “If someone has never made this product before, they can pick up the MMR and figure out how to make it perfectly every time.”

Here FDA cites the company for not having a theoretical yield. This “lily pad” approach to quality is important to help catch issues before product leaves the building. For example, calculating theoretical yields catches issues such as inadvertently omitted ingredients or low capsule fill weight.

• From warning letter. “Statement of the percentage of theoretical yield at appropriate phases of processing”

• Cross-referencing labels to the formula is an essential part of GMPs. From warning letter. “Your MMR did not include a description of packaging and a representative label.”

• From warning letter. “Your MMR for does not include instructions for capsule drying or packaging operations. In addition, the MMR does not contain detailed instructions for the encapsulation process.”

Allergen advisory statements are mentioned in this letter. I have never added this warning ‘because major allergens are either in the product or they are not.’

• From warning letter. The …  product label declares “Allergy warning: Manufactured in facility that also handles milk, eggs, fish, shellfish, tree nuts, peanuts, wheat and soybean.” Advisory labeling is not a substitute for adherence to current good manufacturing practices and, when used by a facility, food allergen preventive controls. See Guidance for Industry: Questions and Answers Regarding Food Allergens Labeling, The firm should make every effort to ensure that they and their suppliers have adequate GMPs in place to prevent the unintentional inclusion of allergens in their products and ingredients.

Read the full letter here.

DATE ORIGINALLY POSTED: 11/6/24

Disclaimer: The educational information provided here is for informational purposes only. Contact an attorney for specific legal advice. Rule #1 in compliance is to ensure marketing is truthful and not misleading.