GMP Pitfalls: Marketing, Manufacturing, & Labeling

We can learn a lot from warning letters. Following FDA enforcement trends is a valuable tool for any savvy marketer, regulatory affairs professional, quality manager, or dietary supplement executive. We can adjust practices before they elevate to warning letters by learning how to read warning letters and act accordingly. This is why I write the weekly Warning Letter Wednesday post on LinkedIn, Twitter, and Facebook. This blog post is an extended version of my Warning Letter Wednesday posts.

This warning letter is a great teaching case. Here are the learning targets.

FDA Inspections Trigger Website Reviews

Marketing Claims

Distributors Responsibilities

Common GMP errors

*Writing and Following Specifications

*Writing Procedures

*Product Returns

*Product Complaints

Certain Herbs Are Not Allowed

Common Allergen Labeling

Domestic Street Address or Phone Number

Languages Must Contain The Same Information

Serving Size and Suggested Use

Plant Parts Must Be Disclosed

Correct Plant Listing

Supplement Fact Panel: Line Thickness

Percent Daily Values Label Requirement

Expiration Dating

FDA Inspections Trigger Website Reviews

The company was inspected by FDA in March 2021 and was issued several 483s. The company's website was recently reviewed in February 2022, which led to a letter. Learn about the difference between a 483 and a warning letter here. Usually the FDA investigator reviews a company's website for disease claims before an inspection. That is likely still happening but this is the third recent warning letter where FDA inspections led to a website review at a later date. These website reviews were then elevated to a warning letter. I write these letters here and here. This is a fascinating enforcement trend to watch and a good reminder for companies to clean up their website claims if they have been inspected. This is one of my favorite services Supplement Advisory Group offers.

Marketing Claims

➡️From warning letter: Although studies (of PS, an ingredient in your product) in humans with Alzheimer’s disease were less dramatic, they still produced significant improvements in cognitive function. In patients with mild dementia, significant cognitive and behavioral enhancing effects were observed.

👉Asa's commentary: These mistakes have been reviewed in previous Warning Letter Wednesday posts; High risk words and video, citing studies, and discussing ingredient benefits.

Distributor Responsibilities

The company uses a contract manufacturer to make their products. This does not mean the company does not have any GMP responsibilities.

➡️From warning letter: Quality control must approve for release, or reject, any packaged and labeled dietary supplement (including a repackaged or relabeled dietary supplement) for distribution, and you must have documentation of the quality control personnel review and approval for release of any packaged and labeled dietary supplement

👉Asa's commentary: This means a company has to conduct some type of review and release before selling the product. This does not have to be complicated but it has to be written down and followed. If it's not written down it didn't happen is an FDA mantra.

➡️From warning letter: Although a firm may contract out certain dietary supplement manufacturing operations, it cannot contract out its ultimate responsibility to ensure that the dietary supplement it places into commerce (or causes to be placed into commerce) is not adulterated for failure to comply with dietary supplement CGMP requirements.

👉Asa's commentary: This is boilerplate language but a good reminder that although working with a contract manufacturer does mitigate some risks, the basics of quality assurance should be in place. We discuss many of these topics here.

Common GMP Errors

Writing and Following Specifications

➡️From warning letter: You failed to have documentation of the quality control personnel review and approval for release of any packaged and labeled dietary supplement for distribution, as required by 21 CFR 111.140(b)(2) [see also 21 CFR 111.127(h)]. Specifically, your firm distributes the dietary supplements that are contract manufactured for you, but you had no records of a quality control review, approval, or rejection for your finished dietary supplement products. During the inspection, you informed our investigator that you do not review the documentation related to the finished dietary supplement products you receive from contract manufacturers to determine if those finished dietary supplement products have met specifications.

👉Asa's commentary: Not having and following specifications is one of the most common GMP violations. Specifications should be reviewed by a member of Quality and then approved, rejected, or quarantined. This allows problems to be found before products are shipped to the public. I write about this here.

Writing Procedures

➡️From warning letter: You failed to establish and follow written procedures for holding and distributing operations, to comply with 21 CFR Part 111.453 that include the requirements for holding components, dietary supplements, packaging, and labels,

👉Asa's commentary: Writing and following procedures is an important part of GMPs. Procedures are the "directions" for doing things, commonly referred to as Standard Operating Procedures (SOPs).

Product Returns

➡️From warning letter: You failed to establish and follow written procedures to fulfill the requirements that apply to returned dietary supplements,