A Must-Read FDA Warning Letter That Truly Inspires

There’s both good and bad news in examining the current state of FDA warning letters. The number of warning letters from the FDA to the Dietary Supplement industry in 2018 is only a fraction of the number received in 2017. Yet the total number of warning letters provided by the FDA to all categories in the same time period in 2018 compared to 2017 is very similar (108 and 128 respectively). That’s the good news. However, important and concerning news is found in one particular warning letter recently issued to Biotek, Inc. of Layton, UT on March 13, 2018 (FDA – Biotek Warning Letter 03/13/2018).

This Biotek, Inc. FDA warning letter is important to all contract manufacturers and the brands that use them because of the attention and extent this particular warning letter calls out in relation to all previous FDA warning letters. If you only read one warning letter this year, read this one.

Biotek, Inc. is an Amazon seller and ecommerce website. The 8-page FDA warning letter begins in typical fashion detailing the concerns surrounding claims made on behalf of the products which makes the product a drug:

Examples of some of the claims that provide evidence that your product is intended for use as a drug include the following:

• “Immune system is improved helping to combat stress and disease”
• “Stress…the cause of all degenerative diseases.” ~ Stress of Life, Hans Selye, M.D.
• “They also protect against toxic reaction and heavy metal poisoning.”
• “Improves Triglyceride Level in Blood”
• “Lipase enzymatically converts triglycerides, which have a tendency to clog veins and arteries…” “Increases Resistance to Disease”
• “Lipotropics, in general, help reinforce the thymus gland to increase resistance to disease by: Increased antibody production; Increased production and action of phagocytes, which surrounds and reduces invading viruses and microbes.*”
• “Lecithin and sphingomyelin help to keep cholesterol more soluble, deterring buildup of plaque or cholesterol deposits in the blood vessels.”
• “To help with Restless Leg Syndrome or Muscle Cramps take one capsule in the morning and two capsules two to three hours before sleep.”

But from there this warning letter goes into greater detail and spells out parts of CGMP regulations, highlighted be FDA, in aspects rarely seen previously:

As a distributor that contracts with a manufacturer to manufacture, package, and label dietary supplements on your behalf that your firm releases for distribution under your firm’s name, your firm has an obligation to know what and how manufacturing, packaging, and/or labeling activities are performed so that you can make decisions related to whether your dietary supplement products conform to established specifications and whether to approve and release the products for distribution [72 Fed. Reg. 34752, 34790 (Jun. 25, 2007)]. Your firm introduces or delivers, or causes the introduction or delivery, of the dietary supplement into interstate commerce in its final form for distribution to consumers. As such, your firm has an overarching and ultimate responsibility to ensure that all phases of the production of that product are in compliance with dietary supplement CGMP requirements.

 The FDA uses this language to reiterate the reality that a brand holder holds complete and final responsibility to ensure the product is made correctly and to specification.

To the extent that you contract with other firms to manufacture, package, and/or label product on your behalf that your firm releases for distribution under your firm’s name, your firm has an obligation to know what and how manufacturing, packaging, and/or labeling activities are performed so that you can make decisions related to whether your dietary supplement products conform to established specifications and whether to approve and release the products for distribution [72 Fed. Reg. 34752, 34790 (Jun. 25, 2007)]. Although a firm may contract out certain dietary supplement manufacturing, packaging, and/or labeling 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 (see United States v. Dotterweich, 320 U.S. 277, 284 (1943) (explaining that an offense can be committed under the Act by anyone who has “a responsible share in the furtherance of the transaction which the statute outlaws”); United States v. Park, 421 U.S. 658, 672 (1975) (holding that criminal liability under the Act does not turn on awareness of wrongdoing, and that “agents vested with the responsibility, and power commensurate with that responsibility, to devise whatever measures are necessary to ensure compliance with the Act” can be held accountable for violations of the Act).

The first bolded statement above further underscores the responsibility inured by the brand holder and not conveyed to the contract manufacturer. In the second bolded statement, FDA confirms the penalty for non-compliance rests with the brand holder.

“Your firm failed to implement a system of production and process controls that covers all stages of packaging, labeling, and holding of dietary supplements to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record, as required by 21 CFR 111.55. Specifically, you do not have a system of production and process controls to ensure the quality of your dietary supplements that you receive from your contract manufacturers and that your dietary supplement products are labeled as specified in the master manufacturing record.”

In this case, the FDA cited the brand holder for not having knowledge of the master manufacturing record and then requested the master manufacturing record from the contract manufacturer.

“Upon our investigator’s request on 8/14/17, your contract manufacturer provided a master manufacturing record for our review. Because there was no batch production record received for this lot, there was no indication this lot met specifications and was approved for release, apart from contract manufacturer Quality Assurance signatures on the bulk finished product Certificate of Analysis.”

Rarely will a contract manufacturer release master manufacturing records but in this case they were forced to release the documents to the FDA. The FDA then used the records to highlight discrepancies and deficiencies of which Biotek was stated to be unaware because they did not have the master manufacturing record when requested at inspection.

“You failed to establish specifications to provide sufficient assurance that the product you receive from a supplier for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier) is adequately identified and is consistent with your purchase order, as required by 21 CFR 111.70(f). Specifically, your firm does not have in place any specification(s) to identify that the products you receive are consistent with your purchase order.

Once you have established specifications, you must determine whether the specifications established under § 111.70(f) are met, as required by 21 CFR 111.75(e).”

In this Trust Transparency column we have repeatedly mentioned the importance of specifications in addition to a purchase order. Many ecommerce sellers simply place a Purchase Order based upon label claim and sometimes bulk availability. Neither of these processes is compliant.

This FDA warning letter stresses the importance of regulatory compliance in every aspect including allergens, master manufacturing records, pest control, cleaning records and more.

Takeaway: If you are a brand seller, holder or contract manufacturer you should make it a priority to read this warning letter as it is an 8-page primer on what the FDA expects at a minimum. The Trust Transparency Center is dedicated to assisting with organizational and industry excellence and the first step begins with knowledge.

~Scott