Beehive Botanicals, a Hayward, WI-based contract manufacturer and distributor of its own branded products, received the warning letter on Feb. 8, after its response to an 483 communication was deemed inadequate by FDA. The company developed a plan to address the deficiencies found in FDA’s inspection on July 23-25, 2012, and subsequently had NSF come in to audit the changes.
“We were taken aback by the Warning Letter because we have made a significant investment in third party cGMP certification by NSF since 2007, including two audits of our facility each year. In fact, we just received 2013 NSF GMP certification based upon an audit they did after FDA issued the 483 observations, and none of those issues were raised, so you can imagine our dismay,” said Linda Graham, Beehive Botanicals’ president and CEO. “NSF apparently missed things that FDA didn’t.”
“I would think any company in any situation like this should be asking their auditor, ‘What did I pay you for? How did I end up with a warning letter like this? How did the auditor not spot specific violations?’ ” Marc Ullman, an attorney with Ullman, Shapiro & Ullman, told NutraIngredients-USA. Ullman’s firm, along with EAS Consulting Group, had been retained by Beehive Botanicals to help craft the response to the Feb. 8 warning letter, which must be submitted to FDA within 15 days.
Second such warning in recent weeks
Beehive Botanical’s warning letter is the second such letter received by a company recently that had been audited by NSF for GMP compliance. Capco Custom Packaging received a warning letter on Feb. 20 listing an inadequate response dated June 11, 2012 to 483 observations from an inspection conducted on May 18, 2012. As of Thursday, Feb. 28, Capco (listed as Capco Labs) was listed on NSF’s website as being certified in compliance with FDA GMP requirements.
In what should serve as a cautionary tale for other companies about when to seek legal help, Beehive Botanicals, relying on the positive opinion they received from NSF on the fixes they made to their operations to address the 483 issues, crafted their response to that document themselves, without the help of counsel.
“Believing NSF would have identified those issues if they were serious, we responded to FDA ourselves, rather than consulting counsel. In retrospect that was a mistake,” Graham said.
The warning letter cited a number of deficiencies in Beehive Botanical’s operations, deficiencies that its 483 response did not adequately address. These deficiencies included:
- Inadequate testing to ensure that product specifications are met
- Inadequate justification that the testing method used is scientifically valid and appropriate
- An inadequate master manufacturing record (MMR) that lacked information such as mixing/blending instructions, times, and equipment, and acceptable capsule weight range during in-process check
- Failure to establish reference standards in the testing of incoming raw material. The warning letter states that Beehive Botanicals was “using the first shipment of raw materials received as the standard for subsequent incoming shipments. However, you failed to establish any criteria to establish a reference standard.”
What to look for in an auditor
Ullman said the episode offers some pointers in what to look for when seeking help with GMP compliance. One thing to ask a company, he said, is how often clients get warning letters even after receiving a clean bill of health. There are other things to look for, too.
“Another thing you can be asking the certifying body is, who developed your standards? Was is sales people or was it serious experts with an expertise on a culture of GMP compliance?” Ullman said.
NSF: FDA ramping up on testing scrutiny
NSF, for its part, says it is committed to determining what went wrong in this case. Ed Wyszumiala, general manager of NSF’s dietary supplement certification programs, said he had not yet spoken with Beehive Botanicals officials about the specifics of the warning letter. But he had some observations based on what FDA cited in the letter.
“We are seeing some new stuff in these audit reports that shows that FDA is ramping up in other areas. So when you are working with a series of auditors that are working for you, whenever you see new stuff you have to recalibrate,” Wyszumiala said.
“Basically this was looking at proper testing and instrumentation. So we have to see what FDA is looking at on this; I have a call in to FDA to get some more information on what they are ramping up because we have not seen some of the specifics on going after certain testing methodologies,” he said.
NSF audits are a quick dive, Wyszumiala noted, and rely on the information being supplied by the company being audited. A company might have thousands of MMRs, for example, and he said he was not sure what the situation was with the specific MMR that FDA cited. He also said he was not sure if this was a case of what he called “auditor calibration,” i.e., an auditor who needs additional training in what to look for.
"We anticipate that as GMPs continue to roll out that we could have a company that is certified that could get a warning letter. That is the nature of the service that we offer. We are not a red stamp for FDA," he said.
“We take this very seriously,” Wyszumiala said. “This reflects on my company just as much as it does on theirs. We want to take a look into to this to see how do we fix it, and what the breakdown was. Was it something that we were not shown, was it an auditor calibration issue, or is it something new at FDA?”