The same GMP violations show up in warning letter after warning letter issued by the Food and Drug Administration (FDA). Lack of specifications, lack of identity tests, deficiencies in master manufacturing and batch reduction records, etc. It has become almost a standard part of any warning letter to a dietary supplement firm will include mentions of problems in one or more of these areas. But Larisa Pavlick, VP, Global Regulatory Compliance for the United Natural Products Alliance (UNPA), says this has much to do with how inspectors go about their jobs.
Pavlick is intimately familiar with the mechanics of an inspection because of her prior experience as an inspector working out of the Denver office. Pavlick said that how an inspector is going to (or at least, is supposed to) conduct an investigation is laid out in a publicly available document, which can be found here. The inspector will use that document as a road map for their inspections, Pavlick said, so companies need not expend any mental energy guessing about how the game is going to be played.
“The compliance program has a number of questions that the inspectors must answer in the course of the inspection,” Pavlick told NutraIngredients-USA. “We are seeing these violations in almost all of the warning letters. If an inspector is focusing in on certain things, those are the violations they will find first. In my opinion, the reason why you see these things in warning letters over and over is because they are easy to find.”
The existence of this document often comes as a surprise to some members of industry (as it did to her when she was in private industry earlier in her career). FDA has not made it a priority over the years to clue companies in that this document exists, Pavlick said. When she came on to the job, she made it standard practice in her inspections to provide the document
“I’d give it to them and say, here, this is what we are going to cover during this inspection,” Pavlick said. “It’s on FDA’s website, but that website historically has been difficult to use.”
Major points of emphasis for inspectors
In the document, the document lists “major deviations from cGMPs,” a list, in other words, of what the inspector will look at first. Having this in hand is akin to finding orders that specify where an opposing general intends to attack, when, and with what force. The list includes:
- Lack of master manufacturing records or significant requirements not included;
- Lack of finished product release criteria or failure to test (all or subset of finished batches) or meet finished product release criteria critical to product safety and quality;
- For significant dietary ingredients, e.g. those that make up the bulk of the product, failure to establish specifications for incoming material or failure to conduct identity testing;
- No quality control review procedures or significant quality control procedures not implemented;
- No batch records;
- Significant physical plant deficiencies.
“It’s really critical for industry to understanding this document. This will guide the inspectors, especially in the case where they might not have a lot of experience in, say, botanicals,” she said.
Pavlick said that from her observations in the field, in many cases deviations came as a result of companies not understanding the official nomenclature. A company might have records of a sort, but if they don’t match the forms that are specified in the regulations and are not as complete as what’s outlined there, it falls into the area of a violation. The goal should be for someone not very familiar with a given product to be able to use those records, that plan, and make a product successfully. It’s not enough to in effect say, “I know how to make x product. I’ve made it for years”. A company must document exactly how that is done.
“It’s pretty uncommon that a company would have no records of any sort. Most people on the market, they know what they are doing. They would have some kind of plan for how to make a product. The master manufacturing record is a blueprint of what you are doing, how you are mixing your ingredients, how encapsulate them, and so forth. The batch production record is kind of like a worksheet of the master manufacturing record,” Pavlick said.
All of these issues will be covered in a select GMP training offered by UNPA in Provo, UT on June 27 and 28. Among the things covered will be the intricacies of documentation.
“When I was an inspector I developed little check lists, things like the 14 elements that should be in every batch record. They are things like lot number, name, the units of measure used,” Pavlick said.“I don’t think this stuff is hard.”
Pavlick said when looking at overall GMP compliance, the major failure is a lack of understanding of the finer points of the regulations. From her point of view, it’s not a case of a large number of rogue companies playing fast and loose and not bothering themselves with GMPs unless and until they get caught.
“We have a small percentage who are willfully deviant, and then a large group in the middle who simply don’t understand. And then on the far end of the spectrum another group, mostly the larger companies, who do get it and are in full compliance,” Pavlick said.
“I want people in this industry to get it, and I really don’t think it should be that difficult. I don’t want the industry showing up on 60 Minutes and I don’t want people telling me that we have no regulation,” she said.