NDIs, GMPs, FSMA: The regulation scene in 2013
NutraIngredients-USA talked with Steve Mister, president and CEO of the Council for Responsible Nutrtion and Loren Isrealsen, executive director of the United Natural Product Alliance on the broad outlines of what to expect in the regulatory sphere in 2013.
Good Manufacturing Practices
The Food and Drug Administration has had a number of years to conduct GMP inspections on dietary supplement companies as mandated by DSHEA, with the last tier of companies, those with fewer than 50 employees, phased in in 2010. Both industry and the agency have learned a lot through the process, and some of the lessons have been hard ones.
“FDA has been really clear that in their view the overall level of competence has leveled off. They are seeing the same mistakes, the same noncompliance issues on a fairly routine basis,” Isrealsen said.
“Enforcement is going to be ramped up. We are going to see companies either figuring out that FDA means business and getting out ahead of the agency in their implementation of GMPs on compliance or we are going to see a lot more warning letters,” Mister said.
Mister said the nature of what FDA is looking for in GMP inspections is evolving. It is moving beyond surface issues, such as whether testing is being done, to a second level of detail.
“The warning letters now are going to companies that are not doing any identity testing. The regulation clearly requires that. So that’s the low hanging fruit,” Mister said.
“The next round is those companies that are doing something but what they are doing is not specific enough to say that that they have the right ingredient. We are going to start to see FDA start to ask more substantive questions such as, are you doing the test that really lets you know with confidence the identity of this product.
"You’ll see the same thing in some of the process requirements, some of the finished product testing requirements,” he said.
“They have a broader range of comparables what a good quality facility should look like,” Israelsen said.
“I also believe that GMP inspections will become the gateway enforcement tool for looking at adverse events reporting goals, whether companies have what appear to have unfiled NDIs, undeclared allergens, (questions about) supply chain and FSMA compliance . . . all of these things are going to bound up to a large degree in GMP inspections,” he said.
New Dietary Ingredients
In early 2012, after significant pressure from industry and members of Congress, FDA agreed to enter into a series of discussions with industry trade organizations on the significant points of disagreement in the draft NDI guidance. Two formal meetings have taken place, the agenda of which was set by the agency.
“I think the meetings have been very friendly and cordial but also very frank,” Mister said. “It’s obvious that we don’t agree on a lot of things. We’re trying to figure out a way to move this process forward."
“Both sides have been trying hard to understand productive points of engagement. Where can we get some things done. That continues. There are some fairly clear areas that will continue to be complicated to resolve,” Isrealsen said.
One of the subjects that has been discussed is the question of what ingredients can be considered ‘Old Dietary Ingredients’ (ODIs), i.e. ingredients that were on the market as of Oct. 15, 1994 and therefore are not subject to a NDI notification requirement. The original NDI draft guidance dismissed out of hand the existing lists of these ingredients.
“Whether an ODI list can be agreed to, that is still a very difficult question,” Israelsen said.
Also a subject of discussion and still a bone of contention is defining what is meant by "chemical alteration”, i.e. those processes that so change an ODI to the point where new safety information via a NDI notification is required.
The issue of synthetic botanicals (specifically excluded as dietary ingredients in the initial draft guidance) has not been a subject of the meetings. But both Isrealsen and Mister said it remains an area of special concern.
Food Safety Modernization Act
FSMA requires every food facility (and dietary supplement manufacturing operation) to file a renewed registration with FDA before the end of January and again biennially thereafter. (The deadline was extended from Dec. 31.) No one is sure how many facilities have complied already, nor how many both within the US and abroad are still confused about the requirement, and believe that the Bioterrorism Act registrations they have already had to complete are sufficient.
“We’ve asked the FDA if they will publish aggregate numbers that will tell us how many facilities have registered in this three month window. So far we haven’t heard from them on that,” Mister said.
One change written into FSMA is that FDA can now bill companies for the cost of conducting GMP re-inspections if the agency believes they are required.
“We warned when FSMA passed that it could become a revenue maker for the agency.
"We hope the agency does this in a measured way, so they do the re-inspections only when they need to and they put a lot of resources into the first time inspections,” Mister said.
FSMA will ramp up the need for companies to come fully to grips with their supply chain issues, Israelsen said.
“Supply chain management is going to become even more important. It’s still a difficult area, and not just for the dietary supplement companies. It’s a difficult issue for all industries that have an international supply component,” he said.
“Very few companies that source from global markets like China can say with confidence that they really know where everything is physically made.”
DSHEA reaches voting age
If DSHEA were a person, it could have voted in the most recent election. Now that the statute is approaching the two-decade mark, what’s the overall picture on implementation?
“Here we are approaching 20 years. That’s a long time to implement a statute. But the fact that we are still 20 years on and still working on what I consider to be central issues (such as GMPs and NDIs) can really be seen as a head scratcher,” Israelsen said.
Some of that has to do with the history of how the statute came about, he said. FDA didn’t want the law and wasn’t happy when it passed, and a period of institutional lethargy concerning its implementation ensued. But that has changed, Israelsen said.
“In the last 12 to 24 months you can see a distinct difference in the nature of FDA’s approach to enforcement and implementation. There has absolutely been a shift in the energy level,” he said.
"I think the lesson for industry is, we have a good understanding of what should be done and we just need to do it."