Vasilios "Bill" Frankos, former director of FDA's Division of Dietary Supplement Programs, left his mark on the industry after shepherding the supplement good manufacturing practices final rule from development to publication and through implementation.

In March, Frankos concluded his more than 13-year career at the agency and headed west to leave his mark on supplements from the industry side - by aiming to make multi-level marketer Herbalife a standard-bearer for safety and quality. He is now senior VP of product compliance and safety for the Los Angeles firm (¹ Also see "Herbalife Hires FDA's Frankos For Compliance/Safety Position" - Pink Sheet, 25 January, 2010.).

Frankos recently spoke to "The Tan Sheet" about the responsibilities of his new role, reflections on his previous job and how supplement GMPs look from the other side of an FDA inspector's clipboard. Excerpts from the July 8 interview follow.

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"The Tan Sheet": A lot of companies in the supplement industry would have been interested in your services once you left FDA. Could you talk about why you chose Herbalife? What are you doing in your new role?

Vasilios "Bill" Frankos: I was impressed with Herbalife's commitment to really set a very high standard for not just themselves but for the whole dietary supplement industry. And they've committed to increasing the quality of their products so that they become really a standard for the whole industry of high-quality product.

When I joined them, they basically gave me this position of senior vice president for product compliance and safety, and have given me the latitude to work throughout the whole company in product quality and product safety. I work with manufacturing, with the regulatory divisions in the company. I work with product development and I try to bring my FDA expertise to their evaluation of products. And that has allowed me to kind of carry on with my FDA experience and bring it to bear whenever issues come up with respect to product safety and quality.

More specifically in my role, I have direct responsibility for all post-market surveillance initiatives within the company, as well as oversight of product GMP compliance and safety.

Tan: Was there any particular reason behind the timing of your departure from FDA?

Frankos: I think I reached retirement age and I had to just make a decision - did I want to continue working in the federal government or do something different? And so I decided to do something different. But it was really a matter of reaching my retirement age.

Tan: Did anything in particular strike you when you jumped from FDA to the industry side? Anything you weren't expecting?

Frankos: I would say that the amount of preparation that the industry has done in getting ready for full implementation of the GMPs, the amount of work involved, was probably more than I realized that a company had to do. Having written the GMP regulations, I knew what was expected. But the full implementation of those regulations is truly a mammoth job for a company - especially when a company is looking at global sales in 73 countries like Herbalife is. So it's quite a big challenge to get all of that implemented.

Tan: Is there anything you could have done differently at FDA in terms of providing additional GMP guidance or shaping the final rule differently to allow more leeway for companies?

Frankos: We knew there was going to be a learning curve when I was at FDA, and we did undertake a lot of training. I made a point of going to various trade association meetings and giving as much of my time as I could to help the industry understand what was needed. The guidance that we provided through the preamble, I think probably was not read by a lot of people because of the size of the preamble. We're talking about a document that - depends how you print it - but we're talking about hundreds of pages, 400 pages.

I believe that the preamble very clearly describes what's expected, but because it's so long, it's something that a lot of people didn't read. And so I've always given the advice that before you read the actual CFR codified regulation, you really need to read the preamble, because that gives you the thought process behind the regulation. And I think, now that I'm out of the agency, I realize how it's a challenge for people to go through 400 pages and understand everything. But that really is the only way to learn about GMPs.

Implementing it, we knew it was going to take some time. We gave small companies three years to prepare; I think three years is quite a long time. But I don't think it's completely sunk in that the GMPs are real and they need to be complied with. So we're just going through a learning curve, that's all that's happening right now. But I don't think I could've done anything different when I was at FDA. We knew we had to do outreach and I think we did very good outreach. But it's when the tire hits the road that you realize that it's really challenging.

Tan: Do you feel you left any unfinished business at FDA?

Frankos: I've been very public about my being disappointed in not having been able to get the NDI notification guidance published before I left. That was something I really was working on very hard, and I'd hoped to have that done before I retired. And that really is the one thing I have some disappointment about not being able to complete before I left.

[Editor's Note: FDA officials, including Principal Deputy Commissioner Josh Sharfstein, have projected the new dietary ingredient notification guidance will be published in 2010 ( ² Also see "FDA Will Enforce NDI Notification Requirement Without Warning" - Pink Sheet, 21 June, 2010. ). The agency initially announced its intent to issue an NDI guidance in 2005 ( ³ Also see "FDA Accomplishes A-List Goals, Will Publish NDI Guidance – CFSAN" - Pink Sheet, 22 August, 2005. ).]

Tan: Could you talk about the progress of Herbalife's vertical integration initiative and any challenges you are seeing in that process ( ⁴ Also see "Herbalife Touts Vertical Integration As Key To Traceability, Cost Control" - Pink Sheet, 28 June, 2010. )?

Frankos: First of all, the commitment to vertical integration is really something that is being pushed because of the dietary supplement GMPs. ... By having vertical integration, you are able to control your product, especially herbals, from the seed all the way into the product. So the company felt that it was easier to control the quality of the product if we had control of all the steps in the growth, in the collection, in the harvesting of products all the way to the point where the product was manufactured.

We're going to be working with Chinese tea farmers on a venture where those committed fields will be providing product directly to Herbalife, and then they will be processed - extracted - in a Herbalife joint venture facility.

We also are bringing manufacturing into Herbalife through our having purchased a manufacturing facility here in California, and that is being converted to allow us to manufacture our own products, which is different than the way it was done in the past where all of our products were manufactured by contract manufacturers. So we're now bringing manufacturing directly under our control. And as I said, that gives you much more control over the quality of your product. So our facility here in California ... we purchased it, we refurbished it and we are starting to manufacture product. So this is a big change for the company (⁵ 'The Tan Sheet' Aug. 17, 2009, In Brief).

Tan: Do you see this model as the future of the dietary supplement industry? Do you think other companies will be able to vertically integrate?

Frankos: I think larger companies will be looking at this as an option to give them more control over their products, definitely - especially companies that are global. And we could see other opportunities for Herbalife to work with individual countries with products that will be directed to ... market in that country, rather than having things shipped long distance from the United States to Asia or to India - have local manufacturing and local growth of products, herbals specifically.

Tan: What lessons were learned from FDA's warning letter to a Herbalife aloe products supplier in violation of GMPs ( ⁶ Also see "First GMP Warning Letter Reflects FDA's List Of Major Concerns" - Pink Sheet, 17 May, 2010. )? Has the company changed its standard operating procedures for dealing with suppliers in light of the warning?

Frankos: I can certainly share some general impressions, I don't want to talk specifically about that warning letter. But what I can say is that it's very important that manufacturers work very closely with their partners. And I think when we are using a contract manufacturer, we are going to be very closely working with the manufacturer. And also we are going to be conducting independent cGMP audits of those facilities. We feel that that's really the only way to understand what's happening in your manufacturer's facility.

So we're committed to independent audits of all of our contract manufacturers. At the same time, we also believe that the identity tests that are used by manufacturers to assure the quality of their products need to have independent validation as far as the adequacy of those tests. And so for each of our manufacturers, we're working through complete confirmation of the validity of all the identity tests that they use in their facilities.

Tan: Could you talk about how Herbalife is handling the collection of serious adverse event reports?

Frankos: We are committed to not just monitoring adverse events here in the U.S. because of the mandatory adverse event reporting act, but monitoring adverse events worldwide. And what we're seeing is, when you look at worldwide adverse event monitoring, each country has different regulations and different requirements as to how to deal with adverse event reports. So it's a real challenge as to how to take the reports and properly communicate that information to the various countries. And that's something that we're doing.

In the meantime, in order to better deal with the adverse event reports, I'm implementing a brand new, state-of-the-art adverse event reporting database. And this is going to allow us to collect data, like I said, from around the world. But all the data will be coded using MedDRA coding.

[Editor's Note: MedDRA, the Medical Dictionary for Regulatory Activities, provides the standard coding language used in pharmaceutical adverse event reports (⁷ Also see "FDA Suggests Supplement Firms Use MedDRA Internally For AER Data" - Pink Sheet, 11 January, 2010.).]

So this new system is going to allow us to do global AER data mining and AER signal detection. And I'm very excited about the commitment of Herbalife to setting this system up and implementing it worldwide.

[Editor's Note: In an e-mail, Frankos says he expects Herbalife's Oracle Argus Safety database "will be the first of its kind in the dietary supplement industry." The system's features include extensive automation, configurable workflow and managerial and executive dashboards. Frankos expects the system to be operational by year's end.]

Tan: What lessons can a smaller supplement company without a lot of resources learn from the GMP strategies of a large firm like Herbalife?

Frankos: I think first of all, quality of your product is sacrosanct; it's the one thing you have to always keep in mind with everything you do. And having ingredient suppliers provide you guarantees based on certificates of analysis that you are not independently verifying is dangerous for you as a small company, because you're depending on somebody else's word. You really need to check the identity of those ingredients, and don't depend on CofAs.

That's kind of the philosophy behind the GMPs, that although the raw ingredient suppliers are not covered by the dietary supplement GMPs, the manufacturer is expected to assure the identity of every one of those ingredients. That part of the GMPs is the part that's difficult to implement for smaller companies because when you're buying ingredients from suppliers all around the world, it's hard to do confirmation of identity, as well as qualifying each of those suppliers. I think it's that part of the GMPs that's the biggest challenge for the small companies. You need to commit the resources to qualify every one of your suppliers, as well as do identity testing of every one of your ingredients.

- Interview by Dan Schiff ( ⁸ d.schiff@elsevier.com )

Herbalife's Frankos Sees GMP Challenges In New Light After Leaving FDA

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