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QUALITY ASSURANCE

A Critique of the Standardized Information on Dietary Ingredients Protocol, Part I
Rick Liva, ND, RPh

Disclosure: Dr Liva is the president, CEO, and director of Quality Control and Quality Assurance at Vital Nutrients, a company certified by the Natural Products Association for current Good Manufacturing Practices.

SIDI Documents

• Various documents on the Standardized Information on Dietary Ingredients (SIDI) program can be found at www.ahpa.org/SIDI/documents.html. • The Standardized Information on Dietary Ingredients (SIDI) Protocol can be found at www.ahpa.org/SIDI/ PDFs/SIDIProtocolV2.1Feb08.pdf. Though SIDI’s goals are both much needed and well intentioned—my hat is off to the SIIP Working Group who has worked so diligently and hard to make this come about; it was surely no easy task—I ask that before you read further you remember the words of one of my colleagues: “Paper never refuses ink.” In other words, people can say whatever they like on a piece of paper because, in the end, the information will most likely be accepted at face value—rarely does the recipient spend time validating the information given, and, hence, nobody is the wiser. In the vernacular: It’s often assumed that everything is cool and as it should be because the paper says it’s so.
A Look at FDA Regulations

Editor’s Note: This is the first of a 2-part article. The second part will run in the next issue, April-May 2010 (IMCJ. 2010;9.2).

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he Standardized Information on Dietary Ingredients (SIDI) Protocol was developed by the Standardized Ingredient Information Protocol (SIIP) Working Group, a joint trade association effort with participants representing both dietary supplement (DS) ingredient suppliers and finished product manufacturers. Members of the working group include the Council for Responsible Nutrition (CRN), the American Herbal Products Association (AHPA), the Natural Products Association (NPA), and the Consumer Healthcare Products Association (CHPA). The objective of the working group is to develop standardized guidelines and protocols that suppliers of vitamins, minerals, botanicals, and other dietary ingredients can voluntarily use to help convey relevant and required information to finished product manufacturers that make capsules, tablets, liquids, etc, from these raw ingredients. The guidelines are intended to be both comprehensive and flexible so as to apply across all product categories. The reason for the guidelines is to address the prevailing need for communicating information in a standardized manner, effectively reducing paperwork and resources currently dedicated to this process. The SIDI protocol achieves 3 main functions: 1) The program integrates information on raw sourcing for dietary ingredients (from suppliers or their brokers and/or distributors; hereinafter just referred to as suppliers) into voluntary, standardized forms (templates), thereby eliminating the need for each manufacturer to have its own questionnaire to certify a supplier; 2) through these templates, the program defines the minimum type and scope of information that should be covered; and 3) these templates provide a forum for suppliers to develop their own dietary ingredient data sheets (DIDS) to be sent to manufactures in lieu of answering disparate questionnaires from each manufacturer. The protocol provides 3 templates: Botanical Materials, NonBotanical Materials, and a Site Quality Overview Data Sheet.

To best understand SIDI, let me give some background on the June 2007 US Food and Drug Administration (FDA) Dietary Supplement current Good Manufacturing Practices (cGMPs) regulations. The regulations are laws subject to legal penalty if not followed by DS manufacturers. FDA’s definition of quality per the cGMP regulations means that a dietary supplement consistently meets established specifications for identity, purity, strength, composition, and limits on contaminants of raw materials as well as that it has been manufactured, packaged, labeled, and held under conditions to prevent adulteration. Since SIDI deals only with the first half of these requirements—specifications for identity, purity, strength, composition, and limits on contaminants of raw materials— that’s all I’ll be addressing in this article (so nothing on finished products). SIDI also addresses labeling and regulatory information as it relates to raw materials, but I won’t delve into that either until Part II. Although the FDA’s definition of quality for raw materials sounds neat and tidy, there are 3 glaring omissions: 1) To date, the FDA has established only a requirement for mandatory identity testing of each incoming batch of material—but it has given no specifics (and very, very little guidance) on how to meet the quality requirements for purity, strength, composition, and limits on contaminants of raw materials. 2) The final FDA DS

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cGMPs do not (preposterously) apply to ingredient suppliers. Thus, the responsibility for ensuring the quality of dietary ingredients falls on the finished product manufacturer rather than the ingredient supplier. 3) Since the FDA has given no specifics on how to meet the quality requirements for purity, strength, composition, and limits on contaminants of raw materials, the exact specifications are set by each individual manufacturer itself and are open to no end of interpretation and fiddling. FDA quite grievously missed the boat on all 3 of these points—and more besides; to see detailed information, please see my article “New FDA cGMPs for Supplements: Smoke or Substance?” (IMCJ. 2007;6.5:28-32) as well as an article by Joesph Pizzorno, ND, in this same issue, “FDA’s Natural Product cGMPs—A Missed Opportunity” (IMCJ. 2007;6.5:8-10). To belabor the last point: Although FDA regulations revolve around setting specifications for DS raw materials and finished products, the exact specifications are determined by individual manufacturers who are provided no standardized requirements. That is to say, the rule requires that manufacturers, not the FDA, define quality specifications for their products—and those specifications can (with very few exceptions) be as loose or as tight as determined by each manufacturer. The law simply requires the manufacturer to define the specifications for identity, purity, strength, composition, and limits on contaminants and to make certain that the processes in place guarantee that the finished products meet those specifications. It seems pretty obvious that the regulations are extremely weak since FDA gives no guidance as to the minimum specifications that must be met. Ergo, 1 DS manufacturer can set minimal specs that it decides will comply and another can set a comprehensive spec that actually does cover all the necessary bases. Unfortunately, however, there is a financial incentive to set minimal specifications because it will cost less money over time to meet them. And no one will really be any the wiser, because the manufacturer has followed the letter of the law. In specific, the FDA regulations state the following. Note that identity is the only required test1: Subpart E § 111.75 What must you do to determine whether specifications are met? Before you use a component [also known as a raw material], you must: (1) Conduct at least one appropriate test or examination to verify the identity [author emphasis] of any component that is a dietary ingredient; and (2) Confirm the identity of other components and determine whether other applicable component specifications established [are met]. . . . To do so, you must either: (i) Conduct appropriate tests or examinations [this means for each lot received]; or [if you are not going to test every lot, you can do the following]

(ii) Rely on a certificate of analysis from the supplier of the component that you receive, provided that: (A) You first qualify the supplier by establishing the reliability of the supplier’s certificate of analysis through confirmation of the results of the supplier’s tests or examinations; (B) The certificate of analysis includes a description of the test or examination method(s) used, limits of the test or examinations, and actual results of the tests or examinations; (C) You maintain documentation of how you qualified the supplier; (D) You periodically re-confirm the supplier’s certificate of analysis; and (E) Your quality control personnel review and approve the documentation setting forth the basis for qualification (and re-qualification) of any supplier. As written, these regulations are nonspecific and leave much room for cheating or doing the very least and falling short. Consider the following: (2) (i) above states that if you are going to follow regulations for each lot received, you need to “conduct appropriate tests or examinations.” The problem is, as explained before, these “appropriate” tests and examinations are never specified so are thus determined by each manufacturer. If you are not going to test each lot received, so are therefore going to do skip lot testing, there are also serious deficiencies in the regulations. (2) (ii) (A) above states that you must confirm the results of the supplier’s tests or examinations listed on the certificate of analysis (COA). The begged questions are 1) what are the minimum tests or examinations that need to be performed for each type of material and 2) since no specific tests are required, how are you to determine if the tests/examinations that the manufacturer chose to do are any good? The answers: For #1, the DS manufacturer gets to choose because no FDA guidance is provided; for #2, unless you have a qualified lab person to ask, you aren’t going to know. There is also a third question: How many times should said tests/examinations be performed (to gain confidence in the supplier) before you can start skip lot testing? No guidance is provided. How often do you skip? No guidance is provided. This is (obviously) extremely unclear and left wide open. (2) (ii) (D) states that “You periodically re-confirm the supplier’s certificate of analysis.” I ask again, “How often?” No guidance is provided. So will it be every 2, 3, 4, 5, or 10 years? Who knows how the FDA left that important detail out! But because it did, there is a lot of wiggle room for doing the least amount of due diligence possible. Another problem is that (2) (ii) (B) states that the COA should include “a description of the test or examination method(s) used, limits of the test or examinations, and actual results of the tests or examinations.” In reality, most COAs don’t

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include this information. Although this should technically mean that a manufacturer shouldn’t do skip lot testing because 1 of the COA requirements is not met, the question remains whether the manufacturer actually adheres to this requirement—since, in reality, so few COAs include it and a large number of manufacturers do skip lot testing.
Life Without SIDI

Typically, quality-minded companies send supplier certification questionnaires asking a myriad of questions designed to elicit information regarding a supplier’s quality practices. Sadly, I’ve always felt that most of these questionnaires are yet another useless paper tiger for 2 reasons: 1) as with SIDI, suppliers can say whatever they want and the sender is still clueless as to the veracity of the info (again, “paper never refuses ink”), and 2) if your supplier is itself a broker or distributor that is getting ingredients from many places (as is often the case with products such as vitamins, amino acids, minerals, etc), the broker or distributor you use may change the supplier it used for previously “certified” material(s) and never tell you. So, even if your broker/distributor provides accurate and complete information today, next week you may be getting raw material that originated from a different supplier, thus negating the original information sent. It is due to all these shortfalls that I created “The IMCJ Supplement Quality Audit Form.” (This can be found at www. imjournal.com. In the menu bar, click on “Resources and Content.” The second listing on the drop-down menu is “Quality Assurance.” On the corresponding web page, you will find the form.) The benefit of this form above others I’m aware of is that it directs suppliers to answer a series of questions but also asks for documentation that helps provide verification that they are, in fact, doing what they claim to be doing. The questionnaire asks for proof as well as yes-or-no answers. It is easy to answer yes to a question on a form; it is more difficult to provide proof.
SIDI Shortfalls

4. Rather surprisingly, the appearance and format of the template provided to the manufacturer is left to the discretion of the ingredient supplier—SIDI only “strongly recommends” that the format and organization of the provided SIDI template be followed. I have a major problem with this, as the template can be changed by the supplier, which could lead to confusion and inconsistency as well as undermine the “template” nature of the program. What is the point of having a “template” if it is left so flexible? 5. And the most major drawback, as I stated earlier, is that the templates are merely ink on paper—how does anyone know that what is written is true? No one knows without the DS manufacturer verifying much of the information provided. Hence, the templated SIDI info that suppliers provide is just the tip of a very large iceberg. Why? Because even after a manufacturer is handed a filled-out SIDI template, the information still has to be vetted through the same scientifically valid comprehensive testing I write about each issue. SIDI is a good first step, but the trade groups that put it together would be wise to tackle 4 much more monstrous problems befouling the industry: 1) a paucity of scientifically valid methods and standards to test these materials, 2) a paucity of trustworthy labs to use those methods and standards, 3) a government that does not set quality standards and enforce compliance of those standards on the labs that test these products, and 4) as shown above, the FDA GMPs’ provision of very wobbly guidance, if any, for what testing is “required” under the regulations to vet a dietary ingredient or finished product or to certify a dietary ingredient supplier’s COA for a specific material. Beyond these limitations that are critical enough to derail any of the good the SIDI program hopes to do, there are numerous other shortcomings: 1. Suppliers can just say, “No, I’m not going to be part of the SIDI program.” And, for now, that is that. Although, to their immense credit, the SIIP Working Group has started the ball in motion to have such a program be a mandatory part of running a DS company. 2. I mentioned in the beginning of this article that the reason for the SIDI guidelines is to “address the prevailing need” to reduce paperwork and resources currently dedicated to the process of determining supplement quality. In the end, however, SIDI could cost the ingredient suppliers more time and money to develop, write, and provide the comprehensive amount of information the templates require. The reason is simple enough: Say you are a supplier with hundreds of raw materials. You would have to pay to have someone to write, compile, and store all of the required SIDI documents—no small task for that many raw materials. In addition, you would have to keep someone on the payroll to revise documents as needed and to prepare new documents as new materials come on line.

The SIDI program concept is to have every supplier use the same template so everyone is providing the same level of comprehensive information to the manufacturer. While that may be very useful (because it might save both sides time and energy, which equals dollars) it may not be practical for numerous reasons. The 5 main reasons are as follows: 1. The program is voluntary and not enforceable. 2. Many of the questions on the template are broad and open ended, leading to potentially inadequate answers. (This occurs even on the example template filled in by SIDI—next issue I will show you this as I go over an example of a completed SIDI Botanical Template.) 3. It does not specifically include all the categories of information that it should. (Again, next issue I will give comments on what the templates are missing.) In regard to both 2 and 3, we hope that the SIIP Working Group will consider upgrading the templates.

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3. Along these same lines of workload and resources, any changes to a product would require updating of all the SIDI forms, whereas now the supplier only has to change its COA—an inherently simpler process. 4. And an insurmountable limitation: Although I wish this wasn’t the case, in my experience, most ingredient suppliers keep their COA and Specification Sheets vague and simple so they don’t have to reveal potentially damaging information such as inadequate testing or the presence of toxins or chemicals. Case in point: In the past 2 years I rejected 3 batches of diindolymethane (DIM) because of high levels of benzene (500-600 parts per million, ppm). The presence of benzene was not even listed on the COA. I found it because we test all materials for 51 solvents—for the exact purpose of catching contaminants not revealed on COAs. The truth is, if the supplier were to reveal this solvent residue on the COA at that level, nobody would buy it due to its toxic nature. If it chose to honestly follow the SIDI protocol of supplied information (and it is doubtful that it would do so then when it did not do so now), it would have to clean up the product to eliminate the benzene, which would cost it money and time—2 costs it doesn’t have now. I can only surmise that this economic disadvantage would keep them out of the SIDI program. To continue the story, I found a new supplier of DIM. Two batches in the past 2 years passed solvent residue testing with no problems. Then, just recently, the third batch showed 280 ppm of chlorobenzene, a less toxic solvent than benzene but one that, in my opinion, doesn’t belong in a “health” supplement. It also was not declared on the COA—yet, as I found out, it is routinely used in the manufacturing process to whiten the material, and then the supplier doesn’t spend the required time to blow it off in the drying phase. So once again, if a supplier chose to honestly follow the SIDI protocol of supplied information, it would have to clean up the product to eliminate the benzene, which would cost it money and time—2 costs it doesn’t have now. It should also be noted that, without the testing I did, neither the SIDI forms nor the FDA cGMPs would have caught either issue. 5. Some of the information that the templates ask the suppliers to provide is possibly of a proprietary nature (intellectual property), such as a method of analysis or an extraction or production process.
The SIDI Program’s Claimed Promises

For both, I don’t see how, just because I’m putting more information on a piece of paper that is not required to be verified, this is going to reduce risk of error or increase the safety and quality of products. It just offers a starting point, while the stated goal of certification is accomplished only by scientifically valid comprehensive testing to vet what is written. If asked, anyone would agree that the safety and quality of dietary supplement products is paramount. However, the SIIP Working Group doesn’t give specifics as to how the program could increase safety and quality (they just allude to it). It would be useful for them to provide detailed, specific information on the points of safety and quality. Hence, I would like to see the SIIP Working Group give suggestions and guidelines for minimum (but adequate) scientifically valid testing requirements for botanical and nonbotanical materials that a DS manufacturer can use to vet a supplier’s information. Since the FDA has chosen to be vague, why can’t the industry step in and provide quality testing guidance parameters for all DS manufactures to follow? It would certainly help to diminish the confusion as to what might meet FDA requirements. As mentioned, next issue I will discuss the sample Botanical Template filled in by the SIIP Working Group and offer suggestions as to what would make the templates stronger. The intent of the SIDI protocol is clearly positive and of significant value for dietary supplement manufacturers. I suggest that it needs a more detailed structure that is not variable and has mandatory compliance if a supplier is willing to adopt it.

Rick Liva, ND, RPh, graduated from Temple University School of Pharmacy in 1975 and National College of Naturopathic Medicine in 1982. He is the managing physician at the Connecticut Center for Health, located in Middletown and West Hartford. Dr Liva is a founding member of the American Association of Naturopathic Physicians and past president of the Connecticut Society of Naturopathic Physicians. As mentioned in the disclosure, he is also the president, CEO, and director of Quality Control and Quality Assurance at Vital Nutrients, a company certified by the Natural Products Association for current Good Manufacturing Practices. Reference
1. Department of Health and Human Services. US Food and Drug Administration. §111.75 What must you do to determine whether specifications are met? Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements: Final Rule. College Park, MD: Food and Drug Administration; 2007:773.

Even with the limitations above, the SIDI program promises that • increased standardization of any process has the potential to reduce risk of error and • a more organized system of vendor qualification could increase the safety and quality of products.

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