Jim Lassiter06.01.03
On March 13, 2003, FDA issued a Proposed Rule on Dietary Supplement GMPs. The document itself was a long time coming and after reading all of it, there is little wonder as to why. Let's start with a little history review and then examine what resulted when FDA completed the task of generating a document ostensibly covering the manufacture, packaging, distribution and holding of dietary supplements.
In October of 1994, Congress passed the Dietary Supplement Health and Education Act (DSHEA). Among the items included in this amendment to the Federal Food, Drug and Cosmetic Act (FFDCA) was an allowance for rulemaking that would result in GMPs for dietary supplements. The requirement for the regulations was that they be modeled after the GMPs for foods. In November of 1995, the dietary supplement industry delivered to FDA a document written in the same style as a regulation detailing what were state-of-the-art practices in the manufacture of dietary supplements. The "industry document" was published by FDA in February of 1997 in its Advanced Notice of Proposed Rulemaking (ANPRM) along with a series of questions FDA wanted answers to as it pondered the matter. Thus began the allowed rulemaking process. After six years of prompting and prodding from the industry, FDA finally performed the next step by issuing the proposed rule.
Proposed rules generally reflect the regulatory agency's perspective on a topic rather than that of the regulated industry. This is very obvious since the difference between the industry document and the proposed rule is well beyond significant. Upon reflection, there is little wonder why so much time passed between the issuance of the ANPRM and the publication of the proposed rule. Apart from most general section headings and a few minor concepts here and there, there is almost no resemblance between the "state-of-art" as presented by the people who actually do the work and FDA's perspective.
What happened is that FDA has attempted to shoehorn a group of other regulations into this proposal, some of which are duplications of existing regulations. To start with, you may recall that the purpose of this rulemaking process was to issue regulations establishing minimum standards for the manufacture of dietary supplements. These proposed regulations would apply not only to the manufacture of dietary supplements but would equally apply to the manufacture of dietary ingredients. Looking at the history for a moment, we find that this was something the industry asked for when it presented its document in 1995, so this matter is now difficult to challenge. However, industry made the mistake of focusing on manufacturing practices only. FDA expanded the scope of what should be covered by determining that this was a great opportunity to fit in other regulations it desired. Interesting concept but wholly inappropriate.
The first case is easy to make. FDA has repeatedly stated publicly that the Proposed Rule DOES NOT ensure the safety or efficacy of the products. However, the agency also publicly stated that these GMPs would ensure that the products deliver on the promises shown on their labels. This does not mean that the label will carry some offering of proof that GMPs were followed in the manufacture of the product. The implication, therefore, is that FDA wishes to use GMPs as a means to validate label claims both for potency and stated effects. Concerning the safety issue, one FDA staffer offered up at the May 6th Outreach Meeting in Oakland, CA, that these products "can be dangerous" when they provide either "more than or less than" the amount of dietary ingredient shown on the label. This last point is truly interesting since FDA has long contended that these products are not effective. It is impossible to determine how consuming less of something that is not effective is potentially harmful. Setting that aside, it may appear that shoehorning label claims and potency evaluation into the GMPs is not so much of a stretch. However, one need only look at the current Code of Federal Regulations (CFR) to find regulations already in existence that specifically address these issues. Why the redundancy? FDA remains silent on this matter. The point to make is that this aspect of the proposed rule is superfluous. But that's not all.
FDA also inserted into the proposed rule a reiteration of the requirement that all materials used in making a dietary supplement or dietary ingredient be acceptable for food use. In case you missed it: According to the FFDCA, dietary supplements are foods and thus already covered by existing food additive regulations. The lone exceptions to the requirements for food additives (those things that go into food products) are dietary ingredients. Thus, through the application of amazingly obtuse logic we have the following proposal: The manufacture of dietary ingredients (exempted from food additive regulations) must be done using only materials that are acceptable when food additive regulations are applied. Again, FDA is attempting to shoehorn redundant and inappropriate regulations into this proposed rule intended to cover manufacturing practices. The results speak for themselves. Yet that's still not all.
The FDA stated repeatedly in the preamble to the proposed rule that it was not implementing HACCP (Hazard Analysis, Critical Control Point) regulations with these GMPs. Yet, there is within the proposed rule itself an awful lot of mandatory activity that looks just like HACCP regulations. Additionally there is (in FDA's self-affirmed simplified language) discussion of what the "critical control points" in the process of manufacturing likely are and what you are to do when you come to one of these. Make no mistake, HACCP regulations add significant layers of complexity (just ask the seafood industry) and many of those complexities are found in this proposal. Moreover, FDA was not granted specific authority to issue HACCP regulations for dietary supplements for some very solid reasons. Among these reasons is the fact that the usual activities performed in manufacturing these products even at "critical" steps in the operation are not at all likely to result in a HAZARD. Without the specific authority to issue HACCP regulations, FDA still determined to put them in place with a thin veil of denial covering them. And that's still not all.
The FDA took this opportunity to insert within a proposed regulation covering manufacturing practices the mandate for a de facto Adverse Event Reporting (AER) system. As with the HACCP shoehorn approach and discussion, FDA goes to great lengths to deny that this is what it is doing. Their presentation includes establishing a category of customer feedback identified as "Consumer Complaints." FDA insists that this is necessary and worthy of inclusion within GMPs. The requirements for handling these consumer complaints include the need to designate someone to determine which incoming complaints are consumer complaints and which are AERs. Once this determination is made, additional actions are described for either category. The obvious truth is that FDA is attempting to fit in regulations that would ordinarily require a separate rulemaking process. The irony is that one industry trade association (The American Herbal Products Association) has formally petitioned FDA to proceed through rulemaking and establish a meaningful AER system for dietary supplements. The anticipated response to this petition seems clear now: Such action is not necessary since these regulations are coming via GMPs.
At the end of the day (plus the preceding six plus years) FDA issued a proposed rule that is extraordinarily more complex than it needs to be so that it can either redundantly issue regulations that already exist (in the case of both the food additive and labeling efforts) or put in place new regulations under the GMP umbrella for which it was not granted authority (HACCP and AER System). These efforts are simultaneously superfluous and completely inappropriate. If FDA wants to issue HACCP regulations for dietary supplement manufacture it should describe the rationale and seek authorization to do so as it did for seafood and some juice products. If FDA wants a workable, meaningful and accurate AER system for dietary supplements it should proceed as requested by petition and initiate a rulemaking process for this. If FDA really wants to enforce food additive and labeling regulations, please proceed. It already has the authority and regulations necessary; it simply has not done the job. These efforts only add unnecessary complexity to the intended regulation. Looking back at the initial authorization:
"The Secretary may by regulation prescribe good manufacturing practices for dietary supplements. Such regulations shall be modeled after current good manufacturing practice regulations for food . . ." [Public Law 103-417 – DSHEA]
The authorization is clear. Without taking to task FDA's discussion of what "modeled" means, there are some obvious points to make: The "good manufacturing practice regulations for food" DO NOT include the establishment of an AER system; the "good manufacturing practice regulations for food" ARE NOT HACCP regulations nor are there redundant regulatory insertions.
Looking once more at the history of this topic, the legitimate question to ask is: Whatever became of the industry document offered up in 1995? Somewhere along the line it got lost. Granted, at the time industry did not directly address the matter of automated equipment in the document it generated (FDA makes strong mention of this), but the industry document did address every other matter pertinent to the manufacture of these products. FDA obviously dismissed the input from industry and chose to go its own way. Thus, rather than accepting the input from those with direct experience in manufacturing these products, FDA elected to push its own unilateral agenda. That agenda includes more than manufacturing concerns. We can learn from the proposed rule that FDA does not believe it has sufficient regulatory authority over such items as label claims for dietary supplements. It also does not believe it has sufficient authority over the composition of these food products. FDA goes on to demonstrate that it believes these food products to be inherently unsafe when manufactured according to normal practices (even with advanced controls as offered up in the industry document). FDA took those beliefs and created a self-justified, complex, unenforceable document intended exclusively to meet its own needs. The dietary supplement industry has repeatedly asked for the rulemaking process to proceed. It anticipated that FDA would listen to the input provided and offer a proposal that incorporated the knowledge of the industry. Instead, after the six-year hiatus from activity, FDA issued a combination GMP/Label Claim/HACCP/Food Additive/AER system proposal.
Industry must comment strongly on this matter, while inquiring deeply as to what happened to the original submission. At the end of the ANPRM FDA asked a series of questions concerning items in which it was interested. These questions bore little to no relationship to the matter of GMPs for dietary supplements. The answers from industry to these nine questions are discussed and dismissed in the preamble to the proposed rule. The answers FDA came up with resulted in the insertion of additional rules under the GMP rulemaking umbrella.
The industry should stand up to these efforts as it formulates its comments to the proposed rule and alert FDA that a solid, enforceable regulation governing the manufacture of these products can be made without having to address other issues or add unnecessary complexity. After all, the dietary supplement industry already wrote one back in 1995.NW
About the author: Jim Lassiter has over 25 years of experience in regulatory affairs and is currently director of consulting and regulatory services at ChromaDex, Santa Ana, CA, a leading global provider of high purity reference standards with top-tier analytical research and regulatory consulting services to the nutraceutical, botanical and phytopharmaceutical industries. Mr. Lassiter can be reached at 2952 S. Daimler Avenue, Santa Ana, CA 92705; 949-419-0288; Fax: 949-419-0294; E-mail: jiml@chromadex.com
In October of 1994, Congress passed the Dietary Supplement Health and Education Act (DSHEA). Among the items included in this amendment to the Federal Food, Drug and Cosmetic Act (FFDCA) was an allowance for rulemaking that would result in GMPs for dietary supplements. The requirement for the regulations was that they be modeled after the GMPs for foods. In November of 1995, the dietary supplement industry delivered to FDA a document written in the same style as a regulation detailing what were state-of-the-art practices in the manufacture of dietary supplements. The "industry document" was published by FDA in February of 1997 in its Advanced Notice of Proposed Rulemaking (ANPRM) along with a series of questions FDA wanted answers to as it pondered the matter. Thus began the allowed rulemaking process. After six years of prompting and prodding from the industry, FDA finally performed the next step by issuing the proposed rule.
Proposed rules generally reflect the regulatory agency's perspective on a topic rather than that of the regulated industry. This is very obvious since the difference between the industry document and the proposed rule is well beyond significant. Upon reflection, there is little wonder why so much time passed between the issuance of the ANPRM and the publication of the proposed rule. Apart from most general section headings and a few minor concepts here and there, there is almost no resemblance between the "state-of-art" as presented by the people who actually do the work and FDA's perspective.
What happened?
What happened is that FDA has attempted to shoehorn a group of other regulations into this proposal, some of which are duplications of existing regulations. To start with, you may recall that the purpose of this rulemaking process was to issue regulations establishing minimum standards for the manufacture of dietary supplements. These proposed regulations would apply not only to the manufacture of dietary supplements but would equally apply to the manufacture of dietary ingredients. Looking at the history for a moment, we find that this was something the industry asked for when it presented its document in 1995, so this matter is now difficult to challenge. However, industry made the mistake of focusing on manufacturing practices only. FDA expanded the scope of what should be covered by determining that this was a great opportunity to fit in other regulations it desired. Interesting concept but wholly inappropriate.
The first case is easy to make. FDA has repeatedly stated publicly that the Proposed Rule DOES NOT ensure the safety or efficacy of the products. However, the agency also publicly stated that these GMPs would ensure that the products deliver on the promises shown on their labels. This does not mean that the label will carry some offering of proof that GMPs were followed in the manufacture of the product. The implication, therefore, is that FDA wishes to use GMPs as a means to validate label claims both for potency and stated effects. Concerning the safety issue, one FDA staffer offered up at the May 6th Outreach Meeting in Oakland, CA, that these products "can be dangerous" when they provide either "more than or less than" the amount of dietary ingredient shown on the label. This last point is truly interesting since FDA has long contended that these products are not effective. It is impossible to determine how consuming less of something that is not effective is potentially harmful. Setting that aside, it may appear that shoehorning label claims and potency evaluation into the GMPs is not so much of a stretch. However, one need only look at the current Code of Federal Regulations (CFR) to find regulations already in existence that specifically address these issues. Why the redundancy? FDA remains silent on this matter. The point to make is that this aspect of the proposed rule is superfluous. But that's not all.
FDA also inserted into the proposed rule a reiteration of the requirement that all materials used in making a dietary supplement or dietary ingredient be acceptable for food use. In case you missed it: According to the FFDCA, dietary supplements are foods and thus already covered by existing food additive regulations. The lone exceptions to the requirements for food additives (those things that go into food products) are dietary ingredients. Thus, through the application of amazingly obtuse logic we have the following proposal: The manufacture of dietary ingredients (exempted from food additive regulations) must be done using only materials that are acceptable when food additive regulations are applied. Again, FDA is attempting to shoehorn redundant and inappropriate regulations into this proposed rule intended to cover manufacturing practices. The results speak for themselves. Yet that's still not all.
The FDA stated repeatedly in the preamble to the proposed rule that it was not implementing HACCP (Hazard Analysis, Critical Control Point) regulations with these GMPs. Yet, there is within the proposed rule itself an awful lot of mandatory activity that looks just like HACCP regulations. Additionally there is (in FDA's self-affirmed simplified language) discussion of what the "critical control points" in the process of manufacturing likely are and what you are to do when you come to one of these. Make no mistake, HACCP regulations add significant layers of complexity (just ask the seafood industry) and many of those complexities are found in this proposal. Moreover, FDA was not granted specific authority to issue HACCP regulations for dietary supplements for some very solid reasons. Among these reasons is the fact that the usual activities performed in manufacturing these products even at "critical" steps in the operation are not at all likely to result in a HAZARD. Without the specific authority to issue HACCP regulations, FDA still determined to put them in place with a thin veil of denial covering them. And that's still not all.
The FDA took this opportunity to insert within a proposed regulation covering manufacturing practices the mandate for a de facto Adverse Event Reporting (AER) system. As with the HACCP shoehorn approach and discussion, FDA goes to great lengths to deny that this is what it is doing. Their presentation includes establishing a category of customer feedback identified as "Consumer Complaints." FDA insists that this is necessary and worthy of inclusion within GMPs. The requirements for handling these consumer complaints include the need to designate someone to determine which incoming complaints are consumer complaints and which are AERs. Once this determination is made, additional actions are described for either category. The obvious truth is that FDA is attempting to fit in regulations that would ordinarily require a separate rulemaking process. The irony is that one industry trade association (The American Herbal Products Association) has formally petitioned FDA to proceed through rulemaking and establish a meaningful AER system for dietary supplements. The anticipated response to this petition seems clear now: Such action is not necessary since these regulations are coming via GMPs.
At the end of the day (plus the preceding six plus years) FDA issued a proposed rule that is extraordinarily more complex than it needs to be so that it can either redundantly issue regulations that already exist (in the case of both the food additive and labeling efforts) or put in place new regulations under the GMP umbrella for which it was not granted authority (HACCP and AER System). These efforts are simultaneously superfluous and completely inappropriate. If FDA wants to issue HACCP regulations for dietary supplement manufacture it should describe the rationale and seek authorization to do so as it did for seafood and some juice products. If FDA wants a workable, meaningful and accurate AER system for dietary supplements it should proceed as requested by petition and initiate a rulemaking process for this. If FDA really wants to enforce food additive and labeling regulations, please proceed. It already has the authority and regulations necessary; it simply has not done the job. These efforts only add unnecessary complexity to the intended regulation. Looking back at the initial authorization:
"The Secretary may by regulation prescribe good manufacturing practices for dietary supplements. Such regulations shall be modeled after current good manufacturing practice regulations for food . . ." [Public Law 103-417 – DSHEA]
The authorization is clear. Without taking to task FDA's discussion of what "modeled" means, there are some obvious points to make: The "good manufacturing practice regulations for food" DO NOT include the establishment of an AER system; the "good manufacturing practice regulations for food" ARE NOT HACCP regulations nor are there redundant regulatory insertions.
Looking once more at the history of this topic, the legitimate question to ask is: Whatever became of the industry document offered up in 1995? Somewhere along the line it got lost. Granted, at the time industry did not directly address the matter of automated equipment in the document it generated (FDA makes strong mention of this), but the industry document did address every other matter pertinent to the manufacture of these products. FDA obviously dismissed the input from industry and chose to go its own way. Thus, rather than accepting the input from those with direct experience in manufacturing these products, FDA elected to push its own unilateral agenda. That agenda includes more than manufacturing concerns. We can learn from the proposed rule that FDA does not believe it has sufficient regulatory authority over such items as label claims for dietary supplements. It also does not believe it has sufficient authority over the composition of these food products. FDA goes on to demonstrate that it believes these food products to be inherently unsafe when manufactured according to normal practices (even with advanced controls as offered up in the industry document). FDA took those beliefs and created a self-justified, complex, unenforceable document intended exclusively to meet its own needs. The dietary supplement industry has repeatedly asked for the rulemaking process to proceed. It anticipated that FDA would listen to the input provided and offer a proposal that incorporated the knowledge of the industry. Instead, after the six-year hiatus from activity, FDA issued a combination GMP/Label Claim/HACCP/Food Additive/AER system proposal.
Industry must comment strongly on this matter, while inquiring deeply as to what happened to the original submission. At the end of the ANPRM FDA asked a series of questions concerning items in which it was interested. These questions bore little to no relationship to the matter of GMPs for dietary supplements. The answers from industry to these nine questions are discussed and dismissed in the preamble to the proposed rule. The answers FDA came up with resulted in the insertion of additional rules under the GMP rulemaking umbrella.
The industry should stand up to these efforts as it formulates its comments to the proposed rule and alert FDA that a solid, enforceable regulation governing the manufacture of these products can be made without having to address other issues or add unnecessary complexity. After all, the dietary supplement industry already wrote one back in 1995.NW
About the author: Jim Lassiter has over 25 years of experience in regulatory affairs and is currently director of consulting and regulatory services at ChromaDex, Santa Ana, CA, a leading global provider of high purity reference standards with top-tier analytical research and regulatory consulting services to the nutraceutical, botanical and phytopharmaceutical industries. Mr. Lassiter can be reached at 2952 S. Daimler Avenue, Santa Ana, CA 92705; 949-419-0288; Fax: 949-419-0294; E-mail: jiml@chromadex.com
