Final Rule. Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements

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1 Docket No. BEFORE THE UNITED STATES OF AMERICA DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION PETITION FOR RECONSIDERATION BY THE AMERICAN HERBAL PRODUCTS ASSOCIATION Final Rule Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements July 25, 2007

2 Pursuant to 21 CFR ("Administrative reconsideration of action"), the undersigned American Herbal Products Association ("AHPA") submits this petition to request reconsideration of certain provisions of Title 21 of the Code of Federal Regulations, Part 111 ( 21 CFR 111 ) establishing regulations for Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements (72 FR 34752, June 25, 2007; Docket No. ). The relief requested is that the Food and Drug Administration ( FDA or the agency ) reconsider the matters set forth in this petition and reach a resolution regarding the regulations requested to be reconsidered, and that such resolution be reached by January 1, 2008, or at least in sufficient time to allow such resolution to be considered in advance of the regulations first compliance date of June 25, AHPA is the national trade association and voice of the herbal products industry, which is comprised of domestic and foreign companies doing business as growers, processors, manufacturers, marketers and distributors of herbs and herbal products. AHPA serves its members by promoting the responsible commerce of herbal products. A. Decision Involved In the Federal Register of June 25, 2007, 72 FR 34752, the agency published a final rule for Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements ( the Final Rule ). The Final Rule is codified at 21 CFR 111. The effective date of the Final Rule is August 24, 2007 and the first compliance date is June 25, B. Action Requested AHPA requests that FDA reconsider the Final Rule in the following respects: - 2 -

3 (1) 21 CFR 111.1(a) states, you are subject to this part if you manufacture, JULY 25, 2007 package, label, or hold a dietary supplement. In the preamble accompanying this section of the Final Rule, FDA states: those who manufacture, package, label, or hold dietary ingredients [emphasis added] are not subject to the final rule. To illustrate, assume you manufacture a dietary ingredient and sell that bulk dietary ingredient to Company X. Company X then utilizes the bulk dietary ingredient in a dietary supplement. Under final 111.1(a), you would not be subject to these dietary supplement CGMP requirements because you are not manufacturing a dietary supplement, rather you are manufacturing a dietary ingredient for further incorporation into a dietary supplement by Company X. If, however, you sell herbs in bulk to Company X, and Company X simply packages the herbs into smaller units for sale as a dietary supplement, you would be subject to the dietary supplement CGMP requirements because you are manufacturing a dietary supplement that Company X is simply packaging and labeling, and not further processing into a dietary supplement. In other words, in the latter example, you would have acted as a manufacturer whose finished product is simply repackaged or relabeled. 72 FR AHPA requests reconsideration of the last sentence of the above quoted commentary in the preamble of the Final Rule so that dietary ingredient companies do not have their regulatory obligations decided by actions that are taken by their customers. To accomplish this reconsideration, AHPA requests that the last sentence cited above be revised to two sentences to state: Similarly, if you sell herbs in bulk to Company X and Company X repackages those herbs into smaller units for sale as a dietary supplement, you would not be subject to these dietary supplement CGMP requirements. In this scenario, Company X would be required to establish specifications under for the herbs that they repackage into smaller units for sale as a dietary supplement and to ensure that their specifications are met under and (2) The Final Rule establishes Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements but nowhere defines manufacturing, packaging, labeling, or holding. AHPA requests reconsideration of the Final Rule to provide definitions for manufacturing, packaging, labeling, and holding. To accomplish this - 3 -

4 reconsideration, AHPA requests that the Final Rule be amended by adding the following definitions in 111.3: Manufacturing means to conduct operations to make from one or more components a finished dietary supplement intended for ingestion in the form of a tablet, capsule, powder, softgel, gelcap, liquid or other form for ingestion, such as a teabag. Packaging means to conduct operations to place a finished dietary supplement into the retail container in which it will be sold to consumers. Labeling means to conduct operations to place labels on packaged finished dietary supplements for sale to consumers. Holding means maintaining and storing packaged and labeled finished dietary supplements for distribution or wholesaling. (3) 21 CFR establishes the requirements for determining that specifications have been met. The Final Rule in this section has set different and less rigorous requirements for firms that package or label a product that [is received] for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier) than for finished dietary supplement batches. AHPA asks that the Final Rule be reconsidered and amended to require that those who package or label products (including dietary ingredients and dietary supplements) that they have received for packaging and labeling as a dietary supplement for distribution rather than for return to the supplier be required to either (1) verify that the specifications they have established for the product that they receive, as required under (f), are met in the same manner as is required under (c) and (d) for finished dietary supplement batches, or (2) visually examine the product and have documentation to determine whether the specifications established under (f) are met, except that this second option only be allowed if the product s recipient makes and keeps written records, which records should be specifically required under , of documentation for why the examination performed on the received product verifies that the dietary supplement meets all product specifications

5 More specifically, and to accomplish this reconsideration, AHPA requests that the Final Rule be reconsidered and amended to replace current (e) with the following: (e) For a subset of dietary ingredient or dietary supplement lots that you receive for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier) that you identify through a sound statistical sampling plan (or for every lot), and before you package or label such product, you must either: (1) Verify, in accordance with paragraph (c) of this section, that the product meets the specification that you established under (f); or (2) Exempt one or more product specifications established under (f) from verification requirements in accordance with paragraph (d) of this section; or (3)(i) Visually examine the product and have documentation to determine whether the specifications that you established under (f) are met. In such a case, you must document why visual examination and documentation will verify that product specifications are met; (ii) Your quality control personnel must review and approve the documentation that you provide under paragraph (e)(3)(i) of this section. In addition, AHPA requests that the Final Rule be amended by adding a new paragraph to accomplish this reconsideration, as follows: (b)(6) Documentation for why visual examination performed under (e)(3)(i) verifies that the dietary supplement meets all product specifications. AHPA further requests that, for consistency, each time the phrase a product that you receive for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier) appears in the final rule, the word product within this phrase be changed to the words dietary ingredient or dietary supplement. (4) 21 CFR describes the requirement to establish a written master manufacturing record, and states: (a) You must prepare and follow a written master manufacturing record for each unique formulation of dietary supplement that you manufacture, and for - 5 -

6 each batch size, to ensure uniformity in the finished batch from batch to batch. JULY 25, 2007 AHPA requests reconsideration of this part of the Final Rule to allow a written manufacturing record to be prepared for a range of batch sizes. To accomplish this reconsideration, AHPA requests that the Final Rule be amended to replace current (a) with the following: (a) You must prepare and follow a written master manufacturing record for each unique formulation of dietary supplement that you manufacture, and for each batch size or range of batch sizes, to ensure uniformity in the finished batch from batch to batch. If the written master manufacturing record contains a range of batch sizes, such record must include documentation for why all batches produced within the range will be uniform from batch to batch. (5) 21 CFR pertains to master manufacturing records and (h) requires written instructions in the master manufacturing to include: (3) Specific actions necessary to perform and verify points, steps, or stages in the manufacturing process where control is necessary to ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record. (i) Such specific actions must include verifying the weight or measure of any component and verifying the addition of any component; and (ii) For manual operations, such specific actions must include: (A) One person weighing or measuring a component and another person verifying the weight or measure; and (B) One person adding the component and another person verifying the addition. AHPA requests that the Final Rule be reconsidered to allow manufacturing operations that consist of just one person and that use manual operations to have additional options to verify the weight or measure and addition of components. To accomplish this reconsideration, AHPA requests that the Final Rule be amended to replace current (h)(3)(ii) with the following: (ii) For manual operations, such specific actions must include: - 6 -

7 (A) (1) One person weighing or measuring a component and another person verifying the weight or measure; and (2) One person adding the component and another person verifying the addition; or (B) (1) If only one person is available for manual operations, specific actions other than described in paragraph (h)(3)(ii)(a) of this section that will verify the weight and measure and the addition of the component. In such a case, you must document why the specific actions will verify the weight and measure and the addition of the component. (ii) Your quality control personnel must review and approve the documentation that you provide under paragraph (h)(3)(ii)(b)(1) of this section. (6) 21 CFR (b) prescribes label reconciliation as follows: (b) You must control the issuance and use of packaging and labels and reconciliation of any issuance and use discrepancies. Label reconciliation is not required for cut or rolled labels if a 100-percent examination for correct labels is performed by appropriate electronic or electromechanical equipment during or after completion of finishing operations. AHPA requests reconsideration of this part of the Final Rule to provide an option for personnel to perform 100-percent examination for correct labels. To accomplish this reconsideration, AHPA requests that the Final Rule be amended to replace current (b) with the following: (b) You must control the issuance and use of packaging and labels and reconciliation of any issuance and use discrepancies. Label reconciliation is not required for cut or rolled labels if a 100-percent examination for correct labels is performed by appropriate electronic or electromechanical equipment, or by personnel, during or after completion of finishing operations. (7) 21 CFR describes means to include in filling, assembling, packaging, labeling, and related operations to ensure the quality of the dietary supplement, including: (f) Assigning a batch, lot or control number to: (1) Each lot of packaged and labeled dietary supplement from a finished batch of dietary supplement; and, - 7 -

8 (2) Each lot of dietary supplement, from a finished batch of dietary supplement, that you distribute to another person for packaging or labeling. In the preamble accompanying this section of the Final Rule, FDA states: We do not require you to affix this batch, lot, or control number to the immediate container or the product label. 72 FR AHPA requests that this regulation be reconsidered to require that each such batch, lot, or control number be affixed to or otherwise marked on the dietary supplement package that is distributed for sale to consumers. To accomplish this reconsideration, AHPA requests that the last sentence of the preamble quoted above be revised to state: We require you to affix or otherwise mark this batch, lot, or control number to or on the immediate container or the product label. In addition, AHPA requests that the Final Rule be amended to replace current (f) with the following: (f) Assigning a batch, lot or control number to, and affixing or otherwise marking the batch, lot or control number to or on the immediate container or the product label of: (1) Each lot of packaged and labeled dietary supplement from a finished batch of dietary supplement; and, (2) Each lot of dietary supplement, from a finished batch of dietary supplement, that you distribute to another person for packaging or labeling. C. Statement of Grounds The requests for reconsideration submitted herein seek to correct sections of the Final Rule that are potentially confusing; that are contrary to the public interest by failing to provide adequate insurance of finished product integrity or traceability, thereby disrupting the rule s intention to ensure dietary supplement quality; or that are unnecessarily prescriptive in a manner that could create substantial damage to manufacturers with no corresponding benefit. More specifically: - 8 -

9 (1) The first topic for which AHPA has requested an action for reconsideration JULY 25, 2007 under the Final Rule, as presented in section B (1) above, is on the statement made in the preamble in which FDA describes a scenario in which a dietary ingredient company might be required to comply with 21 CFR 111 due to its customers use of the company s ingredient. As an introduction to the statement of grounds for that specific requested action as presented here, AHPA wishes to call FDA s attention to the need to read the requested action at B (1) together with the requested action at B (3), this petition s request to amend (e) to ensure that it does not present a loophole that is contrary to ensuring the quality of dietary supplements. These two sections of this petition are interlinked, and are requested to be considered together. FDA asserts in the preamble to the Final Rule that a dietary ingredient manufacturer or supplier may be required to comply with 21 CFR 111 under certain circumstances, which circumstances are under its customers control. AHPA is not aware of, and believes that there has been no prior federal regulation for current good manufacturing practice for any type of food that includes a mechanism whereby a company that provides food ingredients can be required to conform to a specific finished food product cgmp depending on how its customers use its supplied ingredients. It is feasible that an ingredient firm that manufactures or supplies, for example, vitamins or spices, might sell to one company that uses one or more of its ingredients in a low-acid food that is thermally processed and hermetically sealed, to another that adds it to an acidified food product, to a third that includes it in its manufactured fishery product, and to still another that uses it as a flavoring or to increase the nutrition of its fresh juice product. The ingredient firm that sells to these several customers must comply with 21 CFR 110, the standard cgmp for manufacturing, packaging, or holding human food, since this regulation at 110.3(f) specifically states that the definition of food for purposes of this part includes raw materials and ingredients. The firm is not, however, required to comply with the specific and additional elements of the cgmp found in 113 (for thermally processed low-acid foods), 114 (for acidified foods), or 123 (for fish and fishery

10 products), or with the HACCP requirements for juices in 120. If this ingredient company gains one additional customer, however a customer that would simply package its ingredient for sale as a dietary supplement then the ingredient company would automatically, under FDA s interpretation, be required to implement all of the many additional regulatory requirements found in 21 CFR 111. AHPA disagrees with this interpretation, however, and believes that an ingredient supplier should have the same obligation to comply with 21 CFR 110, regardless of the class of foods in which its customers use or package its ingredients. There is, of course, one significant difference between these various special food categories and dietary supplements, since a dietary ingredient may, in some circumstances, be packaged and labeled as a dietary supplement without any further processing. For example, dietary supplement products are available that consist of several ounces of a vitamin or an amino acid packaged in a bottle, or of one or more herbs packaged in a box, bag, or can. This is not the case when a company purchases ingredients that it will use as one of its ingredients in one of the specific food categories mentioned above. But this fact does not, in and of itself, provide a reasonable argument to transform an ingredient company into a dietary supplement manufacturer, or to establish its identity as a dietary supplement manufacturer after the fact of its customer s packaging of its ingredient as a dietary supplement. And it must be acknowledged that FDA s interpretation as discussed here will have the effect of requiring an ingredient company to conform to two different federal cgmp rules if it has some customers that package one of its ingredients as a dietary supplement and others that use that same ingredient in another food class even though their various customers are using the exact same substance, and potentially the exact same lot of the substance. Using the specific example provided in the preamble wherein you sell herbs and your customer simply packages the herbs into smaller units for sale as a dietary supplement, FDA states that the herb supplier would have manufactured the herb. Under this example, FDA asserts that a company that purchases a

11 container of peppermint leaf and resells that peppermint leaf will have manufactured it, if one or more of its customers simply packages it for sale as a dietary supplement. AHPA can find no precedent that provides any reason or rationale for this assertion, and it is simply not logical to identify the process of selling a bulk herbal ingredient as somehow manufacturing that herb as a finished dietary supplement. Early in the preamble s discussion of whether or not the rule should be applicable to companies that manufacture, package, label or hold dietary ingredients, FDA states, In response to comments that questioned the need to include manufacturers of dietary ingredients within the scope of part 111, we have made changes to the scope of the rule, as applied to dietary ingredient manufacturers. This discussion goes on to say: after considering comments about the overall production and process control system, we revised the final rule s approach to ensuring product quality. This approach emphasizes that it is important to ensure the quality of the dietary supplement throughout the production and process control system. This approach emphasizes establishing specifications for components and ensuring those specifications are met. the goal of ensuring the quality of dietary supplements can be achieved without applying the rule specifically to persons who manufacture, package, label, or hold dietary ingredients that will be further processed as a dietary supplement by other persons. Consequently, we revised by deleting dietary ingredient. Therefore, those who manufacture, package, label, or hold dietary ingredients are not subject to the final rule. 72 FR The approach identified here establishes that at some point between the ingredient and the consumer, some person must be responsible for setting specifications and for ensuring that specifications are met. AHPA has no argument with such an assumption and supports this requirement in the Final Rule. It is AHPA s view, however, that FDA has mis-assigned that responsibility to the ingredient manufacturer or supplier in those cases in which an ingredient company s customer packages and labels the company s ingredient to sell as a dietary supplement. AHPA supports FDA s intention to make sure in this scenario that some person should set and meet specifications. But AHPA believes that the

12 responsible person in this scenario should be the company that simply packages the ingredient, and not the ingredient supplier. That company already has obligations under to establish specifications and under and to determine that established specifications are met. As noted at the outset of this part of this petition s statement of grounds, the request articulated in section B (1) and that articulated in section B (3) must be considered together. In B (3) AHPA has requested that FDA amend the Final Rule so that firms that receive products including dietary ingredients for packaging and labeling for distribution rather than for return to the supplier will be held to a high enough standard to prevent such firms from being a weak link in the chain of custody from ingredients to consumers. This will have the effect, if adopted, of assigning the responsibility for meeting specifications for a dietary ingredient that is simply packaged for sale as a dietary supplement to the person that should be responsible for these procedures that is, to the packager. In summary, the concept that an ingredient manufacturer or supplier is transformed into a dietary supplement manufacturer by actions taken by their customer is not rational, and FDA should revise the cited statement in the preamble to clarify that it does not intend for this irrational scenario to apply. At the same time, some person must be held responsible for setting and meeting specifications. FDA should therefore ensure that the company that simply packages a received ingredient bears this burden, by amending (e) as requested in section B (3) of this petition. (2) The Final Rule is meant to apply to companies that manufacture dietary supplements, and also those who package, label or hold them. It is clear from reading the preamble that FDA believes that a company s specific operations are relevant to determining which specific sections of the Final Rule apply to their operations. FDA makes exactly this point in the preamble by stating, you need to comply with the CGMP requirements that apply to your operations related to the manufacture, packaging, labeling, and holding of dietary supplements. 72 FR

13 FDA provides an example of a company that is a packager/labeler but not a finished product manufacturer, and which would not need to comply with requirements that do not apply to it; for example, the packager/relabeler would not have to conduct testing on the finished batch of dietary supplement since it does not manufacture the finished batch of dietary supplement. Id. The agency also notes, if you are a wholesaler, you would be subject to the requirements in final for the dietary supplements you are holding for distribution as well as other applicable requirements, such as those related to personnel, physical plant and grounds, equipment and utensils, quality control, returned dietary supplements, and product complaints. 72 FR Because there are different obligations under the Final Rule for different operations it is essential that the regulated trade clearly understand exactly what FDA means by each of the terms, manufacturing, packaging, labeling, and holding. It is also essential that FDA and industry mean the same thing when each of these terms is used. AHPA is concerned, for example, that FDA may believe that encapsulating a dietary ingredient is a packaging operation, whereas the industry certainly considers this to be a manufacturing operation. Clarity on the meaning of these terms can only be accomplished if each of them is defined within the Final Rule. (3) 21 CFR establishes the requirements for determining whether manufacturing specifications have been met. In (c) and (d) there are specific requirements for finished dietary supplement batches to accomplish this requirement. In (e), substantially different and less rigorous requirements are established for those who package or label a product that [is received] for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier),. In this instance, all that is required is for the packager or labeler to visually examine the product and have documentation to determine whether the specifications that you established under (f) are met. AHPA believes that (e) creates a significant loophole in the Final Rule. AHPA believes that (e) may invite, for example, an unscrupulous packaging company to attempt to skirt the Final Rule by hiding their responsibility to be certain

14 JULY 25, 2007 of the identity, purity, strength and composition of the dietary supplements that they sell behind this paragraph, or a manufacturing company to take advantage of their knowledge that their customers obligations to ensure product quality is limited by this paragraph. Such companies would have unfair business advantages over competitors that must comply with (c) and (d). At the same time, AHPA reads (e) as an attempt by FDA to prevent this rule from requiring unnecessarily duplicative verification that product specifications are met. If the manufacturer that provides a dietary supplement product has met their obligations under (c) and (d), recipients of this manufactured dietary supplement may ensure the quality of the product by the envisioned examination. However, if that manufacture has not done so, this paragraph would not serve to prevent such a product from reaching the marketplace. AHPA s view is that this attempt to prevent unnecessarily duplicative verification that product specifications are met does not provide adequate assurance of the quality of finished dietary supplements. In the proposed amendment to (e) suggested above, AHPA has attempted to provide an option that would prevent duplicative verification when it can be documented that this would be unnecessary, while at the same time insisting on rigorous verification in the absence of documentation that the examination required in current (e) verifies that the dietary supplement meets all product specifications. AHPA has also requested that the word products in paragraph (e) be replaced with the words, dietary ingredient or dietary supplement lots. This request will ensure that firms that receive a dietary ingredient for packaging and labeling as a dietary supplement for example, a box of 4 ounces of peppermint leaves packaged and labeled as a dietary supplement or a bottle of Vitamin C powder packaged and labeled as a dietary supplement meet the requirements of this paragraph for determining whether specifications are met; and that firms that receive dietary supplements for packaging or labeling as a dietary supplement also meet the requirements of this paragraph for determining whether specifications are met. By clearly requiring that this regulation applies when a dietary ingredient is

15 packaged and labeled as a dietary supplement, the rule will ensure that someone in the chain of custody that is, the packager/labeler is held accountable for ensuring the quality of a dietary supplement that consists of a dietary ingredient labeled and packaged as a dietary supplement, by establishing the required specifications and by determining that specifications are met. Also, the word product should be replaced with the words dietary ingredient or dietary supplement wherever the phrase a product that you receive for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier) is found in the Final Rule in order to maintain consistency throughout the Final Rule. (4) Some AHPA members prepare and follow master manufacturing records that are written with an understanding that the same record is relevant to various batch sizes within a known range. This is especially true for herbal products that are manufactured from agricultural products that are grown by or on a contractual basis for the manufacturer, and where the exact yield of a crop from which such agricultural products are to manufactured varies from one harvest to another. Thus, one harvest may yield 73.5 pounds of an herb and the next may yield 128 pounds. The master manufacturing record for a tincture produced from that herb must necessarily be sufficiently flexible to deal with such variations in the quantity of the herbal starting material. If a separate master manufacturing record is required for each individual batch size, companies will be required to maintain dozens (perhaps hundreds or thousands) of master manufacturing records for what is actually a single product. This would create a tremendous recordkeeping and filing burden, especially with respect to revision control. AHPA provided a similar communication in comments filed on August 11, 2003 in response to the proposed rule on dietary supplement cgmp. AHPA is aware that FDA discussed such comments in the preamble to the Final Rule, wherein the agency disagreed with these comments and declared that it was not making the suggested changes to proposed (a), which was the predecessor section for final (a). 72 FR

16 JULY 25, 2007 The preamble s explanation for this unwillingness to revise proposed (a) identified three points: (1) That requiring a separate master manufacturing record for each batch size will lessen the likelihood of mistakes that can happen when a formula is multiplied up or divided down, particularly in light of the requirement that quality control personnel review and approve each master manufacturing record; (2) that it is not clear that the scenario described in the comments would lessen any burden, because a new formula, based on the master formula, would still need to be prepared for each batch; and (3) that removing the requirement for a master manufacturing record to be batch-size specific would have the effect of shifting the burden from a requirement to prepare a master manufacturing record to a requirement to prepare a batch record [which] would defeat the purpose of having quality control personnel review and approve each formula. Id. With regard to the first of these points: There are a number of mechanisms a company could take to prevent arithmetic mistakes, such as (1) the working manufacturing records could be issued using a procedure that requires that quantities be calculated by one person and double checked by a second person or by quality control personnel; (2) the working manufacturing records could be issued using an automated system that makes the necessary calculations, and the issued working manufacturing record could be double checked by a person or quality control personnel; (3) the working manufacturing records could be issued using a validated automatic system that is periodically re-qualified. Any of these options would adequately ensure that calculations are correct and would prevent arithmetic mistakes. With regard to FDA s statement that a firm s burden would not be reduced by deleting the requirement for a master manufacturing record to be specific to a single batch size, this is incorrect. Requiring a company to maintain a separate master manufacturing record for each batch size is, in many cases, tantamount to requiring them to maintain dozens or even hundreds (perhaps even thousands) of master manufacturing records for what is essentially the same product. This would create a tremendous recordkeeping and filing burden, especially with respect to revision control should the formula be updated or changed periodically, or even if the

17 document format, company name or address, or other aspects of the presentation need to be updated periodically. FDA s final point, as noted above, is that allowing a master manufacturing record that does not specify the batch size would remove the authority of quality control personnel to review and approve each formula. But allowing a master manufacturing record for a range of batch sizes, as AHPA has proposed above, would retain the requirement under (a) for that record to be reviewed and approved by quality control personnel. AHPA has also proposed language that would require the master manufacturing record to include documentation for why all batches within the range will be uniform from batch to batch. Taken together, this would have the effect of requiring quality control personnel to review and approve the master manufacturing record, including the described documentation, for use anywhere within the range of batch sizes specified in the master manufacturing record. Finally, FDA s unwillingness to reconsider a revision in this paragraph will create a scenario wherein a single product may have a different master manufacturing record each and every time it is manufactured. Yet the stated purpose of a master manufacturing record is to ensure uniformity in the finished batch from batch to batch. This phrase is nearly illogical when only one batch of each formula is ever produced, as could be the case if a new master manufacturing record is required for every batch size. 5. The Final Rule s requirement at (h)(3)(ii) for a minimum of two persons to perform certain manual operations is unnecessarily prescriptive. There are certainly other means by which the weight or volume and the addition of components can be verified. For example, re-measuring of components by the same person can verify the weight or volume of each, and weighing or measuring the remaining inventory of each component after a batch is assembled can verify that the proper ingredients and quantities were dispensed. As another example, each ingredient dispensed for

18 a batch may be labeled with a sticker which is transferred into the batch record at the time the ingredient is added to the batch; addition of the proper ingredients could then be confirmed through review of the batch record at a later time or date. These are just examples of the types of steps a company may take to verify proper ingredient quantities and additions. In addition, it is inappropriate for this regulation to limit the firms that are allowed under federal regulations to manufacturer dietary supplements in any way that immediately excludes any firm that employs only one person, even if such a firm is in complete compliance with every other element of the Final Rule. (6) The Final Rule is unnecessarily prescriptive in its requirement at (b) to perform 100-percent examination for correct labels only by appropriate electronic or electromechanical equipment in order to be relieved from label reconciliation. Some AHPA members perform examination for correct labels by having personnel who are qualified by education, training or experience perform 100- percent examination for correct labels. In combination with proper controls over label receipt, storage, segregation, and issuance, inspection of finished packages by human personnel is adequate to ensure proper labeling. (7) The absence of a requirement to affix or otherwise mark onto each packaged and labeled finished dietary supplement product the batch, lot or control number that is required to be assigned under (f) may create a potentially significant obstacle to conducting operations that may become necessary in certain rare instances. Recalls routinely utilize batch, lot or control number information and the agency s recall regulations specifically suggest identifying the product, size, lot number(s), code(s) or serial number(s) and any other pertinent descriptive information to enable accurate and immediate identification of the product. 21 CFR 7.49(c)(l)(ii). For drugs, the lot number is so important that an incorrect lot number can be considered misbranding. 21 CFR

19 The preamble states that the Final Rule is in part modeled after infant formula cgmps and low acid canned foods, including their requirements for product coding under 21 CFR and 21 CFR (d). 72 FR The promise of that discussion, however, is nullified by the failure of the Final Rule to mandate that a batch, lot or control number appears on the finished dietary supplement product. Moreover, the requirement related to review and investigation of product complaints, as established by , would be difficult to meet, at best, with no coding on the finished dietary supplement. The failure to require product coding directly on a dietary supplement product will also impose greater burdens on state and agency authorities should a recall be required. Such a recall would inevitably involve more than one particular lot of product because all lots would be put at issue. This would be wasteful of resources and will unnecessarily alarm consumers if only one lot is at issue. In the proposed rule for dietary supplement cgmp, proposed (b) would have required Identifying the dietary supplement with a batch, lot, or control number that can be used to determine the manufacturing history and control of the batch, while the Final Rule only requires that a number be assigned. Also, in discussing this paragraph of the proposed rule, FDA at least implied that a good location for the batch, lot or control number would be somewhere on the actual product. The agency stated: you could recall the batch by identifying the batch number for the problem product. If you did not have a unique identifier, consumers would be unable to determine which product was the subject of a recall, and they may not stop using the product or you will have to recall more of the product. 68 FR It is difficult to comprehend how there could be any communication to consumers as to which batch or lot of a product is in their possession if the assigned number is not affixed to or otherwise marked on the product itself. D. CONCLUSION AHPA has requested herein that FDA reconsider the Final Rule in seven specific

20 sections, paragraphs, subparagraphs, or interpretations. AHPA has identified the specific action requested on each of these topics and has provided statements of grounds to address each requested action. For the foregoing reasons and based on the information provided in this petition, AHPA requests that the Final Rule be reconsidered and that FDA amend the final rule or its interpretations to address the matters raised herein. Respectfully submitted, Michael McGuffin President, American Herbal Products Association 8484 Georgia Avenue, Suite 370 Silver Spring, MD / Anthony L. Young Kleinfeld, Kaplan and Becker, LLP 1140 Nineteenth St. NW Washington, D.C General Counsel, American Herbal Products Association 202/