From: Matt Arveseth [marveseth@albion-an.com] Sent: Monday, August 11, 2003 6:52 PM To: fdadockets@oc.fda.gov Subject: Comments for Docket reference 1996N-0417 Mr. Matt Arveseth Dietary Supplement Private Industry Albion Advanced Nutrition I tried submitting these comments through the website, but was getting an error. Thanks Matt Arveseth Validation of Methods Additional Guidance and clarification is requested on the use of validated methods. In the pre-amble it suggests that USP and AOAC methods are appropriate validated methods. Clarification is requested over the following issues. 1.. Are other validated methods acceptable? For example Albion Advanced Nutrition currently uses inductively coupled plasma emission spectroscopy (ICP) for the testing of our mineral products. Validated ICP methods exist in US-EPA methods as well as other validated method references. Are these other validated methods acceptable? 2.. Is preference or precedence given to USP and AOAC methods? USP and AOAC have methods for testing mineral products using Atomic Absorption and various gravimetric methods. Are these methods preferred by FDA over other validated methods as describe above in item 1? 3.. How much modification of a validated method is allowed before the method must be re-validated by the laboratory? Some methods are required to have unique modifications for use in a particular industry. For example Albion produces a copper mineral supplement which has a low char-point. When performing moisture testing on this product it was determined that the product was charring causing erroneous high moisture values. The method therefore required modification to reduce the charring thereby giving a more valid moisture reading. This deviation is outside the parameters of moisture testing as outlined in official AOAC methods. Would this require validation? If so what is the extent of validation required?’ 4.. New Dietary Ingredients 1.. For new dietary ingredients, how will FDA determine appropriate validated methods, reference standards, etc? 2.. Albion Advanced Nutrition produces a unique mineral amino acid chelates. While Albion does extensive product testing there are not commercially available reference standards or validated methods for testing these ingredients for identity. What does FDA propose for these types of new products? 3.. Additionally there are many items for sale in the industry that do not have standard reference materials, or standard testing procedures. How are companies to show compliance to the proposed rule if testing is not possible? For example on commercially available herbal supplements ingredients such as pineapple enzyme extract or grapefruit seed extract. These products are food ingredients and therefore testing has not been required in the Food GMP. The development costs and research required to determine appropriate testing methods were not accounted for in FDA estimates. GRAS Status of Raw Ingredients The Proposed Final Rule gives requirements that materials used in dietary supplements and dietary ingredients must be GRAS, or precedence of use in the food chain prior to DSHEA. It is requested that additional guidance is given on this requirement. 1.. What requirements are in place for the introduction of new dietary ingredients into the market? DSHEA requires FDA notification 90 days prior. Is this 90 day notification still required? 2.. Albion Advanced Nutrition produces a unique product, mineral amino acid chelates. These products are made from GRAS/USP/FCC ingredients, but the final product is a new, unique, molecule. What are the requirements for notification when the product is not specifically GRAS/USP/FCC, but originated from GRAS/USP/FCC ingredients? What requirements will our customers be subjected to because of this ruling since the “active” ingredient is not specifically stated as GRAS in any official compendium, but the ingredients are GRAS? Exclusions in Proposed Final Rule FDA states that the one of the purposes of Dietary Supplement GMPs is to give legitimacy to the industry and provide for increased safety of dietary supplements. However the Proposed Final Rule lacks several key elements that could allow for possible complacency in the industry. It is the opinion of Albion Advanced Nutrition that several exclusions are evident in the Proposed Final Rule. They Include: 1.. Lack of requirements for written procedures 2.. Lack of requirements for maintenance and upkeep around the exterior of buildings 3.. Lack of requirements for record keeping of distribution of products. 4.. Lack of requirements for specific GMP training requirements and annual GMP training 5.. Lack of requirements for lot number tracking of finished products 6.. Lack of requirements for expiration dating of finished products In FDA public meeting forums these questions have been raised by many within the industry. These missing elements have a detrimental effect on FDA’s purpose for drafting the ruling. For example, a company abiding by FDA regulations may need to issue a recall. Without records of distribution and lot number tracking of product, the scope of recall would likely be very broad and too encompassing. Testing Costs In the proposed Final Rule FDA estimates that testing costs to be approximately $50 per test and 4 tests per product, therefore a total testing cost of $200 per batch. Albion Advanced Nutrition performs testing in house and has estimated the total average cost of testing to be approximately $200 per batch, however; Albion considers this estimation low relative to the industry. Our testing procedures are relatively in-expensive relative to other dietary supplement ingredients and we are testing for only one active component in a majority of our products. Herbal supplements usually contain many components. HPLC testing of a single component can cost as high as $200 in commercially available laboratories. Vitamin/mineral/herbal supplements exist where the label claims nearly 50 active components. Of these 50 components not all have validated methods for testing of finished product or raw material. The testing costs for many of these products will be far in excess of FDA estimates. In this instance just the mineral testing would be above $200. Another aspect of cost estimates not accounted for in FDA’s estimates relates to holding costs and carrying costs of inventory during waiting periods for testing. Companies that may contract out testing services will find that laboratory turn around time of samples is commonly 2 – 4 weeks. A company could not release product for sale until finished product testing is completed. The additional time and cost estimates for carrying inventory was not addressed in the proposed final rule.