Docket #02D-0266From: Kimberly Odekirk [kodekirk@cacegypt.org] Sent: Thursday, December 19, 2002 12:46 AM To: Fdadockets@oc.fda.gov Subject: Docket #02D-0266 Please send a notice of receipt. Thank you. FROM: Kimberly Odekirk C/o Cairo American College PO box 39, Maadi, 11431 Cairo, Egypt E-Mail kodekirk@link.net TO: Dockets Management Branch (HFA-305) Food and Drug Administration 5630 Fishers Lane, rm. 1061 Rockville, MD 20852. or Fdadockets@oc.fda.gov RE1: Comments & Suggestions to change the Guidance for Industry Docket #02D-0266, CBER document #150 Federal Register notice #02-15898 FR Notice Availability to 12/23/2002 RE2: Concerning preventing the transmission of CJD/vCJD by HCT/Ps through deferral of diabetics that have injected beef insulin from the UK RE3; Clips from Guidance For Industry and request for change(s) addressed in the order that the Guidance For Industry, that is open for change, is laid out. "GUIDANCE FOR INDUSTRY Preventive Measures To Reduce The Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Draft - Not for Implementation "Under our Good Guidance Practices (GGPs), we may reconsider our recommendations after reviewing comments and information submitted to the docket, and the effect of donor deferrals on the availability of HCT/Ps or other relevant information." There are three proposed rules: #1 "Has been finalized. "Human Cells, Tissues, and Cellular and Tissue-Based Products; Establishment Registration and Listing; Final Rule" #2 "Suitability of Donors of Human Cellular and Tissue-Based Products;" #3 "Current Good Tissue Practice for Manufacturers of Human Cellular and Tissue-Based Products; Inspection and Enforcement;" INTRODUCTION Warnings concerning a 'possibility' of beef/bovine insulin injection carrying BSE should be eliminated from this and all guidance documents. It is causing an undue restraint of trade of this life source thus causing much pain and suffering and even death to the needy diabetics. I will be responding to and requesting changes to Item #2 above. I will also be addressing the FDA's concern about the deferred donors potential for transmission of classic Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) by transplantation, implantation, infusion, or transfer of Human Cells, Tissues, cellular and tissue-based Products (HCT/Ps) as it concerns Beef/Bovine Insulin. My main emphasis will be on the transfer of CJD and vCJD via Bovine/beef insulin from the UK or anywhere. Addressing the lack of possibility that said diabetics might harbor CJD or vCJD from the UK's bovine insulin. Addressing also the confounding lack of evidence that Bovine/beef insulin could cause CJD or vCJD. Thus proving that the undue deferral criteria of said diabetic donors is based on unreasonable possibilities and unproved theory/hypothesis. I will prove that said criteria should be stricken from all FDA guidelines and web sites. Also, the hardships caused to the insulin dependent diabetics because of inability to purchase Beef/bovine insulin in the United States because of the guidelines that inaccurately infer said insulin 'might possibly' cause CJD/vCJD. The words 'might' and or 'possibly' is inappropriate especially in light of the damage caused to many diabetics. I will point out the references that must be stricken from the current Guidance which is at this time open for correction. You have asked for my comments stating that you "are especially interested in receiving information about the effect that these recommendations might have on availability of HCT/Ps." -------------------------------- PROOFS and RECOMMENDATIONS The committee did not recommend specific deferral criteria because of the scarcity of information available about the transmission of vCJD/CJD in tissues. Yet, still lacking information about the likelihood of transmission or any indication of possibility, Beef Insulin was used by the FDA as an unsupported reason to ban donors who had injected bovine insulin from the UK 1980-96. These incorrect guidance(s) have also caused the FDA to turn down CP Pharmaceutical's, application from Wales, UK. Asking permission to market their 25 year proven bovine insulin here in the US. Because their stainless steel equipment used to manufacture bovine insulin 'MIGHT' have BSE prions stuck to their equipment, their application was rejected. If you would like the reason this is impossible, read on. Asking CP to clean the nonexistent prions off of their equipment would damage their life saving equipment and is not necessary. Read on for reasons why. There has been no prudent reason found for advising that UK Beef Insulin injection by diabetics 'might possibly' carry and or spread the CJD virus. NONE! Such warnings concerning beef/bovine insulin injection should be eliminated from this and all guidance documents. It is causing an undue restraint of trade of this life source thus causing much pain and suffering and even death to a large minority of the insulin dependent diabetic population. There have been no cases of CJD or vCJD caused by BSE in beef insulin. There has never been found any BSE prions in bovine/beef insulin. It is not possible to find what isn't there. With odds of *1 in 100,000,000 years that one 'might' catch CJD from Bovine insulin even if said bovine sources were infected with BSE. (Re III) "We recognize that we may need to revise this draft guidance." It is one of many that needs to be revised in all reference to bovine/beef insulins from all countries. All warnings in any and all guidelines referring to Beef/bovine Insulin's hypothetical ability to cause CJD or vCJD or BSE should be deleted. "CJD is a rare but invariably fatal degenerative disease of the central nervous system, associated with a poorly understood transmissible agent (Refs. 8, 9). Sporadic CJD cases occur at a low frequency by an unknown mechanism." "vCJD is an emerging disease with unique clinical and pathological characteristics." BSE, CJD and or vCJD are NOT valid reasons to keep the restrictive guidelines on beef insulin. The FDA's statement(s) of 'possibility' that Bovine Insulin 'might' carrying BSE is unfounded. BSE has never been found in Beef pancreas nor beef insulin. III. BASIS FOR vCJD RECOMMENDATIONS There are five currently recognized risks of exposure to the BSE agent. The 5th one is the one that should be removed from the Guidance for Industry that is now under consideration for change. As well as from all other guidance documents. "#5 Theoretical exposure to BSE agent through bovine insulin produced from cattle in the U.K." Several facts are available to support the validity of my request. a. CP Pharmaceuticals in Wales does not use UK cattle pancreas to make their insulin. The source of their beef insulin crystals is from US. cattle (born, bred & slaughtered in the US). b. No one has ever found any BSE in beef insulin. c. No one has ever contacted CJD or vCJD from beef insulin d. I will quote 3 scientists from the TSEAC meeting 7/27/2000 stating there is no BSE in Beef Pancreas. And Common Reasons #4-6. There is no foundation for a suspicion that beef insulin carries BSE or causes CJD or vCJD. * 1 * DR. RAY BRADLEY, CBER, no BSE in pancreas * 2 * DR. Gerald Wells, no infectivity * 3 * DR. David BOLTON, Ph.D, TSEAC, propagating BSE prions in [pancreas] Šdoesn't seem to work. * 4 * Filtration 14 times * 5 * Australia, 1 in 100,000,000 years 'maybe' * 6 * CP only uses insulin crystals from the US - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * 1 * DR. Ray Bradley, CBER, Speaker for SmithKline Beecham, head of the pathology at The Central Veterinary Laboratory, now called the Veterinary Laboratory Agency, in the U.K.'s Ministry of Agriculture, and BSE coordinator for MAFF '91 to '95, independent BSE consultant to WHO, OIE, EC, U.K., Argentine and the U.S. governments' committees and expert committees and expert consultation Fisheries and Food, or MAFF, from 1983-91 "I now pass to muscle and pancreas. To summarize these two issues which have been part of the concern, skeletal muscle and pancreas from cattle affected with natural BSE have shown no detectable infectivity after bioassay in susceptible mice. Furthermore, BSE infectivity has not been detected in skeletal muscle or pancreas at any stage of incubation of experimental BSE, also following bioassay in susceptible mice." "So the conclusions from this are that no BSE infectivity has been detected in skeletal muscle, pancreas, spleen, blood or any component of blood of cattle or bovine fetuses in natural or experimental BSE"Š - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * 2 * DR. Gerald Wells, Studies of BSE Infectivity in Tissues of Cattle: United Kingdom "There I'd like to leave it and just to say that, clearly, from these experiments there is no evidence as yet of infectivity in any of the tissues that we are concerned with in this session today. Thank you." - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * 3 * DR. David BOLTON, Ph.D, TSEAC, head of the Laboratory of Molecular Structure and Function, New York State Institute for Basic Research, ,one of the people who helped discovered PrP(prion protein), current researcher & overviewer. "There's somewhat of maybe a dichotomy here. If you look in the normal animal, PrPC is made in many different tissues, including heart and skeletal muscle and lymphocytes [white blood cells including b & t cells] and a lot of different tissues besides the brain. But it's a curious fact that when you try to propagate prions in these other tissues, it doesn't seem to work." ------------------------------------------------------------------------------------ * 4 * Common Knowledge: > FILTRATION: There are 51 amino acids in insulin except for Lantus which has 53 amino acids (it has other problems that I don't wish to address here). BSE prions have 254 amino acids (5 times the size of an insulin molecule). Beef insulin is filtered 14 times. If there were BSE prions they would be filtered out by the 5th filtration leaving no BSE to be included in the insulin composition. Keep in mind, however, that Beef pancreas does not carry BSE. SEE items 1-3. It is unreasonable that The Guidelines For Industry infer that BSE might be in beef insulin. Mentioning a 'possibility' of BSE in beef insulin, which has been proven to not even have an ability to exist or spread through manufactured beef insulin, is improper. The filters block all but the 51 amino acids. BSE has 254 amino acids but they have never been found to be present in the pancreas of a cow. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * 5 * COMMON KNOWLEDGE >AUSTRALIA REPORTS, 22nd March 2001, INFORMATION RELEASED FOR PEOPLE WHO USE BOVINE INSULIN: Professor Smallwood said. "It is clear that the potential risk from this product is infinitesimally small. Nowhere in the world is there any direct evidence to link bovine insulin to vCJD. On a theoretical basis, the risk of contracting variant Creutzfeldt Jakob Disease (vCJD) from this insulin is estimated at one in a 100 million years of treatment in the worst possible caseŠ Professor Smallwood said, that on the other hand there is a very real risk to the health of people if their current treatment using bovine insulin is disrupted." [ALSO RISKS to MANY NEWLY DIAGNOSED WITH IDDM] - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - * 6 * COMMON KNOWLEDGE CP Pharmaceuticals in Wales, UK certifies that their bovine insulin Is sourced from a BSE free country. The USA. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - e. The mention of Bovine Insulin as a possible carrier of BSE should be removed from this Guidance For Industry and all other inference to the possibility in other guidance documents should be removed immediately. Including the FDA site of 'FREQUENTLY ASKED QUESTIONS ABOUT IMPORTING BEEF INSULIN FOR PERSONAL USE' http://www.fda.gov/cder/drug/beefinsulin/default.htm Reason.: There has never been a possibility that beef insulin crystals could carry BSE. FDA's guidance(s) that beef insulin could possibly carry BSE is placing undue guides on those who might otherwise be approved as beef insulin suppliers to the US open market. Said guidance(s) carrying the FDA's BSE warning of a possibility that Beef Insulin might cause BSE is scaring people from acquiring this life source and many have become very sick having lost their quality of life because beef insulin is no longer sold or recommended in the US. Many have already died from the lack of availability. The Guidelines For Industry creates undue mandates on UK beef insulin suppliers. The various BSE guidelines, printed concerning this product, have guided and caused incorrect and unnecessary recommendations in The Guidance For Industry and other similar guidance documents and FDA reference sites such as http://www.fda.gov/cder/drug/beefinsulin/default.htm These references throughout the FDA literature (including the Guidance For Industry) should be removed thus correcting this misinformation and mishandling of applications to market beef insulin in the United States. The Guidance For Industry itself states: III. E. "Exposure to Bovine Insulin "No cases of transmission of vCJD have been reported in recipients of bovine insulin or other injectable products manufactured in BSE- countries. However, as a safeguard, we have recommended that material from cattle in BSE - countries should not be used in the manufacture of FDA regulated products (Ref. 41)Š Therefore, as a preventive measure, you should indefinitely defer HCT/P donors who have injected bovine insulin since 1980, unless you can confirm that the product was not manufactured after 1980 from cattle in the UK"(RE III) Item III. E. in the Guidance For Industry should be eliminated. "IV. RECOMMENDATIONS FOR DONOR ELIGIBILITY" There are 8 items listed in this guidance I wish to bring your attention to item 8. "You should determine to be ineligible any donor who: Š 8. has injected bovine insulin since 1980, unless you can confirm that the product was not manufactured after 1980 from cattle in the U.K." Item 8 should be removed from all guidance documents including the current one which I am commenting on. It is not appropriate. (see III) Not only is #8. not appropriate for it's own sake. It has caused interference with a needed life source and needless agony to many of the unsuspecting insulin taking population. On a minor note but the subject of this guidance that I am referring to. Said item III. E. and IV 8. do in addition to scaring and pushing away beef insulin suppliers and users these restrictions also unnecessarily eliminate many would be diabetic donors. Thus, in the end harming many Insulin Dependent Diabetics and also needlessly differing this group of possible donors. Many insulin dependent diabetics have an urgent medical need for beef insulin. What is available in the US market is not satisfactory to many Insulin Dependent Diabetics. Beef insulin is an 81 year old proven drug and is desperately needed by many. Also, an appropriate match with a recipient needlessly differed outweighs the unlikely/non existent risks of BSE. (see III and the second purposed rule open for comment to 12/23/2002) "V. NON-CLINICAL SCIENTIFIC OR EDUCATIONAL USE" There are 3 items. I will emphasize the 3rd item that directs, "label an HCT/P from an ineligible donor as follows:" 3. Š"Collected from a donor with a potential risk of vCJD," As I have shown, just because an individual has injected Beef Insulin does not put him/her at risk for CJD or vCJD and should not be considered differed. "VI. ASSESSING THE IMPACT OF THESE RECOMMENDATIONS ON THE HCT/P SUPPLY" Assessing one impact is "the effect that implementation of these recommendations could have on the HCT/P supply." By unnecessarily deferring as donors, people who have injected UK beef insulin. Addressing another major impact is the effect that parts of the Guidelines For Industry's recommendations have on people needing beef insulin from the UK. (see III & IV specifically) "VII. IMPLEMENTATION OF RECOMMENDATIONS We are publishing this draft guidance for public comment to present our current thinking about preventing the transmission of CJD/vCJD by HCT/Ps through deferral of donors." Please give my report serious consideration in your reviewal process and report back to me your intentions. Summary: "The benefits of the use of beef insulin outweigh the risks of BSE." 1. It is not reasonable that the FDA should defer people because they have injected bovine insulin from the UK. 2. There is no BSE in beef insulin. Thus, transmission of BSE, CJD or vCJD is impossible (re: III) from Beef/Bovine Insulin. 3. The current guidelines should be changed by deleting all references that Beef/Bovine insulin 'might or possibly could' cause CJD or vCJD or harbor BSE. 4. All warnings in any and all guidelines referring to Beef/bovine Insulin's hypothetical ability to cause BSE, CJD or vCJD should be deleted. Warnings concerning a 'possibility' of beef/bovine insulin injection carrying BSE should be eliminated from this and all guidance documents. It is causing an undue restraint of trade of this life source thus causing much pain and suffering and even death to the needy diabetics and an undue restraint of possible donors. Note: Quotes " " refer to the Guidance For Industry document that is open for comment. By: Marjorie A. Baker E-mail floridacracker@ij.net Phone 727-938-6572