The next couple of issues had to do with evidence linking the new variant CJD and BSE. In March 1996, the British Government announced ten cases of previously unrecognized form of CJD and speculated on a possible relationship to BSE. The Spongiform Encephalopathy Advisory Committee or SEAC in Europe postulated a link between the cases of new variant CJD and exposure to BSE infected beef, most likely before 1989. In April of 1996, WHO experts concluded that while there was no evidence of the link between BSE and the variant form of CJD, the evidence did suggest that exposure to BSE in the UK may be the most likely explanation. In October of 1996, investigators published data suggesting that the abnormal prion found in new variant CJDs resembles the BSE protein rather than that found in sporadic cases of CJD.
A more recent report last year from the United Kingdom concluded that new variant CJD is caused by the same strain of agent that has caused BSE feline spongiform encephalopathy and TSEs in exotic ruminants, transmitting the disease with a unique lesion profile in mice. This is considered strong evidence that the new variant CJD and BSE are linked. To date, new variant CJD has been identified in 24 people in Britain and France.
USDA regulations prohibit or restrict the importation of certain meat and other animal products and by-products from ruminants that have been in regions in which BSE exists. Until recently, these regions included Belgium, France, Great Britain, Northern Ireland, Republic of Ireland, Luxembourg, the Netherlands, Oman, Portugal and Switzerland. On December 12, 1997, USDA extended the restriction on the importation of ruminants, meat and meat products from ruminants, and certain ruminant products and by-products to all of Europe. The USDA Federal Register publication noted that this action was taken because of import requirements, principally from the United Kingdom to other countries, less restrictive than those that would be acceptable for import into the United States, as well as concern about possible inadequate surveillance in Europe.
The USDA further noted that their decision was based on recent developments in Europe that suggested that the BSE agent may be present, but as yet undetected throughout Europe. Finally, the USDA noted that the risk posed by movement of products in Europe is increased in light of new scientific research that has identified BSE infectivity in bone marrow, dorsal root ganglion and trigeminal ganglion. The new research expands the list of specific bovine tissues and organs of concern for BSE infectivity. The new rule does not prohibit the importation of semen, milk and milk products, hides and skins, tallow and tallow derivatives, and certain blood products used in microbiologic medium.
BSE has not been detected in cattle in the United States as reported from the surveillance and monitoring program at the USDA. The USDA, as of February 1998, has examined approximately 6,700 brains of US cattle exhibiting neurological signs, but has found no evidence of TSE. Since 1989, no cattle have been imported into the United States from BSE countries as designated by USDA.
I'd like to move on to the next slide. I'm going to go very quickly through some of the events that have taken place in Europe,t o provide a little bit of a perspective regarding the BSE and actions that are being taken in Europe. This is a difficult area to track and monitor. It's very complicated and sometimes it's hard to get information. So, this is my best effort at summarizing this for you.
The European Commission published a decision on the prohibition of the use of material presenting risk of TSEs in July 1997. This prohibits the use of specified risk materials and prohibits the import into the EU of SRMs and requires certification. This directive was also interpreted to apply to process ingredients such as tallow and tallow derivatives.
The EU defined SRMs as skull, including the brain and eyes, tonsils and spinal cord of bovine animals aged over 12 months and ovine and caprine animals which are aged over 12 months. It also includes the spleens of any aged ovine and caprine animals. This particular action has been delayed and modified. The effective date now is January 1, 1999 with some modifications.
On March 5, 1998, the EC amended the cosmetic directive to specifically allow tallow derivatives in cosmetic products provided that the following methods have been used. They've specified the actual manufacturing conditions. For glycerol, fatty acids and esters, transesterification or hydrolysis at least 200 degrees C and 40 bar for 20 minutes. The second method which is for glycerol and soap was batch process at 95 degrees for three hours using 12 normal sodium hydroxide or continuous process of 140 degrees, two bars for eight minutes.
I believe a similar derogation has been established for pharmaceutical use of tallow derivatives, however, tallow itself is still subject to the SRM prohibition.
Most recently, the Scientific Steering Committee in EU has released its opinion on the safety of tallow derived from ruminant tissues. This was adopted at the SSC meeting held March 26th and 27th of last month. In this opinion, they defined tallow as fats obtained by pressing or any extraction system from ruminant tissues which are derived directly from discreet adipose tissue masses, fat extracted from skeleton muscles, mechanically removed meat, rendered animal waste including bones.
The SSC observed that the question is still open if tallow could transfer the BSE agent to animals or humans. Tallow can be considered safe after appropriate purification, but due to documented possible impurities, the raw materials should be obtained from appropriate sources. These sources being determined by geographical herd, animal and age criteria.
For countries considered to be BSE free or classified as a negligible risk, raw materials fit for human consumption can be used to produce tallow without regard to minimal production process of removal of SRMs. For lower risk countries, SRMs should be excluded. The raw material should be fit for human consumption, and it should be subjected to a purification process. For high risk countries, SRMs should be excluded, the origin of raw materials certified, and the animals should be fit for human consumption, and the tallow should be purified. The SSC has not yet defined what constitutes a BSE free, low or high risk country. I believe this is their next task.
Finally, for tallow derivatives, the starting materials should be produced from raw material that is fit for human consumption and production processes use appropriate, validated and scientifically up-to-date methods for inactivating the agent. These processes, I believe, are to be defined by the respective scientific committees as they've done for cosmetics.
Okay, I'd like to move now on to some of the questions for the Committee and some of the background for those questions. The broad charge for the Committee today is to assess the safety of both imported and domestic tallow and tallow derivatives used in FDA regulated products with regard to the risk posed by transmissible spongiform encephalopathies, specifically BSE. Tallow and tallow derivatives are subject to the guidance issued by the Agency for other bovine derived materials, namely, the materials that come from cattle born, raised, or slaughtered in countries where BSE is known to exist as described in regulations promulgated by the USDA; not to be used in the manufacture of FDA regulated products intended to be used by humans or animals.
FDA has not conducted a rigorous assessment of the manufacturing process for tallow and tallow derivatives and therefore, has not considered whether or not these ingredients can be subject to a different level of control than we currently have. One purpose of this meeting is to obtain information about the sourcing of raw materials, the range of manufacturing processes, and the dynamics of the market in order to better assess product safety and to consider adequate and appropriate controls for domestic and imported products.
Tallow is defined as "animal fat consisting primarily of the fully esterified fatty acid, ester glycerol." Tallow derivatives are the products for the processing of tallow to break it into its component parts. The primary derivatives are, of course, glycerol and fatty acids. Other ingredients are obtained from the processing of tallow and these include various salts of the fatty acids, fatty acid alcohols, hydrogenated fatty acids, tallow glycerides which are principally partially hydrolyzed tallow and hydrogenated tallow and tallow glycerides. There are additional derivatives that are further down the manufacturing line.
When considering the manufacture of tallow, there are two basic categories, namely edible and inedible tallow. Each of these may be further processed into tallow derivatives. Representatives from industry will provide greater detail about this process. We've posted on the wall, both here and on the side wall down there, posters of these processes as we tried to put them together. These are sort of there for reference. We can mark them up or make changes as we go through if the industry has further comments.
The first process we're looking at is edible fat processing. This is the regulatory responsibility of the USDA through the Food Safety Inspection Service and we will have our representative later from the USDA to describe this process in greater detail. Edible tallow begins in food grade slaughterhouses, slaughter establishments. The animals here are inspected and passed for human consumption. The edible fats are separated and then subjected to further treatment. On this chart, the edible fats are heated and cooked and then produce edible tallow. The refining, bleaching, deodorizing hydrogenation step goes underneath the edible tallow box which we've marked up here on these charts. The edible tallow can then be derivatized and either the edible tallow or the derivatives can be used in foods, drugs and cosmetics. These constitute different grades. Slaughter establishments with their own rendering plant are called captive renderers where the render will be right on site.
The inedible fat processing is regulated by the states and the Food and Drug Administration. In this case, a renderer takes materials not fit for human consumption -- and these can include dead animal slaughterhouse waste, restaurant waste and other sources -- and will obtain from these the inedible fats. These are then heated or cooked to produce inedible tallow and again, the refining, bleaching, deodorizing hydrogenation stage should be, as shown on the charts here, moved down to after the inedible tallow step. Saponification produces soap, glycerol, fatty acid, fatty esters. Inedible tallow can be used in animal feed, cosmetics, industrial products and topical drugs. The saponified product can be derivatized and also used in industrial products, cosmetics and topical drugs. It's important to note here that you can not go from inedible tallow to edible tallow. Once it becomes edible tallow, it stays edible tallow. So, once it's in that category, it's my understanding that it doesn't go back.
For purposes of this discussion and from our own discussions on this matter, it is important to provide some definitions. Rendering is a process that heats raw material, raw animal by-products to release fat and remove moisture. You have two types of renderers: a captive renderer which is a slaughter establishment with rendering facilities. If this is inspected, then it can produce edible tallow or lard. Non-captive renderer is separate and is not associated with a slaughter facility, and only inedible products can be produced. Animal feedstocks is a term used to denote the starting raw material used in the production and processing of tallow and tallow derivatives. This is sort of what goes in the front door. Cooking, heat treatment, that facilitates the release of fat.
Okay, I want to quickly go through the FDA regulated products starting with foods. For foods, tallow is animal fat is regulated as a food. Tallow is used primarily for cooking, principally in the frying of foods. Tallow derivatives consisting mostly of fatty acids and glycerin are widely used as additives in various types of food preparations. These ingredients must be obtained from food grade starting materials.
Tallow derivatives may be listed either as food additives for regulatory purposes or as GRAS substances. GRAS means "generally recognized as safe." A GRAS substance is not subject to pre-market approval as a food additive would be. Actually, GRAS is meant to cover food ingredients that have a long history of safe use. This was sort of a feature of the 1958 change in the Food, Drug and Cosmetic Act. GRAS substances include, for example, salt, sugar, baking powder, pepper and so forth.
For dietary supplements, there's little definitive information concerning the use of tallow and tallow derivatives. For dietary supplements in oral dosage form, it's likely that they will use the same ingredients as drug or oral dosage forms. It is also likely that glycerin finds wide use in dietary supplements and that -- I think some dietary supplements are formed much the same way as foods would be. The substance is the actual supplementing agreement. That is the vitamin, mineral, herb or botanical rumina acid is not subject to pre-market approval by FDA. However, the excipient ingredients, the other ingredients that are in the product, are considered the same as food additives and must be either approved or generally recognized as safe.
For cosmetics, tallow and tallow derivatives, as you might expect, are used widely in cosmetic preparations. Of course, hydrolyzed tallow is soap. In addition, various fatty acid derivatives and glycerin are used in all types of cosmetic preparations, both in terms of rinse off products -- the soaps that you use and incur a short exposure time -- and also leave on products, the creams and lotions and so forth. There's some material in your packet that talks about the different types of products.
The next overhead shows some of the long list of ingredients starting with tallow and some of the direct tallow derivatives as well as some of the more exotic, further reacted tallow derivatives. The numbers to the right are the count of products registered in our voluntary program, registration program. So, that count is out of about 16,000 or 17,000 products. That's how many products were reported voluntarily to use these various ingredients. Tallow has not been identified as a significant component of finished medical devices cleared for marketing based on information supplied in the manufacturing section of "Pre-Market Approval Applications for PMAs." It is not necessary for manufacturers to include manufacturing information in 510(k) submissions, although some may be provided.
Glycerin is present in a number of different types of medical devices. For example, glycerin may be used as a softening agent during the manufacturing process of collagen coated vascular grafts. Glycerol methacrylate is a monomer used in the manufacture of some contact lenses. In this case, the monomer may be tallow derived or synthetic. Glycerol is also present in a number of wound dressings and in demineralized freeze dried bone preparations. Glycerol is likely to be contained in or have been in contact through, for example, tissue culture with many devices. The source of glycerine or glycerol, that is whether it's derived from animal or vegetable tallow or derived synthetically is not known in all cases.
Tallow is not identified as an ingredient in pharmaceuticals. However, tallow derivatives are used, including fatty acids, fatty acid esters, and salts, fatty alcohols, glycerides, fatty nitriles and amines and of course, glycerin. These ingredients are used in a variety of oral, topical, and ophthalmic products as well as rectal and vaginal creams and suppositories.
The next overhead gives a summary of the types of the products that a tallow derivative would be used in. Pretty much across the board in many different categories. The next overhead gives a little bit more detail. Dr. Chiu will be providing this in greater discussion later, so I won't go over this right now.
For biologics, tallow is not identified as being used in biologics. However, tween is used as a detergent in blood processing. Glycerine is used in blood products as a stabilizer.
For animal products, for veterinary drug products, the use of tallow and tallow derivatives is the same for human drugs, for veterinary cosmetics and shampoos. These are not regulated by FDA, however, it's likely that these products will use the same types of ingredients that you would find in human cosmetics and shampoos. Tallow is permitted as an ingredient in animal feed.
Again, the charge for the Committee is to assess the safety of both imported and domestic tallow and tallow derivatives used in FDA regulated products with regard to the risk posed by transmissible spongiform encephalopathies. In considering the charge, the basic questions are four. We have narrowed this down to four basic questions.
(1) "For tallow, does the available scientific information justify a change in the current FDA guidelines that feedstock for the manufacturing of tallow derivatives should not come from BSE countries as designated by USDA?"
(2) "If yes, should FDA consider changes to the guidelines for tallow used in foods and cosmetics?" This would relate to sourcing for countries, slaughtering procedures, how the material that goes into the tallow manufacturing process is selected and how this is processed in the rendering step.
(3) "For tallow derivatives, does the available scientific information justify a change in the current FDA guidelines that feedstock for the manufacture of tallow derivatives should not come from BSE countries as designated by USDA?" So, we've broken this down into tallow and tallow derivatives. This is two basic questions.
(4) "If yes, what changes should FDA make to the guidelines for tallow derivatives used in foods, cosmetics and drugs administered via various routes?" Again, on sourcing, slaughtering procedures and tallow quality controls. In this case, we're talking about edible versus inedible tallow, on manufacturing processes and process controls for the various tallow derivatives since these are produced in a variety of ways.
Since tallow and tallow derivatives are processed materials -- that is, manufactured using several well defined steps, we would like the Committee to consider especially processing and process validation. What specific processing procedures are essential in assuming optimum inactivation of the BSE agent? What criteria should be considered in analysis or process validation data? Is there one manufacturing process that's superior for inactivating the BSE infectious agent? Conversely, are there manufacturing processes that should be avoided? In addressing these questions, it is important to consider the sources of raw material in manufacturing processes and the finished product type -- in other words, the exposure.
The agenda for today's meeting has been planned to provide a comprehensive overview of tallow and tallow derivatives, marketing and product use, manufacture and regulation to provide as much information as possible in considering these important questions. In addressing this charge, the Committee will be performing an invaluable service, contributing to a science based approach for decision making ont his issue to assure the continued safety of FDA regulated products.
CHAIRMAN BROWN: Thank you very much, Dr. Bailey, for that background material.
I think I should have mentioned earlier, since in the absence of open public presentations this morning we'll be moving ahead, that we will follow Dr. Bailey's presentations and not take a break until the appropriate time. We'll go right on with Don Franco's presentation from the National Renderers Association and then continue on as though the break didn't exist until the break will actually come at 10:00. It is now shortly after 9:00 -- 9:01 to be exact.
Don, are you ready?
I have to say, I'm always delighted to see the origins of products that I would never have guessed would occur. I mean, from this presentation we just heard, we discover that when we use eye drops for contact lenses or cold cream or Flagyl, the material may have begun life as somebody's leftover T-bone steak in a restaurant. That's always amusing.
DR. FRANCO: We call it ingenuity, Paul.
I commend FDA for bringing together this public advisory committee to evaluate the regulatory aspects of the transmissible spongiform encephalopathies. Again, I commend their concurrent requests of invitees to provide advice and recommendations as applicable to the Agency.
As a special liaison from the rendering industry, our representatives will heighten safety with relevance to tallow, both edible and inedible, with emphasis and their derivatives included in domestic and global issues that the Agency has an interest in assessing. The industrial presenters today are Mike Langenhorst, president of ANAMAX Corporation, Green Bay, Wisconsin, who will provide an overview of raw material sourcing, quality control procedures including hazard analysis, manufacturing processes, time, temperature controls, and product characterization and use.
Mike will be followed by Mitch Kilanowski, vice president of marketing, Darling International and president of American Fats and Oils Association, who will profile market dynamics with emphasis on production, imports/exports, and the applicable utilization of tallow highlighting foods, drugs and cosmetics. The group is accompanied by Tom Cook, executive director of our association who has assisted this initiative.
Tomorrow morning, condensed summary comments of the industry's assessment of issues and regulatory responses will be profiled by Doug Anderson, senior vice president of Darling International.
Mr. Chairman, I want to assure you and the audience, we are committed organizationally to provide technical support on request. As associations go, we are relatively small, but we have a history of working with different branches of government for the past 65 years in the resolution of issues and we see no change in our directional mission. Thank you.
CHAIRMAN BROWN: Thank you, Don, for the introduction to the following three presentations: two by Mike Langenhorst and then one by Mitch Kilanowski.
Mike, you have the word.
MR. LANGENHORST: Good morning and thank you for the invitation to speak at this momentous occasion.
It was interesting coming in this morning, seeing all the familiar faces. They've gotten too familiar in the last couple of years, but as I said it's always interesting and enjoyable to be here.
As Don mentioned, my name is Mike Langenhorst. I'm the president of ANAMAX Corporation, a rendering company in Green Bay, Wisconsin. I'm also the vice president of the National Renderers Association and have served on the Industry Transmissible Spongiform Encephalopathy Committee for the last two years. So, the recap that you've seen this morning has included a lot of work from our industry.
I was asked to cover a few different areas. The agenda I'm going to be covering will be the history of the rendering industry. We're going to have a brief rendering school. Hopefully, it's not too simple, but it will try and get into a little bit more detail about the actual procurement of raw materials and processing, a little discussion on HACCP and a real quick summary.
Walking down the street, if you'd ask ten people what rendering is chances are maybe only one or two could actually tell you what rendering means. But all ten, as you heard this morning, use products that are part of the renderers' art whether it's soaps, tires, plastics, cosmetics, pet foods, glue or concrete, or even new synthetic lubricants. The word "render" is actually an old English verb that means to give back or to return, and that's exactly what the rendering industry does. It recycles by-products of the livestock industry by each year converting over 30 billion pounds of raw materials such as bones, fat, offal and carcasses of fallen animals for items that are used in our everyday life, up to eight billion pounds of tallow and six billion pounds of protein meals.