Gelatin Safety after BSE

Vegetarian capsules, such as Banner's EcoCaps, are becoming popular alternatives to gelatin capsules. Photo courtesy of Banner Pharmacaps.

In December 2003, the first American case of bovine spongiform encephalopathy (BSE) was confirmed in a dairy herd in the state of Washington. The discovery led to measures to keep BSE from entering the food supply, measures that may soon impact softgel capsules for dietary supplements.

Officially, the Food and Drug Administration (FDA; Rockville, MD) has affirmed the safety of gelatin, but the agency is watching BSE very closely.
 

In 1994, FDA issued a "no-objections" letter clearing the use of bovine-derived materials from BSE countries for pharmaceutical-grade gelatin. However, the letter cautioned gelatin manufacturers to "obtain such materials from non-BSE countries whenever practical, and to maintain records as to the sources of the bovine materials used to manufacture pharmaceutical-grade gelatin."

Three years later, FDA's Transmissible Spongiform Encephalopathies Advisory Committee (TSEAC) held a public meeting to assess the safety of imported and domestic gelatin and gelatin by-products. Based on the meeting, FDA issued guidance that charged gelatin importers, manufacturers, and suppliers with determining the tissue, species, and country source of all materials.

The guidance also banned specific risk materials (SRMs), such as brains, spines, and spinal cords from use in gelatin. Bone and hides from cattle showing any sign of neurological disease were prohibited regardless of origin.

Both FDA and the U.S. Department of Agriculture (USDA; Washington, DC) shifted from surveillance to action when BSE arrived in the United States. Within days of the discovery, new regulations were in place to keep BSE from foods. Among the measures: tighter rules governing the use of bovine materials.

FDA expected to finalize the new rules by April 2004. The rules, still not finalized in May, will ban animal blood in cattle feed, as well as ensure that dietary supplements and cosmetics are kept free of materials from "downer" cattle. FDA said it would also ban SRMs from cattle 30 months and older for use in food, dietary supplements, and cosmetics.

Gelatin, for the most part, will not be affected. Studies verify that the extreme pH conditions of gelatin processing, along with sterilization and ion exchange, effectively eliminate the infectivity of prions, the agents thought to cause illness in humans and animals.

However, there is one unknown. In February 2004, FDA said it planned to review the 1997 guidance in the light of the new BSE regulations. No changes are expected, but FDA's final thoughts about gelatin processing remain to be seen.

Of Parts and Presses Although capsules are popular for dietary supplements, tablets remain the best-selling dosage form. Eventually, tablet presses require maintenance. The question is whether to use OEM or generic parts. Keith Lindemann, service manager at Fette America (Rockaway, NJ), says in theory, non-OEM replacement parts for tablet presses seem to represent a cost-saving alternative. But he cautions that on the production floor, aftermarket or "knock-off" parts can end up causing bottom-line losses. "Non-OEM parts can cause serious downtime problems, damage the machine itself, and adversely impact the quality and consistency of the product," says Lindemann. Lindemann described what happens to different press parts when parts are even slightly off specification. "In the turret assembly, if the upper cam track, the turret itself, or the lower cam track are misaligned, the positioning of the dosing cams will be off. Force-fitting connecting bolts of other parts can cause excessive cam damage and compression roll wear." The lower cam track and, in particular, the dosing-station cams are some of the most critical parts on tablet presses. "Non-OEM cams not only cause premature tooling wear and press damage, but also can cause weight and thickness variations in the product itself," he says. The devil is in the details. "OEM cams have specific profiles and designs which are tested at the factory," says Lindemann. "In many cases, non-OEM cams are modified not only in design, but also in material. A non-OEM part may not have the critical tolerances required by the machine." OEM parts can optimize tablet press life and performance while ensuring product quality. Photo courtesy of Fette America. Compression rolls are one of the most abused parts of a tablet press. "Traditionally, rolls were made of standard premium steel," says Lindemann. "Today, rolls have a titanium surface made with a unique hardening process and high-speed custom-sealed bearings. The thorough hardening, along with special tempering and metallurgy, allows for more durability. By comparison, aftermarket rolls might only be surface hardened and therefore have a shorter life expectancy." As compression rolls wear, dwell time is affected, which throws off tablet quality and increases downtime. The weight, thickness, and hardness of the tablets may be affected. The entire performance of the automatic weight-control system may be thrown out of specification. Feeder base plates are critical. "OEM base plates are held to extremely tight tolerances both in hardness and craftsmanship," says Lindemann. "Any deviation from factory tolerances can result in serious damage to the die table surface, one of the most expensive parts of the machine." Base plates impact product yield. "OEM plates have up to seven different seals and configurations to seat the feeder on the die table, depending on the product being made," says Lindemann. "Improper sealing in the lower base plate can mean losses of 50 to 100 kg of product, resulting in yields that drop from 99% down to 95%, 90%, and even lower. Depending on your cost per 1000-kg batch, this unnecessary loss can cost your company thousands and thousands of dollars."

GELATIN SAFETY

Studies confirming gelatin safety were discussed during the Hard Shell & Softgel Capsule Technology 2004 conference April 20–22 in Atlantic City, NJ. The conference was hosted by TechSource Inc. (Ann Arbor, MI).

Walt Johnson, manager of pharmaceutical technical services at Gelita North America (Sioux City, IA), said the Institute of Animal Health (Edinburgh, Scotland) and the Veterans Administration Medical Center (Baltimore) independently affirmed that the acid and alkaline treatments used in gelatin manufacturing effectively remove infective agents. The acid and liming steps of normal gelatin processing, combined with filtration, ion exchange, and UHT sterilization at 160°C (320°F) for 4 seconds, were found to reduce infectivity by a factor of 4–6 logs.

Gelatin can be considered safe for human consumption, said Johnson, based on data from these studies, and FDA and USDA restrictions on materials.

Johnson also referenced work performed by the Gelatin Manufacturers Institute of America (GMIA; New York City) that concludes gelatin processing destroys BSE infectivity.

According to GMIA, during gelatin processing, raw materials are exposed to extensive purification procedures, including prolonged exposure to either acid or alkaline conditions, or both—processes that have been demonstrated to provide a safe gelatin supply for consumption. GMIA also believes sterilization, filtration, and demineralization significantly enhance the safety of gelatin.

BUSINESS AS USUAL

Concern over BSE has prompted many manufacturers to ensure that their gelatin raw materials are properly sourced. Photo courtesy of Shionogi Qualicaps.

At the conference, manufacturers reported increased demand for nonanimal capsules. However, they said demand was rising before BSE was found in America.

"We have not necessarily received many nonanimal capsule requests due to the media coverage of gelatin concerns," says Tamara Smith, marketing director at Shionogi Qualicaps (Whitsett, NC). "However, there has been increased interest in nonbovine and vertebrae-free bovine capsules."

Smith says many customers had been considering contingency plans to bovine capsules before the BSE case was found. "Since 2000, nonanimal capsules have become a mainstream product in health and nutrition," she says. "Pharmaceutical companies are also interested in them."

In response to BSE, several multinational companies have made efforts to use raw materials of nonanimal origin, according to Smith. "This could be to avoid potential hypothetical regulatory problems before they occur," she says. "This was initiated by the BSE problem in Europe, but it is on the same order of response as similar strategies such as limiting colorants usage to pigments, which are insoluble and have the least potential for future problems."

Gelatin manufacturers agree that avoiding products manufactured from bovine sources is an overreaction to an isolated incident. However, they are making doubly sure that their raw materials are sourced properly. "Overreaction or not, we have an obligation to provide our customers with the facts about products so that they in turn can intelligently address the problem to consumers who use medications and supplements regularly," says Jonathan Gilinski, managing director of Farmacapsulas USA (Pompano Beach, FL). "We want nothing more than to assure our customers that the products we develop and manufacture are 100% BSE-free."

Gilinski reports that more supplement companies are asking for nonanimal capsules. "Many manufacturers are turning to vegetable capsules," he says. "We have seen a burst in orders for our K-Caps vegetable capsule products and expect that product line to continue to grow. Companies are just responding to change. It's just another business challenge."

NONANIMAL ALTERNATIVES

A worker operates a gel tank dispenser. Photo courtesy of Shionogi Qualicaps.

Demand for nonanimal capsules drove Banner Pharmacaps (High Point, NC) to develop EcoCaps nonanimal softgels. The capsules are manufactured with a patent-pending process, which converts plant carbohydrates into encapsulating films. The capsules are said to have the same basic performance characteristics as gelatin.

"EcoCaps nonanimal softgels are as reliable as our widely used gelatin formulation, and something that companies can utilize with the utmost confidence," says Roger Gordon, PhD, president and CEO of Banner. "The nonanimal technology fills an expanding demand in the marketplace, which is being driven by an increasing number of corporate initiatives to use materials of nonanimal origin."

The capsules will prove beneficial for consumers who have chosen to make nonanimal products part of their personal healthcare regimen, according to Bev Emerson, director of global communications and consumer healthcare marketing. "Consumers finally have a choice between gelatin and nongelatin products," she says.

At the Hard Shell and Softgel Capsule conference, Christopher Kotevic, director of Cardinal Health Canada (Windsor, ON, Canada), described Seacaps made from fish. "Are fish capsules the perfect answer? No," said Kotevic. "There is a limited supply of raw material, vegetarians may not use them, and their cost is higher than traditional gelatin capsules. On the other hand, they have a certain market appeal, they have GRAS status, and in terms of filling and dosage delivery, they are equivalent to gelatin."

The fish capsules are equivalent to type-A pharmaceutical-grade gelatin. The capsules run on standard hard-capsule manufacturing equipment. Stability and empty-shell performance are comparable to gelatin capsules.

There are differences. The fat content of fish affects glidability. Typically, fish capsules have less glide, meaning they do not slide as easily in capsule fillers. Also, fish capsules are sensitive to temperature. During processing, temperatures must be carefully controlled because fish is not as efficient a gelling agent as gelatin. Temperature must be controlled during shipping and handling as well. Capsules are packaged using standard materials, but shipped under controlled temperatures.

Kotevic sees fish capsules as a niche product. "The days are gone when one capsule solves all your needs," he says. "Fish capsules appeal to one segment of the market. In fact, we recommend that they be identified as fish-derived capsules for discerning consumers."