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Synthesis/Regeneration 18   (Winter 1999)

Seeking the Withdrawal of Approval for Posilac®

by Andrew Kimbrell & Joseph Mendelson III, International Center for Technology Assessment

[On December 15, 1998, the Center for Food Safety (a project of the International Center for Technology Assessment) and 20 co-petitioning groups submitted a Citizen Petition before the United States Food and Drug Administration, entitled "Petition Seeking the Withdrawal of the New Animal Drug Application Approval for Posilac®-recombinant Bovine Growth Hormone (rBGH)." The article below is excerpts from the petition. Ed.]

New Evidence of Imminent Human Health Hazard.

1. New Evidence of Oral Activity and Absorption of rBGH.

In 1990, the FDA published a justification for its determination that milk and dairy products derived from rBGH-treated cows was "safe for human consumption." The article contained seven tables of data supporting its conclusion, including two tables of data taken from an unpublished Monsanto study of rats orally fed rBGH at high levels. In its 1990 conclusion, FDA officials state that the this 90 day rat feeding study showed that rBGH "is not orally active in rats" and found that, "No oral activity was found when rBGH was administered to rats at exaggerate doses." The FDA officials summarized this by stating, "No toxicologically significant changes were noted in the clinical chemistry, hematology, or urinalysis parameters determined in rats administered rbGH orally."

On April 21, 1998, however, health officials from Health Canada issued a comprehensive report finding, inter alia, gaps in the scientific data used in FDA's review of human health risks associated with rBGH use. This Health Canada review included a thorough analysis of the comprehensive data reviewed by the FDA during its decisionmaking process.

Contrary to FDA's conclusions, the Health Canada data review found evidence that laboratory rats orally fed high doses of rBGH were absorbing the substance. More specifically, the report details that a Monsanto 90 day rat feeding study actually found that between 20% and 30% of the rats in the study developed primary antibody response to rBGH-an indication that orally administered rBGH was absorbed into the blood stream and it produced a distinct immunological effect. Additionally, the data showed that in the male rats cysts formed in the thyroid and an increase infiltration of rBGH into the prostate.

Health Canada report's found that the publicly released summary of safety and effectiveness data and information supporting Posilac's new animal drug application used during the FDA decisionmaking process on rBGH did not include the 90 day rat study results or a discussion of its findings.

2. New Evidence Concerning IGF-1.

A. New Evidence of IGF-1 Surviving Digestion. Insulin-like Growth Factor 1 (IGF-1) is a biochemical that mediates much of the cellular response to human growth hormone in cows and humans. In 1990, the FDA found that IGF-1 does not survive digestion based on oral rat feeding studies. A number of scientists have disputed this finding indicating that the FDA's own data suggests that IGF-1 survives digestion. In addition, several oral rat feeding studies published since the FDA approval of Posilac® (rBGH) have confirmed that IGF-1 survives digestion, particularly when it is in the presence of the milk protein casein. The first study found that IGF-1 survived digestion in rat's stomachs and made its way into the intestine. A more recent study found that considerable amounts of IGF-1 were absorbed into the systematic circulation and was physiologically active in rats. As a result, new evidence contradicts the FDA's previous findings that IGF-1 does not survive digestion.

B. New Evidence of IGF-1 Human Health Risks. FDA has been presented ample data showing the levels of IGF-1 are elevated in milk from rBGH treated cows. The Health Canada report also found that the potential adverse effect of elevated IGF-1 levels were not examined until 1995, significantly after the FDA approved Posilac®. The Canadian report continues that when IGF-1 was discussed, it based upon purely speculative reasoning and the rationale for not requiring chronic toxicity or teratology/reproductive studies was premised upon rBGH not being orally absorbed. The FDA's failure to thoroughly analyze the human health impacts associated with elevated IGF-1 levels is grossly negligent. IGF-I is thought to be important growth factor in breast cancer, prostate cancer, and colon cancer. Such data mandates the FDA to follow up the results of the 90 day rat study.

3. New Evidence Concerning rBGH and BSE Exposure

Several lines of new evidence suggest that the use of rBGH could increase the risk of bovine spongiform encephalopathy (BSE) in dairy cows. There are two mechanism whereby rBGH could potentially lead to an increase in BSE. First, increased circulating IGF-1 levels might increase a cow's susceptibility to BSE should an animal be exposed to the infectious agent. Second, rBGH treated cow's increased protein feed needs could magnify the odds of exposure to a BSE-infective agent. This risk should be thoroughly reviewed by the FDA during any new evidentiary investigation concerning Mosanto's Posilac® new animal drug application.

4. Current FDA Response.

In its 1990 human health determination the agency states, "If the initial toxicity study demonstrates that the protein (rBGH) is indeed orally active, additional testing may be required." Such testing has not occurred. Since release of the Health Canada study, FDA, Center for Veterinary Medicine official, John Scheid stated, "We do not have data from that study." The FDA has further characterized its failure to review and follow up on the rat study findings as a reliance upon Monsanto's summary of the study as non-pivotal.

As characterized by the Health Canada reviewers, "The human health implications of the immunological findings in rats should have been thoroughly evaluated and dismissed only if adequately justified by evidence at the time." The Health Canada study states, "Definitive studies demonstrating the lack of absorption of rBST or IGF-I upon oral administration were neither conducted or requested." The report also found that "simply not enough is known about how IGF-I functions to properly evaluate the potential health impacts." In sum, the Health Canada report reveals that to date the FDA has failed to fully evaluate the human health risks associated with oral exposure to rBGH.


The Federal Food, Drug and Cosmetic Act (FFDCA) is to be construed liberally to effectuate its overriding purpose to protect the public health. Under such a mandate, approval for sale of new animal drugs is premised upon applicant demonstrating that it is both safe and effective for its intended use. The burden on a new animal drug application (NADA) petitioner is not light and includes, but is not limited to, the proffering of (1) adequate tests by all methods reasonably applicable to show whether the drug is safe for use under the conditions suggested in the proposed labeling; and (2) evidence consisting of adequate and well-controlled investigations, including field investigation, on the basis of which it could be fairly and reasonably concluded by experts that the drug has the effect it purports to have. If these requirements are not met, the FDA's charge is to reject the new animal drug application.

The new evidence released by Health Canada indicates that FDA failed to ensure that (1) Posilac® (rBGH) was adequately tested to show its safe use and (2) that the evidence supporting Monsanto's original NADA approval consisted of adequate and well-controlled investigations. Moreover, the evidence showing that possible human health risks associated with oral ingestion of rBGH were not adequately studied by the NADA applicant Monsanto and not thoroughly reviewed by the FDA during its administrative review. As a result, either Monsanto failed to meet the informational burden necessary to garner approval of its rBGH NADA and the FDA acted arbitrarily and capriciously in its evaluation of the data used to support its approval of Posilac®.

If the FDA did not have the 90 day rat testing information available when it approved Posilac®, then the Health Canada report is new evidence that suggests that oral consumption of rBGH may trigger human health risks. As such, the Commissioner should suspend Posilac's NADA approval and immediately embark on an investigation of the human health risks associated with rBGH exposure. A failure to take such action could be subject to judicial review. In Rhone-Poulenc, Inc v. FDA, the court indicated that the Commissioner must withdraw her approval when new evidence shows an animal drug to be unsafe. Failing to investigate this new scientific evidence concerning possible human health risks would be contrary to the overarching intent of the FFDCA and a clear error in agency judgment.


Wherefore the reasons contained herein, the petitioner request that the Commissioner:

  1. Immediately suspend the approval of the new animal drug application for Posilac®-recombinant bovine growth hormone (rBGH);
  2. Immediately publish a Notice of Opportunity for an Evidentiary Hearing concerning "new evidence" related to the new animal drug application approval of Posilac® (rBGH) in the Federal Register;
  3. Upon completion of the hearing, issue an order withdrawing the approval of the new animal drug application for Posilac® (rBGH); and
  4. Revoke all regulations associated with the approval of Posilac® (rBGH).


58 Federal Register 59946, 59947 (November 12, 1993).

Chopra, S., et al., "rBST (Nutrilac) "Gaps Analysis" Report," rBST Internal Review Team, Health Protection Branch, Health Canada (April 21, 1998).

Epstein, S.S. "Unlabeled Milk from Cows Treated with Biosynthetic Growth Hormones: A Case of Regulatory Abdication," Int. J. Health Serv. 1996. 26(1), 173-85.

Frederick Bever (AP), "Canadian Agency Questions Approval of Cow Drug by US," Rutland Herald, October 6, 1998.

Health Canada, Minutes of Meeting: Internal RBST Review Team, BVD AD HOC Advisory Committee (May 6, 1997).

Juskevich, J.C. & Guyer C.G., "Bovine Growth Hormone: Human Food Safety Evaluation," Science 249: 875-884 (August 24, 1990) at 877.

Kimura, T., et al., "Gastrointestinal Absorption of Recombinant Human Insulin-like Growth Factor-1 in Rats," J. Pharm. & Exper. Therap., 1997, 283, 611-618.

Lamonerie, T., et al., "IGF-2 Autcorine Stimulation in Tumorigenic Clones of a Human Colon-Carcinoma Line," Int. J. Cancer May 16, 1995, 61(4): 587-92.

Ng EH, et al., "Altered Serum Levels of Insulin-like Growth Factor Binding proteins in Breast Cancer Patients," Ann. Surg. Oncol. Mar , 1998, 5(2): 194-201.

Wolk, A, et al. "Insulin-like Growth Factor 1 and Cancer Risk," J. Natl. Cancer Inst. June 17, 1988, 90(12), 911-5.

Xian, CJ, et al., "Degradation of IGF-1 in the Adult Rat Gastrointestinal Tract is Limited by A Specific Antiserum or Dietary Protein Casein," J. Endocrinology, 1995, 146, 215-225.

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