April 21, 2000
FDA RESPONDS TO CITIZEN PETITION ON BST
On April 20, 2000, FDA responded to a Citizen Petition (Docket No. 99P-4613) from Mr. Robert Cohen concerning Posilac®, the only FDA-approved recombinant bovine growth hormone (rbGH) product for increasing milk production in dairy cattle. FDA's Center for Veterinary Medicine (CVM) approved Monsanto Company's rbGH product, Posilac in November 1993 after a comprehensive review of the product's safety and efficacy, including human food safety.
The petition requested that FDA rescind the approval of Posilac, and immediately remove it from the market based on "new evidence" that the product poses "serious health consequences for human consumers." Later, Mr. Cohen amended this petition, most recently on December 2, 1999. As amended, the petition raised three primary issues in support of the request for withdrawal of Posilac. These issues are as follows: (1) that a recently reported increase in serum levels of insulin-like growth factor-1 (IGF-I) in humans following milk consumption represents absorption of dietary IGF-I, invalidating a basic premise of FDA's safety assessment and proving that IGF-I in milk represents a hazard to human health; (2) that Monsanto changed the manufacturing process for rbGH after the studies supporting the New Animal Drug Application (NADA) were completed, thereby invalidating the research used to support the approval; and (3) that the 90-day toxicology study and/or the information derived from the additional 90 days of the study demonstrate both that rbGH is absorbed and that it is not safe.
In response to Mr. Cohen's petition, FDA said that the Agency believed that these arguments do not demonstrate any human food safety issue related to the use of Posilac. Therefore, the petition requesting withdrawal of the approval of Posilac was denied.
FDA provided detailed scientific information in response to Mr. Cohen's Citizen Petition. Highlights from the Agency's response to the petition are as follows:
(1) The safety of IGF-I
FDA has previously maintained and continues to maintain that levels of IGF-I in milk, whether or not from rbGH supplemented cows, are not significant when evaluated against levels of IGF-I endogenously produced and present in humans. IGF-I is normally found in human plasma at concentrations much higher than those found in cow's milk. Reported percentage increases in IGF-I concentrations in milk of rbGH supplemented cows can be misleading because the levels of IGF-I in milk are so low prior to any increase. IGF-I is a normal, but highly variable, constituent of bovine milk with the concentration depending on the animal's stage of lactation, nutritional status, and age. While some studies indicate that levels of IGF-I may statistically increase in the milk of rbGH supplemented cows relative to unsupplemented cows, reported increases are still within the normal variation of IGF-I levels in milk. The Agency pointed out that even if all of the IGF-I in milk was absorbed, and there is insufficient evidence that it would be, the levels of IGF-I in human plasma would not rise by 1%.
(2) The manufacturing process for rbGH
FDA was fully aware of the change in the manufacturing process prior to approval of Posilac, and the Agency believed that the change did not result in a different product such that the research done with the product prior to the manufacturing change was invalid. However, to reaffirm that the conclusion the Agency reached in this case was correct, FDA re-examined information previously submitted by Monsanto to support the approval of the rbGH. We also made a site visit to the sponsor to examine batch records that are not required to be submitted to the new animal drug files. Based on this examination, FDA reaffirmed its conclusion that the manufacturing changes resulted in only biologically inconsequential variations in the product used in the safety and effectiveness studies, and therefore, the rbGH product we approved is the same as the product used in the studies.
(3) The fate and effects of rbGH in milk
Like most dietary proteins, rbGH is degraded by digestive enzymes in the gastrointestinal tract and not absorbed intact.
In the response, FDA discussed in depth a study that was conducted by Richard, Odaglia, and Deslex, where rats were administered rbGH by oral gavage or subcutaneous injection. The Agency reiterated that no adverse effects of rbGH were observed following 90 continuous days of oral administration or following an additional 90 days of recovery after the cessation of drug administration in this study.
An electronic copy of FDA's response to Mr. Cohen's petition is available on the CVM Home Page . Individuals who do not have access to the Internet, may file a Freedom of Information (FOI) request for this response to: Food and Drug Administration, Freedom of Information Staff (HFI-35), 5600 Fishers Lane, Rockville, MD 20857. FOI requests also may be sent via fax to: (301) 443-1726.
Issued by:
FDA, Center for Veterinary Medicine,
Communications Staff, HFV-12
7519 Standish Place, Rockville, MD 20855
Telephone: (240) 276-9300 FAX: (240) 276-9115
Internet Web Site: http://www.fda.gov/cvm
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