For many years the only manufacturer of chloramphenicol was Parke, Davis & Co., which marketed it in various dosage forms, for example capsules, liquid, and injectables, under the trade name Chloromycetin. However, after Parke, Davis' patent expired in 1967, other companies obtained FDA permission to market the product either under the generic name or under their own trade names. There has been continuing controversy as to whether the newer products are equally as effective as Chloromycetin. This is of particular importance with a drug like chloramphenicol whose use is limited to serious and life threatening disorders, since ineffectiveness of such a drug is equivalent to being unsafe. As I said in announcing the hearings, I realize that the chloramphenicol problem has been dealt with extensively by our own as well as other committees, and we do not intend to retrace the entire history of this drug. Nor is the subcommittee interested primarily in the brand versus generic drug controversy which is currently being considered by other committees. Instead, the subcommittee proposes to deal with the current unresolved problems relating to the safety and effectiveness of the various chloramphenicol products on the market. Some of the problems relating to one form of this drug, Parke, Davis' Chloromycetin Sodium Succinate injectable appeared to be of such urgency that the ranking minority member, Mrs. Dwyer, and I felt it was necessary to call them to the attention of Commissioner Ley on April 4, prior to these hearings, which could not be scheduled until after the Easter congressional recess. The problems were identified in our joint letter as follow: It appears that hospitals, physicians or other interested parties have never been appropriately advised of FDA's decision that there is not adequate evidence that Chloromycetin Sodium Succinate is effective by the intramuscular and subcutaneous routes of administration. These routes were recommended in the previous labeling but were deleted from the labeling approved in September 1968 as a result of a study by the National Academy of Sciences. It appears that there has been no recall from hospitals, pharmacies or other trade channels of Chloromycetin Sodium Succinate which bears the old labeling, and became mislabeled as a result of the September 1968 revision. It appears that FDA has taken no action to assure that the large volume of Chloromycetin Sodium Succinate bearing old labeling, which is only now being recalled from Parke, Davis' widely scattered warehouses, is in fact being appropriately relabeled or destroyed. Mrs. Dwyer and I were concerned over the possibility that physicians were being misled into using Chloromycetin Sodium Succinate by the intramuscular and subcutaneous routes which are recommended by the old labeling and which FDA had concluded were not proven to be effective. We were also concerned that use of the products by these routes, frequently favored in treating small children, could result in unnecessary death since the drug is to be used in life threatening situations. For these reasons we requested Commissioner Ley to advise the subcommittee by April 7 of any actions he proposed to take with respect to this matter. On April 7 a reply was received from Commissioner Ley which stated that Parke, Davis had been told by telegram on April 7 to institute a total recall of Chloromycetin Sodium Succinate bearing any labeling in use prior to that approved in September 1968 and to issue a "Dear Doctor" warning letter by April 21, 1969. In order to make the record complete, I would like to insert at this point both the joint letter from Mrs. Dwyer and myself and Commissioner Ley's reply. (The information referred to follows:) HOUSE OF REPRESENTATIVES, INTERGOVERNMENTAL RELATIONS SUBCOMMITTEE, OF THE COMMITTEE ON GOVERNMENT OPERATIONS, Dr. HERBERT L. LEY, Jr., Commissioner of Food and Drugs, Food and Drug Administration, Department of Health, Education, and Welfare, Washington, D.C. DEAR COMMISSIONER LEY: As you are undoubtedly aware, members of the subcommittee staff recently reviewed FDA files pertaining to chloramphenicol during the period since 1967, when companies other than the original manufacturer made application to market this product. On the basis of this review, it appears that there are a number of unresolved problems concerning FDA's policies and actions with respect to chloramphenicol products. For this reason, the subcommittee is scheduling hearings on this subject beginning on the morning of April 17 and would like you to appear at that time. Further information concerning the exact time, location and other details will be provided early next week. Even though we have not yet been able to communicate with all the other members of the subcommittee, it is our opinion, as chairman and ranking minority member, that there are certain problems relating to Parke, Davis' Chloromycetin Succinate which appear to be of such a serious nature that we wish to call them to your attention immediately. These problems are as follows: (1) It appears that hospitals, physicians, or other interested parties have never been appropriately advised of FDA's decision that there is not adequate evidence that Chloromycetin Succinate is effective by the intramuscular subcutaneous routes of administration. These routes were recommended in the previous labeling, but were deleted from the labeling approved in September 1968 as a result of a study by the National Academy of Sciences. (2) It appears that there has been no recall, from hospitals, pharmacies, or other trade channels, of Chloromycetin Succinate which bears the old labeling and became mislabeled as a result of the September 1968 revision. (3) It appears that FDA has taken no action to assure that the large volume of Chloromycetin Succinate bearing the old labeling, which is only now being recalled from Parke, Davis' widely scattered warehouses, is in fact, being appropriately relabeled or destroyed. Because of its serious and often fatal side effects, the labeling for chloramphenicol has been progressively restricted to limit its use to serious and life-threatening conditions for which there is no effective alternative treatment. Therefore, it would appear that the availability of any dosage form of this product bearing labeling indicating routes of use for which there is not adequate evidence of effectiveness, constitutes a serious danger to the health and lives of patients. This is especially dangerous given the possibly large supply of the mislabeled product which may still be in the hands of hospitals and physicians. It is for this reason that we felt it necessary to call these problems to your attention before the hearings, which could not be scheduled until after the Easter Congressional recess. Because of the urgency with which we view these problems, this letter is being hand delivered on this date, and we request that you advise us by April 7 of any actions you propose to take for their prompt resolution. Sincerely, L. H. FOUNTAIN, Chairman. For many years the only manufacturer of chloramphenicol was Parke, Davis & Co., which marketed it in various dosage forms, for example capsules, liquid, and injectables, under the trade name Chloromycetin. However, after Parke, Davis' patent expired in 1967, other companies obtained FDA permission to market the product either under the generic name or under their own trade names. There has been continuing controversy as to whether the newer products are equally as effective as Chloromycetin. This is of particular importance with a drug like chloramphenicol whose use is limited to serious and life threatening disorders, since ineffectiveness of such a drug is equivalent to being unsafe. As I said in announcing the hearings, I realize that the chloramphenicol problem has been dealt with extensively by our own as well as other committees, and we do not intend to retrace the entire history of this drug. Nor is the subcommittee interested primarily in the brand versus generic drug controversy which is currently being considered by other committees. Instead, the subcommittee proposes to deal with the current unresolved problems relating to the safety and effectiveness of the various chloramphenicol products on the market. Some of the problems relating to one form of this drug, Parke, Davis' Chloromycetin Sodium Succinate injectable appeared to be of such urgency that the ranking minority member, Mrs. Dwyer, and I felt it was necessary to call them to the attention of Commissioner Ley on April 4, prior to these hearings, which could not be scheduled until after the Easter congressional recess. The problems were identified in our joint letter as follow: It appears that hospitals, physicians or other interested parties have never been appropriately advised of FDA's decision that there is not adequate evidence that Chloromycetin Sodium Succinate is effective by the intramuscular and subcutaneous routes of administration. These routes were recommended in the previous labeling but were deleted from the labeling approved in September 1968 as a result of a study by the National Academy of Sciences. It appears that there has been no recall from hospitals, pharmacies or other trade channels of Chloromycetin Sodium Succinate which bears the old labeling, and became mislabeled as a result of the September 1968 revision. It appears that FDA has taken no action to assure that the large volume of Chloromycetin Sodium Succinate bearing old labeling, which is only now being recalled from Parke, Davis' widely scattered warehouses, is in fact being appropriately relabeled or destroyed. Mrs. Dwyer and I were concerned over the possibility that physicians were being misled into using Chloromycetin Sodium Succinate by the intramuscular and subcutaneous routes which are recommended by the old labeling and which FDA had concluded were not proven to be effective. We were also concerned that use of the products by these routes, frequently favored in treating small children, could result in unnecessary death since the drug is to be used in life threatening situations. For these reasons we requested Commissioner Ley to advise the subcommittee by April 7 of any actions he proposed to take with respect to this matter. On April 7 a reply was received from Commissioner Ley which stated that Parke, Davis had been told by telegram on April 7 to institute a total recall of Chloromycetin Sodium Succinate bearing any labeling in use prior to that approved in September 1968 and to issue a "Dear Doctor" warning letter by April 21, 1969. In order to make the record complete, I would like to insert at this point both the joint letter from Mrs. Dwyer and myself and Commissioner Ley's reply. (The information referred to follows:) HOUSE OF REPRESENTATIVES, Dr. HERBERT L. LEY, Jr., DEAR COMMISSIONER LEY: As you are undoubtedly aware, members of the subcommittee staff recently reviewed FDA files pertaining to chloramphenicol during the period since 1967, when companies other than the original manufacturer made application to market this product. On the basis of this review, it appears that there are a number of unresolved problems concerning FDA's policies and actions with respect to chloramphenicol products. For this reason, the subcommittee is scheduling hearings on this subject beginning on the morning of April 17 and would like you to appear at that time. Further information concerning the exact time, location and other details will be provided early next week. Even though we have not yet been able to communicate with all the other members of the subcommittee, it is our opinion, as chairman and ranking minority member, that there are certain problems relating to Parke, Davis' Chloromycetin Succinate which appear to be of such a serious nature that we wish to call them to your attention immediately. These problems are as follows: (1) It appears that hospitals, physicians, or other interested parties have never been appropriately advised of FDA's decision that there is not adequate evidence that Chloromycetin Succinate is effective by the intramuscular subcutaneous routes of administration. These routes were recommended in the previous labeling, but were deleted from the labeling approved in September 1968 as a result of a study by the National Academy of Sciences. (2) It appears that there has been no recall, from hospitals, pharmacies, or other trade channels, of Chloromycetin Succinate which bears the old labeling and became mislabeled as a result of the September 1968 revision. (3) It appears that FDA has taken no action to assure that the large volume of Chloromycetin Succinate bearing the old labeling, which is only now being recalled from Parke, Davis' widely scattered warehouses, is in fact, being appropriately relabeled or destroyed. Because of its serious and often fatal side effects, the labeling for chloramphenicol has been progressively restricted to limit its use to serious and life-threatening conditions for which there is no effective alternative treatment. Therefore, it would appear that the availability of any dosage form of this product bearing labeling indicating routes of use for which there is not adequate evidence of effectiveness, constitutes a serious danger to the health and lives of patients. This is especially dangerous given the possibly large supply of the mislabeled product which may still be in the hands of hospitals and physicians. It is for this reason that we felt it necessary to call these problems to your attention before the hearings, which could not be scheduled until after the Easter Congressional recess. Because of the urgency with which we view these problems, this letter is being hand delivered on this date, and we request that you advise us by April 7 of any actions you propose to take for their prompt resolution. Sincerely, L. H. FOUNTAIN, Chairman. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, CONSUMER PROTECTION AND ENVIRONMENTAL HEALTH SERVICE, Washington, D.C., April 7, 1969. Hon. L. H. FOUNTAIN, Chairman, Subcommittee on International Relations, Committee on Government Operations, House of Representatives, Washington, D.C. DEAR MR. FOUNTAIN: The enclosed copies of telegrams that issued today to Parke, Davis & Co. and Rachelle Laboratories show the actions that we are taking with regard to chloramphenicol succinate injections, about which you and Mrs. Dwyer inquired on April 4, 1969. Sincerely yours, Mr. WARREN T. WHITE, Jr., HERBERT L. LEY, Jr., M.D., Commissioner of Food and Drugs. General Manager and Executive Vice President, Rachelle Laboratories, Inc., Long Beach, Calif. Our evaluation of clinical data on IM (intramuscular): Chloramphenicol sodium succinate in the treatment of typhoid and Rocky Mountain Spotted Fever shows the product to be ineffective. In view of this, as I told you during our telephone conversation this morning, we are proceeding as follows: 1. All certification under the approved labeling of September 1968 is being suspended as of today, April 7, 1969. 2. All manufacturers, including Rachelle, are to revise labeling by April 14, 1969, using the following text in bold type: "Chloramphenicol sodium succinate is intended for intravenous use only. It has been demonstrated to be ineffective when given intramuscularly." 3. After the labeling has been approved, Rachelle will start to replace all outstanding stocks on the market down to the user level bearing the September 1968 labeling by May 15, 1969. This replacement is to be completed by June 30, 1969. 4. All promotional material, including ads and/or written and oral instructions to the detail men should be submitted to the FDA for approval no later than April 30, 1969, In the meantime, no promotional material including ads are to be used by your firm until FDA approval has been received. All ads currently in process are to be canceled until such time. Dr. AUSTIN SMITH, President, Parke, Davis & Co. Detroit, Mich. HERBERT L. LEY, Jr., M.D., Commissioner of Food and Drugs. Our evaluation of clinical data on IM (intramuscular) Chloramphenicol sodium succinate in the treatment of typhoid and Rocky Mountain spotted fever, submitted with the transmittal letter dated March 5, shows the product to be ineffective. In view of this, as I told you during our telephone conversation this morning, we are proceeding as follows: 1. All certification under the approved labeling of September 1968 is being suspended as of today, April 7, 1969. 2. Parke, Davis is to institute an immediate total recall of chloramphenicol sodium succinate bearing any labeling in use prior to that approved in September 1968. 3. All manufacturers, including Parke, Davis, are to revise labeling by April 14, 1969, using the following text in bold type: "Chloramphenicol sodium succinate is intended for intravenous use only. It has been demonstrated to be ineffective when given intramuscularly." 4. After that labeling has been approved, Parke, Davis will start to replace all outstanding stocks on the market down to the user level bearing the September 1968 labeling by May 15, 1969. This replacement is to be completed by June 30, 1969. 5. All promotional material, including ads and/or written and oral instruction to the detail men should be submitted to the FDA for approval no later than April 30, 1969. In the meantime, no promotional material including ads are to be used by your firm until FDA approval has been received. All ads currently in process are to be canceled until such time. |