News from the FDA

Approval of Currently Unapproved Medicines

On Oct. 17, the FDA announced that it will aggressively crack down on the marketing of unapproved drug products. At the same time, the agency proposed new steps to assure the safety and efficacy of certain unapproved but widely marketed medicines. These unapproved drugs include medicines that were developed and marketed before modern standards for drug approval were established. The keystone to this effort is a draft Compliance Policy Guide (CPG) the agency is issuing outlining FDA policies to encourage companies to sponsor these drugs through the approval process. Many of the potentially beneficial drugs in this category could be approved based on straightforward scientific data that would not involve conducting new clinical studies of safety and effectiveness (eg, peer-reviewed medical literature, or other existing data), the FDA stated.

The draft Compliance Policy Guide is posted on the Internet at http://www.fda.gov/cder/guidance/5704dft.pdf. 

Draft Guidance for Labeling of In-Vitro Devices

“Use of Symbols on Labels and Labeling of In Vitro Diagnostic Devices Intended for Professional Use” has been issued. FDA and European Union (EU) regulations require substantial information to appear on the in-vitro diagnostic device (IVD) itself and/or in its labeling. Each EU member state can also require that such information appear in its national language, so that a single IVD could be required to bear labeling in multiple languages in order to be sold in the EU. As an alternative, the IVD Directive encourages the use of symbols from harmonized standards to convey the required information in place of text.

The FDA is seeking comments on the guidance, which has not yet gone into effect. Written and electronic comments may be submitted to the agency until Dec. 29, but the FDA notes that to ensure adequate time for consideration, comments should be submitted by November 28. For more information, see: http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2003/03-27117.htm.

Panel Recommends Silicone Implant Approval

The General and Plastic Surgery Devices Panel met on Oct. 14 and 15 to discuss the premarket approval application (PMA) for Inamed Corporation's McGhan Silicone Gel-Filled Breast Implants. The PMA was recommended for “approval with conditions” by a nine  to six vote. Among the conditions of approval were the development of patient education media, a professional training program and a patient registry. The panel recommended that these efforts be designed and accomplished in collaboration with FDA and professional societies. Another condition is that patients in the Core Study complete their 10-year follow-up as a post-approval study with annual follow-up visits and the MRI screening that should continue at least through year 9.

Proposed Rule Change for Submission of Bioequivalence Data 

The FDA is proposing to amend its regulations on submission of bioequivalence data to require an abbreviated new drug application (ANDA) applicant to submit data from all bioequivalence studies (BE studies) that the applicant conducts on a drug product formulation submitted for approval. In the past, ANDA applicants have submitted BE studies demonstrating that a generic product meets bioequivalence criteria for FDA to approve the ANDA, but have not typically submitted additional BE studies conducted on the same drug product formulation, such as studies that do not show that the product meets these criteria. This change was proposed because the FDA believes additional BE studies may be important in determining whether the proposed formulation is bioequivalent to the reference listed drug. The agency is seeking comments on the proposed changes, which must be submitted by Jan. 27, 2004. For further information, go to: http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2003/03-27187.htm.

Pediatric Use of Antidepressants

The FDA issued a Public Health Advisory Oct. 27 to alert physicians to reports of suicidal thinking (and suicide attempts) in clinical studies of various antidepressant drugs in pediatric patients with major depressive disorder (MDD). The agency has completed a preliminary review of reports for eight antidepressant drugs ' citalopram, fluoxetine (Prozac'), fluvoxamine, mirtazapine, nefazodone, paroxetine (Paxil'), sertraline, and venlafaxine ' all studied under the pediatric exclusivity provision of the FDA Modernization Act (FDAMA, 1997).

The FDA noted that no clear association has been established between the use of these drugs and increased suicidal thoughts by pediatric patients, but that anecdotal evidence indicates there could be a problem with these drugs. In addition, in clinical trials it reviewed, the FDA has established effectiveness only in fluoxetine as a treatment for pediatric MDD. (The Agency emphasized, however, that failure to show effectiveness in any particular study in pediatric MDD is not definitive evidence that the drug is not effective, as trials may fail for many reasons.) The FDA has called a meeting for Feb. 2, 2004 to discuss the issue before the Psychopharmacologic Drugs Advisory Committee and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee.

FDA Issues Warning About Steroid

The FDA issued a statement Oct. 28 warning that tetrahydrogestrinone (THG), a substance used by athletes to improve their performance, is not a dietary supplement, as often claimed by its distributors, but an unapproved new drug. As such, it cannot be legally marketed without FDA approval. THG is a synthetic “designer” steroid derived by modifying another anabolic steroid that is banned in the United States. It has become popular because, until recently, it could not be detected by the standard steroid-use tests given to athletes.

Approval of Currently Unapproved Medicines

On Oct. 17, the FDA announced that it will aggressively crack down on the marketing of unapproved drug products. At the same time, the agency proposed new steps to assure the safety and efficacy of certain unapproved but widely marketed medicines. These unapproved drugs include medicines that were developed and marketed before modern standards for drug approval were established. The keystone to this effort is a draft Compliance Policy Guide (CPG) the agency is issuing outlining FDA policies to encourage companies to sponsor these drugs through the approval process. Many of the potentially beneficial drugs in this category could be approved based on straightforward scientific data that would not involve conducting new clinical studies of safety and effectiveness (eg, peer-reviewed medical literature, or other existing data), the FDA stated.

The draft Compliance Policy Guide is posted on the Internet at http://www.fda.gov/cder/guidance/5704dft.pdf. 

Draft Guidance for Labeling of In-Vitro Devices

“Use of Symbols on Labels and Labeling of In Vitro Diagnostic Devices Intended for Professional Use” has been issued. FDA and European Union (EU) regulations require substantial information to appear on the in-vitro diagnostic device (IVD) itself and/or in its labeling. Each EU member state can also require that such information appear in its national language, so that a single IVD could be required to bear labeling in multiple languages in order to be sold in the EU. As an alternative, the IVD Directive encourages the use of symbols from harmonized standards to convey the required information in place of text.

The FDA is seeking comments on the guidance, which has not yet gone into effect. Written and electronic comments may be submitted to the agency until Dec. 29, but the FDA notes that to ensure adequate time for consideration, comments should be submitted by November 28. For more information, see: http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2003/03-27117.htm.

Panel Recommends Silicone Implant Approval

The General and Plastic Surgery Devices Panel met on Oct. 14 and 15 to discuss the premarket approval application (PMA) for Inamed Corporation's McGhan Silicone Gel-Filled Breast Implants. The PMA was recommended for “approval with conditions” by a nine  to six vote. Among the conditions of approval were the development of patient education media, a professional training program and a patient registry. The panel recommended that these efforts be designed and accomplished in collaboration with FDA and professional societies. Another condition is that patients in the Core Study complete their 10-year follow-up as a post-approval study with annual follow-up visits and the MRI screening that should continue at least through year 9.

Proposed Rule Change for Submission of Bioequivalence Data 

The FDA is proposing to amend its regulations on submission of bioequivalence data to require an abbreviated new drug application (ANDA) applicant to submit data from all bioequivalence studies (BE studies) that the applicant conducts on a drug product formulation submitted for approval. In the past, ANDA applicants have submitted BE studies demonstrating that a generic product meets bioequivalence criteria for FDA to approve the ANDA, but have not typically submitted additional BE studies conducted on the same drug product formulation, such as studies that do not show that the product meets these criteria. This change was proposed because the FDA believes additional BE studies may be important in determining whether the proposed formulation is bioequivalent to the reference listed drug. The agency is seeking comments on the proposed changes, which must be submitted by Jan. 27, 2004. For further information, go to: http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2003/03-27187.htm.

Pediatric Use of Antidepressants

The FDA issued a Public Health Advisory Oct. 27 to alert physicians to reports of suicidal thinking (and suicide attempts) in clinical studies of various antidepressant drugs in pediatric patients with major depressive disorder (MDD). The agency has completed a preliminary review of reports for eight antidepressant drugs ' citalopram, fluoxetine (Prozac'), fluvoxamine, mirtazapine, nefazodone, paroxetine (Paxil'), sertraline, and venlafaxine ' all studied under the pediatric exclusivity provision of the FDA Modernization Act (FDAMA, 1997).

The FDA noted that no clear association has been established between the use of these drugs and increased suicidal thoughts by pediatric patients, but that anecdotal evidence indicates there could be a problem with these drugs. In addition, in clinical trials it reviewed, the FDA has established effectiveness only in fluoxetine as a treatment for pediatric MDD. (The Agency emphasized, however, that failure to show effectiveness in any particular study in pediatric MDD is not definitive evidence that the drug is not effective, as trials may fail for many reasons.) The FDA has called a meeting for Feb. 2, 2004 to discuss the issue before the Psychopharmacologic Drugs Advisory Committee and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee.

FDA Issues Warning About Steroid

The FDA issued a statement Oct. 28 warning that tetrahydrogestrinone (THG), a substance used by athletes to improve their performance, is not a dietary supplement, as often claimed by its distributors, but an unapproved new drug. As such, it cannot be legally marketed without FDA approval. THG is a synthetic “designer” steroid derived by modifying another anabolic steroid that is banned in the United States. It has become popular because, until recently, it could not be detected by the standard steroid-use tests given to athletes.