PURDUE FREDERICK MS CONTIN SUSTAINED RELEASE MORPHINE SULFATE MARKETING WITHOUT FDA APPROVAL IS JUSTIFIED BY AGENCY'S ACUTRIM DECISION, FIRM SAYS

Purdue Frederick is citing the regulatory status of Ciba-Geigy's Acutrim as a precedent for continued marketing of the sustained release morphine sulfate product MS Contin without an approved NDA. Acutrim is a "cogent example," Purdue Frederick said in a Jan. 28 letter to FDA, of "other controlled release products [that] have recently been permitted to be marketed without NDA approval where there is sound evidence to support the determination that the controlled release product successfully produces a relatively constant rate of release of the drug to avoid 'dumping.'" FDA said "that it would take no regulatory action against this new osmotic release oral system for phenylpropanolamine, because the data showed it did not dump and was a successful controlled-release product," Purdue Frederick continues. The firm's letter was in response to a Jan. 14 FDA regulatory letter stating that the agency regards MS Contin to be a new drug and therefore should not remain on the market. FDA maintained that MS Contin is a new drug because the agency is "unaware of any controlled release dosage form of morphine sulfate marketed prior to the introduction of MS Contin, nor are we aware of any scientific studies which establish the safety and efficacy of morphine sulfate in this unique dosage form." MS Contin 30 mg Dosage Form Is Same Strength As Grandfathered Morphine Sulfate -- Firm Responding to the regulatory letter, Purdue Frederick said: "We believe our actions adhere to all legal standards and are consistent with the expressly stated policies of FDA for marketing this controlled release form of a 'grandfather' drug, which has been demonstrated by appropriate published studies and by marketing experience to be safe and effective, and which is generally so regarded by qualified experts." The "essential question" raised in the regulatory letter, Purdue Frederick stated, is: "are all controlled release oral dosage form drugs subject to the requirement of new drug approval?" Under FDA regulation 21 CFR 200.31, the firm asserted, "a sustained release product that is not higher in strength than a conventional release preparation which is not a new drug may itself avoid new drug status. "Morphine sulfate 30 mg tablets in conventional release form for oral administration hae been available for many years. Accordingly, the dosage strength of the MS Contin 3 mg tablet clearly falls within the limits of acceptance set forth in 21 CFR 200.31," Purdue Frederick continued. Administration every 8-12 hours, the firm added, "is well within the established effective dosage regimen for conventional tablets of 10-30 mg every four hours." The firm also noted that Roxane Labs markets a sustained release 30 mg morphine sulfate product Roxanol SR. Roxane Labs also began marketing its product in October. Purdue Frederick further argued that scientific studies it submitted to FDA with its letter -- as well as the marketing of the product in the U.K. under the tradename MST Continus -- shows that MS Contin "is a highly useful, safe and effective product for the relief of severe pain."