APPROVAL OF NOVEL DOSAGE FORM OF SILDENAFIL SUBJECT TO PHASE 4 CLINICAL TRIAL
On January 12, 2016, the Central Drugs Standard Control Organization (CDSCO) made available the minutes of the 15th Meeting of the Subject Expert Committee on Reproductive & Urology, held December 14, 2015, (15th SEC-Reproductive & Urology) at which proposals for clinical trials were reviewed. One of the Subsequent New Drug proposals reviewed by the committee involved a request for a Phase IV Clinical Trial Waiver by the Hyderabad-based Nu Therapeutics Private Limited for its Sildenafil Citrate 25 mg & 50 mg Orally Disintegrating Strips (ODS) drug product for the “treatment of erectile dysfunction”. The committee outright rejected the company’s request and noted that the manufacturing license granted on July 5, 2013 was subject to conducting a Phase IV Clinical Trial within one (1) year of receiving the approval from the Drug Controller General of India (DCGI). Accordingly, the company was given another two (2) months to file a protocol for a Phase IV Clinical Trial for this novel dosage form.
The proposal for the novel dosage form of sildenafil was originally presented to the October 30, 2012 New Drug Advisory Committee (NDAC) for Reproductive & Urology (predecessor to SEC-Reproductive & Urology), but was deferred. The proposal was subsequently reviewed by the November 2012 NDAC which recommended that the formulation should be termed as “lingually disintegrating strips”, and agreed with the proposed bioequivalence (BE) study and, based on the results of the BE study, recommended a comparative clinical trial between the disintegrating strips formulation and tablets. Subsequently, on April 13, 2013 the NDAC recommended the marketing authorization for sildenafil ODS 25mg and 50mg subject to a four hundred (400)-person Phase IV clinical trial to be conducted within one (1) year. After securing approval on July 5, 2013, the company did not submit a Phase IV clinical trial protocol within the requested time period and subsequently requested a waiver of the Phase IV Clinical Trial. The 10th SEC Reproductive & Urology Meeting on January 16, 2015, the Committee noted that it could not consider Nu Therapeutics’ proposal for a Phase IV Clinical Trial.
In addition to Nu Therapeutics, Nagpur-based Zim Laboratories Private Limited also claims to have secured DCGI approval for its Sildenafil ODS 25mg and 50mg although it is unclear when the company received such approval. Both Nu Therapeutics and Zim Labs claim to have obtained GMP status from WHO. However, according to publicly available information, neither company has filed or secured a patent for their respective sildenafil ODS formulation.
Notably, the following companies/inventors have pending patent applications in India for a fast-dissolving film formulation containing sildenafil:
Seoul Pharma Co. Ltd (#1706/MUMNP/2014) Filed August 25, 2014
Title of Invention: HIGH-CONTENT FAST-DISSOLVING FILM WITH MASKING OF BITTER TASTE COMPRISING SILDENAFIL AS ACTIVE INGREDIENT
KATAKAKI VENKATESH (#1973/CHE/2008) Filed August 14, 2008
Title of Invention: ORAL FAST-DISSOLVING FILMS FOR ERECTILE DYSFUNCTION BIOACTIVE AGENTS