Combination product application submitted

An EU application for a combination product that contains previously authorised active substances must be supported by appropriate safety and efficacy data for the combination. However, there is no need to submit data on the safety and efficacy of the components individually. The combination product is considered a unique product distinct from the authorisations granted to the individual ingredients, and will thus have a separate exclusivity clock running from the date when the combination was authorised. 

The homologues of the methylated non-ionic EO/PO surfactant blend were ionised as [M + NH4]+ ions. A mixture of these isomeric compounds, which could not be defined by their structure because separation was impossible, was ionised with its [M + NH4]+ ion at m/z 568. The mixture of different ions hidden behind this defined m/z ratio was submitted to fragmentation by the application of APCI—FIA—MS— MS(+). The product ion spectrum of the selected isomer as shown with its structure in Fig. 2.9.23 is presented together with the interpretation of the fragmentation behaviour of the isomer. One of the main difficulties that complicated the determination of the structure was that one EO unit in the ethoxylate chain in combination with an additional methylene group in the alkyl chain is equivalent to one PO unit in the ethoxylate chain (cf. table of structural combinations). The overview spectrum of the blend was complex because of this variation in homologues and isomers. The product ion spectrum was also complex, because product ions obtained by FIA from isomers with different EO/PO sequences could be observed complicating the spectrum. The statistical variations of the EO and PO units in the ethoxylate chain of the parent ions of isomers with m/z 568 under CID... 

For products containing new chemical entities, existing chemical entities in new dosage forms or combinations or new route of administration, applications are required to submit clinical dossiers which consist of ... 

The applicant must apply for permission to manufacture or import a pharmaceutical product as a sample for registration the information on the labels and inserts must also be submitted to the FDA. In the case of a pharmaceutical product which is not yet registered in Thailand, a certificate of free sales issued by the country of origin is required. The same criteria are applied to new formulas or new combination pharmaceutical products. 

Often a device company will work closely with CDRH staff to develop and submit a combination device drug product, only to find out during the application review that upon consultation by the CDRH reviewer with CDER, new issues are brought up that could have been incorporated into the clinical study design. This points out the importance of early communication with all involved parties at FDA during product development. Assuring that representatives from both Review Divisions are present at FDA sponsor meetings allows for identification and discussion of issues early in the process. 

---