5.2. A streamlined, systematic development approach of branded generics

This approach was then applied to drive the development of a novel taste masked pellet formulation in a proprietary application system (dose sipping technology) for the generic antibiotic, clarithromycin.

ClaroSip ® was designed as a single dose dosage unit, with taste masked micropellets in the SIP ® straw system at the required dose strength for different age groups of children. It was submitted as a generic MAA based on bioequivalence to the originator’s granules for oral dispersion, in a multi-dose container with doses for up to 2 weeks of treatment in a bottle. The originator’s granules need to be re-dispersed with water prior to the first administration and during the in-use time period the required doses are measured and withdrawn from the dispersion in mL either via a measuring spoon or a dosing syringe, equivalent to the dose of drug in mg needed for the treatment of each age group. ClaroSip ® needs no re-dispersion prior to use as the dispersion occurs automatically when the child sips a beverage through the straw system, which works like a drinking straw but contains taste masked granules with the correct dose for a single administration of the drug compound. While drinking through the straw the granules disperse in the liquid and are thus ingested and swallowed almost unnoticed by the child. This improved administration form, together with the superior taste masking and the selection of the child’s preferred flavour for the beverage were considered to improve compliance for children. Children are extremely sensitive to unpleasant flavours and often refuse to take the prescribed medication when the taste of the re-dispersed syrup deteriorates over the in-use period due to the incapability of the taste masking and flavouring to prevent the bitterness from penetrating into the liquid during this extended time period. Furthermore the prefilled system ensures correct dosing of the drug compound, whereas the withdrawal in mL from a suspension often results in incorrect dosing due to sedimentation and foaming after shaking.

In summary this drug product was designed really with the customer, i.e. the paediatric patient in mind and focused to make the treatment of infections with antibiotic compounds more efficacious in children by a dosage form and application system that significantly improve compliance and reduce errors in administration of the correct dose. Relevant input to customers’ needs had been obtained from parents, physicians and children themselves via intensive focus group interviewing and experimental research in the handling and use of the new system using SIP ® straws with placebo granules (handling studies).

All this information representing the voice of the customer was combined with the available prior knowledge for the drug compound and the development of taste masked micropellets to define the Project Target Profile for the drug product (consisting of the SIP straw, the taste masked clarithromycin micropellets and the packaging of each individual system). This profile was set up in the development team including members from marketing, clinical, analytical, pharmaceutical development, quality assurance, regulatory affairs and production.