5.4. The lack of integration backfiring during commercial production

However, as this approach lagged integrating systems such as QRM and PQS to support this systematic, risk based approach throughout the whole company, the contribution of other functions to the target profile and the risk assessment had been purely voluntarily. The initiative also lacked empowerment from top management and therefore the contribution from other functions was quite limited throughout further development activities, whenever resources and prioritisation of resources were required beyond the standard approach.

Therefore, especially production did not stay involved in the ongoing risk assessments beyond the initial risk analysis for the critical quality attributes.

Production had also been hesitant to make any significant investments in the new technologies at production scale until marketing authorisation was expected. Freeing of resources to push for improved process capability under routine manufacturing conditions was also difficult to achieve. Therefore, despite good process capability under development conditions, process capability in production was still poor at the time of launch. Developmental setups had failed to imitate production routines and restrictions like changes of work shifts, limited personnel and insufficient automation of in–process-controls adequately.

As a result the yields at commercial scale production were lower and more operators were required to run batches than expected, thereby deteriorating the contribution margin. No systematic monitoring of process performance had been set up through a PQS to support continual improvement and thus the potentials for improvement which had been established by the knowledge space during development could not be utilised during production.

The low quantities at the start of routine manufacturing also prevented driving down the experience curve quickly and as a result efficiency of manufacturing did not improve significantly within the first year after launch.

Despite the potential of an improved contribution margin through the reduced analytical costs for release testing and the wide range for optimisation of process parameters, the lack of integration had prevented these potentials to be fully utilised and thus reduced the product’s profitability.

The reduced contribution margin also coincided with decreased profits as at the time of launch no premium price could be achieved in most European countries anymore. The product was grouped into the same price group for reimbursement as other clarithromycin generics decreasing the expected profit – even though health authorities and experts had confirmed that ClaroSip ® presented a real improvement in the treatment of bacterial infections in children.