Analyse Phase

E-log book entry for Analyse stage ( Q24h process improvement)

The project is progressing well and we have been meeting twice a week with good interaction between the team and good participation.

We performed a risk assessment that looked at changing the number of timing coats on day 1 from 75 timing coats to a higher number. The risk assessment looked at the absence of I days drying and what impact this could have on the assay and dissolution profiles.

We had a project that had been performed on the drying of batches in ovens previously called the Emerald project and it showed that even though the batches were dried for 20 hours, it had little impact after 4 hours as the purpose of the drying was to take off excess solvent and moisture. The data analysis here showed that there was no risk present.

We also assessed the chances of overtiming the batches. Again the analysis of the data showed that 1 batch of the previous 100 batches was in spec at 95 timing coats but if we gave it another 20 timing coats the batch would still be above the lower spec of 20.

Based on the risk assessment we decided to go with 100 Timing coats for 2 batches and 110 timing coats for 2 batches.

Our manufacturing associate processed the 4 batches at the batches were sampled and sent to the labs for testing. The results were as follows with 100 TC on batches at the upper limit at 59 and 62 and the 2 batches at 110 TC at 53 and 45.

When we look at where the batches have shifted to, we were very happy with our progress. While some of the team were disappointed that the batches could not be used in a bead blend after day 1 timing I was relieved that the results were not much lower as our previous review was indicating 115 TC as the target value.

On further review of our components in stock we decided to call the batch at 45 in spec. the team were now satisfied, as we were starting to show a financial benefit to our project.

The table below shows the run chart including the increased number of timing coats. After processing the 4 batches we reverted to 75 TC while awaiting the results and those batches are also shown on the run chart.

We decided to give the 3 of the 4 batches further timing up to 120 TC as this would give us confidence in the increased number of timing coats.

The 4 batches in the chart below can be seen in a tight range in the middle of the limits after day 2 timing. During our analysis of the data we could calculate that each timing coat would move the dissolution by 0.8 and therefore indicated that we could have given the batches 140 TC and still not have an out of spec batch. The lowest projected at 140 TC would be 21.

Our confidence is growing and the expectation is high. Early indications are that with a higher number than 100 TC would have all batches in spec although they may not be usable in bead blends without further timing for some.

Although these 4 batches were not processed as a design of experiments (DOE) we gained knowledge in this regard. We have performed DOE on our products in the past but after consultation with our Quality and Validation departments and the risk assessment it was agreed that a DOE would not give us any greater information on the number of timing coats as we were not changing any of the processing parameters.

Our processing parameters included

Slit air voume, slit air temperature, Product temperature, rotor speed, Talc flow rates, Solution flow rates, gun solution pressure and dewpoint.

We were happy with the target values of the parameters in the batch record. The CF is run by a COMPU 4 computer system that is recording a large number of variables that are not recorded on the batch record for this process but are available for reference if needed.