Technology transfer of antibacterial oral solid dosage form in a pharmaceutical industry

Abstract

Technology transfer (TT) looks at the transfer of intellectual property from one manufacturing site to another. If carried out successfully, a TT can increase the leveraging capability of the company acquiring the intellectual property together with its brand strength. This in turn aids in a decreased time to market of the final dosage form produced. The aim of the research was to assess the TT of an antibacterial oral solid dosage form from one manufacturing site to another. An expected change of manufacturing equipment from a single-pot to a multi-phase system took place due to the equipment available at the receiving unit. The assessment done by the researcher was performed in the capacity of an observer. The assessment of the TT was performed by observing the critical stages during the transfer process, namely the development and validation stages. Prior to the start of the development stage, a characterisation of innovator was performed. At this stage, innovator batches received from the Sending Unit (SU) were characterised to allow for a means of comparison. The development stage allows for the determination of the robustness of the formulation to be used whilst the validation stage will look at the reproducibility of the chosen formulation. During the development stage, small scale trials were manufactured with amendments made to the original formulation. The amendments allowed for a formulation more comparable to the innovator product with regards to its dissolution profile. The comparable batch produced at a small scale was then up-scaled to a production scale batch and these were compared to the innovator products. The amendments made were on the amount of granulation fluid and binder as well as the method of addition of the disintegrant. When a large scale batch comparable to that of the innovator product was produced, the validation stage was started. With the aim of showing reproducibility of the Receiving Unit (RU) at producing large scale batches, three batches were produced. These were tested for all critical parameters, namely through the loss on drying, particle size distribution, hardness, disintegration and dissolution tests and, the results of the tests were compared to the specifications set by the SU. They were also compared to each other, enabling statistical determination of any significant difference across the batches through the use of comparative statistical analyses. Comparison of batches, at the development and validation stage, was done using the dissolution potential of the batches. These were performed through the use of statistical analyses. The RU made use of the similarity factor (F2) to compare the dissolution profiles. For the purpose of this research, the 1-Way analysis of variance was also used, which compared to the similarity factor, took in consideration the level of variance of the batches produced. Results and discussion: During the development stage amendments were made to produce a batch comparable to the innovator product. The amendments that led to the production of a comparable batch consisted of an extra 14 % of granulation fluid as well as 50 % of the disintegrant being added intra-granularly with the other 50 % added extra-granularly. The amendments were added on top of the amount suggested by the SU. This formulation was used and three batches produced consecutively. On comparison to the specifications set by the SU, the three batches were seen to be within the specifications. On comparison to each other, the dissolution profiles were seen to be different. Conclusion and recommendation: The development stage producing batches within the specifications set by the SU but also comparable with regards to its dissolution profile, was seen to be successful. The validation stage was seen to be unsuccessful. Even though the results of the critical parameters were within specifications, when compared to each other, the batches were seen to be significantly different. This led to the research looking at the TT as a whole as being unsuccessful. The researcher then determined what stage could be improved and how this could be done. The various stages seen as having associated problems were determined and ways to mitigate those were determined. A guideline in the form of a flow chart was proposed to aid a manufacturing facility undertaking a TT to shorten the period of time to completion as well as increase the chance of success