Certain questions and challenges keep recurring during product transfers. It is important to anticipate them systematically and put appropriate preventive measures in place. The critical issues include:
In order to minimise the impact of starting materials on the product quality during the transfer and to reduce the risk of delays, the starting materials are sometimes provided by the contract giver. After formal completion of the transfer, the starting materials should be procured by the contract manufacturer. In some cases, the strategy for the adjustment of the starting materials should be included in the transfer plan. This includes factors such as:
If any problems concerning procurement of the materials should arise thereafter, it is helpful to develop a solution strategy at an early stage.
If new systems have to be procured, the procurement time can become critical in the case of large systems and put the timely completion of the entire project at risk. It is therefore important to identify the potential delays (including the delayed completion of the qualification phase of the system) at an early stage of the project and plan for them.
In the case of scale-up projects, in particular, it is important to consider the calibration tolerances of systems in the comparative evaluation of the systems. The correlation between the tolerance range and the required range of the process parameters must also be taken into consideration in the case of large production systems to prevent variability in the quality of the process.
If the process did not have the necessary robustness prior to the transfer, the variability in the transferred process will be even larger. A simultaneous optimisation of the process during the transfer constitutes an immanent risk for the transfer aims and must be defined as a transfer aim in advance.
It should be ensured before the transfer that the system technology is state-of-the-art (just like the robustness of the processes). A switch to a new system technology during the ongoing transfer has an impact on the schedule and costs and should therefore be defined in advance.
An attempt to solve marketing authorisation issues (e.g. specifications or manufacturing parameters that are not up to date) during the transfer can make it difficult to meet the transfer objectives. If there is an opportunity to adjust the authorisation to the actual transferred manufacturing process, this opportunity should of course be taken.
Processability and process robustness issues can occur during every transfer. They are usually caused by missing or incomplete information about dependencies and relationships. The contract manufacturer can support the error analysis process systematically through
It should be defined in advance how the planned and finished batches should be handled (e.g. storage or destruction). It should be decided at an early stage who is responsible for any costs incurred.
The validation of the transport of products or intermediate products should be discussed at an early stage and included in the transfer plan based on the contractually agreed responsibilities for the transport and possible risk for the products.
It should be clarified in advance who is responsible for carrying out bulk hold time studies to prevent an increase in cost and delays in the project plan. If information about the possible bulk hold times between two process steps is not available (e.g. bulk products before packaging), it will have to be obtained at a later stage. This can lead to delays in the authorisation process or in commercial manufacturing. These studies are usually carried out by the contract acceptor as part of the transfer plan. If the analytics is not performed by the contract manufacturer, it should be specified in an agreement who is responsible for carrying out the studies.
A detailed comparison of the device settings at the two manufacturing sites can be particularly useful for simple measuring devices. Minor changes in the default settings that are not defined by pharmacopoeia standards, for example, can lead to different results (e.g. settings of IR balances used to determine the loss on drying at the end of the drying process). In this example, an extract from the marketing authorisation dossier would not be detailed enough to be used as a source of information. Based on experience, the contract manufacturer can support the process systematically by asking targeted questions.
Christian Gausepohl, PhD
Rottendorf Pharma GmbH, Ennigerloh
This text is an excerpt from the GMP Series Download A Successful Concept for Technology Transfer in Drug Manufacturing
A product transfer is first and foremost a transfer of knowledge. The larger the volume of data and information provided to the contract manufacturer, the smaller the risk of unsuccessful attempts or failure of the transfer. Therefore, the documented knowledge and experience gained during development and manufacture should be passed on in a systematic way.
A Successful Concept for Technology Transfer in Drug Manufacturing covers all aspects you have to consider when transferring - including an example of a transfer plan you can directly work with!
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