GMP 9 Essential Steps in the Technology Transfer of a Pharmaceutical Product
In times of Mergers and Acquisitions, the number of opportunities for transferring products between sites has never been so high. This is not counting divestment of assets by companies like Valeant and Endo, which have until recently been on an acquisition spree.
Business development and top executives are often asking their technical staff for details to get a better understanding of the timeline and costs following or in preparation for a product acquisition.
Transfer can typically happen from R&D to Production or from a sending/donor Site to a receiving site. In the context of assets sale, a donor production site could be the Seller’s own manufacturing site or its Contract Manufacturing Organization (CMO). A receiving site can be the Purchaser’s own manufacturing facility or the one from it designated (or to be determined) CMO.
This article covers 9 essential steps that need to be done in the course of the transfer of APIs or Finished Products between two sites :
1. A technology transfer plan: Outlines all transfer activities and responsibilities in great detail. The project manager needs to get a very good understanding from all departments of what the transfer includes and what it does not include. A visit at the donor site is a must. Especially for legacy products made for so many years by Big Pharma companies, I remember discovering some very old piece of equipment that you no longer see elsewhere than in museums !
2. Compilation of detailed process information at the receiving unit: This is especially necessary when dealing with a new CMO. If a CMO still has to be found, a technical package will have to be prepared.
3. Comparability report: Technical gap analysis exercise between the receiving and sending site. This determines whether key elements such as equipment, raw material specifications and packaging materials are like-to-like, comparable or need to be changed or adjusted at the receiving unit. Probably one of the most important document on which time has to be spent.
4. Analytical methods transfer: This has to be started first in preparation for testing small-scale or engineering batches. Ordering all necessary reactants / standards and product / raw materials / placebo samples can take time so better start with this first.
5. Preparation of master batch records at the receiving site: which are then reviewed by the sending unit. This is one of the many documents to be issued on top of protocols and specifications but it is touching an important area or expertise the documents transferred by the Seller are not always capturing. Ideally have operators or technical specialists witnessing a batch at the sending site and vice versa. The master batch records are first issued for the small-scale, scale-up / demonstration batch and are the basis for the ones used to validate to process. I have seen multiple examples of old processes being handled more as an art than science at donor sites. Documentation will have to assist the operator at the receiving site to perform the right handling or adjustments.
6. Risk assessments: Generates enhanced process understanding: This is encompassing multiple areas from materials to drug product manufacturing and packaging through drug substance process. It can be initially done after the comparability report and new versions are generated along the way of the technology transfer. Critical attributes and process parameters will be identified at this step and will be confirmed during pre-validation batches.
7. Training of work force at receiving unit: Often not captured in the Gantt chart for the overall Technology Transfer activities, special care has to taken on this. After all, this is the analysts and operators who are helping the technology transfer to be successfully completed or not. I like the buddy-buddy training using an operator that had witnessed the process at the donor site and becoming himself a trainer of other operators at the receiving site.
8. Technology transfer report: This key document will include a justification for the proposed process parameters and their criticality. It will guide the preparation of the validation protocol and has to be prepared with this goal in mind.
9. Process validation: The step we have to approach with all uncertainties already covered in the previous steps.
Technology Transfer Consultant
Montreal, Canada Area, Pharmaceuticals