1 – Can your process be manufactured according to the concepts of cGMP?
According to the FDA: CGMP refers to the Current Good Manufacturing Practice regulations. CGMPs assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the CGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations.
If for any reason your product cannot be manufactured according to cGMP regulations (such as it cannot be manufactured in a reproducible fashion or has variable potency) then you don’t have a licensable product.
2 – Have I got enough time?
It typically takes 6-9 months to transfer a simple product / process to a CMO, and this can be significantly longer if the product is a biotechnology / biologics product. Even if you have a well-defined product developed under QbD principles there is a lot of “practical” work to be done, such as transferring and validating analytical methodologies, demonstrating comparability of the equipment used and product produced. If any of the suppliers (materials, components etc.) are to change, then these must be qualified and the resultant finished product suitably qualified. There are many agreements to be completed (commercial, quality etc.) and for biologics looking for FDA approval, validation data for a biopharmaceutical (unlike small molecules) must be submitted up front in an IND filing so that FDA can evaluate the process development. A major issue is usually that the donor companies do not allow for any contingency time – for repeating or performing any additional tests or resolving any process issues that inevitably arise during the transfer process.
3 – Has the product been fully characterised / Do I have a robust process?
Has the process been fully defined, with critical control parameters and allowed variances? Sufficient data is required to be available to demonstrate how the product has been developed, ideally this data should have been collected through good designs of experiments. Is proper data available to support the operating ranges, alert and action limits?
4 – Is the process scalable, or will the CDMO/CMO/receiving site have to redevelop the process?
To be manufactured at a commercial scale the process must be able to be scaled-up otherwise the CMO will have to spend a lot of time (and your money) modifying the process and a great deal of time and effort will have to be expended demonstrating the comparability of the product from the new process with the original. Come to that – product comparability will have to be demonstrated perhaps through the use of scale-down studied.
5 – Do I have a comprehensive Technology Transfer Package (TTP) prepared?
The extent and level of detail in a technology transfer package can vary considerably depending on the stage of development of the product. A comprehensive technology transfer package comprising relevant information from the donor (sending) site should be compiled for technical review, including process description, analytical methods and data, production equipment details, and historical process data. In particular, CQAs and the control strategy for both drug substance and drug product should be provided in final documented form by the sending unit. Once the technology transfer package is completed, the transfer team can use the data to work on the planning and writing of technical documents for the receiving unit. Based on the technology transfer package, the transfer team should also conduct a first high-level risk analysis.
6 – Have I defined acceptance criteria for the success of the technology transfer?
You will need to have an acceptance criteria defined – how else can you know when the technology transfer is complete and successful? This is usually defined in terms of documented evidence that the receiving site can routinely reproduce the transferred product, process, or method against a predefined set of specifications as agreed with donor site.
7 – Do I have an experienced dedicated transfer project manager?
Lack of technology transfer experience can lead to gross assumptions being made and an over reliance on process descriptions and SOPs, neither of which are usually detailed enough to allow inexperienced staff to carry out the process (be it the actual manufacturing or performing an analytical method) in the intended manner, or to be able to recognise and flag up anomalies, faults, or irregularities in a timely manner if at all. Quite often this will result in out of specification products and significant deviation / CAPA generation activities being required.
If the answers to any of the above questions is “no” – then one last question – Have you talked to Bluehatch Consultancy Ltd? If not – trefor@bluehatch Consultancy.com