Documentation is a keystone of Technology transfer so in this memo I thought I would have a quick look at some of the baseline documents that would be needed from both the sending and receiving sides. I believe that the FDA once said that “if it isn’t documented then its only a rumour, and we don’t deal with rumours”.
I once made a list of documents / work packages that would probably be required for a vaccine technology transfer and listed some seventy five (75) work packages that would be needed.
Each project is different and has different requirements, but I have tried to list some of the key documents below.
At the onset of the project the rules / responsibilities and scope of the project should be defined. You really shouldn’t start on a journey unless you know where you are heading. Unless of course chaos and uncertainty are your food of life.
- Quality and Technical agreements – quality and technical agreements are legal documents that defines both specific quality, technical parameters, and responsibilities. It is crucial to set clear expectations and responsibilities between partners to avoiding confusion and/or conflict later.
- “Technology Transfer Charter” or at least a Project Scope and any required by / anticipated timeline in the form of a Technology Transfer Plan. Projects without a scope and anticipated timeline will be subject to constant amendment and change, doomed drift on forever like the Flying Dutchman.
- -clarifies the technology transfer in sufficient detail for all parties to understand the scope of work, their role, the timing, and the resource needed.
Once the project has been initiated you will need to know what to make and how to make it – the details of the product and the process are documented in:
- Research and Development Reports – historical data of pharmaceutical development of a new drug substance and drug products at stage from early development the final application of approval – Quality profiles of manufacturing batches (including stability data) –
- Process Flow diagram / draft process description: Describes the manufacturing process in detail and will be used as a reference source for all parties.
- Critical quality attributes (CQAs): typical properties or characteristics that should be within an appropriate limit or range to ensure the desired product quality.
- Critical process parameters (CPPs): They are generally identified by assessing the extent to which their variation could impact the quality of the drug product.
CQA’s and CPP are often detailed in a “Control Strategy” document
- Bill of material – List of all components and where in the process they are used.
- Analytical methods to be used, the results of the analyses are used for validation & comparability assessments as well as for the release of products from the transferred process. These methods should include test methods for drug substances, intermediates, drug products, raw materials, and components.
The above are sometimes collected in the form of a “technology transfer file” which may include additional detail such as safety, environment / stability, packaging (cold chain requirements etc), cleaning processes, shipment characteristics.
- Technical gap analysis: This is a formal documentation of the assessment of known and potential gaps between the donor and receiving sites’ capabilities. Quite often this can take the form of a Gap Risk Assessment.
After the details of the process and any gaps have been identified & understood
- Process risk assessment (such as a process FMEA). Where are the risk in the receiving site process – how can these risks be evaluated, eliminated, or mitigated? In my experience this is poorly performed, and often treated as just a tick-box exercise or a justification as to why a high-risk item is really just a low risk. This item should be regularly updated as process knowledge increases but rarely is so.
- Detailed / updated process description.
- Detailed project plan.
- Sampling plan for both routine and non-routine (e.g., process validation) samples.
- Supporting studies, there can be many of these but depend on the type of product being manufactured:
- Media fills (process simulations) for sterile products.
- E& L assessments (especially important if single use components are used.
- Filter studies
- Container closure integrity studies
- Dissolution studies
- Validation activities: These are usually detailed in the site Validation Plan (VMP) and can give rise to various sub-plans:
- Cleaning validation plan
- Process validation plan
PPQ preparation & execution
- SOP’s – if not already covered by existing SOP’s, training plans and records for these should also be contemporary.
- Rationale for the number of PPQ batches to be manufactured. There is no longer a requirement to perform 3 PPQ batches – however whatever number is chosen; it must be substantiated by a science-based rationale.
- Protocols – for each activity performed, especially for those validation activities described in the Validation Master Plan. All validation protocols must include pre-determined acceptance criteria.
- PPQ report – listing results (and any deviations) from all PPQ batches. If any PPQ batches have been invalidated, then this and the reason why should also be disclosed.
- Technology Transfer Report- This can be a full detailed description of all technology transfer activities and results but is often simply an update of the “Technology Integrated Technology Transfer Strategy (ITTS) / technology transfer protocol Transfer Charter” demonstrating that all the agreed activities have been performed and that all acceptance criteria have been met. This can in effect be the end of project or handover document.
- Data recording list – online and offline data to be monitored and recorded during the process, and how this will be recorded and assessed as part of the Continued Process Verification.
- Deviation inventory – description in details of the deviations, status, and reporting of the impact on the product quality.