Welcome to the third of my memo’s on Technology Transfer. This month I would like to start looking at the workflow of a typical technology transfer project, which assumes that the product will be outsourced to a CMO. Depending on the exact circumstances these steps can be different or be performed in a different order. Usually, these steps are not performed in isolation and often in parallel.
In this memo I will cover the “initiation” phase of the transfer process which covers the initial setting up of the project, information gathering and gap analysis, and will follow up with the “planning” phase in my next memo.
Select RU / CMO
No two CMOs are the same – they all have different strengths and weaknesses, and no two sponsors will look for the same requirements.
While hiring a CMO might not strictly be a function of technology transfer, it will be a critical decision regarding the success or failure of the technology transfer process.
The starting point should always be to define your own requirements, and to decide which CMO capabilities will be the most important for you such as cost, speed or history of regulatory compliance. You can score your potential CMO’s against your requirement to help you create your shortlist and decide your best fit.
There are many checklists / topics available on the internet (and I’ll expand in future memos) but I would like to add a few “practical” items to the list. Communication is key they say – so finding a CMO with key staff that speak your language fluently – and that includes technical “speak” is crucial and selecting a CMO in your time zone can be classed as important – unless you don’t mind only being able to talk to them in the early hours of the morning!
A very important point to consider, especially if your chosen CMO will be performing analytical or process development for you – you MUST consider your intellectual property, who owns it and what is the CMO’s country’s approach to protecting IP assets.
And lastly – you want to select a CMO you feel comfortable with — not only one that can handle the work. And in this respect the cultural fit — or the ability to work together — may be the most important criterion of all.
Technology Transfer Charter
It is crucial to set clear expectations and responsibilities between partners in order to avoiding confusion and/or conflict later. The initial charter agreed upon by both parties must include the scope of the project, transfer timelines, as well as the team structure, specifying clearly defined roles and responsibilities. The charter should also establish clear paths of communication and a governance structure for addressing issues. Most importantly, success criteria must be clearly documented in the project charter.
Form / Define Steering Team
There is usually a “Governance” structure sitting above the project team who role is to:
- Oversee transfer activities
- Ensure information is effectively shared
- Identify the Project Managers
- Assign a support team and senior management steering committee
- Establish a clear RACI matrix
Tech Transfer and Regulatory Strategies
- Quality and Technical agreements
Quality and technical agreements are legal documents that defines both specific quality and technical parameters for a project and which party is responsible for the execution of those parameters. The level of detail may vary depending on the developmental stage of the project.
- Documents required
The donor (sponsor) / Sending Unit (SU) and receiving unit (RU) must gather and prepare several documents to ensure a successful technology transfer, such as:
- Technology transfer plan: This describes all the activities to be transferred, responsibilities, and the expected outcome.
- Detailed analytical methods: They are crucial to technology transfer success as the results of the analyses are used for validation & comparability assessments as well as for the release of products from the transferred process.
- Manufacturing process description: Describes the manufacturing process in detail and will be used as a reference source for all parties.
- Critical process parameters (CPPs): They are generally identified by assessing the extent to which their variation could impact the quality of the drug product.
- Critical quality attributes (CQAs): A CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality.
- Technical gap analysis: This is a formal documentation of the assessment of known and potential gaps between the donor and receiving sites’ capabilities and of their readiness for the transfer. The document should include a risk assessment.
- Adequate change control management system: Any changes made to the process or equipment should be documented, assessed, and justified with regards to their potential impact on the CQAs and the Quality Target Product Profile (QTPP).
Tech Transfer Scope and Critical Success Factors
Critical success is the demonstration with data conformance of the success factors as outlined in the technology transfer agreements and plan and typically cover process parameters and control mechanisms, material supplies, analytical methods, health, safety and environmental concerns and compliance with regulatory requirements.
Technology transfer can be considered successful if there is documented evidence that the RU can routinely reproduce the transferred product, process, or method against a predefined set of specifications as agreed with the SU [WHO Technical Report Series, No. 961, 2011 Annex 7, WHO guidelines on transfer of technology in pharmaceutical manufacturing].
Appointment of Project Manager
There is often a separate project manager at each of the RU and SU sites. The Project managers have a key role in the technology transfer process, he is often the main point of reference and is responsible for effective and efficient management of the project team and technical support and for co-ordinating, leading, tracking all the project activities to ensure successful technology Transfer.
Form Project Team
Technology transfers are usually performed by dedicated cross-departmental / cross-functional and integrated teams including from both sending and from receiving sites.
Ideally, all functions from both sites are involved to a certain extent with respective partners in the other organization. In this way, subject matter experts can directly communicate with their peers.
As always with such potentially diverse teams the roles and responsibilities should be clearly defined. This is sometimes set out in the form of a RACI matrix or chart.
The client should provide as detailed and complete knowledge transfer package as possible with product information such as:
- raw materials
- analytical methods
- validation reports
- manufacturing procedures
- process parameters
- equipment requirements
- regulatory requirements, etc.
Contract manufacturers refer to these documents as a technology transfer package. The information supplied is assessed by the CMO to help them determine the requirements for any additional equipment and supporting studies as well as to help develop the project plan.
Process Flow Diagram / draft Process Description
Pharmaceutical process flow charts are diagrams of pharmaceutical processes, usually in the form of a series of individual blocks each block linked together to describe a specific process such as a manufacturing process. Each block can depict a specific operation or item of equipment and may include additional information such as flowrates or other operating conditions.
Alternatively, the process can be described in mainly text format.
Gap Analysis and Risk Assessment (GARA)
A gap analysis is usually performed to compare the manufacturing process at the SU and the RU to determine differences in items such as equipment, facility, and methodology.
Once any gaps or differences have been identified these are risk assessed against the impact on product quality using traditional risk assessment tools such as FMEA and mitigation actions determined against medium / high risk items. The gap analysis and risk assessment should be jointly performed by the RU and SU. The outcome of the analysis and assessment are often combined into a single document.