Technology Transfer: Planning for Successful Technology Transfer

Anthony Grenier

In the pharmaceutical industry’s competitive and ever-changing business climate, companies are frequently divesting certain assets and acquiring others. As a result, the industry is often very busy with manufacturing site changes and drug product technology transfers. Technology transfer is also part of the manufacturing life cycle for drug products that companies outsource to contract manufacturing organizations (CMOs). However, while pharma companies systematically follow protocols and issue reports for drug product method transfer or validation, they often fail to take the time to issue a plan and report for technology transfer.

The International Society for Pharmaceutical Engineering (ISPE) technology transfer good practice guide¹ provides a thorough description of technology transfer documentation. In this article, I’ll provide practical information to help scientists or project managers who are new to technology transfer navigate the process and issue their first tech transfer plan. While my emphasis will be on solid oral dosage forms—particularly in the example plan I discuss later—the general approach and structure of a tech transfer plan is the same regardless of the dosage form. The four basic steps for documenting a technology transfer are shown in Figure 1. The steps begin with broad objectives and a high-level timeline and work toward a more detailed assessment and timeline.

Tech transfer charter/proposal 

The first documentation step is to prepare a tech transfer charter and tech transfer proposal, which are often combined into a single document. The purpose of the tech transfer charter/proposal is to provide a general framework for the tech transfer and detail its scope. This should also provide an understanding of the key driver(s) behind the transfer (such as cost savings, divesting a product, or changing the CMO that manufactures the product). 

It’s especially important to outline whether or not the sending and receiving units will collaborate on the transfer. I’m often exposed to projects where a drug product is currently being manufactured by one CMO, but the sponsor is qualifying a second CMO to make the product without the current CMO’s knowledge. This situation obviously brings an additional level of complexity to the tech transfer project and requires that the communications strategy be clearly laid out in the transfer documents. 

The charter/proposal should also include a description of the teams and stakeholders involved in the transfer as well as the process, including a high-level list of anticipated changes (such as sources of materials, equipment, and methods). The charter/proposal will also include the tech transfer’s success criteria, such as process validation performed by a deadline for launch in certain territories. 

Tech transfer package 

The tech transfer package should contain as much information as necessary to ensure that the receiving unit can successfully complete the transfer on time and within budget. This typically includes the documents listed in Figure 2. 

People sometimes confuse the package prepared as part of the request for proposal (RFP) with the tech transfer package. The package for RFP only needs to contain enough information for assessing the feasibility and estimating the costs of the transfer, whereas the tech transfer package is much more detailed. It is intended to consolidate all the product and process knowledge necessary for the receiving site to replicate the process in its own facility. 

If the sending unit or current CMO is not aware of the transfer, I recommend sharing a process flow diagram to the receiving unit rather than providing executed documents. Otherwise, I strongly recommend asking for authorization from the sending unit before sharing documents such as SOPs or manufacturing and packaging records. 

Risk identification and assessment 

Implementing a risk assessment strategy and mitigating those risks will bring a robustness to the transfer process and ultimately prepare it for validation. While I won’t go into the details of how to perform a risk assessment in this article, I will mention a couple aspects that are important when approaching risk for tech transfer.

First, the risk assessment will be part of the tech transfer plan and, like the tech transfer plan, is a live document. You will have approved an initial risk assessment at the beginning of the project, but both your knowledge and the risks will evolve as you deploy the transfer activities. Second, it’s very important that both the sending and receiving units contribute to the risk assessment. While you can identify the risks based on a review of the documents, you should also ensure that subject matter experts from both the sending and receiving units meet to discuss them. 

Tech transfer plan 

As previously mentioned, the tech transfer plan content is similar to that of the tech transfer charter/proposal, but the items are addressed in greater detail. The ISPE good practice guide states that a tech transfer plan should include the following: 

• Scope and objective 
• Resources and budget 
• Timeline and milestone dates 
• Roles and responsibilities 
• Deliverables and acceptance criteria 
• Assumptions, constraints, and risks 
• Detailed risk mitigation plan to address items identified in the gap analysis 
• Work plan and goals for the tech transfer process 
• Work plan and goals for development studies at either the receiving unit or the sending unit 
• Equipment details
• Any demonstration studies required 
• Supply-chain and cold-chain logistics, if applicable 
• Training requirements 

At this stage, the initial project team should also include the subject matter experts and ad hoc personnel required at both the sending and receiving units to successfully conduct the transfer. Next steps 

Once the tech transfer plan is in place, the next steps are to: 

1. Execute the transfer 

Execution usually starts with transferring or ordering materials, analytical supplies, and equipment/parts, followed by analytical method transfer or validation and lab-scale or process scale-up studies, if required. 

2. Qualify the process 

Process qualification usually corresponds to the validation of the processes and the manufacture of the first marketable units. 

3. Finalize the transfer 

Once you’ve validated the manufacturing and packaging processes and have the approved validation report, the final step is to wrap up the tech transfer documents with a tech transfer report. The tech transfer report will assess if the transfer has successfully adhered to the timeline and budget and whether the technology at the receiving unit has performed as expected. For example, if there was an unplanned need to change specifications or use a different grade of raw materials, you should list it in the tech transfer report. Most importantly, the tech transfer report should include a section with lessons learned. This section should compile the receiving unit’s debrief notes to recognize the team’s challenges, achievements, and efforts. 

Example tech transfer plan 

Let’s look at an example tech transfer project in which a client of mine decided to transfer a well-recognized OTC brand from a long-term CMO to a new CMO. 

1. Purpose and scope 

In this section, we discussed the drivers for the transfer and indicated the receiving CMO. In this case, the main drivers for the change were costs and a risk that the current CMO might go out of business due to a lack of investment in its aging facility.

The scope included what needed to be transferred (process, analytical, packaging, and equipment), any anticipated major changes or need for development, and markets where the products would ship. 

2. Product and process overview 

Product description. We detailed the qualitative and quantitative registered formula for the product, which was a chewable tablet. We provided the claim/tab, international units, any overage, quantity per tablet, and percentage formula for each medicinal and non-medicinal ingredient. 

Process overview. We listed all process steps and equipment from the sending site. We also included a flow diagram, which is ideal. 

Packaging overview. We listed all the packaging SKUs and mentioned any that were discontinued.

3. Transfer team responsibilities 

In this case, the sending unit was not included, because the tech transfer wasn’t collaborative between the two sites. We listed the following groups: technical development and process; quality assurance; quality control; manufacturing; engineering; and health, safety, and environment. We also included the representatives assigned for each group, and they formed the core team. 

4. Documents and information to be transferred 

We provided the receiving unit with the documents listed in Figure 2. In our case, it was a straightforward process using an active ingredient made specifically for the company and with a history of sticking during compression. We made sure to include a CofA and specifications from the active ingredient supplier (including the supplier item number) as well as the active ingredient characterization report (the supplier provided a specific particle size distribution). Because the active ingredient had a history of sticking issues, we made sure to include in the package not only the drawings of the tooling but also a copy of the order to the tooling manufacturer so that the receiving unit would know which coating or treatment was applied. (Don’t assume that the tooling supplier will remain the same; it may change.) 

5. Side-by-side comparison and risk assessment 

A side-by-side comparison, as shown in Figure 3, is a good way to visually compare the process at the sending unit with the proposed process at the receiving unit. Following the gap analysis and identification of risks from the potential and proposed changes between the sending and receiving units, we provided an initial risk assessment, as shown in Table 1. 

6. Planned transfer activities 

Pilot batches. The company decided to perform a functionality characterization of the active ingredient and critical excipients, which involved manufacturing several small pilot batches to confirm the feasibility of compressing the product using the active and excipients that the receiving unit would be using. This step was essential because the product was a direct-compression tablet. 

We performed a first screening of the different active ingredient suppliers by testing different lots for chemical and physical characteristics (bulk and tapped density, particle size analysis, and flow properties). The technical group summarized these trials in a technical report, which should also document changes made to the compression tooling, if any. 

Stability batch. Based on the recommendations of the technical report, the company manufactured a stability batch, still at pilot scale, and issued a manufacturing/ packaging protocol and batch reports as well as a stability protocol. 

Scale-up. As part of the transfer to the commercial-scale equipment, we evaluated and confirmed the critical process parameters and implemented in-process testing/controls during the stability batch. We issued a protocol and batch reports, which then served as a reference for the process validation documents. We also used the tablets generated at this stage to assess the packaging tooling prior to qualification and determine whether a new tooling or packaging configuration was required. 

Other studies. We also performed a process validation, cleaning verification/validation, bulk holding time, and packaging validation studies. 

7. Conclusions 

In this case, we concluded that changing the active ingredient supplier will justify performing and budgeting for pilot batches and pre-market stability studies. These lots would also allow the receiving site to confirm that the sticking issue was not present at pilot scale, though it would still need to be monitored at larger scale. 

8. Attachments

This section includes any attachments used to prepare the tech transfer plan. In this case, we included formal documents such as process validation reports from the sending site along with meeting minutes for key project decisions and the initial risk assessment.

Conclusion 

A tech transfer plan is a living document that captures all activities, changes, and risks involved with a technology transfer. It should not be something that you generate at the beginning of a transfer process and then forget, but rather a valuable tool that the project manager or technical lead maintains from the project inception up to the completion of all activities. Following the disciplined approach I’ve described in this article can help pharmaceutical companies and CMOs increase the success rate of future technology transfer projects. 

References 

1. ISPE, Good Practice Guide: Technology Transfer, Third Edition (2018). https://ispe.org/publications/guidancedocuments/good-practice-guide-technology-transfer- 3rd-edition.