Some years ago, “tech transfer” meant moving products out of the development stage, getting them into production, and then sending them out the door. Today, it is more of a paradigm shift and a business strategy, according to Russ Somma of SommaTech Consulting. It is using the knowledge gained early on, codifying it internally so that it becomes part of the company memory, and then leveraging that background to move the products ahead.
Somma and Christoph Haas, Principal Consultant at HAAS PharmTech Consulting, examined the ins, outs, ups, and downs of technology transfer in today’s pharmaceutical environment as part of the INTERPHEX Live series.
We caught up with Somma and Haas in a Q&A prior to the show for a preview of the topic, “War Stories: Another Look at Tech Transfer.” Below are edited excerpts of their comments.
Q: What are some of the main challenges faced today in pharmaceutical tech transfer?
Haas: Time to market versus quality of process and product design, robustness, and stability. There will always be pressure and tension between corporate business goals to launch a new product as soon as possible to maximize revenue stream versus the scientific team to develop a robust reproducible process to ensure a high-quality product over the life cycle of the product.
The scientific team’s key challenges and decision points involve robustness of the data package available for submission. The desire is to have a submission package that will ensure a first time review and approval process by the health authorities.
Questions and challenges back from the reviewer could significantly extend the approval and therefore launch timeline. Incomplete experiments and inadequate data may lead to a refusal to file.
Is the submission defendable with six months or 12 months accelerated stability data? Are the process and equipment changes within like-for-like guidelines or is a more extensive qualification and validation package required? Is the clinical data package comprehensive and complete for the intended use of the product? Always make sure that the data output makes sense before moving to the next step.
Plan as realistically as possible and don’t overextend your goals.
Q: Are those types of challenges the basis for the ‘war stories’?
Somma: The ‘war stories’ that we talk about are usually the ‘crash-and-burn’ classics. Let’s say you make a tech transfer to a new facility, but somebody on the team missed something—perhaps checking part of the infrastructure. It could be something as non-transparent as their waste treatment system. You go over, put all of the latest equipment in, you transfer all the coding, but when you go to wash the equipment the water coming out of the system cannot be put into the standard sewer system. It has to be drummed up and moved offsite.
Tech transfer is an all-encompassing business strategy. It’s about shared experiences. The war stories involve what happens when it falls off the track.
Q: What are some of the big mistakes that companies make during tech transfers and how can they be avoided?
Haas: There are two categories of mistakes: managerial and technical.
On the managerial side, the biggest mistake is to create technology transfer ‘monster teams’ with update meetings where 40 to 50 people are sitting in a room for half a day, and their respective contribution may be five minutes. Not productive or effective.
A good design for a tech transfer team organization is to establish a core team consisting of one representative from each functional area: manufacturing, analytical, regulatory CMC, packaging, engineering, and technical services from both the transferring site and the receiving site. That will result in 12 to 14 people at the meeting including the project manager and the technical project lead.
This team represents the strategic execution portion of the project. The hands-on tactical portion is being managed by the representatives from each area, which are sub-team leads.
On the technical side, the biggest challenge is not to ignore the data for the sake of rushing towards the end. Believe the data, act upon the results, improve or change the process if required.
If the blend uniformity data are borderline passing, it will only get worse when the product is launched. You’ve got to fix the issues before submission and validation. A poorly developed process will result in challenges and potential rejections post launch, which will be costly in the long run.
Launching then not being able to supply the market due to process issues is way costlier and image damaging than producing a couple more experimental qualification batches, which may take an additional three months on the development timeline. Update your resume if this happens.
Q: Can you give an example of a tech transfer gone bad? What went wrong? What delays and additional costs were faced?
Haas: Technology transfer and product introduction of a triangular shaped tablet. Soon after the launch, complaints poured in regarding chipped and broken tablets. Investigation into the issue revealed that already during the development and validation phase, the friability data for the triangular shaped tablet was on the high side.
It was noted as such in the validation reports, but for the sake of expediting the launch, it wasn’t addressed at that point. Complaints about broken tablets also reached the agency, which in turn wanted to have an explanation from the company as to the root cause and corrective action.
In short, the tool design for the triangular shape was not optimal. Together with the tool manufacturer the dimensions of the thickness and the curvature of the corners were redesigned, which gave the tablet a more robust shape. This, however, required additional stability studies, as well as an update to the original filing documents.
In general, tech transfers should not go bad in the 21st century considering that most of the developing companies are following Quality by Design (QbD).
Q: What’s the key to making a successful tech transfer?
Somma: It comes down to good communication. To this day we’ll transfer a very unique product into a facility, everybody understands what the formulations are, then someone will say, ‘my goodness, it is hard to clean.’ You knew what the agreement was. Don’t come back with a show-stopper six months into the process and say that’s a deal breaker? That’s as good as saying the product doesn’t work.
There’s give and take. It’s business collaboration and should be openly discussed with the client. It should be a quality working agreement between the firm that is transferring it, such as a Big Pharma company, and the one accepting it, such as the CMO, so there are no surprises in the end.
Otherwise, it becomes a ‘war story’ because there was no conversation about a particular issue and it falls off the track as though the product itself didn’t work.
Q: Do companies follow a standard set of industry guidelines for tech transfer or do they set their own metrics? Does the FDA get involved?
Somma: Not guidelines, per se, but the FDA will send inspectors, who look for and follow a list of components, specifications, process tests, manufacturing procedures, and solution data. As they go down the list, if the company hasn’t combined its collective knowledge during the tech transfer process to address the various steps during the Pre-Approval Inspection, the tech transfer is going to be a flop.
People think it’s all about the validation. Yes, it’s a mandated requirement, but remember that the FDA is always going to look at Good Manufacturing Practices (GMP) and the various steps for pre-approvals. That’s your guidance.
I think people get wrapped up in QbD, which is extremely helpful but it’s an enabler. Tech transfer is a component in the whole QbD concept. It is all about the knowledge that you have to make the product, to educate the participants, so that they can test it, make it, and ensure patient safety. All of this is what the FDA looks for.
Q: How do companies monitor progress along the way?
Somma: A lot of companies just take the ‘phase development’ approach common in FDA-type trials, i.e., Phase 1, 2, 3. They establish a phase gate of evaluation, which may include an internal review among people not necessarily involved in the product, assembling a check list internally, looking at regulatory aspects, and doing a heavy-duty assessment.
Companies do a lot of different things to make sure they don’t get to Phase 3 and find they didn’t do some part of the process.
Q: From conception to completion, what timeframe is typically required for tech transfer within a Big Pharma environment? How about when transferring tech to a CMO?
Haas: A typical tech transfer project usually takes about 24 to 30 months from inception to submission ready. Then it might take four to six months for approval. However, it really depends on the product and process complexity—i.e., a simple direct compression formula for a tablet may take significantly less than an aseptically manufactured, lyophilized vial product.
Transferring to an internal facility or a CMO should not make a significant difference in timing and execution if the technology transfer management process is being followed and applied. You may consider an internal facility as an internal CMO versus an external CMO.
Planning of the transfer project, a well-established communication stream, agreed-upon regular team updates and project reviews, an issue escalation path, and quick resolution of challenges or unexpected hurdles are keys to success.
A thorough project management structure and a recognized technical leader that share the responsibility of managing the team and project will ensure a successful project completion.
Q: But, isn’t transferring tech internally much less complicated than transferring to an outside CMO?
Somma: You’d be surprised. It’s not as obvious, but when you’re talking about these giant multi-nationals, it’s often a cultural breakdown that becomes the problem. Probably the biggest stumbling block in the large companies comes about when you hear the comment, ‘It’s not the way we do things here.’
Tech transfer has been happening everywhere, not just pharmaceutical. Unless communication and knowledge is transferred throughout the process, it’s going to crash and burn.
Q: How do internal teams interact with the external teams at the CMO?
Somma: Generally, the company puts together cross-functional teams examining the development piece, the manufacturing elements, the regulatory requirements. And, embedded in regulatory, is the compliance aspect, which goes beyond regulatory.
That’s how the internal team is assembled. Everything is communicated within that group. On the flip side, hopefully in all cases, your team has a mirror image at the CMO.
Hopefully, when sitting across the table, all of your functions are reflected back at you from the CMO. If they are not, you have to wonder if you’ve been very clear about what you expect.
Prior knowledge of the infrastructure also is important, especially if production is transferred to another country. Ensure that the supportive infrastructure extends beyond quality control and GMP to include a range of other crucial factors that cannot be taken for granted. Otherwise, the project may be headed down a path to disaster.
Q: Do pharma companies have dedicated internal teams to plan and follow through with tech transfer or is that something that is often handed over to outside consultants?
Haas: Quite a few companies have dedicated technology transfer management groups/departments that may be part of a global technical services structure interacting with the local technical services departments.
Companies also develop internal guidance documents that define the elements of the technology transfer management process outlining a RACI matrix for all pertinent departments involved in technology transfer activities: that is, transferring and receiving information on site manufacturing operations, analytical (testing, stability), materials management, technical services, regulatory, engineering, ad hoc marketing, safety, health, and environment.
Q: What kinds of services do the consultants typically perform when assisting and advising companies during tech transfer?
Haas: Consultants offer a variety of services from IQ, OQ, PQ execution for equipment to generation of process validation protocols and reports, analytical methods transfers, cleaning validation projects, etc. For smaller companies, it is definitely a viable approach to work with consultants during the labor and activity intense phase of the project.
One must consider the training and SOPs that an external contractor/consultant must follow. There are companies that exclusively offer this service.
The advantage is that smaller companies don’t have to staff for peak demands on technical services staff.
The downside of using consultants is that the expertise and first-hand knowledge will not be available after the project is complete, unless manufacturing and technical services people are working very closely with the consultants during the execution phase.
Q: Are there certain new technologies, e.g., cloud and other systems, that are beneficial during the tech transfer process?
Haas: There are definitely significant new technologies available today that make information exchange and data transfer a lot more convenient and efficient. Sharepoint sites for projects are effective so that the team can have access to all the project pertinent information.
Information can be well organized into folders for technical documents, SOPs, meeting minutes, etc., which are easy to retrieve, easy to share. This is important especially when we are dealing with transfers to the Far East where time differences may hamper the flux of communication without those electronic capabilities. Using systems for team review of documents is also very efficient as reviewers can see each other’s comments and respond accordingly.
Video conferencing is also affective as it allows teams to have face-to-face meetings without the costly travel expenses to far remote places.
This article can also be found in the INTERPHEX 2016 Show Daily: Thursday, April 28.
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