Technology Transfer by Design

The next stage in operational advantage

By Pedram Alaedini, Ronald D. Snee and Brian W. Hagen

Accelerating trends in the pharmaceutical industry have made successful technology transfer more critical than ever. Mergers, acquisitions, the rise of generics, the closing of plants and the construction of new ones — these trends and events typically entail the transfer of products and processes from one site to another. New products, too, must often be moved from the development site to a manufacturing site prior to launch.

Technology transfer becomes even more challenging when several dozen products must be transferred at the same time and in parallel, as often happens following a merger, acquisition, or alliance, the closure of a facility, or the need to quickly develop and manufacture a large number of generic drugs. Cost pressures, market needs, government regulations, tax benefits, and logistic issues have also greatly magnified the importance of technology transfer.

The decision and plan for technology transfer is a direct result of several factors, such as corporate vision and business requirements, sourcing and manufacturing strategies, and the overall company strategy. All of these parameters together dictate the site and product transfer strategies and plans.

With these trends likely to continue for the foreseeable future, companies can no longer afford to treat technology transfer as something that “will get done anyway.” Whether transfer takes place between two sites, two companies, a company and a third-party manufacturer, or even from R&D to a pilot plant or commercial facility, the ability to do it faster, more compliantly, and less expensively can confer significant competitive advantages. Successful companies will therefore make technology transfer a core competency to ensure that they can compete effectively today and in the future.

They can establish this critical core competency through Technology Transfer by Design (TTbD), based on the principle that technology transfer is a process that can be designed, improved, and controlled, much like other processes. Just as at the product level, where Quality by Design (QbD) depends upon an understanding of the interactions in manufacturing processes of multiple variables that keep the resulting product within specifications, TTbD at the portfolio level provides a systematic way to understand all of the elements that go into the design of the tech transfer process and ensure that they stay in synch to produce a successful transfer.

The Trouble with Technology Transfer

Pharmaceutical technology transfer is a complex and multi-faceted process. Further, every pharmaceutical product and process undergoes one or more technology transfers during its life cycle; and, at every technology transfer stage, knowledge is transferred from one group to another. At any stage of the process, challenging problems can arise, problems with which even the most successful companies wrestle.

Consider, for example, the experience of a major, U.S.-based pharmaceutical manufacturer. The company decided to close five of its 34 plants around the world and transfer all of the products to other plants and third-party contract manufacturers. Senior management decreed that the entire effort be completed within 18 months. They directed the plant managers at the five plants designated for closing to establish where their products were to be transferred and to manage all transfer activities.

Six months into the project, senior management asked for a progress review. The information that was shared at the meeting stunned them:

• One of the five plant managers had left the company.
• Of the 145 products in play, not one had yet been transferred.
• No clear understanding existed of what products were to be transferred to what facilities.
• Although several third-party contractors had been contacted, no manufacturing agreements had been reached and no specific timelines established.
• No teams in corporate or plant locations had been given responsibility for transfers.
• Some of the company’s other plants had been contacted about the possibility of transferring the products into their facilities, but due to the number of other initiatives in those plants they had shown no interest in participating.
• No budget had been established for the transfers or for the capital projects associated with them.

The company had fallen prey to many of the most common mistakes made in technology transfer. They had failed to think through the entire process and make sure every task was completed in a timely way. There was no real buy-in on the part of senior management with regard to cost, resources, and time required for such a massive, complicated undertaking, all of which resulted in unrealistic expectations and the assumption that the transfers would just somehow happen. Ignoring the human element involved in tech transfer, senior management appointed neither a strong project manager to lead the effort nor a team of top talent to assist with it. On the technical side, no time had been allowed for scale-up, the needed process understanding had not been developed, and there was no regulatory strategy put in place. After six months, the project remained essentially at square one.

A Better Approach to Technology Transfer

TTbD provides a better way. By applying to the technology transfer process the advances made over the past 25 years in process and risk management, TTbD offers a uniform process for successfully transferring technology, whether for one product or many. TTbD is based on the assumption that, like any process, pharmaceutical technology transfer needs to be assessed, defined, designed, and managed from a comprehensive value perspective. Just as Quality by Design is employed to create the design space for the successful manufacture of a product, TTbD maps the “transfer space” within which technology transfer will succeed. It includes a structured set of requirements, activities, and decision points. And it provides an integrated approach to best practices to be systematically managed so that transfer is timely, effective, within budget, and well documented with minimal impact to current and future sales of the products involved. Critical success factors include:

• Clear bottom-line financial focus
• Active senior management leadership
• A disciplined approach at the program and project levels
• Sequenced and linked tools
• Rapid project completion
• Clear definition of success
• Supporting infrastructure, including roles, responsibilities, and management systems, and adequate staffing
• Creation and use of process understanding
• Use of data and statistical modeling

Looked at another way, these critical success factors are, in effect, the multiple input variables that interact to produce the output: a well-designed technology transfer process.  The effective “setting” of the parameters for each of these factors together constitutes the transfer space within which a successful transfer process can occur. If one or more of these factors exceeds its parameters, the transfer process is likely to experience problems ranging in severity from delay to failure. For example, inadequate senior management leadership attention in the previously cited example of a failed transfer design was largely responsible for many of the subsequent breakdowns in the effort.

Note that these factors are not synonymous with the process itself, just as, say, the temperature of a dryer in a pharmaceutical manufacturing process is not the process but an input variable in the process. TTbD seeks to make sure that each of those variables that feed into the design of the transfer process are adequate, taken together, to produce the desired outcome.

Depending on precisely the kind of transfer taking place, the number of process steps may vary, but in a typical site-to-site transfer there are roughly 10 steps involved. Note, too, that there is both the overall transfer program management process (Program Level) at work as well as the sub-process for transferring each individual product or process (Project Level).

The 10 steps constitute the focal points to be considered – both in creating the transfer process and investigating problems that might arise – when dealing with a multitude of product transfers. For any given step, the relevant “input variables” must be “set” properly or the step is likely to encounter problems. The steps, and the relevant input variables that determine the degree of success for the step, include the following:

1. Determine scope, strategy, and risks

In designing the strategy for transfer, you must first scope the overall project: number of plants and products involved, the markets that these products supply, the regulatory agencies where submissions will be filed, and the staffing and skills requirements. This information should be documented and approved by senior management and it should include assessments of regulatory, financial (sales and costs), marketing, and public relations risks. (Input variables: bottom-line focus, active senior management leadership.)

2. Determine overall gaps

Determine what shortfalls for undertaking the project exist in plant capabilities and capacities, personnel in headquarters or plants, and project management capability. (Active senior management leadership, clear definition of success.)

3. Develop governance body, champions, mentors

Design and establish a governance body consisting of senior management from stakeholder departments such as operations, supply chain, quality, regulatory, and marketing. In addition, designate project champions from these departments and select mentors for each project champion. (Active senior management leadership, disciplined approach at program level, supporting infrastructure.)

4. Determine communication and reporting channels

These channels should be clear and unambiguous including the relationships among receiving and transferring sites, the reporting structure to senior management, and communication modes and intervals with all parties involved. (Disciplined approach at program level, supporting infrastructure.)

5. Determine performance measurements

These measurements could include but are not limited to: meeting budget, meeting timelines, validation success rate, number of FDA observation during Pre-Approval Inspection (PAI), regulatory submission approval rate, labor hours by job title, labor costs (internal and external), capital, expense, potential sales impacts. (Clear definition of success, disciplined approach at program and project levels, use of data and statistical modeling.)

6. Develop and train transfer teams

Select the transfer teams in headquarters and in the sending and receiving plants. The team in headquarters should include project managers. Teams in both the sending and receiving plants should include senior employees from major departments such as manufacturing, quality, technical services, engineering, and supply chain. The teams must be trained in basic team activities, troubleshooting and problem-solving, communication, and time management. (Active senior management leadership, disciplined approach at program and project levels, supporting infrastructure.)

7. Determine responsibilities for each group and individual

A RACI chart to identify who is Responsible, Accountable, Consulted, and Informed must be developed for each activity and for each member of the organization involved in tech transfer. (Active senior management leadership, disciplined approach at program and project levels, supporting infrastructure.)

8. Conduct gap analysis for each product

At this stage the teams should perform a gap analysis for each product or group of products. The key here is to assess current process understanding and what will be needed for success at the receiving site. The tools of process mapping, value stream mapping, process capability and control, and statistical modeling are particularly useful here. This gap analysis should include manufacturing processes, documents, analytical methods, equipment, plant capabilities, and regulatory and safety issues. (Disciplined approach at project level, sequenced and linked tools, process understanding, data and statistical modeling.)

9. Determine tech transfer strategy for each product

Based on the gap analysis, a detailed strategy document must be developed to include all gaps, the means to fill those gaps, and a description of the overall transfer strategy with measures for success. This document should be approved by upper management. (Active senior management leadership, disciplined approach at program and project levels, sequenced and linked tools, rapid project completion, process understanding.)

10. Manage all activities, follow up, and keep at it

Of particular importance here are management reviews at both the program level and the individual transfer level. (All of the success factors or “input variables.”)

For the foreseeable future, the need to transfer technology is likely to continue to grow. Because speed to market, the ability to provide uninterrupted supply, and the drive to achieve ever greater efficiency and cut costs all affect the bottom line, effective technology transfer is all the more important. Organi-zations that view technology transfer as a core competency and adopt TTbD to design, control, and improve their approach to technology transfer will enjoy a great advantage over companies that treat it in an ad hoc manner. Such organizations will have a ready framework for the increasingly crucial task of technology transfer. Just as importantly, they will also have a cadre of experienced personnel who can rapidly deploy TTbD to consistently achieve successful technology transfer more rapidly, consistently, and at lower cost.

Copyright Pedram Alaedini, Ronald D. Snee and Brian W. Hagen 2007

References

1. ICH Harmonised Tripartite Guideline: Pharmaceutical Development, Q8, Current Step 4 version, November 10, 2005
2. Snee, R.D.(2006) “Lean Six Sigma and Outsourcing – Don’t Outsource a Process You Don’t Understand”, Contract Pharma, October 2006, 4-10.

Pedram Alaedini is a principal in Tunnell Consulting Life Sciences Practice. He has worked extensively in manufacturing and plant operations, parenterals, liquids and solid dosage.

Ronald D. Snee is a principal and Lean Six Sigma Initiative Leader at Tunnell Consulting in King of Prussia, PA.

Dr. Brian W. Hagen has been a practicing corporate decision consultant for 20 years in the life sciences and other industries. He is the co-author of “Solving the Corporate Value Enigma: A System to Unlock Shareholder Value.”