Is Tech Transfer Broken? Can the Principles of QbD Fix It?

While scant data exists to suggest how efficient, or inefficient, technology transfer is within drug manufacturers' development efforts, it's pretty clear that most companies hardly have tech transfer down pat, and still others just don't get it at all. That's a recurring theme in a podcast posted on PharmaManufacturing.com yesterday, in which tech transfer experts Stephen Perry, Russ Somma, Emil Ciurczak, and Paul McKenzie offer harsh criticisms of the tech transfer projects they've witnessed first hand. And thankfully they offer advice as well.

Sometimes the problems are simple--development teams just fail to write critical information down in their notebooks, "something they should have learned in college!" Ciurczak says. But the experts also make clear that practices associated with Quality by Design--namely, proactive risk assessment and data management--can eliminate problems in the early stages of development and facilitate later transfer. Perry notes how developers typically send data on successful process studies to their partners, but not data from failed studies that can be just as enlightening.

Perry is the author of Pharmaceutical Manufacturing's January cover story on doing tech transfer the right way, and he suggests that one thing that often dooms tech transfer projects (internal or external) is the inability of the technology sender to share necessary information with its partner:

There is no such thing as “too much” or “too detailed” information. Such dedicated tools as assay summaries, detailed process descriptions, and bills of materials should be created and used . Other information from the sender, such as regulatory submissions, development reports, raw data, validation reports, etc., can be extremely useful. This work would have to be done anyway as part of the future process validation and to support regulatory submissions.

One of Somma's mantras is simplifying tech transfer, which seems to run counter to the idea of providing as much detailed information as possible. He, as well as Oracle's Arvindh Balakrishnan, explain how this paradoxical challenge can be overcome in a podcast which is now the lead feature on our PharmaQbD.com site.

Finally, Centocor's McKenzie is a proponent of recipe-based development as a means of ensuring consistency throughout scaleup and as handoff occurs between partners. Here is a summary of McKenzie's philosophy from last fall's Bioprocess International conference, as well as a blast from the past: Pharmaceutical Manufacturing's September 2007 cover story featuring McKenzie in his days with BMS.

The success or failure of tech transfer is hard to measure, but that doesn't mean that it shouldn't be a key focus of initiatives to accelerate and lessen the costs of drug development.

QbD for Biotech in Three Parts

Biopharm International has just published the third installment of a three-part series on Quality by Design for biotech products, written by members of PhRMA's Biologics and Biotechnology Leadership Committee. Links are as follows: Part 1, Part 2, and Part 3.

QbD News Delivered to Your Desk

For those unaware, PharmaQbD.com's pharma QbD Enews is a twice-monthly electronic newsletter that features QbD-related news items plus a few feature articles. Here's today's issue, with a special focus on best practices in tech transfer from Stephen Perry of Kymanox and Suraj Mathew of Tefen.

Looking for a Few Good Authors: QbD "From Theory to Praxis"

PAREXEL's Siegfried Schmitt is looking for chapter authors for a book titled, "Quality by Design: From Theory to Praxis," to be published by PDA. You may contact Siegfried via his LinkedIn posting, or directly at siegfried.schmitt@parexel.com.

The following are some parameters that Schmitt has shared with us:
• Authors may write part or a whole chapter (or several)
• Authors should outline either in bullet points or in prose what they want to cover (structure and contents of their contribution) by mid-February 2010
• Schmitt will provide feedback and suggestions
• Drafts should be completed by June 2010
• Revisions are expected by the end of August 2010

Authors may include text from existing publications, Schmitt says, provided they have been adapted for this publication. References should be listed in a separate table.

Tufts Center: Approval Times Have Dropped, But Is It Enough?

For those of us who work in and follow the drug industry, winter is always made a bit brighter and warmer with the coming of the annual Outlook paper by the Tufts Center for the Study of Drug Development. The Tufts report is one of the definitive measures of where we are, where we're heading, and what hoops we have to jump through to get there.

This year's report (here's the Center's summary; the full Outlook 2010 will be made available to non-subscribers this spring) has plenty to chew on, but here are a few of the more relevant points that drug developers and QbD professionals need to consider:

--Few drugs make it to market, but it's important to remember that of those that do, only 3 of 10 generate enough revenue to sustain R&D.
--Drug developers don't just need to improve time to market, they need to dramatically change what they're doing--to "transform the way they conduct research and development over the medium and longer term to be more efficient and productive."
--Collaboration is critical. R&D success will depend upon how developers engage their partners at critical points in the product lifecycle.
--Risk management will continue to balloon in importance. With FDA and global regulators limited in their resources, it will be left up to developers to show expertise via Risk Evaluation and Mitigation Strategies (REMS)
--Biotech products will boom, but take longer to get to market due to increased clincial trial requirements.

Just a few thoughts to warm your winter.

Visualizing the Golden Batch with S88

ISA-S88 is a standard for batch control that many proponents of Quality by Design are adopting. S88 is a design philosophy for processes and recipes (see here for Wikipedia’s pretty good summary) that is becoming more and more relevant in the pharmaceutical industry.

One S88 believer is Centocor’s Paul McKenzie, formerly of Bristol-Myers Squibb. McKenzie, who spoke at the Bioprocess International Conference last fall, explains the value of S88 as follows (as related by Agnes Shanley, who was in attendance):

Each process will have its own raw materials, quantities, process parameters, recipe procedures, and equipment requirements. . . . With a portable recipe, equipment is separated out as its own class, and you assign an equipment class to each area, a good approach for when a process is changing, McKenzie said.

The approach allows users to create a series of recipes. Everyone collects data in the same way, he explained, so that tech transfer becomes ownership of that recipe. As it moves along, you have a master recipe and then a control recipe specific to each actual unit you run. . . .

This in turn facilitates a QbD approach.

“I don’t want people innovating on what they call something in a MS word doc,” McKenzie said, but in terms of parameters, using a common global language to describe process and product.” With this approach, one recipe can be used across the world and global facilities, he said. The method makes it easy to link to regulatory filings and to visualize the “golden batch.”

For the full summary of McKenzie's talk, see "Paul McKenzie's Recipe for Success with QbD".

Quality Risk Management: Looking North

Kevin North is a busy guy. As President and CEO of software and solutions provider Dyadem, he's no doubt got a lot on his plate, and has overseen the growth of a company whose products have been winning awards and winning converts among pharma Quality professionals. North was also a finalist this year for Ernst & Young's Entrepreneur of the Year.

All of which meant that I wasn't surprised when my list of questions to North about Dyadem and its pharma initiatives went unanswered for a few months. He did, however, promise that he would answer them when he could. True to his word, North followed up with me this week. Here is our conversation on Quality Risk Management, and we'll also be following up with Dyadem in the future about another of its core competencies, FMEA.

If there's one thing that strikes me about his replies, it's that the solutions that Dyadem offers are beyond what many manufacturers have even considered as a means of improving QRM and complementing Quality by Design programs. He says:

"Most FDA-regulated companies will tell you that they believe in the FDA’s QbD initiative, but they have a hard time putting it into practice efficiently, especially since many haven’t updated their risk management procedures since the advent of spreadsheet software. Many companies use Excel spreadsheets or customized software for each department and then spend hours trying to cut and paste information together to represent quality for the whole company. Companies that take Quality Risk Management seriously need software that was designed for risk management, not accounting."