At a recent IBC conference on Product and Process Validation, I moderated a panel discussion on this topic with four panelists in addition to myself.  They included two from Pfizer, and one each from Genentech/Roche and Shire Pharmaceuticals.  What were the conclusions:

1. All companies were finding the efforts of QbD painful and laborious and were only just beginning to touch on the new PV guidance.  This was true for the larger companies and especially so for the smaller ones.
2. Some were seeing a back pedalling by the regulators on what benefits the companies might reap for this added work.
3. All recognised that the very small company might find it exceedingly painful if not impossible.

The panel discussion was published in Pharma QbD and I have included a link so you can read more.

Stay tuned, I will be writing more on the topic.

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The second part of the article I wrote on the above topic has been issued in the December issue of BioProcessing International.

Click here for the article.  Good Reading

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If you following the link here, you will see an article I recently wrote on the topic.  Good reading.  If you have any questions email me at peterc@calcott-consulting.com

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At a course I was recently teaching at the University of California, Berkeley on Biotech Pharmaceutical Quality and Compliance, the topic of how to implement the ICH Q9 was brought up.  One attendee indicated that his company had tried to implement it and had run into trouble.  They had set up a Quality Risk Management (QRM) department and it just appeared that all they had done was create another function that had to review all work, SOP’s and reports.  It was like a further level of QA.  Processes were operating even slower than normal and it appeared the amount of work had mushroomed.  He indicated that in the presentation, I made it seem so easy.  he posed the question:

Where had we gone wrong? And was it to late to get back on the right path?

In reality, I find many companies that implement QRM do make it too complicated.  It should not be a separate department but rather the tools should be incorporated into your everyday processes so that simply there is just a further step in your pre-existing processes.  These processes could be change control, investigations, CAPA, complaints, environmental monitoring, testing schedules, raw materials programs, vendor qualification.  You get the picture.  Put it where it adds value.

I am reminded of one of the first times I heard an FDA’er articulate on QRM.  A few years ago (quite a few actually) I was at a conference where an FDA’er was describing Quality Risk Management (QRM) and their expectations.  It was a few months after the ICH Q9 was issued.  the speaker described agency expectations and since I knew him very well (having had lunch and a few beers socially), I approached him and indicated that I thought what he was describing was already in place in most progressive companies.

He replied:

You are right, it is.

I continued:

So what is different now?

He replied:

The agency just wants it to become second nature and get it integrated formally into your processes and, of course, document decisions and assumptions.

That was one of the most valuable set of comments I have received on the topic.

So I recommend that when making QRM mainstream, you need to do the following:

1. Learn the tools and examples of where it can fit in.  There are many webinars out there offering the know how.  Tungsten Shield does offer some good ones on this and other topics.
2. Examine all your business processes and incorporate QRM steps into the process that exists.  Try one first and slowly roll out across the other processes.  Change Control is an excellent one to start on.
3. Examine after a period of time to see what works and what does not.  With QRM you have begun continuous improvement so expect changes over time as your skill increases and you find out how the company likes to operate.
4. Remember to document all your decisions and most importantly assumptions.  Be prepared to go back if your assumptions are found to be wrong or new information  surfaces.
5. Do not fall into the trap of setting up a QRM department or you will be mired in bureaucracy.

And, most importantly, enjoy what you are doing.

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After participating on a panel discussion at an IBC conference on Quality by Design (QbD) and the new Process Validation guidance issued earlier this year by FDA, I was approached by a process development scientist who asked my advise on the value of implementing  QbD in their company.

He explained that his company was extremely small and did not have a a large number of staff in his discipline or even other related ones such as quality and manufacturing.  In fact, he indicated that the clinical manufacture would be 100% outsourced. However, they were entering phase 1 soon and he was afraid to miss the opportunity to incorporate this new approach into their process development activity.

Over the next 20 minutes of discussion, the following points were raised which led to the following conclusions:

1.)  He was using a platform technology for the process to make clinical materials.
This platform would not be the process that they would commercialise by.  Therefore spending a lot of resources homing in on the role of inputs (raw materials), control points and control strategies did not make sense at this stage.  However, developing a set of critical quality attributes for the product did.  This would serve as a spring board
as they begin to develop their phase 3 process which would be the commercial one later in the cycle.  This commercial process may not look at all like the early clinical stage product.

2.)  These critical quality attributes would be important to have as early as possible for the drug product and the active pharmaceutical ingredient at least. This was particularly true for the biological product they were developing and would also be applicable to small molecular weight products as well.

This gave him quite a bit of relief that he had some time to work through the details before rushing headlong into the activity.

There was a question I posed to him that got him thinking and that was. “You are working for small company, highly outsourced.  Is you business model to take this product to market yourself or with a partner?  Or perhaps to get Phase 1/2 data and sell the product to a big Pharma?”

He responded “Why would it matter?”

“Because if you take it to market with or without a partner, you will need to begin the work on QbD as soon as you start the Phase 3 process development.  If you plan to sell it, the buyer will want to develop the process and they will do the QbD.  Any Phase 3 process work you do may not be valued by the buyer as much as the product, so your ROI on this work may not be as much as that for the product.”

So the take home messages are:  know your business model for your company and be sure to consider the ROI on the work you put into your product and processes.

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