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
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.
A few years ago, the FDA issued a guidance to the effect that for Phase 1 clinical manufacturing, GMP’s were not required. However, patient safety had to be assured etc. A while later the guidance was retracted to indicate that GMP would, after all, be required. And that is how it was left. For both clinical and commercial manufacturing, GMP’s would be required. Because manufacturing of clinical and commercial materials does pose different sets of challenges, many people have had problems in interpreting this situation.
During a recent class that I taught on the topic of Investigational Medicinal Products, one of the attendees asked a question. He began: “At my company, we have clinical manufacturing facilities and GMP facilities for commercial products……”. The actual question he was about to pose is not really relevant to the point. In fact, the description of the two facilities is the point in question. He seemed to imply that while the commercial facility was GMP, the clinical one was less so and perhaps not even GMP. The two instructors present (another person and myself), both interceded immediately to question this description.
We asked whether he meant that the clinical manufacturing was not really GMP or perhaps, he meant something else. Clearly understanding the point, he indicated that what he meant to say was that the clinical facility operated at a lower level of GMP. We questioned whether he meant lower or perhaps differently. Quickly to the point he said – differently. And that is the situation for clinical versus commercial operations. The two situations require GMP but execute the GMP’s differently to meet the needs of the two situations. For example:
These are but a few of the differences and they contribute to the way the standard Quality management System is designed to meet the different challenges. This is exemplified by how change control, lot disposition, audits, documentation and other systems are operated: all designed to meet the specific challenges of the GMP’s for that specific operation.
It also illustrates how we need to assure we formulate our thought process and communication. While this slip was made during a “friendly” encounter, this thought if expressed to an EU inspector who was evaluating our clinical manufacturing systems might have dire consequences. We are fortunate that FDA does not inspect our clinical operations.