Editor’s note: In our recent webcast, “Operational Excellence for Building Better Partnerships”, Russ Somma outlined the application of QbD principles to outsourcing partnerships. The following is a transcription of the main elements of that talk:
We need to be clear about scope. The present climate looks upon Quality by Design as an approach or option for the filing of NDAs. But option is the operative word here. The aspects of QbD can be looked at as a business practices manual, and many fail to leverage the opportunity to use aspects of QbD to focus business and development plans.
Within those plans are contract agreements with various product and service providers. QbD does not become the driving factor of partnerships, but it becomes the philosophy against which one sets up strong partnerships.
Just as Quality by Design is best defined in ICH guidances Q8 through Q10, so, too, can partnerships (Figure 1):
ICH Q8 (Pharmaceutical Development): Collecting the knowledge needed to cast a partnership.
ICH Q9 (Quality Risk Management): Application to our sourcing needs using the knowledge.
Q10 (Quality Systems—i.e. “The Enablers”): The maintenance of our product, process and the partnership through the lifecycle of the product, and the fostering of understanding between the two organizations in an outsourcing situation.
Figure 1. How QbD Supports Partnerships
The Sourcing-QbD Connection
Manufacturers have always questioned whether there is significant payback in Quality by Design. They might say, “I don’t see the flexibility, I see a lot of data being shared, no clear pathway is provided for filing, and it’s expensive.” Those are all true statements, but what we’re talking about here are the precepts of Quality by Design—the way you think about putting things together and how you leverage them when you go to procurement, when you go to setting up partnerships. Let’s not focus on the regulatory aspects, but on what Quality by Design tells us to do.
In establishing and maintaining partnerships, were we working under the delusion of Quality by Accident before? Of course not, but QbD affords us the opportunity to rethink and enable our sourcing initiatives.
We make our own opportunities, and Quality by Design is very clear. The items in Table 1 can be looked at as an inventory of information. If we forget the buzzwords like Quality Analysis and Design Space and look at drug substance aspects or product requirements, we start to see that we have a blueprint to understand better what our product expectations are and how we move forward.
Table 1. Building an Inventory: Define Our Quality Analysis and Design Space
- Drug substance specifications which include physicochemical properties
- Drug product specifications as well as basic knowledge of excipient interactions and process understanding
- Raw material characteristics and variability
- The envisioned sourcing partner and their related facility design, and capacity through the product lifecycle
- Target product profile, “desired state”
- Stability of clinical forms / prototype as well as drug substance
The target product profile should be emphasized—it is absolutely imperative but some companies fail to do it. Yet it provides documented proof of what we expect the product to be, and what we expect the capacity to be. And this is looking forward. It is the lifecycle. This is the flag under which everybody marches, internally and subsequently externally to the outsourcing partner.
Leveraging QbD, Crafting a Strategy
Components which are needed to address a conventional regulatory review are fundamentally those needed to craft a sourcing strategy. We call it Quality by Design, we may just as well call it good development. Whatever it is, these things all have to be leveraged in putting together a sourcing strategy:
- An understanding of the product and process in terms of fundamental, mechanistic properties as opposed to empirical.
- Utilization of prior knowledge in defining product, process and facility—either your own or that of your partner.
- Partnerships to accommodate the product’s lifecycle.
Lifecycle is the key word. That’s the business driver. If we apply this to partnerships we have, we’re going to reduce costs and shorten time to market. We’re not going to have the inevitable accidents. Quality by Design enables the inventory of information and how to think about the data objectively.
Many industries, from biotech to medical devices, have used the precepts of QbD effectively in a range of situations. They all share a similar vision speed to market, cost reduction and flexibility:
- A small biotech firm conducts a knowledge inventory / design space as they approach submission of a novel delivery system for a vaccine.
- A start-up molecular design/discovery firm looking to develop an early stage CMC package with the required “curb appeal” for potential partners.
- A large-scale device manufacturer looking toward seamless process introduction and cost reduction as they enter the combination product market place.
These are examples of companies that have put these ideas into practice. It is not Quality by Design to make a filing. It is Quality by Design to enable a business plan, and from that business plan to foster outsourcing or whatever partnerships are necessary.