Quality And Regulatory Professionals Joined At The Hip
By Louis Garguilo, Chief Editor, Outsourced Pharma
In preparation for our recent Outsourced Pharma Live – Strategies For Today's Top Quality & Regulatory Outsourcing Challenges, Bikash Chatterjee, Chief Science Officer, Pharmatech Associates (a USP company), sent me “notes” worthy of extrapolating and relating to readers.
I’ve also edited and included some key comments Chatterjee made during the event. These specifically pertain to the idea that today more than ever, when it comes to development and manufacturing outsourcing, quality and regulatory teams need be “joined at the hip.” We’ll start there.
Paradigm Shift
New modalities, therapies, vaccines, and delivery formats, and accelerated approvals, have presented us with novel frameworks for process and product design that have pushed the envelope in terms of classical regulatory expectations to where there's a convergence between technical, quality and regulatory folks.
You have to understand each other's worlds first to make a coherent argument that will then be compelling to a health authority. It’s a different paradigm today. And when you add a CDMO to the mix, it becomes a very interesting conversation.
That conversation starts at contract service provider selection. Often, this partner will be with you through the entire journey, and subsequently they will be representing you in the pre-approval inspection.
Questions to ask:
What are the characteristics you need to consider as you move your program from early-stage development to mid- and late-stage development?
What are the core elements, characteristics, and capabilities you need at our CDMO partners?
For all CMC professionals, it's an enriched and interesting conversation today.
Speed It Up
Our digital event later moved to a discussion of the volume of development programs that today enter accelerated regulatory pathways.
Particularly in cell-and-gene therapy, there are so many accelerated designations because the focus has been on orphan drugs, ultra-rare diseases and breakthrough drug therapies.
As positive as this might be, it creates a conundrum for both the drug sponsor and the CDMO’s quality and regulatory organizations when you are thrust from Phase 1 into Phase 2, and now Phase 2 or 2B is going to be your pivotal points ideally moving your program forward.
You have to lay out the groundwork to set a regulatory strategy at the IND stage. That includes fully contemplating your outsourcing strategy right away. Nowadays, this means you've already started to think about what your quality argument's going to be around your product control strategy.
This quickening may sound great for investors and shareholders, but not so great for drug sponsors and CDMOs that suddenly need a mature set of processes around their QMS, operational infrastructure, and full supply chain in order to effectively and consistently manufacture product.
For certain, an intensified focus needs to be on your demonstration of manufacturing controls.
Are We In Control?
How do you begin to define quality attributes? For example, you may have viral vectors involved. How are you defining those viral vectors as part of the drug substance? Answering these questions takes inter-discipline conversations.
For many novel drug therapies the mechanism of action is not clear. It's not a one-for-one like you might have in a classical small-molecule disease-treatment therapy. So you end up with a matrix approach. You may have biomarkers, or a suite of different elements which are part of your overall argument for demonstrating control.
This is a complicated context for both the process and product development teams, and of course the quality and regulatory professionals. Everyone has to ensure you’re not missing something.
All this increases the challenge for your outsourcing partner if they're participating in that design, which is increasingly the case.
This intensifies that pressure to select the right CDMO – one with experienced quality and regulatory professionals who can get on the same page with you.
Take Note
Now to Chatterjee’s pre-event notes. They provide a simple blueprint to think through this new paradigm for quality, regulatory, and technical professionals (at both sponsors and CDMOs).
They are reproduced with some editing, and start off with our digital event’s summary.
Accelerated development schedules; quicker pathways to approvals; emerging technologies and therapies; more outsourcing than ever – often at locations across the globe. All this presents opportunity, and also steepening challenges for your quality and regulatory teams. For one thing, quality and regulatory need to be joined at the hip.
- Every drug sponsor faces the same question when selecting a CDMO partner. Should I choose an organization excellent at development to support the design and advancement of my manufacturing process and control strategy, or a CDMO proven at the commercial scale? This decision is more problematic with accelerated regulatory frameworks which could bring forward pivotal studies from Phase 3 to Phase 2B.
What are some strategies for ensuring you select the correct partner, and your CDMO is ready for this level of responsibility?
- Start direct and detailed conversations during due diligence
- Ensure contractual agreements allow for items such as mock inspections
- Put in place and then update quality agreements as needed
- Plan for data exchange – how, when, what format, etc., especially as it relates to data for regulatory submissions
- Remember, it is your CDMO who will be in front of the FDA during the PAI (pre-approval inspection), defending the work done in support of your filing, and being measured in terms of their quality maturity, decision-making processes, and governance framework.
What are some effective strategies to ensure your CDMO is up to the challenge?
- Set roles and responsibilities for handling questions between CDMO and drug sponsor
- Understand/negotiate inspection-presence support
- Mock inspections by an independent party can reduce biases
- Taking advantage of accelerated regulatory frameworks requires being able to capture and utilize quality data without compromising data integrity or data quality.
What are some strategies for engaging with your CDMO around data?
- Discuss data systems and approaches starting at due diligence for CDMO selection
- Plan carefully for data exchange at the beginning of the relationship – items such as format, platform(s), frequency
- Conduct periodic audits with data quality as the focus
Denouement
It is suggested the idiom “joined at the hip” originated in the U.S. in the 1960s. We’ll leave that etymology alone. Today in our industry, the phrase is articulated for the reinforced connection among quality, regulatory, and technical professionals at both sponsors and service providers. It's an old saying for our advancing context.