The role of clinical manufacturing has grown ever more important in recent times. As supply chain processes become more intricate, having the right people in place throughout the product cycle is integral to a trial’s ultimate success.
In this Industry Viewpoint, CTA Editor Henry Kerali sits down with Gowri Sukumar, the Associate Director of CMC and Regulatory Affairs at ESSA Pharmaceuticals. Overseeing both the drug substance and drug product, Sukumar’s role is wide-ranging as she controls all matters from process development and drug manufacturing, all the way to when it’s packaged and sent to the clinic.
What’s more, she liaises with multiple contract manufacturing organizations (CMOs), and is involved in the decision making of all manufacturing issues. In this compelling interview, Sukumar offers insight on handling IMPs, from a small company perspective.
Henry Kerali: From a small company perspective, what are some of the unique challenges you face when manufacturing IMPs for clinical trials (e.g. financing, regulatory approval, etc.)?
Gowri Sukumar: Typically, I feel small pharma faces three unique challenges. The first being funding from venture capitals. The major drug manufacturers, with profitable products already in the market, don’t usually require ongoing fundraising that start-ups usually do. For start-ups, obtaining funding is a significant barrier because they don’t have any commercial products or revenue to point investors towards. What’s more, funding is slowly drying up, especially for early phase development. This is largely because venture capitalists typically evade risk and try to invest in later-stage trials (phase II and beyond) as they’re confident the drug is most likely going to make it.
The second major barrier small companies face is the challenge to build sufficient infrastructure, which may affect manufacturing and clinical supply timelines. Therefore, these challenges are largely overshadowed by limited resources and funding, which in turn fuel demand for short timelines to appease investors. The third challenge is small pharma’s reliance on CMOs for drug substance, drug product manufacturing and packaging activities. Although these have a numerous benefits, there are always risks. Sponsors have to ensure the CMOs are reliable and consistent in terms of successful technology transfer, product delivery, and ensuring the intellectual property possession is intact.
HK: Are these issues commonplace for similarly small-sized companies?
GS: Yes, absolutely. Because there is limited funding, there are restrictions in terms of resource utilization. From a small company perspective, this means working with minimal capital and aggressive timelines, so it’s important to minimize costs towards development and manufacturing. Additionally, working with CMOs can be tough. At ESSA, we do virtual manufacturing, so the sponsor has to ensure the processes that are carried out are compliant, the product is delivered on time, and the quality and regulatory aspects are met.
HK: Could you provide a real-life example of a trial that didn’t go according to plan, and how that had a knock-on effect on handling CMOs?
GS: I can describe the scenario I had encountered, where a temperature excursion occurred during a cold chain shipment to the packaging and labelling site. Temperature excursions can mean a lot since the quality and stability of the medicinal product can become questionable and often raises a red flag. Likewise, this excursion triggered a deviation at the packing and labelling site upon receipt and thus was not staged for packaging activity until the deviation was successfully closed. This delayed the timeline for getting the packaged drug product to the site(s).
To prevent a patient from being turned away at the clinic, it was crucial to take the right next steps to remedy the situation. As a result, paperwork was provided in support of the stability of the drug product at the given temperature range at which the excursion occurred. Additionally, efforts were taken to accelerate the paperwork approval process by the quality team to minimize the delay as much as possible.
HK: What are keys to developing a successful supply chain strategy?
GS: In my experience, it’s important to develop a holistic strategy that combines people, processes and technology, so there’s minimal impact or delay. Early in the process, involve the logistics experts in the planning stage. Factor in the risks one might encounter, as well as forecasting (in terms of scaling up and patient recruitment), as these are important aspects that should be integrated into the strategy. It is equally important to consider simulation of the clinical supply chain.
Nevertheless, it’s not all about the logistics – it’s very important the sponsor has a thorough understanding of the local regulations, as well the distribution issues that can occur in every country. For certain countries, especially in emerging markets, regulations can change rapidly. Sponsors must, therefore, engage local consultants to provide regulatory input specific to the country in which it is dealing.
Lastly, automation is another consideration. It’s key to integrate support systems across all active sites as it provides full visibility to sponsors in terms of the supply chain and quality control.
By connecting these services, guided by holistic project management, sponsors can reduce risks while enabling responsiveness to real- time events.
HK: What advice would you give to industry professionals, especially smaller-sized sponsors?
GS: For small pharma, communication is paramount. In a small company, especially, it’s essential each team member interacts well within the cross-functional teams. This will enable a more robust strategy that involves a better-informed decision-making process. Additionally, it’s equally important to re-evaluate study objectives from time to time, as to where the core operational skills should lie and ensure processes are in line, matches the budget, and yet meets the quality standards within the given timeline.
Associate Director, CMC and Regulatory Affairs