Need A Drug Delivery Conversation Starter? Try Target Product Profile
By Tom von Gunden, Chief Editor, Drug Delivery Leader
Several years ago, I refocused my professional lens from a broader look across the life sciences to drug delivery specifically. To launch a deeper dive into that space, I reached out to numerous industry vets to glean their takes on what value an online community and digital publication focused on delivery might usefully provide. Nearly to a person, those thoughtful recommenders encouraged me to do whatever I/we could do to help bridge what they identified as long-standing gaps in cross-functional communication and collaboration during drug product and delivery development.
These communication breakdowns or missed opportunities were described to me as the result of a frequently occurring organizational or structural divide: On one side of the chasm sat the formulation “front end” of drug product development. On the other side was positioned the delivery design and engineering “back end.” All too commonly, it seemed, the lab science folks and the folks concerned with delivery devices, platforms, systems, and dosage forms hadn’t been talking early enough, often enough, or perhaps much at all.
As an “I’ll know it if/when I see it” kind of inquisitor, I made it a mission, of sorts, to position myself for a down-in-the-trenches look-see to confirm these perspectives driving a shared desire for cross-function unification. Short of being able to walk directly into a biopharma organization to gain a vantage point, I set out to do so virtually and vicariously whenever an opportunity arose to validate (or not) with formulation and delivery practitioners the existence of said cross-functional gaps.
What Drives Formulation And Delivery Device Alignment?
As I will illustrate below, my investigations thus far have been somewhat confirming, but only somewhat. I have discovered that lines of demarcation between functional areas, though in some instances usefully blurred, have not been completely obliterated. Nor should they be. After all, in contributing to product development, people have distinct roles to play, specific tasks to perform.
Yet, what I’m seeing and hearing is more reassuring than concerning. Put simply, cross-functional bridging of communication (channels, terminology, participants) is happening apace and for good reason: alignment of drug product formulation and delivery method is becoming increasingly complex, particularly around the delivery of biologics, necessitating at least some foundational degree of familiarity with both components.
As just one example, consider the concept of drug-device combinations referred to as such: as combination products. In developing one of those, the “drug people” and the “device people” are pretty much yoked as partners by definition. (For a related take, see my prognostication about combination.)
Summarizing the most commonly expressed sentiments that I encounter, I would put the current state of collaboration across formulation and delivery as evolving along this trajectory:
- Such collaboration is an increasingly intentional and structured practice that, ideally …
- starts early and happens often …
- is glued conceptually by a central term within a “common language,” if you will …
- and that guiding concept and terminology is the Target Product Profile (TPP).
The Target Product Profile (TPP): The Undisputed King Of Cross-Talk
For one of my deep-dives, I was graciously joined by three folks from GSK for “Developing A Combination Product: Early-Stage Formulation And Device Considerations,” an episode in my In Combination videocast series. Sharing their perspectives on interactions across roles, functions, and responsibilities during product development and delivery selection were functional area leads Kris Angamuthu, Scientific Leader in formulation; Dominick DeGrazio, Associate Director in Early Engagement and Deviceability; and Sindhuja Kuchibhatla, Associate Director in Device Technology and Innovation.
Introducing a thread that would be picked up by the others, DeGrazio immediately pointed to the TPP as the starting point for their interactions within the context of developing a combination product. “Typically, it [development and collaboration] will ultimately be driven by the TPP, the Target Product Profile,” he said. “[The TPP] includes a list of various things, including route of administration, dose frequency, potential dose volumes, number of injections that would potentially be administered, [and] whether this is supposed to be for at-home use or to be administered solely in the clinic.”
Formulators And Delivery Device Assessors Agree: It’s The TPP
From the lab perspective, Angamuthu agreed regarding the TPP’s centrality, even in the earliest formulation considerations. “It would all start with the formulation because, depending upon what the TPP is, if we're saying that this has to be for subcutaneous administration, ideally, they would want this to be in a liquid dosage form,” he explained. “So, formulators have to develop this to be in a stable liquid formulation to begin with, and at the appropriate concentrations. But that's a general starting point. It all starts from that TPP.”
Angamuthu went on, joined by Kuchibhatla, to describe how the TPP feeds decisions around packaging and device design considerations. “From the formulation standpoint, the drug concentrations and the dose volume required for the administration are determined, and the formulation screening and development work begin with an intent to have a stable formulation that's safe and efficacious,” said Angamuthu. “And then as a follow-on for the combination product development, aspects like identifying the suitable primary pack container for device administration while still retaining the quality target profile of the product.”
Echoing Angamuthu as she moved into describing the device assessment and selection process (i.e., the landscaping process), Kuchibhatla offered, “The TPP really allows us to open up a whole new set of criteria that we can start then diving into the primary pack in the device. What that list of requirements from the project team allows us to do is develop a new set of requirements from a technical standpoint for the device and the primary pack and be able to then create a set of criteria that we’re assessing the landscape for.”
How Often Should Cross-Functional Collaboration Occur?
Given that Angamuthu, DeGrazio, and Kuchibhatla had all emerged from their functional roles to join me and, more tellingly, each other for the conversation, it was no surprise, really, that the conversation did not reveal anything like an impassable valley of mis- or non-communications among them.
Nonetheless, to glean more about how the process works when up-on-its-feet, I asked about the frequency of collaborative interactions around common, crossover concerns such as the TPP. “How often are you or your groups in conversation with one another along the way?” I wondered aloud.
Kuchibhatla responded by illustrating the timeframe for delivery device landscaping to assess options. “Our evaluations are happening within days, within weeks. We're not spending months on these evaluations, which I think is very critical because we're just looking for an initial read to help us to not focus on evaluating 20 or 30 technologies at a time,” she described. “So, we are in constant communication.”
Further illustrating how cross-functional communication is key to timely decision-making, Kuchibhatla noted, “When we look at some of these newer devices — we're working with very high springs or motors, sometimes, or things like that — that have physical impact on how the formulation is delivered, we very quickly need Dominick's and Kris's input on those things before we go too far in assessing those devices.”
DeGrazio echoed Kuchibhatla’s description, layering in the additional benefit of frequent touchpoints allowing for (while minimizing any downside from) differences in functional area or departmental processes. “Early on, there's typically a lot of communication and pinging going back and forth, especially between the drug product team and myself and Sindhuja [Kuchibhatla],” he said. “Each program has its own team and each team works differently. It isn't standardized or harmonized, per se.”
The TPP’s Journey Through Development
At a later Drug Delivery Leader Live online event, “Large Molecule Biologics Delivery: Aligning Formulations, Doses, And Devices,” I asked about the frequency and flow of communication across functional areas during product and delivery development. Once again, I confirmed that such communication does happen and, when it does, the TPP provides a shared focal point for establishing and furthering cross-functional collaboration, accountability, and consensus.
For the Live event discussion, a returning participant was GSK’s Dominick DeGrazio, this time joined by two panelists who, coincidentally, have had overlapping career stints at Merck: Rubi Burlage, Merk’s AVP for Sterile Product Development; and John Higgins, who retired in 2025 as Executive Director of Merck Research Labs and now serves as a consultant and adjunct professor at the University of Pennsylvania.
Offering his perspectives on early-stage discovery and formulation in the context of managing a large molecule biologic, Higgins established the now familiar foundation. “It all starts with input to the TPP. What kind of attributes do you need for your biologic to meet the target profile? What sort of attributes can we build into the molecule to move quickly if we're interested in, let's say, sub-Q delivery?” Higgins said.
He then described the utility of having teams — in this case, teams of drug discoverers — in which members exhibit expansive knowledge bases, developed either by training/experience or by interaction with others who bring those perspectives to the function. “And I think we need a group that is versed in both formulation and characterization skills to guide the discovery organization, to build in the right physical and chemistry attributes to a lead,” Higgins suggested. (To hear Higgins’ full response on the topic of early-stage considerations and the role of the TPP, view “Selecting The Molecule For Biologics Product Development,” a video clip from the Live event.)
Drug-Ability And Device-Ability: A Delicate Dance Of Development
Picking up the topic of considering delivery routes even as formulations are in early stages of development, DeGrazio reiterated points he had made in his previous videocast appearance about the role of the TPP in device-ability considerations. “The TPP really is the focal point for the drug development. It will establish the dosing, the frequency, the target population within the therapeutic area, the route of administration,” DeGrazio said. “All of that will define whether or not you can at least leverage a device that you already have that is considered a platform, or whether you need to do landscaping — device landscaping —for new technologies to accommodate the new need that this asset might be looking for.” (For DeGrazio’s full take on device-ability, see the Live event video clip “Determining The Drugability And Deviceability Of A Biologic.”)
Burlage also underscored the role of the TPP as the glue throughout product development and layered in specifics pointing to the broader view of patient needs within particular therapeutic targets. “Hopefully, what the audience is getting is the critical importance of the Target Product Profile and how much of an anchor that is right from discovery all the way through until you commercialize a product. Most decisions, trade-offs, considerations, are really linking back to the Target Product Profile,” Burlage asserted. “It basically is your blueprint of what that disease state that patient population needs in terms of dose, in terms of efficacy, in terms of stability, and then, of course, in terms of the route of administration, convenience, frequency of dosage, et cetera.” (For the full context of Burlage’s comments on the TPP within the entirety of product development, including in later clinical stages, see the video clip “Applying Clinical Data And Process Controls In Biologics Development” from the Live online event.)
How To Know When A TPP Is The TPP
About the TPP, Burlage acknowledged potential fluidity during development. “That can change, by the way. That can change from when you first start your journey in discovery and what you envision that product to be and how it can serve the patients,” she said. Possibly in large part because of that description, I later fielded an audience question about the timetable for finalizing the TPP.
When I directed the question to her, Burlage responded with a reminder about the typical length of a product development cycle and the potential for clinical trial data, especially, to force alterations in the TPP along the way. “It's not as if you decide something in discovery and then you never change it. That's probably not the best for the patients because, once again, the clinical data informs the TPP,” Burlage said. “All of these drugs take at least five years, maybe up to 10 years from discovery to commercialization. A lot can happen in 10 years to those patients and to the available treatment conditions that they have. Hence, the Target Product Profile for your product ought to take into account that evolution.” [Burlage’s complete answer, including her recommendations for TPP finalization, can be seen in the Live event clip “Knowing When To Lock Down A Biologics TPP.”)
The Ideal Cadence For Cross-Functional Interaction
Burlage’s descriptions of the iterative nature of a TPP reinforced the overarching theme of cross-functional communication throughout product development. Pondering both the commonality of the TPP as primary guide for the work of each functional area and the reality of it likely changing over time, I returned to John Higgins, whose perspectives represent those of lab scientists at the earliest stages of the process.
“You mentioned those downstream folks,” I reminded him before asking, “What questions do you hope that they have as they come into your world in the earlier stages that would help you feel like, okay, we're arriving at good understanding here. We're all asking the right questions and we're thinking about this in the right ways together?”
In his response, Higgins unhesitatingly cut to the chase: “Moving quickly, killing bad compounds early so that we have the best success. Moving a compound, progressing it from discovery into development,” he asserted. “And I think we need to know from our downstream partners, what are the ‘must haves’ and what are the ‘nice to haves’?” [For Higgins’ full response, in the context of determining the delivery approach for a biologic product, see “Guiding Biologics Product Development From Delivery Preferences,” a video clip from the Live online event.)
Given his propensity to align molecule selection with delivery preference as early as possible, Higgins was no doubt reassured, as was I, to hear that those responsible for device-ability are similarly eager for early-stage, cross-functional collaboration. Representing the device-ability perspective, DeGrazio put it this way: “We try to get involved early on from candidate selection to enable input from our end so that formulation scientists can consider it as they make a more formal selection for the final lead and/or backup formulations.”
So, with the Target Product Profile clearly front-of-mind for all involved, we have at least one highly effective cross-functional conversation starter readily at hand. And from what I learned from those with experiences inside large biopharma organizations, such TPP-centered conversations seem to be well underway.