Combination Product Industry News & Guidance
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How to build a successful combination product program
“I’m in my phase 2 clinical trial…now what?”
One of the common challenges we run into in the combination product industry is clients who don’t understand the impact of developing a combination product. Specifically, for people who are new to drug delivery devices, it’s not always clear what it takes with regard to areas such as development processes, human resources, cross-functional coordination, budgeting, and timelines (to name a few). And, for “startup” Pharma, many of the decisions you make surrounding the creation of your combination product program are driven by your short and long-term corporate goals. Are you currently looking for financing? Are you building your company for acquisition or licensing? Do you plan to develop for multiple therapeutic targets?
This article will answer many of the questions that clients who are new to combination product development tend to ask our team members on a regular basis. We will be building on the topic weekly, adding new answers to the questions commonly posed by new and evolving Pharma companies. Check back for more regularly!
Questions about human resourcing:
What is a combination product device development team?
If you’re developing a combination product, then you’ll need to integrate knowledge and expertise related to each of the constituent parts. If you’re developing a drug/device combination product (e.g. a drug delivery system), then you’ll need the expertise of drug development team members AND device development team members. This is true even if you are not developing a bespoke drug delivery device from scratch! You’re going to need a device development team. If the appropriate quality system requirements are in place, your device development team can be comprised of employees, contractors, or outsourced teams.
Won’t our component vendors do all this for us? Most often, no, and not completely. You may have a great supplier that can provide some development templates. They may even have human factors data a generic implementation. That doesn’t mean the work is “done.” Those are great starts, but a pharmaceutical company developing a combination product still holds management responsibility to complete the quality system requirements, establish a device quality system, develop a combination product design history file, perform post-market surveillance, and many other activities.
You need a combination product device development team to integrate your drug with a device. A combination product device development team plays a critical role in bringing innovative medical treatments to patients. This team requires expertise and practical knowledge that go beyond drug development and even “standalone” device development. The integrated system requires more than just two separate parts. In pharma, device development team is responsible for taking a drug and increasing its value to patients by creating a solution that delivers both the effective, therapeutic benefits of a drug and the safe delivery mechanism of a medical device. This team must know device development from a quality, regulatory, engineering, manufacturing, and commercial perspectives. The team must also recognize how to integrate devices into the drug development process. The team needs to stay apprised of the the ever-changing regulatory requirements that are unique to combination products.
A combination product device development team differs from a pharmaceutical company’s drug development team. The primary focus areas of each team are different, but must be integrated in timelines, execution, and compliance. The drug development team concentrates on researching, formulating, and testing pharmaceutical compounds to ensure they are safe and effective for treating specific medical conditions. On the other hand, the device development team is responsible for designing and manufacturing the delivery systems, such as inhalers, auto-injectors, or implantable devices, that will deliver the drug to the patient’s body.
The collaboration between these teams is essential because the success of a combination product hinges on the seamless integration of the drug and the device. They must work closely together to ensure that the drug remains stable and effective within the device, that the device delivers the correct dosage, and that the combination product “system” meets regulatory requirements for both the drug and the device. This involves coordination to optimize schedules, integrate decisions, and address any potential issues or challenges that may arise during development.
The problems in each domain are different, and device development (even for “off-the-shelf” devices that are already commercialized) requires unique skillsets and knowledge that are not part of the drug development lexicon.
Who do I need to be successful in combination product development? What types of expertise, roles and responsibilities should my combination product team have?
A common problem in pharma is the long development and approval timelines. Regulations and practices change, and having experience on only one or two programs is often not enough to develop a fundamental understanding of product development requirements for programs that “look similar.” This can result in even longer timelines. Smart teams can all eventually figure out what needs to be done, but the full potential of a product (and ROI to a company) is in getting the project done right the first time (without a 3, 6, 12, or 18 month delay in the project schedule and/or regulatory approval cycle).
Below is a list of common roles, responsibilities, and expertise that will be needed for the successful execution of a drug delivery program from the device perspective. Note that you will usually find team members with experience assigned to more than just one drug-device program at a time.
Executive Sponsor
An executive to support the cultural, organizational, and resourcing needs of a combination product program with leadership, knowledge, and alignment. It is critical that the executive team understands the unique needs of developing a drug-device combination. If the executive team does not understand the impacts on the development process, it is often the case that “local optimums” are created within organizational silos and the overall organization suffers unnecessary setbacks or fails. If the executive team is not “device experienced,” this is a major risk to the successful roll out of a product.
Project Manager
We’re all aware of the value of a good project manager. They coordinate key stakeholders, project timelines, and deliverables. It’s critical to bring in program and project management with device expertise, even in a part-time role. Doing so will avoid the pitfalls and mistakes that are avoided by seeing the problems coming before they arrive.
Technical Program Lead
Sometimes referred to as the “Device Lead” or “Device Responsible Person,” this is the primary technical/engineering lead and development point of contact, who is typically an experienced device engineer accustomed to necessary cGMPs like Design Controls. This person is the technical owner of all project deliverables, resources, and desired outcomes. They provide technical oversight and functional execution through individual workstreams in support of the project. This technical expertise is applied to the technical execution of the program, as the project manager is to the project management and coordination or resourcing and timelines. To learn more about one important task that falls on your technical team’s checklist, the Design History File (DHF), click here.
Functional Team Managers
These managers oversee the individual workstream execution in support of the Technical Program Lead. On more complex systems, these may include mechanical, electrical, elecro-mechanical, software, and other functional area experts.
Regulatory Planning & Strategy Expert
Provides regulatory planning & strategy expertise as it pertains to the unique needs of your combination product project. Assists with the strategic planning of how to maneuver through the FDA’s departments and takes lead in FDA communications and meetings to provide optimal and speedy results.
Regulatory CMC Expert
It is the specific role of the Regulatory CMC Expert to ensure a drug/biotech drug delivery system is safe, effective, and consistent in quality. Their focus is chemistry, manufacturing, and controls (CMC) aspects of drug development, throughout the product’s complete lifecycle, including postmarket.
Regulatory Device Expert
While sometimes one in the same with the Regulatory Strategy Expert, you’ll need someone, or someone(s), to execute regulatory activities related to the device portion of regulatory filings and approval of your combination product submission.
Quality Experts (Device Quality)
This is a critical and REQUIRED role which provides quality expertise as it pertains device development. Specifically, the Quality Expert manages and executes the program process to ensure that your processes are in compliance with the regulations applicable to the device constituent part, and that your project is complaint to your processes. To learn about some common misconceptions about implementing a Quality Management System, click here.
Risk Management Experts
Risk management falls within your Quality activities, and specialists are required who understand how to perform accurate risk assessments and how to recommend the appropriate actions for risk reduction to a level that suits both regulatory requirements and your business needs. For more on risk management, read “Risk Management Assessment 101 for Combination Products.”
System Engineering Experts
For larger programs, these are specialists responsible for creating the organizational systems and processes that will merge a successful device development program efficiently into your existing drug development program. They cross-functionally align all involved departments and ensure that your systems support compliance with combination product regulations (which are unique and not the sum of drug and device regulations). For smaller projects, these responsibilities may fall on the Technical Lead.
Human Factors Lead
The Human Factors Lead is the primary manager and point of contact for all study and HF-related work. For more information pertaining to Human Factors oversight, click here for articles.
Human Factors & IFU Experts
These specialists execute the individual workstreams in support of the Human Factors Lead.
Labeling & Packaging Experts
These experts develop labeling and packaging strategy that satisfies drug, device, regulatory, marketing, commercialization, and business inputs. Labeling and Packaging Experts also oversee execution of labeling and packaging design and production.
Manufacturing/CMO/Supply Chain Experts
Responsible for overseeing the scale up and manufacturing of your combination product, Manufacturing, CMO, and Supply Chain Experts work closely with the Drug and Device Development teams as well as the Quality team for the sake of managing vendor relationships and quality systems. For more information on vendor quality management, read “Are You Managing Your Supplier Relationships Well Enough?”
Combination Product Postmarket Activities Expert
The Combination Product Postmarket Activities Expert is a specialist in setting up and overseeing postmarket activities needed for the combination products continued lifecycle post-launch. Responsibilities include activities such as the safety, risk management, customer feedback, training related to patient or caregiver-use of combination products, and change management. The checklist for this team member’s knowledge-base is unique from that of someone who oversees drug-only postmarket activities.
Change Manager
A Change Manager may support the project manager in managing development and sourcing and revisions.
Drug Delivery Device System Commercial/Marketing Expert:
Commercial and marketing activities for a drug delivery device system are not the same as for a drug alone. These departments become involved in device design as the voice of the customer, have a more user-based focus for marketing strategy, and have an expanded role in supporting the customer after launch. For a more in-depth look at Commerical considerations of launching a combination product, click here.
[Updated 4/22/2024]
What combination product experts should I hire in-house vs capabilities that I need to (or should) outsource?
Strategic decisions around resourcing your new combination product development team can have a large impact on budgets, timelines, scalability, level of expertise, and your organizational maturity curve. Your short and long-term business goals should be taken into account, but we can go over some considerations, pros/cons, and common practices.
It is common practice for pharmaceutical companies, big and small, to outsource the following functions:
- Device creation/supply (OEM) – Most pharmaceutical companies will buy their device, custom-made or off-the-shelf, from a trusted third party. Here’s a checklist for ensuring you are selecting the right device-constituent suppliers.
- Testing – Tests such as CQA and EPR performance testing, biocompatibility testing, and extractable and leachables testing are not something that Pharma usually handles in-house. There may be some testing that can be done by your OEM, but most likely you will engage additional external vendors for these functions.
- Manufacturing – It is not common practice for Pharma to set up internal manufacturing operations for drug delivery devices. This is another area that requires an outsourced partner.
- Contract Research Organizations (CRO) – It is common for Pharmaceutical companies to outsource clinical trial-related duties to a CRO to create efficiencies and ensure better regulatory results through expert execution.
- Other Services – Additional services that are generally outsourced to experts / not invested in as a function of Pharma companies are: sterilization, packaging and information for use (IFU) design, human factors / usability, and design verification / stability.
The scope of the team required to develop a drug delivery system is much larger than the list above, and as a startup, you have a big decision to make with regard to building a team vs. buying expertise; in other words, to hire and execute in-house vs outsourcing for each team function. Let’s start with the general positives for each option:
In-house Pros
- Dedicated employees whose time can be allocated as your priorities require.
- Long-term investment in people that will grow with your company and become familiar with your company culture.
- More direct control and oversight into work, priorities, and timelines.
Outsourced Pros
- Faster scale up without the need for recruiting, interviewing, and the potential for needing to fire and rehire when employees do not work out.
- Easy scale down when workload reduces between projects to optimize resource allocation.
- Practical, hands-on experience is not limited to only your company’s projects.
- Flexibility to bring in a variety of specialists to fill a particular role vs. being limited to the expertise of one direct hire.
- Cost efficiency of paying for services rendered and avoiding overhead costs associated with in-house staff.
- Expertise and best-practices that can be transferred to in-house staff and implemented on future projects.
Many businesses opt for a hybrid approach, combining in-house expertise with outsourced specialists to strike a balance between control, infrastructure, cost-efficiency, and specialized skills. With that in mind, let’s take our list from above of combination product device development team roles one by one to discuss common practice and recommendations for hiring vs. outsourcing.
Executive Sponsor
This role clearly needs to be in-house, taken on by an internal executive who understands, or is trained to understand, combination product development. The Executive Sponsor is an in-house advocate for ensuring CP projects and overall program structure has the resources and corporate buy-in it needs to be successful.
Project Manager
The Project Manager for a given combination product or combination product platform program can begin as an outsourced expert to provide combination product management structure and execution knowledge to a startup. As your company grows, this position is generally transitioned into an in-house hire. They should intimately understand corporate goals and be aligned with the executive team and other in-house stakeholders and departments that will give input or provide support for their project/program.
Technical Program Lead
This role can be managed by either an in-house hire or an outsourced expert, reporting to a Project Manager who, as discussed, is generally/eventually an in-house employee. Hiring an internal lead can give you more hands-on control of the project, while outsourcing experts can result in faster start up, wider knowledge base of best practices, a more targeted specialist for the needs of that project, and an option to scale down post-project.
Functional Team Managers
More so than even the Technical Program Lead, it makes good sense to outsource functional team managers and members for the sake of targeting needed specialties, flexibility, and budgeting purposes. They are focused in on project goals and can be managed by higher-ups that connect their work to corporate goals.
Regulatory Planning & Strategy Expert
Given the often-changing regulatory landscape in the United States and globally for combination products, it is recommended that regulatory planning and strategy experts be outsourced to ensure your regulatory pathway is being directed by someone who has current experience across multiple device types and global territories. The longer a regulatory strategist is with one company, the more limited their pool of knowledge becomes.
Regulatory CMC Expert
While a startup may want to consider outsourcing a CMC Expert in order to scale up quickly and tap into a highly experienced resource immediately, this is a role that, generally, is filled in-house as a company grows.
Regulatory Device Expert
As with Functional Team Members, your Regulatory Technical Experts can be hired in-house or outsourced. In-house employees will offer a cultural continuity over time, but your pool of experts will be more limited in variety of practical experience than if you were to outsource to technical experts based on each project’s needs. As a drug company just getting into combination products, this is a good role with which to take on a less costly, non-permanent consultant vs. hiring within right away. This is particularly true when you want an FDA expert on your team…there are only so many FDA experts to go around! The best ones have insider knowledge and relationships that come from working directly for the regulatory body and have had leadership positions within the FDA and involvement in crafting the standards you now follow. If you are lucky enough to find one of these unicorns and have the ongoing work to keep them busy, do it! If not, hire one to consult as needed.
Quality Experts (Device Quality)
Our recommendation would be to outsource the strategic planning and “set up” of Quality Systems, allowing for specialists who have seen Quality Systems, good and bad, across the industry to assess current systems and upgrade or customize them as needed. Quality experts whose role it is to provide oversight of quality systems during device development, both internal and for external vendors and suppliers, can be outsourced or hired within, dependent on budgets and workload.
Risk Management Experts
Risk management is another area for which, depending on budgets, workload, and availability of qualified experts, it can make sense to either hire employees or outsource experts. Industry-wide best practices will come along with consultants, unless you invest not just in your employee but also in their continued education.
System Engineering Experts
Similar to Quality Experts, we would recommend outsourcing the function of strategic planning and set up of system engineering to an expert with current hands-on experience across many companies…then you could either extend their role to oversight or, with enough of a resource need, hire someone internally to mind the shop. If you choose the latter, it’s always smart to tap back into external expertise for periodic system reviews to allow for continuous improvement.
Human Factors Lead
HF is an area experiencing big innovation as corporations begin to acknowledge its benefits and necessity in the improvement of efficacy, safety, and user experience. Areas of innovation are generally best lead by experts who have wide-reaching hands-on experience, and we would recommend you start your combination product development team with an outsourced Human Factors expert as your lead.
Human Factors & IFU Experts
Human Factors and Instructions For Use (IFU) experts are called in for targeted tasks within the larger CP development timeline. Until a pharma company gets “big,” it is cost-effective to delegate those tasks to external resources and consider the ROI of scaling up to full-time employees when workload makes it a more reasonable option.
Labeling & Packaging Experts
Larger Pharma companies tend to have in-house departments dedicated to labeling and packaging. However, until a full department is needed to churn out this kind of work year-round, it is cost-effective for most other Pharma companies to hire outside experts that can apply your brand standards and marketing directives toward compliant, compelling, and user-friendly labeling and packaging.
Clinical Development Device Experts
While you could invest in a clinical device expert in-house down the road, hiring an experienced consultant to create your strategy for device integration into clinical development is a smart, cost-effective move during scale up. From there, you can continue with their outside expertise for execution and future project, or take the systems they put in place and move forward with a more permanent hire running things.
Manufacturing/CMO/Supply Chain Experts
Although you will outsource the manufacturing of your combination product, you will still need an expert on your side of the partnership to make sure manufacturing is running smoothly with your own best interest in mind. This can be an outsourced expert keeping a watchful eye and managing vendor relationships for one or more projects, or it can be an in-house hire with manufacturing and vendor management experience taking on broad oversight responsibilities.
Combination Product Postmarket Activities Expert
This role can be cost-effectively assigned to an outside consultant who works with, or helps build up, your internal post-market team to ensure that combination product systems are put in place and executed effectively after your combination product hits the market.
Change Manager
Depending on skill sets and availability/priorities, this role can be taken on by the Executive Sponsor, Project Manager, or Technical Program Lead. If you have chosen to hire those roles in-house, you may want to look into either education/training for these employees or hiring a specialist with practical experience in change management at technical/systems and cultural/organizational levels to set an appropriate strategy.
Drug Delivery Device System Commercial/Marketing Expert
If your in-house Commercial and Marketing teams have limited experience launching drug delivery devices, and especially if it is their first time to this particular rodeo, it is a wise choice to outsource strategic planning and execution oversight to an expert. These experts can also be brought in to do the necessary trainings to get your in-house team knowledgeable on their new, expanded roles and responsibilities as well as on the activities of other functional drug delivery device development teams with which they will need to provide inputs and collaborate.
This article will be added upon over the course of the next few months, as we continue to field client questions and compile worthwhile answers that can help our readers. Please keep an eye out for updates by subscribing to our email list and following our LinkedIn page.
Coming soon…
Questions about Combination Product Development Timelines
First question:
What are the key steps in the process of developing a Combination Product?
Coauthored by:
Steven Badelt, Phd, Founder & CEO – Steve is a seasoned expert in combination products, engineering management, systems engineering, and business development. He has over 20 years of experience in the design and launch of combination products and medical devices, including auto injectors, insulin-pumps, implantable defibrillators, connectivity, and patient management software. In 2012, Steve founded consulting firm Suttons Creek, which serves as the device team for Pharma on over 120 programs.
Courtney Evans, Principal Consultant – Courtney has over 8 years of experience in medical device and drug delivery development and regulation, including over 4 years at the FDA as a Reviewer and Team Leader of injection device combination products. They bring a passion and natural proclivity for complex combination product regulatory strategy, as evidenced by their contributions to policy development of connected “smart” drug delivery devices, on-body delivery systems, emergency-use injectors, and implantable infusion pumps.