When the creation of a combination device is at hand, the Initiation side will be a problem because of the lack of procedures, team members and regulations of a brand new combo device will be an issue when looking to start up. And you must insure that the project is a necessity or maybe a necessity and the complications of the projects that may arise in places like sales representatives and customer service reps. With the planning phase you must have team memebers that are able to work with each other and create a drug that is a combination device. Insure they can create a workable timeline for each other to develop the drug aspect and the biologic aspect to harmonize.  And execute the plans and make sure that you can nimbly manage changes within the project.  

I would assume that with the addition of a drug/biological aspect to a device there would be additional FDA regulations & safety measures that would need to be met. This would increase the risk for those working with the development of the device as well the customer, so the project manager would have to take extra caution during the planning phase to ensure that all regulations/safety measures will be met, and also closely monitor and keep record during the execution phase. 

One thing that comes to mind when discussing combination devices is the regulatory pathway that it will take. The FDA has three seperate departments for reviewing products. Medical devices fall under the Center for Devices and Radiological Health (CDRH), drugs fall under Center for Drug Evaluation and Research (CDER), and biologics fall under the Center for Biologics Evaluation and Research (CBER). Combination devices, which combine two or more of these, are assigned to one of these by the FDA based on the primary mode of action (Is it more of a device or more of a drug?). This will dictate which regulatory path needs to be taken and how long it may take to get a new product to market. A project manager will need good input from the Regulatory Department in order predict how the FDA will designate the device, and how to plan for what needs to be done.

For more on this topic: https://www.meddeviceonline.com/doc/combination-products-a-primer-for-medical-device-makers-0001

In my opinion, it is possible for a medical device to include drug and/or biologic aspects, which makes it a combination device, the most important thing is to abide by the law. These rules will result in some limitations when assembling devices, including device limitations, data usage limitations, biotechnology limitations and so on. Therefore, in the processes of project management, these restrictions will increase the workload of five phases. Project leaders and members need to strictly abide by these rules and pay attention to legal issues during the five phases of project.

Combination devices would need to follow the sum of the rules and regulations required for each separate aspect, in addition to rules and regulations required for combination devices. This makes combination devices more resource heavy as far as time and money go. As a result, these combo devices may be looked at as small programs just as much as a large project, due to the opportunity it presents to use multiple team efforts to satisfy the objectives of the overall device. If the device represents both a drug and a biological aspect, for example, there may be two project leaders from the drug and biological departments collaborating on device development efforts with their respective teams. The challenge, therefore, is to decide the scale of the workload on developing the device that would require the most efficient labor while minimizing resources. Is it a small program or a large project? How many resources will be dedicated to the project in contrast to the rest of the company workload?

I have been involved in several combination products and what I find interesting is that the pharma drug development and the device development seem to be treated as separate projects. An example is the drug product formulation is done first with no considerations to the medical device, then after the formulation is considered "complete" then the device is worked upon such as an autojector or dual chamber syringe. The impact can be very serious not only to the project time line but potentially need to go back to formulation development for changes. 

I believe that combination products need an integrated project approach to not only support device specific activities which are different than the drug side but also provide the project team with collaboration across the project to ensure early activities and decisions are done with both sides. As per the syllabus, we will be reviewing the project phases including design controls which stress important milestones for medical devices but the healthcare industry will be seeing more combination products in the future so this integrated approach will be vital for successful projects.

The most challenging part for combination device is to know to what FDA Department it will be classified under (CBER, CDER and CDRH). As each one of these department has it is own rules for reviewing the product. Depending on the device, several regulatory pathways are available to the applicants including 510(k) premarket notification, reclassification, product development protocol (PDP), and premarket approval (PMA) application.

Combination devices (if not proven to be substantially equivalent to other products on the market) often require multiple levels of testing and validation before they can be approved by the FDA and given to the public. In terms of managing the development of such a device, the initiation phase may prove challenging because it is not always possible to predict if the product concept will pass through the levels of testing and validation quickly and efficiently. Even if the concept is strong, there may always be complications that slow the development and are thus difficult to predict. This can potentially cause increased stress in the company as if a team mis-predicts the timeline of the project and the project becomes delayed by issues in the testing and validation those with a stake in the project may become frustrated.  Since the initiation phase is defined by time, money, and resources, any delay in such can mess with how the project proceeds. Similarly, the strict rules and regulations for the creation of combination products may make it challenging to organize the planning phase of device development.  While it is always possible to plan for and around dealing with potential delays, there may once again be issues in the device that were not predicted at all and that may require further testing, materials, and time.  

A project management challenge for a combination product, as many of previous replies mentioned, are the regulations and requirements to have the product accepted and approved by the regulatory body. An additional aspect not yet touched upon is the verification and validation of the project that involves a clinical study. There are many considerations for the project manager such as the timeline for the clinical study and when is the critical time for the project to be finished, the amount of studies that need to be complete (totally novel product vs a product similar to a competitive product), and the cost associated with the studies that may be an extremely large sum that has to be factored in early in the project. Finally, different levels of verification are needed for different countries and regulatory bodies so the project manager must understand which markets that are trying to enter and what requirements that be different for clinical studies that must be scrutinized.