Combination Products

Enabling localised care

1. What are the forces driving this convergence?

Healthcare in general is moving away from "one size fits all" / systemic approaches to more targeted treatments. Patients are demanding better therapies with fewer side effects, and combination products offer a safe and effective solution.

Increasing competitive pressures are playing a role in driving convergence too. Until recently, the rate of innovation appeared to be slowing in the medical device and pharmaceutical industries. There were a lot of incremental improvements, line extensions, and "me-too" offerings, but very few breakthroughs. Today, you see more companies adopting an open innovation model for developing products. They are looking outside their organisation for new ideas and partnership opportunities. Combining drugs, devices, and biologics appears to be the logical next step.

Finally, technology improvements have fundamentally enabled this convergence. Recently, drug-eluting coatings have played a big role in cardiovascular stenting and implantable orthopaedics. In the future, we'll see more use of gene therapies, human growth factors, and pharmaceuticals where devices will serve as a vehicle to deliver the therapeutic agent or as a scaffold to encourage the body to actually heal itself. Miniaturisation will also change the way we use medical devices as manufacturers will be able to create implantable devices for diagnostic and therapeutic delivery at the micro to nano level.

2. How is this convergence changing patient care?

Simply put, the convergence is leading to better products and better outcomes for patients. To give you a few examples, coronary stents and orthopaedic implants have benefited from improved efficacy; the former for the treatment of cardiovascular artery disease and the latter for improved acceptance of things like joint replacements. Pacing leads and glucose sensors could benefit from better biocompatibility and a lower risk of inflammation and rejection. In cases such as cancer and diseases of the retina, systemic treatments may be ineffective or potentially harmful. Combination products will enable healthcare providers to treat diseases with localised drug delivery and fewer/less severe side effects.

3. These are two very different industries which have evolved in their own way; how easy or difficult would it be for them to work together?

Working together can be very challenging and it requires a robust approach. Products and technologies have gotten more complex and the lines between them are becoming blurred. It will require a more integrated approach to development. For example, most device manufacturers have little or no experience working with the drug that will be included in the device or its coating. They not only have to decide how to select, modify, and incorporate the drug into the product. They must also demonstrate its acceptable toxicity and shelf life and characterise its release into the body.

As the products and technologies have gotten more complex, so has the proper application of quality system and regulatory requirements. For example, device manufacturers are collecting requirements and developing specifications for components that may include engineered devices, drugs, or biologics with pharmacological, immunological, or metabolic mechanisms of action. In addition to designing better products, they must perform robust and thorough testing.

They must also define the types of changes that can be made to the commercial manufacturing process with an understanding of the effect on the product, its sterility, and its stability. The people aspect should not be overlooked; that is, the difficulty in bringing together the various viewpoints, practices, and experiences from the different worlds of drug, biologic, and device development. Companies must address the change management issues that are inherently associated with combination product development.

We advise all our clients to define their approach to commercialising combination products. The four areas that need to be considered are 1) formulating a development strategy to address the unique challenges of combination products, 2) building the right skill sets and capabilities, 3) creating an integrated drug-device development process and quality system, and 4) driving organisational changes for implementation.

4. What are the legal, ethical issues involved in the convergence?

As more combination products reach the market, the difference between products may come down to the drug/biologic component. As a result, I think, you will begin to see new ways of marketing combination products. In the past, devices were marketed exclusively to physician, surgeons and hospitals as surgical tools. In the future, companies will look to create consumer demand for their products. This will be especially true with drug-delivery systems. Combination product manufacturers will need to deal with the direct to consumer marketing and patient education issues that the pharma industry faced.

5. Apart from the huge success of Drug Eluting Stents, has the response to other combination products been good / satisfactory?

Depending on whom you talk to, the exact numbers may vary. But the overall market for combination products is large and growing. Initial estimates put the total value in the range of US$ 40-50 billion and it’s growing at a rate of about 14% annually. This growth is being led primarily by inhalation devices, including intranasal and pulmonary systemic therapies. Transdermal delivery will also contribute significantly. Drug-enhanced technologies—like stents, orthopedics, and electrodes—are also expected to contribute as well. It’s important to point out that these numbers do not include regenerative medicine products (wound management, dermal substitutes, artificial organs, etc.) that hold tremendous potential.

6. With reference to the success of the Drug Eluting Stents, the stent manufacturers have built more brand value than the drug manufacturers. Is there enough incentive for pharma companies in the convergence?

Returns for traditional prescription products are typically higher than devices. But if there is the potential to increase the market for an existing drug by partnering with a device company, then why not pursue the opportunity?

7. How do you assess the initial response from the pharma companies?

Drug companies see this as a way to get more out of their existing products by enabling new indications and uses and extending patent protection and intellectual property rights. For example, compounds like Sirolimus and Pacitaxel, which were originally indicated for the prevention of organ rejection and as an anti-tumour agent for the treatment of cancer, have found new life for the treatment of restinosis for patients that have received stents.

8. Are the two sectors doing enough to create a platform for knowledge sharing that would drive the innovations in the future?

A tremendous amount of learning has taken place and the industry is starting to pay attention to combination products. For example, there are now conferences focused exclusively on combination products. Several large companies have even created combination product 'centers of excellence' to consolidate lessons-learned and to help match the needs of combination product development programs with the right resources and expertise.

However, one of the biggest challenges—and opportunities for knowledge sharing—is in the regulatory environment. There are still no specific regulations or regulatory submissions that are unique to combination products. It would be great to see the leading industry players and regulatory bodies work together to develop a consolidated set of requirements and guidelines for combination products.

9. What can be learned from the convergence that has happened in other industries like the Telecom and the IT industry?

The concept of ‘total solutions’ or bundling products, services, and business model changes to create a better customer offering has driven value in the telecom and IT industries. In life sciences, knowing how and when to partner will be important for success. For example, device companies have typically focussed on internal development pathways, whereas development partnerships and collaboration are more the norm in the pharmaceutical industry. Strong partnering and co-development capabilities will be required to successfully develop and commercialise new combination products.

10. Any other comments you would like to make?

It’s good to see that the FDA is putting more focus on combination products by establishing the Office of Combination Products (OCP). It is responsible for the prompt assignment of a new combination product to the lead FDA agency (i.e. - CDRH, CDER, or CBER) and coordinating the cross-agency review process. However, the regulatory oversight model and requirements for combination products are still evolving. This trend is likely to continue for the next few years. As a result, companies looking to bring new products to market should take a proactive approach to working with the FDA on pre-market review/approvals.