Advances in Science and Medicine with Combination Products - Gadgets Price
Advances in Science and Medicine with Combination Products

The global combination products market is accelerating rapidly, primarily due to the increasing prevalence of chronic diseases and a steadily increasing number of geriatric populations, plus the infusion of advanced technologies. However, the nature of a “combination product” encompassing a set of drug/device/biological components creates a wide variety of challenges, many of which fall into the regulatory category, as the primary and ancillary functions determine whether the product or device should be regulated as medicinal or medical.

Progress in this area is highly involved and complex. From the various entities and stakeholders involved in the development and distribution of combination products, to the different regulatory pathways required for each component, manufacturers navigate intricacies that become more complex as the current regulatory framework continues to evolve.

Two world-renowned experts in this field are Asmita Khanolker, Senior Director, Cambridge Pharma SMC, and Alie Jahangir, Ph.D., Senior Principal Engineer, Quality Engineering (QE) Combination Products, Product Quality Management (PQM) Jansen, Pharmaceutical Companies of Johnson & Johnson, who will both be keynote speakers at Medical Design & Manufacturing (MD&M) East. The East Coast’s most comprehensive design and fabrication event, taking place Dec. 7-9 at the Jacob Javits Convention Center, is strategically designed to connect the industry and deliver technical and forward-looking insights that impact engineers of medical devices.

As we prepare for the event next week, I spoke with Asmita and Alie about the dynamic world of combination products and what attendees can expect to learn in their December 8 keynote session entitled “Creating a New Mind Set for Combination Product Development”. .”

Combination products open the door to technological progress. Can you tell us something about these possibilities?

Kanolker: It is a very exciting time for combination products with some new therapies in the pipeline; in many cases it is groundbreaking for advancing science and medicine, but these also pose many challenges. Recent trends in long-acting injectable formulations with high viscosities and intravenous to subcutaneous biotherapeutics requiring high doses/large volumes push the limit of traditional drug delivery platforms. There is a need for a new auto-injector technology that can withstand high pressures while providing patient benefits.

The ArQ-Bios technology from Oval Medical Technologies, a company of SMC Ltd., has a modular approach. The power pack, primary drug container and patient interface can be replaced with minimal impact, making it a truly flexible adaptable design for different viscosities and volumes of drug formulations. Patient benefits include silent, gentle activation of the device even when the drug is under pressure of 300 bar and a 360-degree viewing window during administration. The modular approach helps to optimize each of the requirements individually; internally adapted to the challenging technical needs of the application and externally adapted to patient contact points to eliminate user errors and successful self-administration; enabling a subcutaneous delivery technology for challenging formulations and better solutions for patients that did not exist before.

Given the complexity of these systems, there are many challenges during the production process. Can you meet these challenges?

Kanolker: The new complex formulations are not exactly suited to deliver with existing standard device technologies, and the device must be designed to properly deliver the specific formulation. This is challenging as there are iterative cycles in all manufacturing processes during formulation development as drug delivery and dosing are optimized for therapy outcome.

SMC Group Ltd. offers an integrated production path from early research to launch. The integrated approach combines simultaneous involvement in development, production and testing and removes the fragmented approach and can reduce the time to the clinic. Starting with casting and assembly, PDC casting flexibility and design for production (DFM) inputs are important manufacturing considerations. PDC molding allows custom designs to be adapted to the needs of each drug. Tolerance control on the device assembly stack ensures repeatability and improves reliability of device performance. Adaptive manufacturing, including customizable fill-finish processes and flexible lines suitable for GMP manufacturing, provide an integrated approach to successful development through the commercial launch of new therapies.

What tools can designers and manufacturers implement to overcome these challenges?

Kanolker: Modern digital and mathematical transformation techniques such as predictive modeling and simulation offer opportunities to optimize the design. It can predict delivery time of challenging formulations and predict shear dependent behavior of formulations. The simulations can look at probable variations of injection times across millions of simulated devices constructed by random selection of different input variables.

Oval’s methodology includes a thorough understanding of patient population needs and formulation characterization to define device requirements very early in the customization process. We have developed an injection characterization system that can analyze drug formulation, vital for non-Newtonian suspensions and two-phase systems. This system can truly measure viscosity in an auto-injector context, including an indication of the fluid’s homogeneity, revealing the influence of a range of variables on the fluid, and generating a numerical model. The result of this approach is a thorough understanding of the formulation delivered in the context of the drug’s delivery mechanism and susceptibility to environmental influences. Combined with early user research and formative studies, the path to device design is based on a thorough understanding of needs.

What are quality considerations that are crucial for combination products?

jahangir: One of the most important aspects of successful market approval for any combination product is ensuring that the appropriate regulatory requirements and quality system management are followed. Since each component of the combination product retains its legal status (eg drug, biologic or device) even after they have been combined, the key question for many manufacturers is what legal requirements should be applied to the final combination product as a whole?

In accordance with the FDA’s Final Guidance on GMPs (2017), a manufacturer of combination products can meet the requirements of both cGMPs for drugs (21 CFR parts 210 and 211) and the quality system (QS) regulations for devices (21 CFR part 820) by designing and implementing a cGMP operating system that demonstrates the most efficient compliance. However, to reduce the burden on manufacturers of combination products, the FDA proposed a “streamlined” approach under 21 CFR 4.4(b) to demonstrate compliance with specified provisions of cGMP requirements and eliminate cGMP requirements common in the regulations for medicines and devices. Therefore, depending on whether the manufacturer of combination products is a pharmaceutical company or a medical device company, section 4.4. indicates that:

  • A pharmaceutical company with a QMS that complies with 21 CFR 210/211 (drug cGMPs) may only implement certain sections of 21 CFR 820 (device cGMPs).
  • A medical device company with a QMS that complies with 21 CFR 820 may only implement certain sections of 21 CFR 210/211.

In summary, because of the regulatory complexity of combination products, management should be actively involved in overseeing, developing and implementing an effective end product quality system. In particular, this involvement should start from the early stage of product development, when both device and drug teams initiate the process of creating or reviewing policies and procedures to ensure that it operates under an appropriate GMP system and meets each set of regulatory requirements are met or exceeded. with integrity.

You will both deliver the keynote address at MD&M East. What can participants look forward to learning?

jahangir: Our keynote address and related roundtable will address some critical innovation, quality and manufacturing aspects of combination products and provide practical guidance to leverage this unique knowledge and tools to develop safe, effective and functional combination products in a more efficient way at a lower cost. In particular, we will discuss the application of computational modeling and simulation (CM&S) in designing and validating specific drug delivery devices aligned with ASME’s new verification and validation guidelines.

What fascinates you most about personal contact with your community in December?

jahangir: While virtual technologies/tools have enabled people to collaborate and communicate globally during the pandemic, they still struggle to replicate the richness of face-to-face encounters. I am therefore excited to deliver my talk and roundtable discussion on the topic of computational modeling and simulation of drug delivery devices to a live audience at the MD&M East event in NYC. Again, I’m really looking forward to networking personally and building new relationships with colleagues from different industries. I would like to thank the organizers of MD&M for this great opportunity and would like to ask everyone to join me in the above sessions!

To tune in to the keynote session and more forward-looking educational content, register for MD&M East today.

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