What Is There to Learn from a Combination Products Handbook? Plenty!
Overview: Why This Book? Why Now?
In this initial episode of The Combination Products Handbook: The Series, a chapter-by chapter videocast series introducing topics from The Combination Products Handbook: A Practical Guide for Combination Products and Other Combined Use Systems (CRC Press, 2023), host Tom von Gunden discusses the book’s intent with its editor, Susan Neadle. The discussion focuses on the rationale for each chapter and the expert contributions of various chapter authors and co-authors.
Purchase your copy today!
The Combination Products Handbook: A Practical Guide for Combination Products and Other Combined Use Systems Edited by Susan W.B. Neadle, CRC Press, 2023
Episode Transcript
Tom von Gunden, Chief Editor, Drug Delivery Leader:
Welcome to the Combination Products Handbook: The Series, an episode-by-episode, chapter-by-chapter look at The Combination Products Handbook: A Practical Guide, published by CRC Press in 2023. My name is Tom von Gunden, Chief Editor and Community Director at Drug Delivery Leader, and I will be your host for this series. I am joined today, as I will be for most of the episodes, by the book’s editor and coauthor for many of the chapters, Susan Neadle.
Welcome, Susan.
Susan Neadle:
Thanks for having me, Tom.
Susan, I think it would be helpful for the audience if we got an overview and general take on why this book? Why now? Why the focus on combination products and the impetus for its existence?
There are a few things behind it. Towards the latter part of my career at Johnson & Johnson prior to retirement, I worked heavily in the combination products field, probably for the last ten years of my career there. Towards that latter part of my career, I started teaching and became very involved with the Xavier Combination Products Summit. I was also involved at the University of Maryland’s Baltimore Campus, where we created a combination products graduate school curriculum.
As I was teaching these different courses, I started to realize that there was no book that we could reference for the students in these classes, which seemed a shame. To further that, when I retired, I decided to start consulting. As I started consulting for different companies across the industry, I started to realize that those problems or challenges that I dealt with are really common across businesses and across the entire industry globally. I recognized that the challenges aren't unique, and the solutions are also not unique. Even though the products may vary, the basic foundation of what needs to happen is pretty consistent.
I realized that there was an opportunity to create a book. I had a lot of contacts who were people I worked with in the industry, taught courses with, or were in my network. I was chair of the International Society of Pharmaceutical Engineering (ISPE) Combination Products Community of Practice (COE). I reached across my network to find people that could help tell the story of the best practices, end-to-end, across the entire combination product lifecycle, pre-market to post-market. That became the foundation of the book.
At that time, Antonio Marrero, who recently passed away, was the dean for the School of Natural Sciences and Mathematics at the University of Maryland, under which our course was taught. He encouraged me to write the book for the class. I mentioned in the acknowledgments that he helped spur me to write this and make it something that could help the industry globally.
I appreciate the acknowledgment of your inspiration and all the reasons why you put it together. Thinking about a book called The Combination Products Handbook and referring to it as a “practical guide,” who does it target as a practical guide? What sorts of roles and organizations would benefit from the practical advice provided in the book?
If you walk through the book, from the introduction through all the different chapters, it literally covers the lifecycle of a combination product. The intent is to help people who are stakeholders throughout that process: pre-market, clinical, regulatory, quality, R&D, procurement, tech services, design transfer activities, process validation, post-market safety reporting, and medical affairs. It's end-to-end across the lifecycle. Who are all the stakeholders that are going to be involved?
It's also something that can be helpful as a reference for regulators around the world. There is an appendix that was developed to touch on all the global regulations that are still evolving for combination products. They are able to look at this reference and determine how one country has successfully managed [combination products] and differences in other countries. You can start to compare and contrast and see the things that are working well versus the things that are still giving people challenges. As this space keeps evolving globally across different regulatory jurisdictions, people have an opportunity to refine their own regulatory constructs to accommodate the challenges that combination products present.
It's intended for the entire industry, from basic to expert. There are also templates built into the book for people who are trying to do design controls and may not understand what that means. There are also examples in risk management. For people who are struggling with how to practice what these regulations are telling [them] to do, the book doesn't just explain what they are, it also helps you execute them.
When you were recruiting experts in the field to join you to coauthor chapters in this book, what range of perspectives were you looking for?
The way I thought about the people that I wanted to bring in to help coauthor this book was based on the skill sets that I knew. I wanted the book to reflect the scope of the entire combination products lifecycle. I started focusing on my contacts across different working groups, industry forums, presentation venues, and teaching, looking for people who were considered key opinion leaders across the field. That's what drove who I included in the book.
The book is broken into two parts. The first part is foundational, and the second part is special topics. Beyond how I thought about the people that I would recruit based on their skillsets, let me take you through the people who did participate. One, because I'm grateful for their participation and want to recognize them, and two, it helps you understand the depth and breadth of the people that participated.
The very beginning of the book, the introduction, which is on key considerations that are advanced throughout the book, was authored by John Barlow Weiner, who at the time was the Associate Director for the Office of Combination Products at the FDA. I'll go into more detail about that when we get into a discussion of that chapter of the book, but he provided very valuable feedback. He also helped personally to reach within the FDA and get peer review of all the chapters of the book, which I think was invaluable.
I then wrote a chapter about what a combination product is, which, I'm sure as we go through the different discussions on the chapters, we'll get into in more detail. For my background, I was heading up combination products at Johnson & Johnson for several years, where I had a range of positions. I was also the Executive Director for Regulatory, Combination Products and Devices at Amgen. I teach at the University of Maryland, I do consulting, and I’m very active in a number of industry working groups.
Chapter 3 is about the combination product regulatory landscape. I have presented a number of times at the PDA [Parenteral Drug Association] and through the Xavier Conference on Combination Products and Combination Products Coalition. Suzette Roan, who works at Sanofi, is very active and well respected. I asked her if she'd be willing to participate, and she, thankfully, jumped in and wrote that chapter and did a wonderful job.
The following chapter is about cGMPs for combination products, and, at the time of this writing, I had quite a lot of expertise in the U.S., but was less familiar with what was going on in Europe. I wanted to make sure I could bring somebody in who had that expertise so I reached out to Mike Wallenstein, who I hadmet through the European Federation of Pharmaceutical Industries and Associations (EFPIA). We also had been teaching together at the University of Maryland, and I felt confident that he could help with that part of the book. He did a great job.
Chapter 5, as we move through this life cycle, is focused on integrated development. I wrote that chapter based on my own personal experience and background in product development all the way through design transfer. I want to specifically thank Amit Khanolkar who is at Janssen and Alie Jahangir, who was at Janssen and is now at Biogen, for their peer review and feedback as I was writing that chapter.
Combination products risk management is another one of my favorite bailiwicks. I reached out to people that I've worked with through working groups and teaching. Rick Wedge is at Pfizer, and very active, especially in platform combination products. Ed Bills served on the committees for ISO 14971 and ICH Q9R1. [I brought them on] to make sure we brought in the full expertise on risk management to the book.
Another key aspect of risk management is human factors engineering, which is where the book went next. For our chapter on human factors engineering, design development, and life cycle for combination products, I reached out to Shannon Hoste, who is ex-FDA and was very active in human factors there. She now runs her own consulting business. Through Shannon, I met Stephanie Canfield, who is a human factors engineering expert consultant. I wrote part of the chapter as well as Bjorg Hunter, who is at Novo Nordisk, and Theresa Schueble, from Janssen and Johnson & Johnson. She worked actively with me when I was working at Johnson & Johnson.
As we keep moving through the life cycle, we've now made it to design transfer and getting the product to market. The next section of the book is about combination product post-market and life cycle management. For this, I reached out to Khaudeja Bano for the focus on post-marketing safety reporting for combination products. She is considered one of the world experts on [this topic]. She and I have become dear friends through the Combination Products Coalition, ISPE, and multiple other forums. She helped with the latter part of that chapter while I wrote the beginning based on my experience working with various companies
For the final chapter in the first half of the book, I reached out to Kim Trautman on inspection readiness. She was formerly at the FDA where she was instrumental in the authoring of the quality system regulation [QSR] when it [was] originally issued. She is now doing consulting, and I've done some work with her. I respect her a lot; it was wonderful to bring her on to help write the chapter on inspection readiness.
That brings me to the second half of the book. Part 1 is all foundational things that you must address. The one chapter in Part 2 that could have been in Part 1, is Chapter 10, which is on considerations for supplier quality, raw materials, components, and constituent parts. I say that it could have been in Part 1 mostly because when it comes to supplier quality, most companies in the combination product space purchase their products from third parties, their device constituent parts, or their drug, depending on what their base business is.
Fran DeGrazio, who was at West Pharmaceutical at the time and is now a consultant at Strategic Parenteral Solutions, had been very active at the Xavier Combination Products Conference as well as teaching, working with ISPE, and through other venues. Fran brings a wealth of expertise from her years at West, and an understanding of what's unique and what's expected for suppliers and supplier quality agreements. I heard Meera Raghuram, from Lubrizol, speak at the Xavier Combination Products Summit. She did a great job talking about raw materials, components, and opportunities for combination product companies to manage those. I reached out to her, and she happily agreed to participate in the writing as well. I was grateful for that.
As I keep working my way through the life cycle, another key aspect of combination products development is an understanding of the analytical testing considerations that are unique for combination products. For this, I reached out to Jennifer Riter, who is now at Kindeva, formerly at West Pharmaceutical, and she was a great help. I know her through many different industry forums, and she is an expert in analytical aspects for combination products. She drew in one of her colleagues from West who is now at Terumo, Daniel Bantz. Daniel did a great job filling in more technical information throughout that chapter to make sure it was well-rounded for those reading it.
One of the growing areas of combination products are biological products. I knew I wanted to have a chapter dedicated to that. I reached out to Manfred Maeder, who is at Novartis and was a co-instructor with me at the University of Maryland. He is part of the Combination Products Coalition and is one of the first members of my ISPE Combination Products Community of Practice. He has been a great friend and is very experienced in biological products.
Throughout, there is the thread of the Xavier University – now AFDO RAPS – Combination Product Summit. It has been a wonderful forum for several years for people to attend. It brings a lot of insights into combination products. Through that specific forum, I also met Ryan McGowan. Ryan, who is ex-FDA, wrote a chapter on digital combination products and software. He is now at AstraZeneca and he presents frequently. He is very active in the Combination Products Coalition and in working groups on digital combination products. I thought he'd be great and was thrilled that he agreed to contribute to the book.
The last chapter of the book is a general overview of the global combination products regulatory landscape. In Chapter 3, Suzette Roan goes through the regulatory strategies. But then, you have to take a giant step back. It’s pretty complex as you look around the world, and there is no harmonization whatsoever. I present at a number of conferences, a number of venues, and one of those venues was a conference on combination products in Berlin, Germany. This is where I met Stephanie Goebel, who is now at Roche, and Viky Verna, who is a combination product consultant. Each of them did wonderful presentations, one about the EU MDR [European Union Medical Device Regulation] and the other one about countries in the Asia Pacific region and other parts of the world. I reached out to both for their help. I bring expertise on the U.S. into it. Through Viky, I met Cherry Marty, who jumped in to help us with some of the other international venues where combination product regulations are growing. That chapter was probably one of the most challenging to write.
Finally, there is an appendix, which is about 70 pages of content, that is a survey of combination product regulations around the world. You can imagine, given how they are ever-changing, that it was a challenge to go after that. I reached out to Janine Jamieson, who is at IPQ [International Pharmaceutical Quality], and Janine referred me to a PhD student named Dhiraj Bell. Dhiraj was absolutely wonderful about working with me to build that appendix. It has a wealth of content and hyperlinks in it. I'm happy to say that Dhiraj got his PhD last year, so he is now Dr. Dhiraj Bell. With that, you now have the full framework of what went into the book, why it went into the book, and who helped contribute to creating it.
Thank you, Susan. That was excellent coverage of the book's contents, its purpose, and some of the perspectives that we'll see from various authors who joined you in its creation. I’m looking forward to the chapter-by-chapter episodes to come, starting with Chapter 1. As people prepare to join us for additional chapter-by-chapter coverage of the book, what do you see as the way that the video series may extend and supplement the work that you did in the book?
The guidance and regulations keep evolving. It has been a very active year with EDDO [Essential Drug Delivery Outputs] guidance, which used to be Essential Performance Requirements (EPR). New URRA [Use-Related Risk Analysis] guidance has come out on some of the expectations for your filings and the fees associated with it. This is an opportunity to hear experts’ perspectives on their experiences with what they wrote and what went into it, as well as their reflections on how it continues to evolve and opportunities or challenges that the industry still faces with both domestic and global regulations as they continue to evolve.
Excellent. I look forward to you joining me for our coverage of Chapter 1 in the next episode. As folks in the audience prepare to take in that episode, if they're interested in reading the book itself, where can they find it?
You can get it on routledge.com. It’s also available on Amazon.
Excellent. We’ll see you folks in the audience next time. Thanks, everyone.