• 00:55 – Ed, Meranda and Brian welcome today’s guest, Mike Carroll, who speaks to his background in microbiology and product development  
• 04:28 – Mike talks about his involvement in the Parenteral Drug Association (PDA)  
• 07:51 – Lessons Mike has learned throughout his career and expounds on the relevance of PDA technical reports  
• 15:03 – The evolution of regulatory approvals in the pharmaceutical industry  
• 17:34 – Mike describes the influence of the PDA today, given the pandemic  
• 20:18 – Mike explains a typical day working in microbiology and quality control and assurance
• 23:11 – The pressure of working in pharmaceutical drug development and final comments from Mike  

“The PDA was kind of the bridge. It’s the Parenteral Drug Association – its focus is sterile injectable product. But it’s into all kinds of different things.” 

“The biggest things that are most frequently used in my case are the media fill, as Brian mentioned, and environmental monitoring.” 

“When you cite regulations from Europe, it used to be you would pull the British because they were gonna be the standard. If you could pass Brit, you could worry about anybody else at all; you were fine.”

“It’s an entire system that you’re trying to get where every little thing that fits into the process has been qualified and can be depended on. From the raw materials coming in the door to the viles, to the stoppers, to the machinery, the environment, the filters, the air quality and differentials – all of that stuff fitting together.” 

“With drug development, you’re not having a life depend on you. You’re having tens of thousands of lives depend on you.”

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Michael Carroll on LinkedIn

PDA

• 00:54 – Ed, Meranda and Brian welcome a special panel of guests to break down today’s topic: Quality Management Systems (QMS) Explained!  
• 07:53 – The panel expounds on the timing necessary for QMS and what role the quality manual plays  
• 13:06 – The panel explains the Code of Federal Regulations (CFRs)  
• 17:30 – The panel defines Phase Appropriate as it pertains to QMS
• 23:12 – Identifying which guiding documents to follow  
• 27:29 – The value in having an experience quality professional  
• 31:54 – Why a quality agreement is necessary  
• 35:32 – The panel provides final words of wisdom on Quality Systems Management  

“Quality System Management provides an infrastructure for a company to ensure the quality of your drug product with patient safety in mind as its primary function.” 

“It helps determine and define management’s commitment to quality. Because if you don’t have senior management commitment, all could be lost.”

“To begin at the beginning, when you set up your QMS, you need to start with the procedures and processes that will reduce risk and help you prepare for your submission in the long run. That would come through managing your documents.” 

“Guidance documents are just an opinion. And they actually say that in the documents. So, you kinda try to do a combination of everything.”

“The biggest thing is that when you have somebody who’s experienced and they’ve been through various things like FDA audits or have worked with a very small company versus a very large company, they can differentiate what you really need right now.” 

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Edward Narke on LinkedIn

Bettina Kaplan on LinkedIn

Susan Fasso on LinkedIn

Robbi Freisem on LinkedIn

Maria Arakil on LinkedIn

• 00:52 – Ed, Meranda and Brian welcome back Jim Mencel who shares his extensive experience with process validation
• 07:46 – The importance of Proven Acceptable Range (PAR) and Critical Process Parameter Program (CPP)  
• 11:14 – The evolution of the batch documentation and the value of critical parameter studies  
• 18:07 – Registration laws and gathering necessary stability data  
• 20:49 – How validation material can be used for launch  
• 24:15 – Jim speaks to the importance of writing a Protocol and having a quality supplier team  
• 32:34 – Jim discusses timing when moving towards validation  
• 38:02 – Jim reinforces the notion that communication is key when it comes to process validation  
• 40:42 – Final recommendations Jim would give regarding process validation  

“Validation’s very formal. Validation really, in a stage analogy, is Opening Night. This is where the critics are all present, everybody’s breathing on you, you’re gonna be in the headlines the next day and everything needs to go right. So, when you think about it in that context, the validation batches are very visible to regulatory authorities.”

“Your batch record really is a document that’s going to evolve. And if you look at the batch record for even the same step of a process, what that’s going to look like when you’re in the early phases of clinical development is different from what it’s going to look like towards the end. It’s going to be much more refined.”

“There is a point where the process is the process. And as inefficient as it may be, it’s what you have.” 

“Yes, your validation batches certainly count as launch stock as long as they pass all specs.” 

“When you go into validation, you’ve gotta have your suppliers identified. And quality plays a huge role in assessing your suppliers” 

“What it all comes down to is that preparing for the validation is something that you should be thinking about as you’re making your later clinical batches, your Phase 2 batches especially.”

“When you’re in Phase Three it’s not a place to be penny-pinching. The old saying is, ‘you drive for show, you put for dough.’ When you’re validating, you’re putting for dough.” 

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Jim Mencel on LinkedIn

• 00:51 – Ed, Meranda and Brian introduce today’s guest, Shelli Connelly, who discusses her background and speaks to some of the elements of filter validation  
• 05:41 – Shelli talks about the process of selecting a filter and why not all filters are the same
• 09:03 – The evolution and importance of sizing filters  
• 11:26 – Shelli speaks to the shift to single-use disposable filters  
• 13:05 – Qualifying a filter before validation  
• 16:51 – Shelli explains the Bubble Point test  
• 18:53 – Shelli expounds on everything that goes into filter validation
• 22:57 – How to use filters in a media simulation challenge  
• 25:07 – Shelli’s philosophy on what to include in your filter validation  
• 28:28 – Final recommendations Shelli would give regarding filter validation  

“I highly recommend reaching out to the filter vendors. They’re your best support, especially with this process.”

“Most people when you start with a drug process you’re looking less than a hundred liters, knowing that your commercial back size could actually be 1500 liters. And then the question comes down to are you doing redundant filtration, are you utilizing two filters, are you utilizing one? To understand your product, I think the filter vendor can definitely still help with that.” 

“Normally if you’re utilizing a sterilizing filter, you definitely have to run it through some type of sterilization process.”

“A Bubble Point test is related to the micron-size of your filter, meaning if you have a 0.2 or a 0.45, those bubble points are gonna be different.”

“I think utilizing your filter validation in conjunction with your media fill program – whatever that may be – they have to be synced and in alignment.”

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Edward Narke on LinkedIn

Shelli Connelly on LinkedIn

• 00:51 – Meranda and Ed discuss the Regulatory Odd Couple blog series and constructing the CTD Module 3  
• 11:54 – Ed explains the importance of building the Quality Overall Summary (QOS) and the different starting points for drug process development  
• 19:45 – Ed and Meranda talk about characterization, the process of manufacturing drug substances/products and the importance of excipients  
• 37:44 – Ed expounds on the analytical aspect of API and regulatory drug development  
• 46:55 – Ed and Meranda share their thoughts on the process of packaging drug substances  
• 49:09 – Ed and Meranda discuss the role that stability plays in development methods  
• 53:42 – P2 Pharmaceutical Development  

“If anyone’s listening and not familiar with the drug development process, the one area that’s most important is the FDA guidance.” 

“Characterization is, in my mind, one of the fundamentals of a product and a process and a program. If you don’t know what you’re dealing with to start, it’s hard to catalog it, make it consistently and answer questions about it.”

“This is probably, in some folks’ minds, the most important. It’s the manufacturing of the drug substance and the drug product. If you don’t have a process, you don’t have a product.” 

“There are a few caveats to excipients. One of the things you’ll want to recognize and a question that might come up is ‘are they of human or animal origin?’ And the other big thing is ‘are they novel?’” 

“Any changes to anything in the program – process-wise or control-wise – late in the game could be a problem because you’re gonna have to generate additional data. There’s an unknown there. What does that change mean?” 

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Odd Couple Series

• 00:54 – Meranda and Brian flip the script by introducing fellow host, Ed Narke as today’s guest
• 01:56 – Ed speaks to his extensive background in CMC and the importance he places on building relationships based on trust
• 11:06 – Ed expounds on his role at DSI and the impact he, Brian, Meranda and the entire DSI team are having on the CMC industry
• 17:11 – Ed talks about his personal background and roots and the value of being adaptable and the impact COVID-19 has had on his business
• 21:36 – Ed thanks some of the many mentors and friends who have assisted him throughout his career
• 26:48 – Ed provides best practices and advice for operating within the CMC industry
• 30:55 – How Ed strives to build trust in relationships
• 37:27 – Ed shares some of his thoughts on the keys to his success
• 40:32 – Ed answers a listener question about microbiome-based products
• 43:31 – The value of developing powerful, positive routines
• 45:46 – Understanding the urgency of self-improvement

“I look back on my career and I kind of made a few big mistakes. For example, I went into the office of the Vice President at this company to resign. I was a kid and I was just upset about certain stupid little things. And, when I walked in there, instead of leaving the job, I made a connection with him as another lifelong mentor.” 

“Comparing INDs, NDAs, BLAs, I’ve always had this fascination with putting stuff together into a story.” 

“I hope I look back in fourteen years and say, ‘These are the best days of my life.’” 

“One of the things I have to remind myself every day is that life really hasn’t changed, I have.”

“Everything I learned that is valuable and dicey and on the edge I learned from Dan [Torok].” 

“My goal, hopefully, is to grow CMC Live, make it more interactive and maybe have a live audience with questions.” 

“To truly build trust, I learned it’s better for my colleagues to get to know me as a person.” 

“Two things control the way we operate and who we are: our brains and our gut.” 

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Edward Narke on LinkedIn

• 00:55 – Ed, Brian and Meranda welcome to the show Paul Long who shares his well-rounded background as a project management consultant and speaks to some of the benefits and challenges of virtual project management
• 17:09 – How Paul manages working with clients virtually
• 19:08 – Tools Paul integrates in his project management process
• 21:17 – Paul provides examples of how project management fits into drug development
• 24:52 – Paul shares some project management tools that he utilizes, including the Gantt Chart
• 29:35 – Paul makes a final case as to why project management is important
• 33:41 – Paul differentiates between a project coordinator and a project manager
• 34:28 – Ed, Brian and Meranda thank Paul for joining the show

“We’re fairly comfortable with the virtual environment that allows us to be flexible in who we staff. That’s a plus. It allows us to be flexible in our time when there is a global project. That flexibility has always been there at DSI.” 

“It’s similar to managing the communication prior to the COVID environment. You have to establish how the person wishes to communicate, what level they wish to communicate on. So, when I meet a client, I ask them these questions directly. ‘Are you comfortable with this kind of communication? Do you want a weekly update? What’s the cadence for meetings?’” 

“I have to integrate our team and the client’s needs into a common goal and make sure we’re meeting that.”

“The challenges haven’t changed with COVID, but our work environment has.”

“Again it comes down to communication, transparency and open discussion. And that’s one of the things I try to drive as a project manager.”

“Keeping the communication up avoids risk. We don’t want surprises, unless they’re good.” 

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Edward Narke on LinkedIn

Paul Long on LinkedIn

• 00:43 – Ed, Brian and Meranda introduce today’s 2020 Year-In-Review show and look back on learnings from Jim Mencel, Dave Adams and Daniel Torok
• 10:11 – Ed, Brian and Meranda reflect back on their conversations with Rick Offerman, Les Mintzmyer and Dave Blasingame
• 19:06 – Ed, Brian and Meranda talk about a recent panel discussion they held with other CMC experts
• 21:00 – Ed, Brian and Meranda recap episodes featuring Kyriakos Michailaros, Bettina Kaplan and Colman Byrne
• 31:06 – Ed, Brian and Meranda highlight a very special external guest, Hedley Rees who spoke with them about how to create a value chain
• 37:39 – Ed, Brian and Meranda speak to their discussions with Judy Magruder and Catherine Bernard
• 43:05 – Ed, Brian and Meranda wrap up this 2020 Year-In-Review, thank the listeners for their support in 2020 and look forward to what 2021 has in store

“One of the things that resonated with me on that particular podcast was how Dave [Adams] took a step back and said, ‘You really can’t underestimate the importance of the skilled technicians that actually run the process.’” 

“The reality is they still need that person-in-plant. So, I think what Dan [Torok] brings to the table is what a lot of clients look for. Some clients don’t have that infrastructure and they blindly trust the CMO – and sometimes not always to the right result.” 

“I think people are now realizing that they do need to take a lot of different factors into consideration when selecting their CMO and they might need that assistance from experts like us.”

“If you know that you have properly identified and characterized the development history of your product, and its pitfalls, and its areas of concern – and you’ve explored those – it really makes for a much more robust filing that stands up to scrutiny.” 

“We had a special external guest, Hedley Rees, who talked a bit about supply chain and how to create a value chain.” 

“Our job as regulatory reviewers, strategists, authors, CMC experts, is to decipher what the data is saying.” 

“I think that’s the experience that Judy brought to bear is that holistic approach to a client’s program.” 

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Edward Narke on LinkedIn

Brian Lihou on LinkedIn

Meranda Parascandola on LinkedIn

Taming the Big Pharma Monster

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