Siegfried Schmitt, PhD, is Vice President Technical at Parexel International, Siegfried.Schmitt@parexel.com.

Siegfried Schmitt

Q: We are updating our training program for this year and wondered if you are aware of any new regulations for data integrity?

A: No new regulations were published in 2025 specific to data integrity. The evolving global regulatory systems do, however, address data integrity within the context of revised or new parts of the legislation.

The European Commission (EC) has published

 the revision of Good Manufacturing Practice (GMP) Guidelines Chapter 4 (Documentation), Annex 11 (Computerised Systems) and New Annex 22 (Artificial Intelligence) for public consultation. All three documents address data integrity, namely:

Chapter 4 clarifies the requirements for the management of electronic records, signatures, and data integrity while ensuring consistency with the concurrent revision of Annex 11.

Annex 11 strengthens controls related to the assurance of data integrity, audit trails, electronic signatures, and system security.

Annex 22 addresses the quality of model training data, and the management and processing of test data for AI models.

FDA published the Center for Drug Evaluation and Research 2026 Quality Management Maturity (QMM) Prototype Assessment Protocol Evaluation Program in February 2026.

 The QMM program aims to encourage drug manufacturers to implement quality management practices that go beyond current good manufacturing practice requirements. Data governance is a topic covered by this program.

This clearly shows that it is necessary to search beyond the term “data integrity” to stay abreast of developments in this field. Furthermore, these updates continue to emphasise the need to comply with good practices, such as good documentation practices. This may sound trivial, but it isn’t. The many inspection observations relating to data integrity are often nothing more than a lapse in having documented processes or creating records that are true and are documented in a timely manner.

As mentioned, there are no new regulations on data integrity, per se. Instead, new or updated regulations are necessary to cover advancements in science and technology. Data integrity remains a key concept throughout and importantly, the requirements for data integrity compliance remain unchanged. You may refer to them as ALCOA+ (attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available).

Stakeholders’ Consultation on EudraLex Volume 4 - Good Manufacturing Practice Guidelines: Chapter 4, Annex 11 and New Annex 22. European Commission. 

https://health.ec.europa.eu/consultations/stakeholders-consultation-eudralex-volume-4-good-manufacturing-practice-guidelines-chapter-4-annex_en

CDER Quality Management Maturity. FDA.gov. February 11, 2026. 

https://www.fda.gov/drugs/pharmaceutical-quality-resources/cder-quality-management-maturity

Lopez J. Quality Essentials: Inspectional Coverage of QMS and Data Integrity. Presentation at the Compounding Quality Center of Excellence Annual Conference September 11, 2023. 

https://www.fda.gov/media/179075/download

Siegfried Schmitt, PhD, is vice president, Technical at Parexel. 

Articles

No 2025 regulations were issued that exclusively target data integrity, but multiple evolving frameworks reinforce it within broader GMP and quality initiatives. The European Commission opened consultation on revised GMP Chapter 4 and Annex 11, plus a new Annex 22 for artificial intelligence, each strengthening expectations for electronic records, audit trails, signatures, security, and AI training/test data controls. FDA’s 2026 CDER Quality Management Maturity prototype program also elevates data governance. Persistent inspection findings often reflect weak documentation and untimely, non-contemporaneous record creation against ALCOA+ principles.

It is necessary to search beyond the term “data integrity” to stay abreast of developments in this field, says Siegfried Schmitt, PhD, vice president, Technical at Parexel.

Evolving Regulatory Systems Stress Importance of Data Integrity

Ask the Expert: Working with Regulators to Develop Orphan Drugs

 video series. This series is an extension of the 

 Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This video series expands on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to 

, and it may appear in a future episode or print column.

In this episode of the Ask the Expert video series, Susan J. Schniepp, Distinguished Fellow, Regulatory Compliance Associates, a Nelson Labs Company, and Siegfried Schmitt, Vice President, Parexel, answer the question:

“We are a medium sized company and are looking to develop a new drug and are thinking of applying for orphan drug status. Do you have any suggestions for working regulators?”

For medium-sized pharmaceutical companies considering developing a drug for orphan drug designation, the transition from traditional development to rare disease therapy requires a shift in regulatory, clinical, and operational planning. An orphan drug is defined by the size of the population it treats; in the United States, this generally refers to conditions affecting 200,000 or fewer people,

 while the European Union uses a threshold of approximately five in 10,000.

What are the regulatory and financial incentives

According to Schniepp and Schmitt, the orphan drug designation route offers government-backed incentives designed to offset the limited blockbuster potential of these products. These include financial support that includes government funding, grants, and tax credits. In the US, fees under the Prescription Drug User Fee Act may be waived for orphan drug developers. Regulators also offer more support for applications and faster approval timelines.

What challenges does the Orphan Drug pathway bring?

Orphan drugs must meet the same rigorous quality and compliance standards as traditional drug approvals , Schmitt and Schniepp emphasize. An accelerated approval process often means manufacturers must be more agileto apply high-level quality systems within a shorter timeframe.

Orphan drugs may also introduce specific manufacturing complexities. Producing smaller batches for clinical trials or commercial use is often more difficult than large-scale production.

Smaller companies without internal facilities may need to utilize contract development and manufacturing organizations (CDMOs). However, CDMOs may find it harder to integrate low-volume runs into their schedules compared to large-scale large tank production.

Because the patient population is small and globally dispersed, distributing small batches of product to far-reaching locations may also be a logistical hurdle.

Patient enrollment for rare-disease treatment development may be difficult, especially if multiple companies are competing for the same eligible participants. Medium-sized firms lacking regulatory experienceshould seek external expertise, according to Schmitt, and work in close collaboration with regulatory authorities. While these therapies may be commercial risks, they may lead to the discovery of broader indications for other diseases, Schniepp suggests, making them even more worthwhile to pursue.

FDA. Office of Orphan Products Development. FDA.gov. Oct. 1, 2024 

https://www.fda.gov/about-fda/office-chief-medical-officer/office-orphan-products-development

EMA. Orphan Designation. Overview. Ema.europa.eu. 

https://www.ema.europa.eu/en/human-regulatory-overview/orphan-designation-overview

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates and a member of PharmTech’s Editorial Advisory Board.

Siegfried Schmitt, PhD, is vice president, Technical at Parexel and a member of PharmTech’s Editorial Advisory Board.

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Hi, everyone. Welcome back to Ask the Expert. I'm Sue Schniepp, and I'm with Nelson Labs, and I'm with my colleague, Siegfried Schmitt, with Parexel, and we're here to talk about, I think Siegfried has a question on orphan drugs. So, let's go for it, Siegfried.

Thank you, Sue. Yes, thanks for the introductions. In fact, yes, the question that came in is:

"We are a medium-sized company, and we are developing a new drug, and we are currently thinking of perhaps applying for orphan drug status with the regulators. Would you have any suggestions, comments, recommendations in that context?"

So, Sue, maybe you would like to start off with this.

Well, that's interesting, 'cause sometimes companies do choose the orphan drug route. Now, there's some advantages to choosing that. So first, we should clarify, an orphan drug is a drug that's treating a condition in people. In the United States, I think it's two hundred thousand or less people are affected by the condition, and I think it's a little different in the European Union.

It's, like, five in a thousand or something, or do you know, Siegfried, what that...?

I don't know the precise figure, but I know that there are slight differences between EU, US, and I believe also in other jurisdictions. You have not exactly the same threshold. Right.

But I believe in most cases, when you're looking at an orphan drug designation, you're probably looking at a rather small population that is affected by the particular disease for which you're developing your drug. Right.

So having clarified that, then the thing that always comes to mind with me is there's a couple of advantages. So, if you go the orphan drug route, you do get assistance from governments, because they realize that if you develop the orphan drug, you probably will not make a lot of money on it, right?

It's not gonna be your next blockbuster because of how few people you're going to really affect with the drug. Once they get out on the market, they're high-priced too, but they are reimbursed typically by insurance. But, you still need to meet all the standards of quality when you're developing an orphan drug.

The thing that I think you need to work the closest with the regulators on are on your clinical trials, because it can be difficult to get patients enrolled in your clinical trial, and that's what the success of your drug is based on.

You know that better than I do, Siegfried.

Well, you're right, Sue. You need to think about where you can find eligible patients, and of course, not every eligible patient will also want to take part in a trial. And interestingly, just because you may be developing a drug for a rare disease, doesn't mean that you're probably the only company doing that.

There are often many competing companies developing drugs for a similar rare disease. So, it's not that you're out there on your own, and you are without competition.

As you quite rightly say, you need to work closely with the regulators, and the regulators offer a lot of support there. And what is also very important is you have to have the same quality and compliance standards as if you go the normal drug approval route.

Yes, you have advantages time-wise. You don't have to wait as long for approval as you have to do with the normal approval pathway, but because things happen faster, you also have to be more agile. You have to work harder and faster to have the same standards, the same levels of quality, and just apply them in a shorter timeframe.

So, perhaps this is something that some companies may not fully understand, particularly when we look at the type of companies that often develop these rare disease drugs.

Very often, these are fantastic scientists, spin-offs from universities, perhaps, and as this particular person who put the question forward said, they're a medium-sized company, and that means they may not have as many people with the right experience in regulatory affairs, in bringing drugs to market, et cetera. So perhaps you need more external help there. What do you think, Sue?

I think so. I think it is a desirable route to go, too, though, because you do get some advantages. I know even in the EU, right, as a developer, so you do get funding, right? And you do get some tax credits, at least in the US. I don't know if you do in the EU.

I think both. We have a Prescription Users Drug Act here, where you pay a fee, and those fees are waived for people who are developing orphan drugs and as you said, grants or help from other sources.

So, I think it's kind of, it's not where I've actually played in the game, but I understand the attraction of it. If you are doing that, oftentimes, too, and I'd like to hear your comments on this, once the orphan drug is developed, it can go on to prompt, develop [other drugs] I think the statins came out of the development of an orphan drug; although, I'd have to check that.

But it started with an orphan drug that they somehow found at the time. I can't remember what it was for. I'm gonna have to look up my history, but they found at the time it lowered the cholesterol of the patients that were getting the orphan drug, and that turned into the statin that we now prescribe readily to patients with cholesterol. Am I remembering that right, Siegfried?

I don't know this particular case, but it's quite possible, because very often you'll find, that a particular drug that you developed for one indication is very helpful with another indication you didn't even know about, you didn't think about. So that doesn't have to come from an orphan drug designation, but it could indeed.

So, I think what companies need to weigh up very carefully is, yes, you have lower fees, you have expedited pathways, you have, much more support for your applications if you go the orphan drug route. But on the other hand, it comes with obligations, as I said, to do things faster, but to the same high standards.

Whether this is, the best possible way, again, is something you need to discuss on a regulatory perspective, but also from a commercial perspective indeed. So, it all has to be balanced out to be right.

Yeah, and your commercial perspective, I like in terms of, sometimes you don't have access. This is where it gets a little bit tricky, too. You need to make sure that you have a contract manufacturer if you're doing that route. You don't have access toa manufacturing facility. You're a smaller company, right, without that, so you're gonna have it contracted. You need to make sure that you have space on their line, line time. It's harder for a contract manufacturer to produce a smaller batch clinical trial material, than it is to produce, you know, a large batch.

At least from my experience, I would say it's easier to do, you know, a big tank and thousands of vials than a smaller clinical trial.

Indeed, and also, once you commercialize your product, again, we know it is a small population that you are servicing here, and, so the batch size, again, with a CDMO will be relatively small.

But it's also the distribution of the product, because it's very likely that your population is distributed, spread out, maybe all over the world, and it can be more challenging to distribute smaller size product batches, than it would be if you have a large commercial product.

Yep, exactly. Well, I don't really have any other advice for people other than, you know, it could be a viable pathway. Just make sure you get the right help and assistance, and work closely with your authorities.

That's exactly it. Seek help, seek expertise. If you don't have it inside, there are plenty outside, and also the regulators.

Thanks, Siegfried. I look forward to our next conversation.

Videos

In this episode of Ask the Expert, Susan J. Schniepp, Nelson Labs, and Siegfried Schmitt, Parexel, discuss the benefits of orphan drug development and how a mid-sized company can work with regulators through the pathway to approval. 

k the Expert: Collaboration Ensures Effective Procurement

To ensure the long-term success of a drug product, pharmaceutical manufacturers integrate procurement, manufacturing, and quality departments early in the development process to ensure material reliability and regulatory compliance from clinical trials through commercialization, according to Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, a Nelson Labs company, and Siegfried Schmitt, PhD, vice president, Technical at Parexel.

Effective procurement is not merely about finding the lowest-cost materials; it requires a clear communication channel between several key departments. R&D and manufacturing teams must establish detailed specifications and grades (e.g., for microcrystalline cellulose) rather than simply requesting a generic ingredient. The involvement of the quality assurance (QA) department ensures that suppliers meet good manufacturing practice expectations. QA is responsible for verifying that materials are made to the right standards, often through audits or by reviewing certifications from industry organizations. Finally, by understanding the product lifecycle, procurement can investigate the long-term availability of specific material grades and identify commercially viable suppliers for the future.

How does collaboration ensure quality and mitigate risks?

Using substandard or incorrect grades of materials during clinical trials can lead to significant setbacks. If a company uses a material in early trials that is later found to be unsuitable for large-scale manufacturing, they may be forced to redo research and development. For startups and entrepreneurial firms, these delays can lead to a total loss of funding before the product ever reaches the market.

As a product moves toward commercialization, the supply chain must adapt to changing needs. Early development requires small amounts of high-grade materials, while commercial production requires much higher volumes that may only be available in different grades or from different suppliers.

The handover between Phase II and Phase II clinical trials is a critical point for reassessing the supply chain. This is often when larger companies take over, potentially shifting production to different geographic regions like Asia or America, necessitating a new risk assessment.

To secure the supply chain, manufacturers should ideally qualify backup suppliers to hedge against the risk of a primary supplier going under.

In this episode of the Ask the Expert video series, Sue and Siegfried, answer the question:

“My company is developing a new drug product. What departments in our company should we involve in materials procurement to maintain a reliable supply chain for the lifecycle of the product?”

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to 

My name is Sue Schniepp. I'm a Distinguished Fellow with Regulatory Compliance Associates, which is a division of Nelson Labs. And with me is Siegfried Schmitt. And Siegfried I'll let you introduce yourself. Thank you. Sue Siegfried Schmitt, Vice President technical with PAREXEL consulting, and together with Sue we are answering questions to ask the expert. And so today we got another question in

it says, My company is developing a new drug product, excellent. So what departments in our company should we involve in materials procurement, so we're making sure that we get all the right materials to maintain a reliable supply chain for the life cycle of the product. So very clearly that person is thinking not just about the moment now, but the whole life cycle. So perhaps, so you would like to start with giving an answer to that. I really like this question because, like you said, Siegfried, this person is thinking ahead. So they're not just going to go with whatever purchasing puts in front of them. They're going to investigate it. And I think that's a critical issue that they're talking in the purchasing arena, which usually isn't involved in these types of decisions. They kind of, you know, somebody says, I need micro crystal and cellulose. And purchasing goes out and gets some.

This person is thinking of sustainability through the life cycle of the product, so they're willing to kind of do that outreach and get purchasing to procure the right grade, the right requirements of that inactive ingredient that they're wanting to use in the formulation of the product. So I think that's really telling that is one area we forget about, is procurement. And I think it's really great that this person is thinking along those lines. There's so many ways to go here, so I'm going to let you go some down another path, Siegfried.

Well, as you say, Sue procurement needs to know what they should be procuring. So, as you said, maybe just micro cellulose. But of course, there are many grades, and so someone in manufacturing, maybe someone in development needs to put together the specifications, and it's these specifications that need to be shared with procurement.

So there has to be a communication channel between the various departments in the company that may not necessarily be established yet, or maybe it's not really clear, there may not be a process, a process flow for who is telling procurement from the manufacturing side or the development side, or maybe even the quality control, laboratory side, what needs to be procured. That is one thing, but with that, we also want a particular quality, a particular specification. So you may not only want the product, you may also want to have certain testing done by the company you're buying your materials from. So there is more to just handing over a piece of paper and say, Please get me the cheapest microcellulars that you can get. And we just need half a kilogram of this. So that's that's not enough of a specification, I'd say,

I think so. Best Practices involves the procurement and purchasing department, because the last thing that you want to do is run your clinical trials. This is more your area of expertise than mine, but you want, you don't want to be using a substandard micro crystal and cellulose in your clinical, clinical trials, and then have developmental issues as you're trying to establish the requirements to go into manufacturing for once the products approved, right? You don't want to step back and have to re do research and development all over again, because you didn't spend the time upfront to involve purchasing and procurement to get the right grade of material in the first place. That happened so many times, where companies just set themselves back on their timeline and and in some cases.

Because they're entrepreneurial or startups, we lose the product we don't have. You know, the product never does make it to market because the funding runs out, right?

As we said at the beginning, so this person that sent in the question is thinking ahead. And of course, in the early stages of development, you need small amounts, and they may be available in very high grade qualities. Whereas if you're looking to the future because you want to bring your product to market, then you have much, much higher volumes, and your material may only be available in a different grade of quality. So you not only that, maybe you have to go to different suppliers. Maybe one supplier only provides high, high grade, small amounts, others may provide a different grade, much larger amounts. So it you really have to have a conversation with procurement about what is available, what may be available, because it may well be that at the moment, no one is thinking about providing this particular grade in a large volume, but if it is commercially viable, they may be willing to provide it to you in future. So there

again, as we say, we need to have conversations, and these conversations are not just between the development team the production team, but it's also the quality team, because in the end, of course, you are likely to get a certificate of analysis from the provider of the material, but you can't just rely on that. You have to perform certain tests when you receive your materials. And that, again, is your expertise, so isn't it? Yeah, yes, it is. And I kind of want to lead us You said something very critical in the beginning, and that was about GMP expectations. So even though you're in the development side of or the clinical trial material side, you still need to ensure that the purchase, the people you're purchasing, whatever grade micro, crystalline cellulose or whatever inactive ingredient do meet GMP standards You can't buy the you know, cheapest is not always the best. And purchasing and procurement want to involve quality in those that decision just as much as quality wants to involve them. Because quality is going to have to go in and take a look at the manufacturer of the material to make sure that they are making GMP grade material. I think that's kind of, you know, critical there. I'm glad that you mentioned that, because I'd almost kind of forgotten it's not just about, okay, here's our specs, here's what quality wants, here's what R and D want. It's also about and can they make it under GMP conditions.

And as you said, someone at the company has to verify that not only the material is the right material, the right quality, but it's also made to the right standards. And if you think about many of the companies that develop new products, many of them are small and medium sized companies, so they may perhaps not have the resources if they even have all the know how what needs to be done to ascertain whether this these companies do the right thing. So not so,

especially when we think about excipients rather than the active pharmaceutical ingredients. So a lot of these manufacturers wouldn't really let you into an audit, but many of them actually provide certificates that they are producing to the relevant standards. May be IPEC. IPEC is one of these organizations that helps with these programs, but still ultimately, it is always the responsibility of the manufacturer that all the materials used are of the right quality.

So perhaps coming back to what you said about quality assurance, so how should quality.

Insurance be involved in all these procurement activities, I agree, and when the last thing, I kind of want your opinion, because I don't really know where to go with this. It's kind of difficult when you're securing the supply chain. You always kind of want to hedge your bets to make sure that

you have a backup supplier. So I think an early stage of development, it's hard to kind of, you know, qualify two suppliers for the same material. I mean, when does that ideally? When do you ideally do that? When you pass, you know, phase one, I don't know. It's kind of one of those weird questions I've always had.

Well, I think we could look at what typically happens in industry. Quite a large number of companies will take a product up to and including phase two clinical trials, because that is typically a financial involvement that can be managed once it comes to phase three trials. We are talking about very big money, and that requires, typically larger companies. So there is a handover, typically between phase two and phase three clinical trials, and certainly at that point, it is prudent to reassess the supply chain. What are their materials? Where are they coming from? Because even now, when you have this handover, you see, your development company may be sitting in Europe, but the company that will take it to market may be sitting in Asia

and or in America, for example. So they may perhaps want a slightly different supply chain. They may have a different risk assessment about the supply chain. So again, what we are looking at is a life cycle. So nothing is really, really constant over the years when the product is being developed and the materials are being purchased. I mean, I just read in the papers about some of the ingredient suppliers in Germany that struggle to stay afloat, that are really struggling to make a living these days. So even in well established companies may go under at some point, and you may have to change your supply chain, your suppliers.

Wow, and maybe that's another topic for our next as the expert, how do you change suppliers without disrupting your supply chain or your to market, the product to market. Wow, that was great. Thanks. Siegfried, always pleasure to talk with you. Thank you. Sue Totally agree. We should

Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, a Nelson Labs company, and Siegfried Schmitt, PhD, vice president, Technical at Parexel, discuss how involving procurement early on in drug development can ensure a quality product.

Ask the Expert: Collaboration Ensures Effective Procurement

Ask the Expert: Training for a Skilled Workforce

Geopolitical stressors, such as trade policies put in place by the Trump administration in the United States, have pushed some pharmaceutical companies to invest in moving production and building new facilities in the US (1). With expansion, however, comes the need for qualified personnel to run operations in these manufacturing facilities.

But the industry has been struggling in recent years in obtaining the personnel with the proper skill sets to meet demand. And because pharmaceutical development and manufacturing are regulated industries, training personnel is crucial to ensure safe and effective medicines reach the patients that need them. So how can pharma companies ensure their staff, new and current, are up to speed on the latest tools, processes, and regulations?

Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates (RCA), a Nelson Labs company, and Siegfried Schmitt, PhD, VP Technical at Parexel, delve into the complexity of training in this episode of Ask the Expert.

“I think the question on training is really fascinating, says Schniepp. “We do keep hearing there is a shortage of workers for these facilities. I think there's going to need to be a lot of training fast to bring workers up to date and up to speed to man these new facilities. And I think the whole concept of training has changed from internal, where we did it internally with our little PowerPoint slides and somebody watching to more virtual training has undergone in the last 2030, years, massive changes, and we use AI tools.”

“We need to talk about delivery [of training],” Schmitt stresses. “There are many more ways to deliver these days than we had 1020, years ago. You and I, we've been a while in this industry, but certainly we find that almost every day we learn something new, we hear something new, we had no idea about something interesting comes about. So, learning doesn't stop. And the other thing that I certainly look back to when, when I started in industry and I needed to learn all the basics, it was learning by watching, by being told by the people who have been in the industry for a while. So, it's not so much in the first instance about reading the books or reading the standard operating procedure, reading the instruction. It's a lot about learning from those who've done it before. So there needs to be a mix, I'd say. You can't just throw out instructions and give it to people and say, ‘here you read and you understand and you sign off’. You still need some experienced workforce that holds your hand and that guides you through what needs to be done.”

Click the video above to watch Sue and Siegfried answer the following question:

“My company is building new manufacturing facilities in the US, which will require additional workforce and skill sets. What kind of training is required and how can we deliver that training?”

Cole, C. How 100% Pharmaceutical Tariffs Will Impact Domestic Manufacturing and Supply Chains. 

https://www.pharmtech.com/view/how-100-pharmaceutical-tariffs-will-impact-domestic-manufacturing-and-supply-chains

Susan J. Schniepp, distinguished fellow, Regulatory Compliance Associates, a Nelson Labs company

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates and a member of 

Siegfried Schmitt, PhD, VP Technical at Parexel

Siegfried Schmitt, PhD, is vice president, Technical at Parexel and a member of 

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to 

In this episode of the Ask the Expert video series, Susan J. Schniepp, Regulatory Compliance Associates (RCA), and Siegfried Schmitt, Parexel, tackle the ever-growing problem of having a properly trained workforce with a variety of needed skill sets. 


Ask the Expert November 2025: Audits, Inspections, and CDMOs

Contract development and manufacturing organizations (CDMOs) typically have multiple clients who each have specific needs. When regulators perform audits and inspections of CDMOs, it is sometimes unclear who is responsible for any deviations the inspector might have. However, ultimately, the sponsor company is responsible for ensuring that any contract organizations are following good manufacturing practices.

But what happens when a CDMO has a client that has specification and/or requirements that infringe on that contractor’s ability to work with other clients? How should the CDMO respond to audits and their clients? In this episode of Ask the Expert, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, a Nelson Labs company (RCA); Siegfried Schmitt, vice president Technical at Parexel, and Anita Michaels, executive pharma compliance expert and principal consultant at RCA, give advice on how contractors and clients can work together to prepare for inspections and address regulatory actions.

“A lot of CDMOs utilize their clients' inspections to prepare for inspection. But I think you could level up, level that up higher,” Michaels says. “The first thing is you want to have a robust quality system. And you also want to integrate the other five systems into your facility. Then you'll receive, if it's a regulatory authority like the FDA, they could come to inspect you for a GMP or pre-approval inspection, which will be specific to the product they're covering. And then the GMP portion, if you have been approved for a United States product, would cover the six systems. So, I think holistically, a CDMO should prepare, number one, to handle a GMP covering the six systems and have a robust quality system, such as policies in place for your CAPAs [corrective and preventative actions], investigations, deviations, your KPIs, your tracking, and trending holistically across your facility. And then also understanding the approach for a preapproval inspection for your clients.”

Click the video above to watch Sue, Siegfried, and Anita answer the following question:

“How does a CDMO organization handle multiple client input and perspective with regard to general GMP inspections without compromising or setting up different standards within their Quality Management System?

Susan J. Schniepp, Distinguished Fellow, Regulatory Compliance Associates, a Nelson Labs company

Siegfried Schmitt, PhD, Vice President, Technical at Parexel

Anita Michael, executive pharma compliance expert and principal consultant, Regulatory Compliance Associates, a Nelson Labs company

Anita Michael is RCA’s Executive Pharma Compliance Expert & Principal Consultant. She has 24+ years of global regulatory and quality experience, including 16 years direct FDA experience operating globally as their Pharmaceutical Expert, FDA Investigator and FDA Pre-Approval Manager. Anita has excellent interpersonal, empathetic communication and client management skills that enable her to skillfully coach and collaborate with clients at the highest levels of an organization and prepare them for successful FDA inspections (ANDA/NDA/BLA/PMA Pre-Approvals) and global regulatory and quality assurance audits across Biotech, Biologics, Sterile Operations, Drug Substances, and 503A/B. She has been Keynote Speaker for the Pharma Industry and internally to the FDA throughout her career.

In this episode of the Ask the Expert video series, Susan J. Schniepp, Regulatory Compliance Associates (RCA), Siegfried Schmitt, Parexel, and Anita Michaels, RCA, explain how CDMOs can best handle regulatory inspections and client expectations. 

Audits, Inspections, and CDMOs

Ask the Expert: Commenting on Draft Regulations

Regulatory agencies, such as FDA and the European Medicines Agencies, and other industry standard setting bodies, such as the International Council for Harmonisation and the US Pharmacopeia, often publish draft versions of the guidance documents they are developing to gather feedback from the public, which includes those scientists and engineers working in the pharmaceutical industry. But who should comment and why?

“You know, there's an opportunity before regulations get approved for industry to participate and offer their comments on the regulation. This has worked in many cases where, for instance, in the US, way back in 2013, 2014, there was a proposal for metrics. And it was through the commenting period that was open to the public, where industry

was able to put forth a case to get the agency to consider some other metrics

that we thought were important, that they were not originally in the proposal,” explains Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates. “So, the way it works is anytime there's a new regulation or a change to an already existing regulation, the FDA will announce it in what we call the Federal Register. It's kind of like the daily newspaper for the government. It's that time when they open it up for comments from industry. And so, it's very important because you can change the final regulation before it becomes official by putting your comments in through this vehicle.”

“Absolutely anyone can comment,” stresses Siegfried Schmitt, PhD, is vice president, Technical at Parexel. “You don't have to be the ultimate expert. If you feel you have something to say, absolutely, you can. Now, perhaps it is advisable or sensible to not just comment as an individual but perhaps comment through your company. Perhaps your company as such is interested in providing comments.”

Both Schmitt and Schniepp also suggest commenting through a trade association, such as the Parenteral Drug Association. “I like commenting through industry associations because usually, they gather a group of experts together proposed regulation topic, And you get to hear not only your perspective voiced, but other experts' perspectives voiced,” Schniepp says. 

“I often see regulators publishing draft guidance documents for public consultation. Can I and should I comment?”

Editor's note: This transcript is a direct, unedited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Okay, hello, everyone. My name is Siegfried Schmitt. I'm vice president technical with PAREXEL, and I'm one of the Ask the Expert experts for the series here, and I'm Sue Schniepp, and I'm part of regulatory compliance associates, which is a subsidiary of Nelson labs, and I am Siegfried's counterpart for Ask the Expert series.

Okay. Oh, hello, Sue. Nice to see you again. Hi, Siegfried, good to see you too well.

So we got another question here for Ask the Expert series, and this is that there are several new regulations being published in draft in Europe. And of course, there are always some being published in the US as well, and the person writing in was wondering, so how can one do this? This commenting and well, is it the done thing? Because he or she feels well, perhaps this is not something that everyone should do. Can you perhaps comment on this?

Yeah, you know, there's an opportunity before regulations get approved for industry to participate and offer their comments on the regulation. This has worked in many cases where, for instance, in the US, now you're the expert on the European arena, but in the US, way back in 2014 2013 there was a proposal for metrics, and it was through the commenting period that was open to the public, where industry was able to put forth a case to get the agency to consider some other metrics that we thought were important, that they were not originally in the proposal. So the way it works is, anytime there's a new regulation or a change to already existing regulation, the FDA will announce it in the what we call the Federal Register. It's kind of like the daily newspaper for the government, and it's that time where they open it up for comments from industry. And so it's very important, because you can change the final regulation before it becomes official by putting your comments in through this vehicle.

That's very interesting. Thank you. Sue and perhaps to add, in Europe, not every regulation is open for public comment, but many are, and so as the person writing in was asking is, can anyone do this? Absolutely, anyone can comment. You don't have to be the ultimate expert if you feel you have something to say absolutely, you can now perhaps it is advisable or sensible to not just comment as an individual, but perhaps comment through your company. Perhaps your company as such, is interested in providing comments many companies do, or perhaps through an industry association like ispe, PDA, raps, you name it there. There are many out there. So perhaps so, because you have done this many times, you could say a few words why this is such a good way to comment. If you do it through an industry association.

Well, I like doing it through the industry associations because usually they gather a group of experts together on the topic, proposed topic, regulation, topic, and you get to hear not only your perspective is voiced, but other experts perspectives are voiced. So I like the broad scope information that working with a team of experts on this topic brings you, it makes the comments more robust. And I, I think the trade organizations have a certain because they're representing multiple experts, multiple companies. There's a little bit more weight kind of associated with it, from my perspective as a commenter, right rather than an individual. I'm not saying that the FDA or the regulatory authorities puts more weight in the comments of a trade organization over an individual. I'm saying that as. As a commenter, I feel there's more weight in my comments when they go in under a trade association. That's a personal feeling, though.

Well, to pick up on this Sue, particularly if you're an inexperienced person in commenting on regulations, I think it's very valuable to be part of such a group, in an industry association, because many of those who will be part of this group will have done it before, and there are certain things that regulators will simply ignore if you put things in that cannot be acted upon. So you can learn an awful lot how you can effectively influence, a regulation, a guidance, and what things are best left out. So it's a very good learning experience, and it helps one understand how, in fact, these regulations are being put together.

Yes, it puts a perspective for the the new person who might be new to this commenting game. I think we've restricted our discussion right now to regulation proposals, but there are other publications that are open for comment, such as the European Pharmacopeia or the United States Pharmacopeia, and it's important for people to understand those two have a comment period where You can influence the outcome of the work that they're doing and establishing, you know, the standards and some of the guide interpretation of guidances and how to enact those do?

They also have these expert advisory groups. I believe they're pharmacopeias.

They do. They have expert committees, both in the EU and the USP, I think that I'm not sure about the Japanese Pharmacopeia. And those advisory panels will propose the change to the Pharmacopeia, and then it will go, usually, through what they call, at least in the US, it's called the pharmacopeial forum, where it's open for review. I forget what they call it in Europe, but it's kind of similar to the same process.

Okay, yes, and perhaps, as you say, it's not just these draft regulations that are open for comment, where you can influence what will be the ultimate regulation, or how things will be regulated, because you and I, we are both members of industry associations and help them write best practice guides, yes, and these best practice guides are sometimes even cited by the agencies like FDA and Emma and so on, because they complement the regulations. Yes, not everything can be in a regulation. Certain things are better said in a guidance document, which may come from an industry association. Well,

there's also, and you're very active in PDA, as I am, and to use them, and as an example, we do publish technical reports on topics that may not quite have made it into the regulation, but are important and implementing some of this standards and expectations of regulatory authorities, and those often can be cited by the regulators, as as you said, Best Practice documents indeed. So coming back to the question that was asked of us, really, it is, it is very advisable to get involved. You do not have to be the ultimate expert, but you learn for yourself also about the processes. You learn about how regulations are being put together, and how, really, industry does have quite an influence on how these regulations will be written. So we can only encourage, I think, become part of these associations, be become an active part, not just the consumer, yes, and I think there's many more, you know, you're touching on a topic near and dear to my heart there. Siegfried, it's not only just commenting, but try to get involved. You know, if you think you have an expertise, maybe you want to put in your nomination. And for a USP expert committee or EP expert committee member. There's also American National Standards Institute. If you're in the US, you can join ANSI, or you can try to join a organization that works to develop ANSI standards. And then there's Amy, right So, and I know there's European organizations, maybe you have some of those that you but to put your name in the hat and say, I'd like to volunteer and I'd like to be on this committee is another great way to try and influence or get the best regulation out there.

And again, if you do work for a company, then your managers will be very interested in this, because it really helps you, but it also helps the company. It raises the profile, doesn't it?

Well, thank you very much. So I think we've covered this topic for today.

I agree. Thank you. Siegfried, always a pleasure to talk with you.

In this episode of the Ask the Expert video series, Susan J. Schniepp, Regulatory Compliance Associates, and Siegfried Schmitt, Parexel, give their opinions on why those working in the pharmaceutical industry should lend their voices to draft regulations.