Many companies view the FDA as a gatekeeper—an obstacle to overcome on the path to clinical trials. But what if you saw them as a partner? An effective Investigational New Drug (IND) application is built on a foundation of clear communication and a proactive relationship with the agency. From Pre-IND meetings to responding to feedback, how you interact with the FDA is just as important as the data you present. A thoughtful IND preparation strategy includes planning these interactions to build trust and alignment from the very beginning. This guide will show you how to work effectively with the FDA, turning a potentially adversarial process into a collaborative effort that moves your product forward.
Key Takeaways
- Patient safety is the core of your application: Frame every piece of data—from your manufacturing process to your animal studies—as evidence that you have thoroughly assessed and mitigated risks to human subjects.
- Proactive planning prevents costly delays: A successful IND submission can take up to 18 months to prepare. Start early with a realistic timeline and allocate the right resources to avoid rushing critical steps that can lead to a clinical hold.
- Tell a clear and cohesive scientific story: Organize your application into a logical narrative that connects your lab findings to your clinical plan, making it easy for FDA reviewers to follow your reasoning and trust your research.
What is an IND Application? (And Why It Matters)
Think of an Investigational New Drug (IND) application as your formal request to the FDA for permission to start testing a new drug in humans. Before you can begin any clinical trials, you must submit this application and get the green light. It’s a critical checkpoint in the drug development journey. The IND isn’t just a form; it’s a comprehensive package of information that tells the FDA everything they need to know about your drug before it’s given to the first human volunteer.
The core purpose of the IND is to demonstrate that your proposed clinical trial is reasonably safe for participants. The FDA meticulously reviews all the preclinical data you’ve gathered from lab and animal studies to ensure that people in the trials won’t be exposed to unnecessary risks. You’re essentially making a case that your product is ready for the next step and that you have a solid plan to monitor safety throughout the study. Without an approved IND, you simply cannot move forward with human testing. It’s the official gateway from preclinical research to the clinical phase.
The IND’s Role in Drug Development
Before a new drug can be sold, it needs to go through rigorous testing and gain final FDA approval. But even before that, federal law prohibits the distribution of unapproved drugs across state lines. This is where the Investigational New Drug (IND) application comes in. It provides a legal exemption, allowing you to ship your investigational drug to clinical investigators in different locations. This permission is essential for conducting the multi-site trials often needed to gather enough data on a drug’s safety and effectiveness. The IND is the mechanism that makes modern clinical research possible.
How the FDA Ensures Patient Safety
The FDA’s primary goal during the IND review is to protect the health and safety of people participating in clinical trials. The main objective of this early stage is to show that your drug is safe enough for initial human testing and holds promise for treating a specific condition. Once you submit your IND, a 30-day waiting period begins. During this time, the FDA’s team of experts, including pharmacologists, toxicologists, and chemists, scrutinizes your application. If they don’t see any safety concerns that warrant a “clinical hold,” you can proceed with your trials after the 30 days are up. This review ensures that every study is built on a foundation of safety.
What Goes Into Your IND Application?
Think of your Investigational New Drug (IND) application as the complete biography of your product. It’s your formal request to the FDA to start testing your drug in humans, and it needs to tell a compelling, data-backed story. This isn’t just about filling out forms; it’s about presenting a comprehensive package that demonstrates you’ve done your due diligence to ensure the product is reasonably safe for initial human trials. The FDA reviews this information to protect volunteers and patients from unnecessary risks.
Your application is built on three core pillars that work together to justify your proposed study. First, you’ll present all your preclinical and animal study data, which establishes the foundational safety profile of your drug. Second, you’ll provide detailed information on your manufacturing process, assuring the FDA of your product’s quality and consistency. This is often called the Chemistry, Manufacturing, and Controls (CMC) section. Finally, you’ll lay out your exact plan for the human trials, including the clinical protocols and the qualifications of the investigators who will run the study. Each piece is critical, and a weakness in one area can jeopardize the entire application. A well-prepared Investigational New Drug (IND) Application is your ticket to moving forward with clinical development.
Preclinical Data and Animal Studies
This is where you prove your drug is safe enough to move from the lab to human trials. The preclinical section of your IND application summarizes the results from all your pharmacology and toxicology studies. Essentially, this data helps the FDA determine if your product is reasonably safe for initial testing in people. You’ll need to provide detailed reports from animal testing that explore the drug’s effects, both intended and adverse. The goal is to show that you understand your product’s potential risks and have a solid scientific basis for believing the benefits will outweigh them. This evidence forms the bedrock of your argument for why the study should proceed.
Manufacturing and Quality Control Information
The FDA needs to know exactly what your investigational drug is and how you make it. The Chemistry, Manufacturing, and Controls (CMC) section provides a complete picture of your product’s composition, stability, and production process. You’ll need to describe how the drug is manufactured and detail the quality control measures you have in place to ensure its identity, strength, quality, and purity. This information assures regulators that you can produce a consistent and stable product for your clinical trials. Any ambiguity here can raise red flags, so clear, thorough documentation of your manufacturing process is absolutely essential for a smooth review.
Clinical Protocols and Investigator Details
Once you’ve established your drug’s safety profile and manufacturing quality, you need to present a clear and detailed plan for your human study. This section includes your clinical study protocol, which is the step-by-step blueprint for how the trial will be conducted. The FDA reviews this plan carefully to ensure that you are not placing human subjects at an unreasonable risk. You’ll also need to provide an Investigator’s Brochure, which is a comprehensive summary of all the information gathered so far, for the medical professionals conducting the trial. Finally, you must include information about the qualifications of your clinical investigators, demonstrating they have the experience to run the study safely and effectively.
Your Step-by-Step Guide to IND Preparation
Putting together an Investigational New Drug (IND) application can feel like a monumental task, but breaking it down into manageable steps makes the process much clearer. Think of it as building a detailed, evidence-based case for why your product is ready for human trials. Each step builds on the last, creating a comprehensive story for the FDA. Following a structured approach not only keeps you organized but also significantly strengthens your submission, helping you put your best foot forward from the very beginning.
Conduct Thorough Preclinical Studies
Before you can even think about testing in humans, you need to prove your drug is reasonably safe. This is where preclinical studies come in. This phase is all about gathering data, typically from animal models, to assess the safety and efficacy of your product. You’re looking for a solid pharmacological profile and initial toxicology data to justify moving forward. The FDA needs to see robust scientific evidence that you’ve done your due diligence to understand potential risks. This foundational data is non-negotiable and forms the scientific backbone of your entire IND application.
Compile Your Application Package
Once you have your preclinical data, it’s time to assemble the full application. This is more than just filling out a few forms; it’s a comprehensive package that tells the complete story of your drug. Your submission must include official FDA forms like 1571 and 1572, a detailed table of contents, your investigation plan, and an Investigator’s Brochure that summarizes everything known about the drug. You’ll also need to include your study protocols, Chemistry, Manufacturing, and Control (CMC) data, and the full results from your nonclinical studies. Each piece provides a critical part of the puzzle for FDA reviewers.
Perform an Internal Review
With so many moving parts, it’s easy for inconsistencies or errors to slip through. That’s why a thorough internal review is a critical step you can’t afford to skip. Before you submit, have multiple stakeholders—from your scientists to your quality assurance team—review the data and documentation. This process helps catch discrepancies, ensures your narrative is consistent, and strengthens the overall quality of your application. A fresh set of eyes can spot issues you might have missed, saving you from potential delays or questions from the FDA down the road.
Follow FDA Submission Procedures
After you’ve compiled and reviewed everything, you’re ready to submit your application to the FDA. Once submitted, a crucial waiting period begins. You must wait 30 calendar days before initiating any clinical trials. This gives the FDA time to conduct a safety review of your application to ensure that research subjects will not be subjected to unreasonable risk. If you don’t hear from the agency within those 30 days, you can proceed with your study. Following the official Investigational New Drug (IND) Application procedures precisely is key to a smooth start.
Overcoming Common IND Preparation Hurdles
Preparing an Investigational New Drug (IND) application is a major undertaking, and it’s easy to get tripped up along the way. Knowing where the common pitfalls lie can help you prepare a stronger, more complete submission. Think of it as mapping out the tricky parts of a trail before you start your hike. By anticipating these challenges, you can build a clear strategy to address them head-on, saving you time, resources, and a lot of stress.
Data Integrity and Documentation Gaps
One of the biggest hurdles is simply the sheer volume of paperwork. The FDA requires extensive documentation to support your application, and any gaps can bring the review process to a halt. You’ll need to provide comprehensive data covering Chemistry, Manufacturing, and Controls (CMC), pharmacology and toxicology studies, and detailed clinical study protocols. The key is to maintain meticulous records from the very beginning of your development process. If your data isn’t well-organized, complete, and easy to follow, it raises red flags for reviewers. Start with a robust data management system to ensure every piece of information is captured accurately and is readily accessible when you need it.
Chemistry, Manufacturing, and Controls (CMC) Complexities
The CMC section of your IND is where you prove you can consistently produce a safe and stable product. This is often a complex area, as you need to demonstrate that your drug will be manufactured to the required quality standards every single time. Challenges frequently pop up around drug stability, validating the manufacturing process, and implementing the right quality control measures. You have to show the FDA that you have complete control over your entire production line, from raw materials to the final packaged product. This isn’t just about having a recipe; it’s about proving your recipe works perfectly on a consistent basis.
Meeting All Regulatory Requirements
Regulatory compliance is more than just a checklist; it’s the foundation of your entire IND application. The FDA has stringent requirements that can vary significantly depending on your product type and its intended use. A common mistake is failing to fully understand and address every applicable regulation. Sponsors must ensure that every single aspect of the application is compliant. This means staying current on FDA guidance and understanding the scientific principles behind the rules. A misstep here can lead to a clinical hold, so it’s critical to get this part right from the start.
Managing Your Timeline and Resources
Many teams underestimate the time and resources needed for a successful IND submission. Depending on the project’s complexity, preparation can take up to 18 months. This isn’t something you can rush in the final few weeks. Effective project management is crucial. It’s essential to start early, create a detailed timeline with clear milestones, and allocate the necessary budget and personnel. Proactive planning helps you avoid costly delays and ensures your team has the support it needs to compile a high-quality application without cutting corners. A well-managed timeline keeps everyone on track and focused on the goal.
Meeting Manufacturing and CMC Requirements
The Chemistry, Manufacturing, and Controls (CMC) section is the part of your IND application where you prove to the FDA that you can consistently produce a safe, high-quality drug. Think of it as the detailed recipe and instruction manual for your product. It covers everything from the raw materials you use to the final packaging. A weak CMC section is one of the most common reasons for a clinical hold, so getting this right is absolutely critical.
This isn’t just about ticking boxes; it’s about demonstrating a deep understanding of your product and manufacturing process. You need to show regulators that you have control over every step, ensuring that the product tested in clinical trials is the same, batch after batch. A well-prepared CMC section builds confidence and shows the FDA you’re ready for the next phase of development. It’s your chance to tell the complete story of how your product is made and why it’s ready for human trials.
Good Manufacturing Practice (GMP) Standards
Good Manufacturing Practices (GMP) are the bedrock of your CMC section. These are the FDA-enforced standards that ensure your product is consistently produced and controlled according to quality standards. Adhering to current Good Manufacturing Practice (cGMP) regulations is non-negotiable. The primary goal is to guarantee that your investigational drug is safe and effective for human testing, which is essential for a successful IND submission. Following GMP from the very beginning helps you avoid contamination, mix-ups, and errors, building a strong foundation of quality that will support your product throughout its entire lifecycle. It’s about creating a robust system that protects patients and your product’s integrity.
Key Quality Control Documents
Your CMC section is built on a comprehensive set of documents that provide a complete picture of your manufacturing process. This is your paper trail of proof. Key documents include official FDA forms like Form 1571 and 1572, a detailed Investigator’s Brochure summarizing your drug, and the specific study protocols. The heart of this package, however, is the detailed CMC data. This is where you lay out the specifics of your drug substance and drug product, including its composition, manufacturer, and specifications. You’ll also need to describe the manufacturing process and the controls you have in place to ensure product quality. Compiling these IND application reporting documents meticulously is crucial for a smooth review process.
Supply Chain and Stability Planning
A strong IND application looks beyond the first batch and plans for the entire clinical trial supply chain. A key part of this is establishing your product’s stability. Early stability testing is vital because it demonstrates how your drug’s quality holds up over time under various environmental conditions. For Phase I trials, you don’t need to have full, complex validation completed. Instead, the focus is on showing that your stability tests are effective and suitable for their intended purpose at this stage of development. This foresight shows the FDA you’re thinking ahead about potential issues, ensuring that patients in your trials will receive a product that is both safe and potent from start to finish.
How to Write an Effective Clinical Protocol
Your clinical protocol is the detailed instruction manual for your human study. Think of it as the master plan that outlines exactly what you’re going to do, how you’re going to do it, and why. This document is a cornerstone of your IND application because it shows the FDA you have a scientifically sound, well-reasoned plan that prioritizes the safety of your participants. A strong protocol demonstrates that you’ve thought through every step, from your study’s objectives to how you’ll handle the data you collect. It’s your chance to build the FDA’s confidence in your research and your ability to conduct it responsibly. A clear, comprehensive protocol isn’t just a requirement; it’s the foundation of a successful clinical trial.
Designing Your Study and Monitoring Safety
When you’re preparing an Investigational New Drug (IND) application, your primary focus must be on designing a study that is both scientifically valid and safe for participants. Your protocol must clearly outline the study’s objectives, design, methodology, and statistical considerations. It also needs a robust plan for monitoring and reporting adverse events. As the ‘IND Sponsor-Investigator,’ you are responsible for compiling all the necessary information for the submission. This means creating a detailed clinical protocol that leaves no room for ambiguity and proves you have put every possible safeguard in place to protect the people who volunteer for your trial.
Selecting Endpoints and Biomarkers
Choosing the right endpoints and biomarkers is critical for proving your drug works. Endpoints are the outcomes you’ll measure to determine if the drug is effective, while biomarkers are measurable indicators of a biological state or condition. It’s vital to identify and test biomarkers that can be measured consistently across laboratory, animal, and human studies. A key part of a successful Investigational New Drug application is establishing how your lab results correlate with clinical outcomes. This connection, known as in vitro-in vivo correlation (IVIVC), strengthens your argument by showing that your preclinical data is relevant to human studies.
Connecting Preclinical Data to Human Studies
This section of your protocol serves as the bridge between your lab work and your human trial. It’s where you present the evidence from your animal studies and explain why it justifies testing the drug in people. The goal is to demonstrate that the drug is reasonably safe for initial human trials based on your preclinical findings. If you are repurposing an approved drug for a new use, this section should provide a clear, compelling rationale for why you believe it will be effective for the new indication. This narrative is crucial for convincing the FDA that moving forward with human testing is a logical and safe next step.
How to Work Effectively with the FDA
Think of the FDA not as a hurdle, but as a partner in bringing a safe and effective product to market. Building a positive, professional relationship with the agency can make your entire IND process smoother. The key is proactive, clear, and organized communication. When you show the FDA that you’re prepared, thoughtful, and responsive, you build the trust needed for a successful review. Let’s walk through how you can establish this effective working relationship from the very beginning.
Pre-IND Meetings and Communication Tips
While a Pre-Investigational New Drug (IND) meeting is optional, I always recommend it. This is your best opportunity to get direct feedback from the FDA on your development plan before you formally submit your application. To make the most of this meeting, you need to be thoroughly prepared. This isn’t a casual chat; it’s a strategic discussion where you can get clarity on potential issues and align on the path forward. Your goal is to present your case clearly and ask targeted questions that will help you refine your application. A well-planned meeting demonstrates your commitment to the process and can save you significant time and resources down the line.
Create a Comprehensive Briefing Package
Your Pre-IND meeting hinges on a strong briefing package. This document, typically 30 to 50 pages, is your formal introduction to the FDA. It should outline your product, manufacturing plan, preclinical safety data, and the proposed design for your human trials. Don’t just present information; use the package to guide the conversation. Include five to seven specific questions about areas where you need FDA input, especially if your approach differs from standard practices. It’s also smart to propose alternative strategies, like different trial designs. This shows the agency you’ve done your homework and are thinking critically about your development program.
Respond to FDA Feedback and Questions
The conversation doesn’t end when the meeting is over. Your follow-up is just as important. Within 30 days of your Pre-IND meeting, send a letter to the FDA summarizing the key discussion points and any agreements that were reached. This creates an official record and ensures everyone is on the same page. Internally, you need a clear system to track every piece of feedback and every question from the agency. Document how you plan to address each comment and who is responsible for the changes. Responding to the FDA in a timely and organized manner shows that you respect their guidance and are a reliable partner in the regulatory process.
How Long Does IND Preparation Really Take?
One of the most common questions I hear is about the timeline for preparing an Investigational New Drug (IND) application. It’s a critical piece of the puzzle, impacting everything from your budget to your go-to-market strategy. The short answer is: it takes time. This isn’t a process you can rush, as every piece of data needs to be precise to meet the FDA’s rigorous standards.
The journey to a successful IND submission is a marathon, not a sprint. It involves meticulous planning and a deep understanding of regulatory requirements. Building a realistic roadmap that accounts for preclinical studies, manufacturing, and potential hurdles is key. Let’s break down what that timeline looks like and how you can plan your resources to stay on track.
Setting Realistic Timeline Expectations
Let’s get straight to the point: preparing for an IND submission takes a significant amount of time. Depending on your product’s complexity, you could be looking at a preparation period of up to 18 months before you can even begin your IND program. This lengthy timeline accounts for everything from initial preclinical studies to compiling the final dossier.
Because the process is so involved, the best advice is to start as early as possible. Getting a head start allows you to thoughtfully conduct your research, address data gaps, and ensure your manufacturing is compliant. Rushing can lead to mistakes that cause delays or even a clinical hold from the FDA. Setting a realistic timeline gives your team the space to do things right the first time.
Planning and Allocating Your Resources
A successful IND submission is a major milestone that shows your product’s safety and efficacy. To get there, you need more than just time—you need a solid plan for your resources. This includes your budget, personnel, and the expertise required to manage each part of the application. Proper resource allocation is directly tied to your timeline, ensuring you have what you need at every stage of the 18-month (or longer) process.
This is where you’ll align your team and ensure your manufacturing follows Good Manufacturing Practices (GMPs). A well-managed project is crucial for a successful IND submission support strategy. Mapping out your needs early helps you avoid bottlenecks and keep your submission on track.
Best Practices for a Successful IND Submission
Submitting an Investigational New Drug (IND) application is a major milestone. While the process is complex, a few core practices can significantly improve your chances of a smooth review. It’s not just about having the right data; it’s about presenting that data with clarity, precision, and a compelling narrative. The FDA reviewers are tasked with ensuring patient safety, and your job is to make it easy for them to see why your proposed study is scientifically sound and ready for human trials. By focusing on storytelling, rigorous review, and logical organization, you can build an application that stands out for all the right reasons.
Tell a Clear Scientific Story
Your IND application should read less like a data dump and more like a compelling scientific narrative. Don’t make reviewers hunt for the information they need. Instead, guide them through your research with a clear and logical story. Start with the drug’s Mechanism of Action (MOA), explaining exactly how it works in the body. Connect the MOA directly to its intended therapeutic use and any potential safety concerns. Using straightforward language, visuals, and diagrams can help simplify complex concepts and demonstrate a thorough understanding of your product. A well-told story helps the FDA quickly grasp the science behind your drug, building confidence in your proposal from the very first page.
Implement a Multi-Level Data Review
To ensure your data is accurate, consistent, and error-free, you need more than one set of eyes on it. A multi-level review process is your best defense against inconsistencies that could delay your application. Start with the scientists who generated the data, then have team leaders review their specific sections. From there, department heads can check for regulatory and procedural compliance. The final step should be a cross-functional review, where experts from different areas examine the entire application for gaps or contradictions. This tiered approach ensures that every detail is scrutinized, strengthening the integrity of your submission and demonstrating a commitment to Good Documentation Practices.
Organize Your Narrative for Clarity
A successful IND application creates a clear and logical bridge between your animal studies and your proposed human trials. The FDA needs to see how your preclinical data supports the safety and design of your clinical protocol. Your narrative should cohesively link your drug’s mechanism, its effects in animal models, and any potential side effects to the plan for human testing. This involves creating a strong translational plan that justifies your starting dose, dose escalation scheme, and safety monitoring procedures. By clearly organizing your story, you show reviewers that you have thoughtfully considered how your drug will behave in humans, which is a critical factor in gaining approval to proceed.
Common IND Mistakes (And How to Avoid Them)
Navigating the Investigational New Drug (IND) application process is a major milestone, but it’s also filled with potential pitfalls that can cause significant delays. Even the most promising therapeutic can be held up by simple, avoidable errors in the submission. Understanding these common mistakes is the first step toward sidestepping them entirely.
The good news is that most of these issues fall into a few key categories: problems with the foundational science, how the information is presented, or the overall project timeline. By focusing on a well-planned study design, clear documentation, and a patient, methodical approach, you can build a much stronger application. Let’s walk through the most frequent hurdles and discuss how you can clear them with confidence.
Inadequate Preclinical Study Design
Your preclinical data is the foundation of your entire IND application. If that foundation is weak, the whole submission is at risk. A common mistake isn’t a lack of data, but data from studies that weren’t designed to answer the specific questions the FDA has about safety and dosing. The agency requires comprehensive preclinical study results to feel confident that your product is safe enough for human trials.
To avoid this, start with the end in mind. Before you even begin your studies, map out exactly what safety and toxicity questions your research needs to answer. Your study design should be robust, well-documented, and directly support your proposed clinical trial. Working with a regulatory strategy expert early can help ensure your preclinical program is built to meet FDA expectations from day one.
Poor Documentation and Data Presentation
You could have the best data in the world, but if the FDA reviewer can’t understand it, it won’t get you very far. Many applications get bogged down by disorganized data, overly dense text, or the inclusion of unnecessary information. These issues create confusion and force reviewers to hunt for the information they need, which can lead to questions, delays, or even a clinical hold.
Think of your IND submission as a clear, compelling story. Your job is to guide the reviewer through your research logically. Use clear headings, summaries, and a well-organized structure to make your key findings easy to locate and digest. Every piece of information should have a purpose. If it doesn’t support the safety and rationale of your proposed study, consider leaving it out. A clean, professional presentation shows respect for the reviewer’s time and reflects the quality of your work.
Rushing Through Critical Development Steps
In the race to get to the clinic, it’s tempting to cut corners. However, rushing through crucial preclinical and manufacturing steps is one of the most damaging mistakes you can make. Misconceptions about the importance of thorough planning often lead to sponsors trying to move too quickly, which almost always causes bigger setbacks down the road. A gap in your stability data or an incomplete animal toxicology study can bring your entire program to a halt.
Treat each step of the early development process with the attention it deserves. Building a realistic timeline with built-in buffers is essential. This allows you to address unexpected challenges without derailing your entire project. Remember, a well-executed plan is your fastest path to a successful IND submission. Taking the time to get it right the first time will save you months, or even years, in the long run.
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Frequently Asked Questions
When exactly do I need to file an IND application? You need to file an Investigational New Drug (IND) application before you can legally ship an unapproved drug across state lines to a clinical investigator. More importantly, you must have an approved IND before you begin testing your new drug in human subjects. Think of it as the official gateway between all your laboratory and animal research and the first phase of human clinical trials.
What happens after I submit my IND application to the FDA? Once you submit your application, a 30-day waiting period automatically begins. During this month, a team of FDA experts reviews your submission to ensure that your proposed study does not place human participants at an unreasonable risk. If you don’t receive any communication from the FDA placing your study on a “clinical hold” within those 30 days, you are clear to proceed with your trials.
If I had to focus on one part of the application, what’s the most critical section to get right? While every section is important, the preclinical data from your pharmacology and toxicology studies is the absolute foundation of your application. This is the evidence you present to prove your drug is reasonably safe to test in humans. Without strong, well-documented preclinical data that directly supports your proposed clinical plan, the FDA will not allow you to move forward.
Is a Pre-IND meeting with the FDA really necessary? While it’s not mandatory, I strongly recommend a Pre-IND meeting. This is your single best opportunity to get direct feedback from the FDA on your development plan before you invest the time and resources into a formal submission. A productive meeting can help you identify potential issues, clarify regulatory expectations, and align with the agency on your study design, which can prevent major delays later on.
Why is the Chemistry, Manufacturing, and Controls (CMC) section so challenging? The CMC section is often a hurdle because it requires an incredible amount of detail and precision. You aren’t just describing how you make your drug; you’re proving you have complete control over the entire process to ensure every batch is consistent, stable, and pure. This involves complex process validation and quality control measures that can be difficult to document perfectly, making it a common area for FDA questions and scrutiny.