Regulatory Submission Process: Types, Phases, and Management

Last Updated: November 2026

What is the regulatory submission process, and how do teams manage regulatory submissions from planning through approval and beyond?

A regulatory submission is a formal request asking a health authority, such as the FDA or EMA, to let a medical product enter clinical trials or reach the market. The process runs in five phases: pre-submission planning, document compilation, submission assembly and publishing, agency interaction, and post-approval lifecycle management. Regulatory submission management is the work of planning, tracking, and controlling every one of those submissions, along with the documents, deadlines, and agency correspondence behind them.

Table of Contents

• What Is a Regulatory Submission?
• Types of Regulatory Submissions
• Regulatory Submissions in Clinical Trials
• What Is Regulatory Submission Management?
• Key Phases of the Regulatory Submission Process
• Common Pitfalls (and How to Avoid Them)
• Submission Process Variations by Product Type
• How Regulatory Platforms Compare
• RIM: Your Regulatory Backbone
• FAQ

What Is a Regulatory Submission?

At its core, a regulatory submission is a formal request to a government agency for approval to begin or continue a specific activity related to a medical product, usually clinical trials or commercial distribution.

It’s the bridge between your development work and a regulatory decision.

Submissions include detailed documentation to demonstrate that your product is safe, effective, high-quality, and meets the relevant regulatory requirements for the market you’re targeting.

Types of Regulatory Submissions

The main types of regulatory submissions are clinical trial applications (an IND in the U.S., a CTA in the EU), marketing applications for drugs and biologics (NDA, ANDA, BLA, and MAA), medical device submissions (510(k), De Novo, PMA, and EU technical documentation), and post-approval submissions such as supplements, variations, and periodic reports. The terminology and requirements vary by product type and market.

Here’s a quick snapshot of the most common submission types:

Drugs (U.S.)

• IND (Investigational New Drug): Required before starting clinical trials
• NDA (New Drug Application): Submitted for market approval
• ANDA (Abbreviated New Drug Application): For generics

Biologics

• IND (same as above)
• BLA (Biologics License Application): For market approval of biologic therapies

Medical Devices (U.S.)

• 510(k): Shows substantial equivalence to an existing device
• PMA (Premarket Approval): Required for high-risk devices
• De Novo: For novel, moderate-risk devices with no predicate

Diagnostics and IVDs

• Often follow device pathways (510(k), PMA)
• EU submissions follow IVDR-specific requirements

Combination Products

• Submitted based on primary mode of action (drug, biologic, or device)
• Often require coordination across multiple regulatory divisions

European Union

• CTA (Clinical Trial Application): Required to start a clinical trial in the EU, submitted through CTIS
• MAA (Marketing Authorisation Application): Required for most drugs and biologics
• Technical Files and Design Dossiers: Used for medical devices under MDR or IVDR

Post-Approval Submissions

• U.S. drugs and biologics: supplements to an approved application (prior-approval supplements and CBE-30 or CBE-0 changes) and annual reports
• EU medicines: variations (Type IA, IB, and II) and renewals
• Medical devices: PMA supplements, or a new 510(k) for a significant change to a cleared device

Regardless of submission type, the goal is the same: demonstrate that your product meets the regulatory standards for safety, efficacy, and quality.

Regulatory Submissions in Clinical Trials

Before a clinical trial can start, the sponsor must submit a clinical trial application to each regulator involved. In the U.S., that is an IND, and under 21 CFR Part 312 the trial can begin 30 days after FDA receives it unless FDA places it on clinical hold. In the EU, it is a CTA filed through the Clinical Trials Information System (CTIS) under the EU Clinical Trials Regulation (No 536/2014), which has applied to all EU trials since January 31, 2025. Significant-risk device studies in the U.S. need an approved IDE instead.

Submissions continue while the trial runs:

• Protocol amendments for new protocols and changes to existing ones
• Safety reports, such as IND safety reports for serious and unexpected suspected adverse reactions
• Annual reports, due within 60 days of the IND's anniversary date in the U.S.
• Information amendments with new chemistry, manufacturing, or nonclinical data

What Is Regulatory Submission Management?

Regulatory submission management is the process of planning, assembling, tracking, and maintaining every submission a company makes to health authorities, along with the documents, timelines, and agency correspondence tied to each one. It covers a submission's full life: the content plan, document status, the publishing handoff, agency questions and commitments, and changes after approval.

In practice, good submission management answers five questions at any point in time:

• What are we submitting, to which agencies, and when?
• Which documents are final, approved, and the correct version?
• What has already been sent, and in which sequence?
• Which agency questions and commitments are still open?
• Which post-approval changes, variations, or renewals are coming due?

Small teams often start with spreadsheets and shared drives. As products, markets, and partners multiply, most move this work into a regulatory information management (RIM) system so plans, documents, and correspondence are tracked in one place. The phases below show where that tracking matters most.

Key Phases of the Regulatory Submission Process

Most regulatory submissions move through five phases: pre-submission planning, document compilation, submission assembly and publishing, submission and agency interaction, and post-submission lifecycle management. The exact steps vary by product type and pathway. For context on scale: CDER alone approved 46 novel drugs (new molecular entities and new biologics) in calendar year 2025, and that count doesn't include the far larger volume of supplements, generics, and device submissions agencies review every year.

Understanding these stages helps you plan ahead, assign responsibilities, and avoid surprises.

1. Pre-Submission Planning

This is where strategy takes shape. Before you ever submit a document, your team is developing a regulatory plan, identifying target markets, mapping submission timelines, and possibly engaging with agencies through pre-submission meetings (e.g., FDA Pre-IND, EMA Scientific Advice).

This stage is also where you define the structure and scope of your submission content. A well-organized plan makes the entire process smoother later on — see how a RIM system supports global submissions planning for more on mapping timelines across multiple markets.

The most useful technologies during pre-submission planning are going to be a strong Regulatory Information Management (RIM) system and regulatory intelligence tools.

A great RIM system helps teams map out what needs to be submitted, when, and by whom. It brings structure to the process early on, making it easier to coordinate across regulatory, clinical, CMC, and quality functions. 

Regulatory intelligence tools help your team understand current regulatory requirements by region, assess potential risks, and choose the right submission pathway. This is especially valuable for first-time submissions, new markets, or products in evolving categories like diagnostics or gene therapies. 

2. Document Compilation

Once your content plan is in place, it’s time to gather and prepare all the necessary documents. This often includes:

• Clinical trial data and study reports
• Nonclinical safety data
• Manufacturing and CMC documentation
• Product labeling and packaging info
• Administrative forms and certifications

Each document typically goes through multiple rounds of authoring, review, and approval. Version control and traceability are critical, especially when working across internal departments or external partners.

The most useful technology during document compilation is a centralized document management system (DMS), ideally one that is purpose-built for regulatory work. 

A great life sciences DMS allows teams to store, organize, and collaborate on documents across functional areas like clinical, nonclinical, CMC, and labeling. More importantly, it helps prevent compliance issues across version control, user permissions, and audit trails.

3. Submission Assembly and Publishing

Once your documents are final, they need to be formatted and organized according to regulatory guidelines, most often in eCTD (electronic Common Technical Document) format for drugs and biologics, or as structured technical files for devices.

This phase includes:

• Linking and formatting documents
• Performing validation checks
• Using publishing tools to build the final submission package

The eCTD standard itself is mid-transition globally. Japan's PMDA became the first ICH region to require eCTD v4.0, for new applications filed from April 2026. In the EU, v4.0 has been optional for new centralised marketing authorisation applications since December 2025, and EMA's published timeline plans mandatory use for those applications from early 2028. The FDA has accepted new applications in v4.0 on a voluntary basis since September 2024, began accepting v4.0 for existing v3.2.2 applications in October 2026, and has not set a mandatory date. That staggered timing is worth tracking if your submissions span multiple regions.

The two most useful technologies during submission assembly and publishing are regulatory submission software and an eCTD publishing  solution, especially for drug and biologic submissions, which require strict formatting, metadata, and validation to be accepted by agencies like the FDA or EMA.

Kivo's regulatory submission software makes a big difference during submission assembly. It ensures the documents you’re pulling together are already approved, versioned correctly, and organized in a way that mirrors the final submission structure, so when it’s time to publish, you’re assembling, not scrambling. See what a connected regulatory submission system needs for a closer look at what "connected" actually requires.

Kivo intentionally doesn't include eCTD publishing itself — doing so would mean marking up a white-labeled third-party tool or locking customers into one vendor. Instead, your submission can be exported to a great eCTD publishing solution like Lorenz DocuBridge that will build the final submission package, check for technical errors, and ensure everything is formatted correctly before it's sent. Once submitted, the eCTD remains viewable in Kivo's own eCTD Viewer, linked back to the source documents in the DMS.

4. Submission and Agency Interaction

Now it’s time to submit. Depending on your region, you may upload files to a regulatory portal (like the FDA’s ESG or EMA’s IRIS system) or send them directly to a notified body.

After submission, expect follow-up:

• Agencies may request additional information (e.g., Information Requests, Deficiency Letters)
• You may need to submit responses within tight timelines
• Some products will go through advisory committee reviews or require inspection coordination

How long that follow-up window lasts depends on the review track: under PDUFA VII, the user-fee agreement in effect through September 2027, a standard FDA drug/biologic review carries a 10-month goal from acceptance, priority review shortens that to 6 months, and a major amendment during review can extend either goal date by 3 months.

Once a submission is sent, the focus shifts to tracking interactions with regulatory agencies and managing requests, correspondence, and follow-up tasks.

The most useful technology during submission and agency interaction is a strong RIM system.

A RIM system with correspondence and commitment tracking gives your team a structured place to log agency communications, assign follow-up tasks, track deadlines, and ensure nothing slips through the cracks. Instead of reacting to requests as they come in, you can respond strategically and with full visibility into what was submitted, when, and by whom.

5. Post-Submission and Lifecycle Management

Approval isn’t the end of the story. Ongoing responsibilities may include:

• Submitting updates and variations
• Tracking post-market commitments
• Managing labeling changes and periodic reports
• Renewing licenses or certificates

While you can technically track these manually, the more products and markets you support, the harder it becomes to stay on top of everything without missing a deadline or repeating effort.

The most helpful technology during post-submission and lifecycle management is, once again, a strong RIM system.

A RIM system with built-in lifecycle management keeps track of every commitment made to health authorities, every label that needs updating, and every country-specific variation that needs follow-through. Instead of piecing together emails or spreadsheets, your team can see exactly what’s due, when, and why, helping you stay compliant and responsive long after the initial approval. For companies running several products or indications, see what a RIM system needs to manage multiple indications.

Common Pitfalls (and How to Avoid Them)

The most common submission pitfalls are fragmented document storage, weak version control, rushed reviews, formatting errors at publishing, and poor lifecycle visibility. Most are preventable with clear planning, structure, and the right tools.

1. Fragmented Document Storage

When submission documents are scattered across email threads, personal folders, SharePoint sites, and local drives, things get lost. And when the clock is ticking, no one wants to hunt for “final_FINAL_v3_clean.docx.”

What helps: Centralizing your documents in a single, controlled system like a DMS or DMS-integrated RIM, ideally one designed for regulatory with access controls, version history, and automated workflows.

2. Lack of Version Control

If multiple people are editing the same document in parallel (or worse, from outdated copies), it’s only a matter of time before something slips through.

What helps: Use tools that track document ownership, changes, and approvals. RIM platforms often include this natively, giving everyone confidence they’re working on the right version.

3. Rushed Reviews and Missed Deadlines

When timelines aren’t clear or approvals get stuck in someone’s inbox, reviews pile up at the last minute. That’s when errors happen, and quality suffers.

What helps: Clear task assignments, automated reminders, and dashboards that show what’s done, what’s pending, and what’s at risk. This is where structured workflows really shine.

4. Submission Formatting Issues

Even strong submissions can be delayed by technical issues: broken links, formatting errors, or missing metadata during eCTD publishing.

What helps: Use publishing tools that validate your submission before you send it. Many RIM platforms white label publishing as a "built-in" feature, while others (our recommendation here at Kivo) integrate with best-in-class publishing software, allowing for more flexibility. 

5. Poor Lifecycle Visibility

Once a submission is complete, the work isn’t over. Teams often struggle to track commitments, variations, or labeling changes months (or years) down the line.

What helps: A RIM system with built-in lifecycle tracking keeps ongoing requirements visible and manageable, even as teams change or grow.

Avoiding these pitfalls isn’t about working harder, it’s about building a more sustainable, scalable process.

Submission Process Variations by Product Type

Submission requirements differ mainly by product type. Drugs and biologics use eCTD-formatted applications built around clinical and CMC data, devices follow risk-based pathways with more format flexibility, and combination products need coordination across FDA centers.

ATMPs, Biosimilars, and Other Specialized Categories

There are other fast-growing or niche categories (like cell & gene therapies, biosimilars, or veterinary products) that follow their own regulatory pathways. These often involve even greater documentation complexity, regional variability, and evolving guidelines.

No matter what type of product you’re working on, the core submission principles apply, but understanding what’s expected for your specific category is essential to building the right submission strategy, timeline, and team.

How Regulatory Platforms Compare for Submission Management

Many teams evaluate a dedicated platform once spreadsheets stop scaling. The options below are a starting point, not an independent ranking. This table does not assess implementation quality, market share, or fit for any particular organization, so validate every option against your own requirements.

RIM: Your Regulatory Backbone

The regulatory submission process has a lot of moving parts, and the more products, partners, or markets you’re managing, the more complex it gets.

That’s why a great RIM system isn’t just a nice-to-have. It’s the regulatory backbone supporting you through the entire journey.

From mapping out submission plans and tracking timelines, to keeping documents organized, approvals on schedule, and post-submission commitments visible, a good RIM platform keeps everything (and everyone) moving in the same direction. For a checklist of what to look for, see the features that define a modern RIM system. It gives you confidence that nothing’s slipping through the cracks, even when you’re juggling multiple submissions at once.

At Kivo, we’ve built a RIM system that does exactly that without the complexity or cost of traditional enterprise tools. It’s fast to implement, easy to use, and purpose-built for life sciences teams that want to work smarter, not harder. Kivo RIM is rated 4.9/5 on G2 — the highest-rated RIM software on the platform — and more than 200 sponsor, consultant, and CRO teams currently run their regulatory operations on Kivo.

If you're curious to see how it works, we’d love to show you. Click below to book a demo and chat with our team of life sciences specialists. 

Frequently Asked Questions

What is regulatory submission management?

Regulatory submission management is the process of planning, assembling, tracking, and maintaining a company's submissions to health authorities such as the FDA and EMA. It covers the content plan, document versions and approvals, the publishing handoff, agency questions and commitments, and post-approval changes like supplements, variations, and renewals.

What are the main types of regulatory submissions?

The main types are clinical trial applications (IND in the U.S., CTA in the EU), marketing applications for drugs and biologics (NDA, ANDA, BLA, MAA), medical device submissions (510(k), De Novo, PMA, EU technical documentation), and post-approval submissions such as supplements, variations, and annual reports.

What regulatory submissions does a clinical trial need?

A trial needs an approved or cleared clinical trial application before it starts: an IND in the U.S., which can proceed 30 days after FDA receipt unless placed on hold, or a CTA through CTIS in the EU. During the trial, sponsors submit protocol amendments, safety reports, and annual reports.

How long does an FDA regulatory submission take to review?

Under PDUFA VII, in effect through September 2027, a standard NDA or BLA review carries a 10-month goal from FDA acceptance, while priority review shortens that to 6 months. Device pathways like 510(k) and De Novo generally move faster, though a major amendment can extend any goal date by 3 months.

What's changing with eCTD 4.0 for global submissions?

Japan's PMDA has required eCTD v4.0 for new applications filed since April 2026. In the EU, v4.0 is optional for new centralised MAAs, and EMA plans to make it mandatory for them from early 2028. The FDA has accepted v4.0 voluntarily since September 2024, extended that to existing applications in October 2026, and has not set a mandatory date.