A regulatory submission requires a structured dossier containing quality, safety, and efficacy documentation compiled according to the relevant regulatory framework. For medicinal products in the EU and most global markets, this follows the Common Technical Document (CTD) format. The exact documents required depend on the product type, the regulatory pathway, and the target market.
Getting the documentation right from the start is one of the most important factors in achieving a smooth approval process. Missing or poorly prepared documents are among the leading causes of delays, questions from authorities, and outright rejections. The sections below break down what goes into a regulatory dossier and how requirements vary across product types.
What types of documents make up a regulatory dossier?
A regulatory dossier is a structured collection of documents that demonstrates a product’s quality, safety, and efficacy to a regulatory authority. For medicinal products, the internationally accepted CTD format organises this into five modules covering administrative information, summaries, quality data, nonclinical data, and clinical data. Together, these modules give regulators everything they need to assess a product.
The five CTD modules are:
- Module 1: Administrative and regional documents, including application forms, product information, and labelling
- Module 2: Summaries and overviews of the quality, nonclinical, and clinical data
- Module 3: Quality documentation covering chemistry, manufacturing, and controls (CMC)
- Module 4: Nonclinical study reports, including pharmacology and toxicology
- Module 5: Clinical study reports and post-marketing data
Not every module needs to be equally complete for every submission type. A generic medicine application, for example, may rely on bibliographic references for nonclinical and clinical data rather than original study reports. The scope of the dossier is always shaped by the regulatory pathway chosen.
What are the CMC documents required for a regulatory submission?
CMC documents, found in Module 3 of the CTD, describe the chemistry, manufacturing, and controls for both the drug substance and the finished drug product. These documents must demonstrate that the product can be manufactured consistently to the required quality standard. CMC is often one of the most extensive and technically demanding parts of a regulatory submission.
Drug substance documentation
For the drug substance (the active ingredient), CMC documentation typically includes a description of the manufacturing process and process controls, characterisation data confirming structure and properties, specifications and analytical methods, reference standards, container closure system details, and stability data supporting the proposed retest period or shelf life.
Drug product documentation
For the finished drug product, the required documents cover the formulation and its development rationale, the manufacturing process, including in-process controls, excipient information, specifications and validated analytical methods, container closure systems, and stability studies under appropriate conditions. For biologics and biotechnology-derived products, additional requirements apply, including detailed characterisation of the biological material and validation of the manufacturing process. If you are unsure which CMC documents apply to your specific product type, our regulatory services cover the full scope of dossier preparation across all product categories.
What clinical and nonclinical documents does a submission need?
Nonclinical documents (Module 4) include reports from pharmacology and toxicology studies conducted in vitro and in animal models. These establish the safety profile of the compound before human exposure. Clinical documents (Module 5) cover the full clinical development programme, from Phase I through Phase III trials, along with any post-marketing study reports if applicable.
The key nonclinical documents include:
- Pharmacodynamic study reports
- Pharmacokinetic study reports
- Toxicology study reports, including single-dose, repeat-dose, genotoxicity, carcinogenicity, and reproductive toxicity studies
- Local tolerance studies
The key clinical documents include:
- Clinical pharmacology reports (bioavailability, pharmacokinetics, pharmacodynamics)
- Controlled and uncontrolled clinical study reports
- Integrated summaries of safety and efficacy
- Synopses of individual study reports
For products using a well-established use or bibliographic approach, published scientific literature may substitute for original study reports, provided it meets the evidentiary standards required by the relevant authority.
How do document requirements differ for medical devices versus medicinal products?
Medical devices do not follow the CTD format. Instead, they require a Technical Documentation file compiled in accordance with the EU Medical Device Regulation (MDR 2017/745) or the In Vitro Diagnostic Regulation (IVDR 2017/746). The content and depth of this file depend on the device classification, ranging from Class I to Class III, with higher-risk devices requiring significantly more evidence.
For medical devices, the Technical Documentation typically includes:
- Device description and specification, including intended purpose and user population
- Design and manufacturing information
- General safety and performance requirements (GSPR) checklist with supporting evidence
- Benefit-risk analysis and risk management file (aligned with ISO 14971)
- Product verification and validation data, including usability and biocompatibility testing
- Clinical evaluation report (CER), including a clinical evaluation plan
- Post-market surveillance plan and periodic safety update reports (PSURs)
- EU Declaration of Conformity and, for higher-class devices, a Notified Body certificate
For drug-device combination products, the requirements from both frameworks can apply, making documentation particularly complex. The regulatory pathway depends on the primary mode of action and whether the product is classified as a medicinal product or a device. Learn more about our team’s background and experience in navigating these complex classification decisions.
What happens if documents are missing or incomplete in a regulatory submission?
If documents are missing or incomplete, the regulatory authority will issue a list of outstanding issues or a request for supplementary information. In the EU centralised procedure, this typically comes in the form of Day 120 or Day 180 questions from the EMA. Responding to these questions adds months to the review timeline and requires significant internal resources.
In more serious cases, a submission can be declared invalid at the outset if it fails to meet the minimum administrative completeness requirements. This means the clock on the review period does not even start. For national procedures, similar validation checks apply, and incomplete submissions are returned to the applicant before assessment begins.
The most common documentation gaps that trigger questions include:
- Insufficient stability data to support the proposed shelf life
- Analytical methods that have not been fully validated
- Inconsistencies between the summary documents and the underlying study reports
- Missing comparability data for biologics following manufacturing changes
- Inadequate justification for the chosen regulatory pathway or product classification
Thorough pre-submission planning and a structured internal review process are the most effective ways to reduce the risk of incomplete submissions. Engaging with regulatory authorities through scientific advice procedures before filing can also clarify expectations and prevent avoidable gaps.
How Starodub helps with regulatory submissions
At Starodub, we support biopharmaceutical and medical device companies at every stage of the regulatory submission process, from early dossier planning to the final filing and beyond. Our team brings hands-on expertise across small molecules, biologics, vaccines, and medical devices, which means we understand the specific documentation demands of each product type.
Here is what we offer:
- Dossier gap analysis: We review your existing documentation against current regulatory requirements and identify what is missing or needs strengthening before submission
- CMC documentation support: We prepare and review Module 3 content, including drug substance and drug product sections, stability summaries, and manufacturing process descriptions
- Medical device Technical Documentation: We compile and review Technical Files and Design Dossiers in line with MDR and IVDR requirements for all device classes
- Regulatory strategy: We advise on the most appropriate submission pathway, product classification, and timing to avoid unnecessary delays
- Submission management: We coordinate the full submission process, manage timelines, and handle responses to regulatory authority questions
With over 400 completed projects and more than 300 clients supported, we know what it takes to get a dossier approved efficiently. If you want to make sure your next submission is complete, well-structured, and ready for review, get in touch with our team today to discuss how we can help.
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This content was generated with the help of AI and it may contain mistakes
