If you're new to regulatory submissions, they can seem a little confusing - and not just because there are some many acronyms to learn. To help you navigate the landscape, we offer this short guide to the most common regulatory submission types in the United States (FDA) and European Union (EMA), with links to more detailed information.
Regulatory submissions are comprehensive packages of documents and data submitted to health authorities, such as the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA), to demonstrate the safety, efficacy, and quality of a drug, medical device, or biotherapeutic. These submissions are a crucial part of ensuring the safety, efficacy, and quality of therapies, medicines, and devices.
The purpose of regulatory submissions is to provide detailed information about a product or service, including manufacturing processes, clinical trial results, labeling, and proposed usage. Regulatory authorities review these submissions to assess the risks and benefits associated with the product or service and make informed decisions about its approval, labeling, and post-market surveillance.
Understanding the regulatory submission requirements and processes is essential for companies operating in regulated industries, such as pharmaceuticals, medical devices, biotechnology, and food and beverages.
In life sciences, a regulatory submission can be the culmination of many years of work - and is a major factor in bringing a new product to market. Thus it's important to have a complete understanding of the submission process and how to set yourself up for approval!
There are many types of regulatory submissions, each serving a specific purpose on the path to approval in a given country or region. The most common types include:
- Investigational New Drug (IND) Application: Sponsors submit this application to the US Food and Drug Administration (FDA) to initiate clinical trials for new drugs. It includes data on the drug's safety and efficacy, the study protocol, and investigator information. Note that some drugs (or biologics) may quality for an Emergency Investigational New Drug (EIND) Application.
-Clinical Trial Application (CTA): The CTA is the European equivalent of the IND. To submit a new CTA to the European Medicines Agency (EMA), you'll need to leverage the Clinical Trial Information System (CTIS) portal.
- Pre-Market Approval (PMA) Application: This submission is required for the approval of many medical devices in the US. Note that if your device is similar enough to an existing, approved device - you may be able to submit a simpler 510(k) Premarket Notification instead. It's important to evaluate your device's Class and relation to any such 'predicate' devices to determine your submission path.
- New Drug Application (NDA): This FDA submission is required for the approval of new pharmaceutical drugs in the US. It includes comprehensive data on preclinical studies, clinical trials, manufacturing processes, labeling, and proposed usage. NDAs are managed by FDA’s Center for Drug Evaluation and Research (CDER).
- Abbreviated New Drug Application (ANDA): The ANDA option is a streamlined version of the New Drug Application for generic versions of brand-name medicines that have already been approved by the FDA. ANDAs can rely on existing data to demonstrate bioequivalence. ANDAs are regulated by the Office of Generic Drugs (OGD).
-Biologics License Application (BLA): In the US, Biologics - that is, drugs that are derived from living organisms - are classified separately for marketing approval. BLAs are overseen by the FDA’s Center for Biologics Evaluation and Research (CBER).
- Marketing Authorization Application (MAA): This submission is required for the approval of new pharmaceutical drugs in the EU. It includes similar data as the NDA, but follows the guidelines set by the EMA. The Committee for Medicinal Products for Human Use (CHMP) evaluates marketing authorization applications, with input from the Pharmacovigilance Risk Assessment Committee (PRAC) on aspects of the risk-management plan and the Committee for Advanced Therapies (CAT) for advanced-therapy medicines.
These are just a few examples of the various types of regulatory submissions that companies may need to prepare and submit to regulatory authorities. It's important to stay apprised of the differences between countries. Efforts to align and coordinate global submissions, led by the International Council of Harmonisation (ICH) and ISO, are always ongoing.
| United States (US) | European Union (EU) | |
| Regulatory Authority | Food & Drug Administration (FDA) | European Medicines Agency (EMA) |
| Authorization for Clinical Investigations | Clinical Trial Application (CTA) | |
| Pre-Authorization (for Medical Devices) |
N/A | |
| Marketing Applications | Marketing Authorization Application (MAA) |
The regulatory submission process typically involves several stages and requires careful planning and coordination. Some key steps in the process often include:
- Preparing for the Submission: Companies need to gather all the required data and documentation for the submission, ensuring compliance with regulatory guidelines and requirements. In many cases, teams will request preliminary meetings with representatives from the relevant agency, which can be helpful in determining areas of focus for their submissions. Leveraging regulatory software to assist with authoring, submission building, and project management can significantly reduce human errors and ensure your documents will meet compliance requirements.
- Submission Compilation: The collected data and documentation are compiled into a submission package in the required format, which may include forms, reports, clinical trial data, labeling, and manufacturing information. For FDA submissions, the required format is the Electronic Common Technical Document (eCTD) format. Teams typically used specialized software to 'publish' their submissions in the eCTD format.
- Submission Review: Regulatory authorities review the submission package, assessing the data and information provided. This may involve multiple rounds of questions, clarifications, and additional data requests. Sponsor teams will often track this agency correspondence carefully, as can be critical to their successful approval.
- Approval Decision: Based on the review, the regulatory authority makes a decision on the approval or rejection of the submission. They may also provide specific labeling requirements or post-market surveillance obligations.
Navigating the regulatory submission process requires expertise in regulatory affairs, a thorough understanding of the applicable regulations, and effective communication with regulatory authorities. Kivo has been fortunate to partner with a number of excellent regulatory consultants - just let us know if you'd like a recommendation!
The regulatory submission process can be complex, and there are common pitfalls that companies should be aware of - both to increase their likelihood of approval and to avoid delays on their path to market. Some of these pitfalls include:
- Inadequate Data: Insufficient or incomplete data can lead to delays or rejection of the submission. It is crucial to gather robust and comprehensive data to support the safety, efficacy, and quality of the product or service. Preliminary agency meetings early in the submission process can be a great way to learn which areas may be most important to support with comprehensive data.
- Non-compliance: Failing to comply with regulatory guidelines and requirements can result in rejection of the submission. It is essential to stay updated on the latest regulations and ensure full compliance throughout the submission process. A key mistake we often see is documents stored in file sharing systems that do not meet Part 11 requirements. This can be mitigated with a fit-for-purpose RIM system that will automatically assemble the audit trail as well as capture digital signatures.
- Poor Communication: Lack of effective communication with regulatory authorities can lead to misunderstandings and delays. It is important to maintain open and transparent communication, promptly addressing any questions or requests from the authorities.
- Inaccurate or Inconsistent Documentation: Errors or inconsistencies in the submission documentation can raise concerns about the reliability and accuracy of the data. It is crucial to review and double-check all documentation for accuracy and consistency.
By being aware of these common pitfalls and taking proactive measures to address them, companies can increase their chances of a successful regulatory submission.
We hope this guide proves useful as you begin your regulatory journey. As you can see, the path to approval can be somewhat complex and requires a great deal of collaboration - both internal and external. In fact, that's one of the main reasons we created Kivo GO, to help teams work together more efficiently on their path to regulatory approval.