Last month (October 13, 2021), the Food and Drug Administration (FDA) held a conference that is part of the CDER Small Business & Industry Assistance (SBIA) Regulatory Education for Industry (REdI) series.
This meeting aims to offer an Electronic Drug Registration and Listing or the eDRLS system that provides basic instruction in the registration and drug listing policy and process for those who are new to this regulatory program as well as offers regulatory professionals more in-depth information on issues and current events affecting FDA Drug Registration and Listing. It also allows FDA to maintain an updated listing of all drug manufacturers and all drugs manufactured and distributed in the United States. (1)
According to the FDA, owners or operators of establishments that manufacture drugs have to register with FDA. They have to list each drug they manufacture that is intended for commercial distribution and to update the listings twice each year notifying the Administration if this information has changed. This can be done electronically through a structured product labeling or SPL format. (1)
Registration and listing SPL files can be easily created through third-party tools that require an official FDA WebTrader (https://esg.fda.gov/login) account for submission. Each submission, regardless of the source and tools used, passes through a rigorous process. (1)
So, who needs to register with FDA? Any drug establishments that formulate, develop, manufacture, prepare, compound, or process drugs that are marketed in the United States must register with FDA. Foreign companies need to identify a U.S.-based agent and importer or importers when they register. This requirement applies to any bodies that elaborate drugs, but not to most pharmacies, hospitals, clinics, healthcare entities, licensed practitioners, companies that manufacture drugs for research or analysis rather than for sale, manufacturers of inactive ingredients (like colorings, flavorings, preservatives, etc. that might be used as drug components but are not active), and storage facilities. (2)
In addition， medical supplies manufacturers, distributors, and sales organizations that create and distribute drugs have to register within five days of starting to introduce drugs into commercial distribution. They can renew their registration between October 1 and December 31, and this must be done annually, while listing updates can take place at any time. (1-2)
How can you register? You need to create and submit a registration SPL document, created with software that includes all the required information, such as the Data Universal Numbering System (DUNS) number of your establishment or its name and Dun and Bradstreet verification, contact information for the individual who will handle correspondence and communication with FDA, all the applicable business operations that your establishment carries out (e.g., repackaging, relabeling, manufacturing drugs, etc.), and the DUNS of your U.S. agent or importer if applicable. (2)
Even if you are not making changes, you need to renew your registration using one of the available applications and submit a No Change Notification type document. If you need to make changes, you also need to submit through one of the applications the SPL that features all the information about the drug. FDA offers resources to help individuals manage this procedure and training for handling the systems that are in place for an electronic registry. You can also deregister through the application, selecting the document type of Establishment De-Registration. After successful submission, you will receive a renewed expiration date for your establishment within 24 business hours. (2)
Furthermore, you need to include a listing of all the drugs that will be commercially distributed in the U.S. under their labeler code, which is something you must request from the FDA. This needs to feature all the required information for all products featuring active and inactive ingredients, dosage and administration route, 10-digit National Drug Code (NDC), proprietary and non-proprietary names, a copy of updated labeling and an image of the packaging, and the DUNS for each establishment that is involved in manufacturing. Once submitted, you can renew each year without changing the product listing. (2)
An NDC is a unique three-segment number that serves as an identifier for FDA. NDC numbers have to be submitted when doing drug listing and are assigned previously, which identify the labeler, the product, and the commercial package size. In order to apply for an NDC, the labeler must apply online with an NDC Labeler Code Request SPL through the same applications used for drug listings. Note that having an NDC is not the same thing as having FDA approval. The Labeler code process of registration is required for getting an NDC. (3)
In order to submit an NDC, you need to be part of an establishment that is officially registered and has a DUNS number, as well as begin production or commercialization of a drug product that is approved for sale and manufacturing within the United States. You need to provide all the requested information and the NDC, in particular, and familiarize yourself with systems like CDER and the documents listings that use the SPL format. You can find additional training materials on the FDA website that will walk you through the process. Remember that you must submit five days after you begin commercializing a drug and you must offer a drug product listing three days after and include all drug products with the information the organization requests. There are three main steps to the process overall that takes place over the same electronic system: first, the establishment registration, then the labeler code, and finally the drug products. (3)
In addition to this, FDA will use automated validation rules to avoid incomplete data submissions. They use different monitoring methods to ensure all the data in their databases is accurate. If there are inaccuracies, they will contact the manufacturer to correct the information. If these corrections are not made, FDA might remove the data. Some inaccuracies might result in even stricter sanctions and problems, like the data being inactivated, the company receiving a warning, or more depending on the severity of the issue. The warning letters, for instance, can be consulted on the FDA website and are publicly available. (4)
Overall, the process of electronic submission has clear guidelines in regards to time and the documentation necessary. It is possible to consult tutorials or take the SBIA webinar offered by FDA to understand the process more in-depth, however, the main information required for the process can be found here: https://www.fda.gov/drugs/electronic-drug-registration-and-listing-system-edrls/electronic-drug-registration-and-listing-instructions.
It is worth noting that eDRLS is important for any domestic and foreign manufacturing company or exporter of drugs into the United States and plays an important role for a successful commercialization of a product.
1. FDA. (2021). Electronic Drug Registration and Listing System (eDRLS). https://www.fda.gov/drugs/guidance-compliance-regulatory-information/electronic-drug-registration-and-listing-system-edrls
2. FDA. (2021). Electronic Drug Registration and Listing Instructions. https://www.fda.gov/drugs/electronic-drug-registration-and-listing-system-edrls/electronic-drug-registration-and-listing-instructions
3. FDA. (2021). National Drug Code Directory. https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory
FDA. (2021). Electronic Registration and Listing Compliance Program. https://www.fda.gov/drugs/electronic-drug-registration-and-listing-system-edrls/electronic-registration-and-listing-compliance-program
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