Beyond the 50 States: Puerto Rico Licensing and Registration Requirements for Drug and Device Companies

Puerto Rico is a U.S. territory with its own regulatory framework for pharmaceutical manufacturers, distributors, and medical device companies. Federal registration alone is not sufficient. This guide covers what is required to enter the Puerto Rico market and remain compliant.

Non-Resident Licensing: Repeal of Special Authorization

Effective June 17, 2025, Administrative Order No. 612 repealed the Special Authorization License requirement for all non-resident pharmaceutical entities, including manufacturers and wholesale distributors.

This is a common point of confusion, as non-resident licensure was once required, but today, it no longer exists.

The repeal does not eliminate other regulatory obligations, however. Any facility shipping product onto the island must be licensed in its home jurisdiction and provide documentation as proof.

Non-resident organizations must also complete a business registration, designate a Representative Agent on the island, and submit their product registrations.

Requirement #1: Business Registration

Any company doing business in Puerto Rico must complete two registrations before shipping products or engaging customers:

• State Department: Obtain a certificate of authorization to do business in Puerto Rico.
• Treasury Department (Hacienda): Register for tax compliance purposes.

Requirement #2: Designate a Representative Agent

Any company that passes title to pharmaceutical products in Puerto Rico must designate a licensed Representative Agent with a physical presence on the island, registered with the Puerto Rico Secretary of Health.

A Representative Agent must register with the Puerto Rico Secretary of Health and serve as the company's official liaison with the Department of Health. The agent handles regulatory communications, license filings, and product registrations on the company's behalf and must be physically located on the island.

Failure to maintain a qualified Representative Agent puts the company's registrations and compliance status at risk.

Requirement #3: Drug and Product Registration

The label holder, otherwise known as the manufacturer, is responsible for registering all pharmaceutical products with the Puerto Rico Department of Health before they can be sold on the island. This is separate from FDA approval.

Wholesale distributors that sell products directly into Puerto Rico must also register those products, even if they are not the label holder. A wholesaler may register as an interested party regardless of whether they appear on the label.

All other business models, including 3PLs, do not register products themselves, but must ensure that any product they sell or distribute into Puerto Rico is already registered before doing so.

Each registration requires:

• Home state license documentation
• FDA approval documentation
• DEA license documentation (*for controlled substances only)
• Labeling and package inserts
• The Representative Agent's license information

The Department of Health issues an official Certificate of Registration upon approval. Drug registrations do not expire. They are filed once and remain valid until the product is withdrawn from the Puerto Rico market, or a change occurs, such as a change in Representative Agent or product name.

Requirement #4 (As Needed): Controlled Substance Registration

Separate registration is required for any controlled substance product that will be distributed to the island.

The Controlled Substance Product Registration must be obtained in the name of the company as well as the Representative Agent, at the address on the island where shipment records are stored.

This means that two separate registrations need to be filed:

1. Controlled Substance Registration for Representative Agent
2. Controlled Substance Product Registration

These controlled substance registrations must be submitted to Puerto Rico, even if you already have DEA approval.

Timeframes for Puerto Rico Registration

• Business registration (State Department and Hacienda): Two to four weeks with complete documentation.
• Drug product registration: Several weeks to a few months, depending on submission completeness and DOH review volume.
• Controlled substance registration: 2-3 months, depending on submission completeness and DOH review volume.

Rules for Medical Devices

For standalone medical devices that are FDA-cleared (510(k)) or FDA-approved (PMA), a separate Puerto Rico product registration is generally not required.

If the device is a combination product that includes a drug component or API, the medical device must be registered with the Puerto Rico Department of Health under the standard drug registration process.

Virtual Manufacturers Must Register

Earlier this year, the Puerto Rico Department of Health Division of Controlled Substances confirmed that virtual manufacturers selling controlled substances in Puerto Rico are now required to obtain a Controlled Substance Registration for Representative Agent. This applies to Schedules II through V.

Previously, no registration pathway existed for virtual manufacturers. Companies that have been distributing controlled substances in Puerto Rico without this registration are out of compliance as of the agency's confirmation.

Virtual manufacturers cannot file directly. The registration must be obtained through a licensed Representative Agent.

The Division of Controlled Substances will also request documentation from the CMO, including:

• Quality agreements between the virtual manufacturer and the CMO
• The CMO's registrations and licenses
• Documentation of the oversight structure between the two entities, including SOPs for the sales process and license verification of their clients

Common Challenges and Causes for Delay

• Incomplete product registration packages: missing labeling samples, incorrect Representative Agent information, or absent FDA documentation are the most frequent causes of delay.
• Missing CMO documentation: virtual manufacturers seeking controlled substance registration must have quality agreements and CMO oversight documentation ready before filing.
• Representative Agent lapses: the Agent's license must remain current. Lapses affect the company's ability to maintain and file registrations.
• Assuming FDA approval means no Puerto Rico filing: true for standalone devices, not for drug-device combination products.

Assistance with Puerto Rico Licensing and Registration

LighthouseAI provides professional support for state licensing and product registration on the island, and can serve as your Representative Agent through staff physically located in Puerto Rico.

As your Representative Agent, we act as your official liaison with the Department of Health, handling regulatory communications and filings on your behalf so you can focus on bringing your products to market.

If you have questions about Puerto Rico or are ready to get started, we are here to help. Contact Us