By Bryan Coleman, EAS Senior Director Pharmaceutical & Device Consulting Services, and Victoria Pankovich, EAS Regulatory Specialist
The FDA’s regulatory requirement for foreign firms to have a U.S. Agent can be confusing, to say the least. There are very specific requirements for foreign firms to have a U.S. Agent, and failure to have a competent and responsive U.S. Agent can cause significant compliance issues, delays in applications and submissions and can even impact the importation of their product into the United States. The information below is provided to offer clarity to these requirements and help firms understand this area of the FDA’s governing requirements.
For FDA purposes (as defined in section 201(e) of the Federal Food, Drug, and Cosmetic Act), a U.S. Agent means a person who is physically residing or maintaining a place of business in the United States. A U.S. agent cannot be in the form of a mailbox, answering machine or service, or another place where an individual acting as the foreign facility’s agent is not physically present. U.S. Agent is not the same as a shipper’s U.S. Agent for CBP (Customs and Border Patrol).
What does a U.S. Agent do? Your appointed U.S. Agent will become your firm’s first point of contact with the FDA. They will facilitate communications between your company and the FDA in the area of applications, site inspections, regulatory notifications and resolution of formal compliance concerns (FDA 483s and Warning Letters).
This is particularly beneficial when time zones put your normal operating hours out of synch with the FDA’s routine working schedule. For all human and animal drug application holders and sponsors (DMF, VMF, NDA, BLA, ANDA and NADA, etc.) the U.S. Agent can work to assist and coordinate the migration to electronic submission filing submitting your Amendments, Supplements, Annual Reports, LoAs, etc. via the FDA ESG system.
The FDA eCTD requirements for submissions to CDER and CBER went into effect May 5, 2017, for NDAs, ANDAs and BLAs and will go into effect May 5, 2018, for DMFs and INDs. Submissions of 10 GB or smaller MUST be sent via the FDA ESG. After these dates, only submissions greater than 10 GB will be accepted via physical electronic media.
Who is required to have a U.S. Agent? All foreign establishments and firms who wish to ship their products into the U.S., firms who have an active regulatory submission or are required to be registered with the FDA are expected to have an appointed U.S. Agent. This includes any drug product applications (INDs, NDA, ANDAs, BLAs, NADAs, DMFs, VMFs, etc.) whether pending or approved, the distribution of drug substances, intermediates and finished dosage forms into the U.S. for either commercial or research and development purposes.
A U.S. Agent must be identified for every single foreign facility registration. This includes food facilities (21 CFR 1.232 (d)) under which dietary supplement facilities fall (21 CFR 1.227), drug establishments (21 CFR 207.40 (c)) and medical device facilities (21 CRF 1.232 (d)). A U.S. Agent appointment is required for all ANDAs (21 CFR 314.95(7)) and NDAs (21 CFR 314.52(7)) as well as foreign color manufacturers (21 CFR 80.21(d)). It is highly recommended, although not necessary, to have a U.S. Agent appointed to your DMFs. While INDs do not require a U.S. Agent, it is certainly beneficial to have one.
When is a U.S. Agent required? The U.S. Agent must be appointed before any registration, application or communications with the FDA can begin. As a foreign firm, at the time of registration and listing, you will be asked to provide the name and contact information for your U.S. Agent. Likewise, at the time of submission of any application to CDER, CBER, CDRH, an appointment letter must accompany each specific submission and be on file with the FDA to facilitate any communications.
EAS Consulting Group offers the full breadth of U.S. Agent services to clients around the globe and we are prepared to assist you with meeting the regulatory requirements in this area. Let us know how we can help you.