EAS Offers U.S. Agent Services for Foreign Companies

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.

FDA Combines Old and New Inspection Tools for Imported Foods

The Food and Drug Administration is using a combination of old and new tools to improve the safety of imports and a quick look at the numbers explains why.

We’ve seen the familiar statistics: Almost 50 percent of fresh fruit, 20 percent of fresh vegetables, and 80 percent of seafood is imported. The U.S. imports from more than 200 countries and from about 125,000 firms, so a risk-based approach to inspection is really the only kind of oversight that makes sense.

FDA’s Don Prater, in his new role as acting assistant commissioner for food safety – which makes him the agency’s new point person for FSMA – discussed this in an FDA Constituent Alert last month.

FDA activities related to imported foods are undergoing big changes, largely due to FSMA, he said.

Overseas inspections are very resource intensive because of the need for coordination with national and local authorities, visa requirements, logistical arrangements, language (need for interpreters), and other challenges, he said. So the agency will keep focusing on facilities that pose the highest risk.

The agency currently uses the Predictive Risk-based Evaluation for Dynamic Import Compliance Targeting (PREDICT) system to electronically screen all regulated shipments imported or offered for import into the U.S. In addition, it is now using data analytics to get a deeper understanding of the global inventory of regulated entities, he said. This will help the agency target its resources.

Traditional inspection will continue, Prater said, so facility inspections and examination at the port of entry will continue to be important tools. The challenge is integrating the old and new tools. The agency currently has several FSMA implementation groups working on this issue.

One challenge involves using information from third parties for oversight activities. A big question is how the agency can use this information in planning its work, he said.

Integrating open source material, such as new reports and social media, has great potential, but is challenging to evaluate and confirm. FDA historically has been very conservative in using unofficial and unconfirmed information to direct its focus. Data analytics may offer some degree of confidence as FDA gains experience.

The agency has recognized just three countries as providing the same level of public health protection – New Zealand, Canada and, just last month, Australia. It is still too early to know when and what will be a recognizable difference in FDA surveillance activities compared to those prior to recognition.