Draft Guidance Falls Short on Providing Clarity for Companies Denied Certificates to Foreign Government

One of the most painful consequences of a bad inspection at a U.S. facility is FDA’s resulting refusal to issue certificates to foreign governments (CFGs) until the issues are resolved. CFGs are quite often a requirement to renew licenses and permits to sell in various foreign markets. Although typically linked to a warning letter, sometimes a Form 483 can trigger this refusal. Sometimes it can take many months, or more than a year, for FDA to begin issuing CFGs again. During that time period, a manufacturer may find itself unable to sell product into certain foreign countries.

Section 704 of the FDA Reauthorization Act (FDARA) amended Section 801 of the Federal Food, Drug, and Cosmetic Act to require FDA to provide additional clarity to the bases for denying CFGs. The statute requires that:

• FDA must provide a written statement of the basis for denying a request for a CFG “and [must] specifically identify the finding upon which such denial is based.”
• If the denial is based on a routine inspectional finding that a facility is out of compliance with the QSR, FDA must “provide a substantive summary of the specific grounds for noncompliance.”
• A CFG may not be denied if it is solely based upon the issuance of a Form 483 if the manufacturer “has agreed to a plan of correction in response.”

FDARA also directed FDA to set up a process that appears to be essentially equivalent to supervisory appeals of significant decisions. A manufacturer denied a CFG may at any time “request a review in order to present new information” relating to corrective actions.

In accordance with FDARA, on August 17, FDA issued draft guidance, “Process to Request a Review of FDA’s Decision Not to Issue Certain Export Certificates for Devices.” The short, seven-page guidance is intended, according to FDA, to clarify the new statutory requirements related to CFG denials. In our reading, however, it leaves open more questions than answers and mainly reiterates the statutory requirements.

For example, the statute states that a CFG may not be denied based solely upon a Form 483 if the manufacturer “has agreed to a plan of correction in response.” The guidance requires the following steps to satisfy this standard:

1. The owner, operator, or agent in charge of the establishment should submit a plan of correction in writing to the appropriate FDA office. The plan should include steps the owner, operator, or agent in charge of the establishment will take to correct observations documented and timeframes for completing such steps.
2. The FDA will review the plan and notify the owner, operator, or agent in charge of the establishment whether the plan is sufficient to address the violations documented in the inspectional observations. If the plan is agreed to, FDA will issue a CFG.

Step 1 sounds to us like a well-prepared 483 response. As any manufacturer will tell you, FDA virtually never notifies a company that it is in agreement with its corrective actions outlined in a 483 response. The Agency’s agreement is commonly assumed through Agency silence (e.g., lack of a Warning Letter or other enforcement action) and is often confirmed when an Establishment Inspection Report is issued documenting that the Agency has closed out the inspection.

Therefore, Step 2 appears to be entirely new requiring FDA to affirmatively notify the company that its plan is “sufficient to address the violations documented in the inspectional observations.” FDA provides no details about how this process will unfold. For example, how long will it take FDA to review a company’s response? What if a plan is generally sufficient but the Agency has minor changes, will FDA provide that feedback to the company so it can modify its plan and then reach agreement? We hope that FDA will provide additional clarity regarding this new process in the final guidance.

Another area that warrants further clarification is the process for reviewing a CFG denial. The statute required FDA to set up a process for a company to “request a review in order to present new information” relating to corrective actions. The guidance essentially states that if a manufacturer wishes to obtain such a review, it should email the applicable export branch (CDRH or CBER) and provides the respective email addresses. The guidance states “if the issue cannot be resolved by the [applicable export branch], each Center’s review process will be followed.”

For CDRH appeals, the guidance references another guidance document specific to the CDRH appeals process, but notes that the request is not considered to be a 517A “significant decision,” and therefore is not subject to the 30 day filing and review timeframes. (For CBER-regulated products, FDA references the Formal Dispute Resolution Request process, but explicitly disclaims its ability to resolve issues within 30 days per the FDRR guidance.) It provides no further information as to how long it might take for the export branches to address a request for review. Nor does it state whether or how an export branch might communicate its process, timeline, or status to a company with a pending request for review. In our view, these additional details are essential to a well-established process. We hope that FDA will provide additional clarity in its final draft so that the positive intentions of Section 704 of FDARA may be realized for industry.