ANDAs: Pre-Submission Facility Correspondence (PFC) Associated with Priority Submissions

Introduction

The Abbreviated New Drug Application (ANDA) is a vital pathway for the approval of generic drugs in the United States. In order to market a generic drug, an ANDA submission must demonstrate that the proposed product is bioequivalent to the reference listed drug (RLD). One important aspect of the ANDA submission process, particularly for priority submissions, is the Pre-Submission Facility Correspondence (PFC). This correspondence is a crucial part of the process and ensures that the FDA has all the necessary information to evaluate the ANDA submission effectively and efficiently.

This article will delve into the role, importance, content, timing, and procedure associated with Pre-Submission Facility Correspondence for ANDAs, especially in the context of Priority Submissions.

1. What is Pre-Submission Facility Correspondence (PFC)?

Pre-Submission Facility Correspondence (PFC) refers to communications between the applicant of an ANDA and the FDA before the formal submission of the ANDA. These correspondences are an essential part of the process, particularly for facilities involved in manufacturing or testing the generic product. PFC is particularly important for Priority Submissions, which are applications that the FDA deems as having significant public health impact, such as those for drugs that address critical unmet medical needs.

PFC may involve discussions about a facility’s compliance with FDA regulations, Good Manufacturing Practices (GMP), bioequivalence testing, or specific questions regarding the ANDA submission. These interactions are designed to ensure that the facilities involved in the production of the generic drug are adequately prepared for inspection and comply with all relevant regulatory standards.

2. The Role and Importance of Pre-Submission Facility Correspondence (PFC)

1. Ensuring Facility Readiness:

• PFC helps ensure that manufacturing and testing facilities are ready for FDA inspection. It provides an early opportunity for the FDA to assess whether the applicant’s facilities comply with relevant regulations.

1. Facilitating Early Resolution of Issues:

• By engaging in PFC, applicants can raise any concerns related to facility operations, GMP compliance, or other technical issues well before the submission of the ANDA. Early resolution of potential issues can prevent delays during the ANDA review process.

1. Expediting the Review Process:

• For priority submissions, where the applicant seeks faster approval due to a significant public health need, PFC helps streamline the application. It provides the FDA with the necessary information up front, helping them prioritize and review the submission more efficiently.

1. Supporting Regulatory Compliance:

• PFC ensures that facilities meet FDA’s regulatory requirements such as compliance with GMPs and other safety and efficacy regulations. This reduces the likelihood of delays or complications arising due to facility-related issues during the ANDA review.

1. Facilitating Communication with the FDA:

• PFC serves as an official communication channel between the applicant and the FDA. Through this correspondence, applicants can clarify expectations and receive guidance directly from the FDA, ensuring that they meet all necessary criteria for approval.

3. Content of Pre-Submission Facility Correspondence (PFC)

1. Facility Information:

• Name and location of the manufacturing and testing facilities involved in the ANDA submission.
• Contact information of key personnel, such as facility managers or regulatory affairs staff, to ensure easy communication.

1. GMP Compliance Status:

• Documentation or evidence demonstrating that the facility is compliant with Good Manufacturing Practices (GMP) and has passed previous FDA inspections.
• If applicable, a description of any corrective actions taken following previous inspection findings or audits, along with evidence of remediation.

1. Bioequivalence Testing Information:

• Details of the bioequivalence studies conducted at the facility, which demonstrate that the generic product is equivalent to the reference listed drug in terms of efficacy and safety.
• Information about the methodology and protocols used in the bioequivalence testing, including clinical studies, laboratory data, or analytical techniques.

1. Questions or Concerns about the ANDA Submission:

• The applicant may raise any specific questions or concerns about the ANDA application that they would like clarification on from the FDA.
• This may include queries about any new or unusual technologies being used or concerns about facility-specific issues that might affect the submission.

1. Inspection Status:

• Information about the previous FDA inspections and inspection status of the facilities. If a facility has had a recent inspection by the FDA, this may be referenced, including whether any Warning Letters or Form 483s (inspectional observations) were issued and the current status of corrective actions taken.

1. Other Relevant Documentation:

• Compliance records, certifications, and quality assurance documentation to demonstrate that the facility is operating in accordance with FDA regulations.

4. When Should Pre-Submission Facility Correspondence (PFC) Be Submitted?

PFC should be submitted before the formal ANDA submission, allowing the FDA to evaluate facility compliance, manufacturing capabilities, and other relevant factors early in the process. The timing of PFC submission is crucial and depends on the type of ANDA being filed:

1. For Priority ANDA Submissions:

• Priority ANDAs are processed faster due to their public health significance. It’s **recommended that PFC be submitted at least *60 days* before submitting the actual ANDA** to allow the FDA sufficient time to review the correspondence and resolve any potential issues with the facility.
• The applicant should also ensure that any necessary facility inspections are scheduled in advance.

1. For Standard ANDA Submissions:

• While there is generally no specific timeline for submitting PFC for standard ANDA submissions, applicants are advised to submit PFC well before submitting the formal ANDA to avoid any delays.

5. Procedure for Submitting Pre-Submission Facility Correspondence (PFC)

1. Preparation of PFC Documentation:

• The applicant prepares all necessary documentation, ensuring that it addresses all the critical points mentioned above, including GMP compliance, bioequivalence testing, and any facility concerns.

1. Submission to the FDA:

• PFC is usually submitted electronically through the FDA’s Electronic Submissions Gateway (ESG). For paper submissions, the FDA may accept them in limited circumstances, but electronic submission is the preferred method.

1. FDA Review:

• Upon receiving the PFC, the FDA will review the information provided and may request additional information if necessary. The FDA may also schedule an inspection of the facility if it has not been inspected recently.

1. Communication of Findings:

• If the FDA has concerns or additional questions regarding the facility, it will communicate with the applicant. This may involve further correspondence or a meeting to resolve issues before the formal ANDA submission.

1. Follow-Up Actions:

• If the facility is deemed to be non-compliant or there are serious concerns, the FDA may request corrective actions before the ANDA is submitted. Failure to address these issues can delay the ANDA approval process.

6. Key Considerations and Relevant Information for PFC Submissions

• Ensure GMP Compliance: Facilities should be fully compliant with GMP regulations. Any non-compliance should be addressed and resolved promptly before submitting PFC.
• Bioequivalence Testing: Clearly demonstrate bioequivalence through robust testing data. The FDA requires detailed protocols and results to substantiate claims of equivalence to the reference product.
• Timeliness: Submit PFC well in advance of the ANDA submission to allow adequate time for review and feedback.
• Transparent Communication: Be proactive in addressing any facility-related concerns, potential deviations, or corrective actions. Transparent communication with the FDA can expedite the approval process.

Conclusion

Pre-Submission Facility Correspondence (PFC) plays a critical role in the ANDA submission process, particularly for Priority Submissions, by helping ensure that the facilities involved in the production of generic drugs meet the necessary compliance standards. By addressing facility-related concerns early in the process, applicants can reduce the likelihood of delays and ensure a smoother review of their ANDA. Adhering to the proper procedure, submitting PFC in a timely manner, and ensuring compliance with FDA regulations are essential steps in securing approval for a generic drug.