FDA has guidance on how to implement manufacturing and site changes, as well as reporting to the application, listed in references below.
CDER remains fully capable to continue daily activities, such as drug reviews, while responding to the public health needs of the current COVID-19 outbreak. As this remains an evolving and very dynamic situation, the FDA will continue to be flexible and as transparent as possible.
- Due to the COVID-19 pandemic, FDA announced that we are temporarily postponing all domestic and foreign routine surveillance facility inspections. These facility inspections are assigned biannually using a risk-based Site Selection Model.
- Similarly, routine surveillance inspections in support of the Bioresearch Monitoring (BIMO) program are currently postponed. Postponed inspections are being prioritized for completion when travel restrictions are lifted.
- Where possible, other pathways are being used to inform decisions regarding pending applications including requesting existing inspection reports from other competent authorities, requesting information from applicants, and requesting records from facilities and other inspected entities directly.
- Pre-approval and for-cause assignments deemed mission-critical will still be considered for inspection on a case-by-case basis.
During a mission critical assessment, FDA weighs concerns about the safety of its investigators, employees at a site or facility, and in some cases clinical trial participants and other patients at investigator sites, against the public health benefits to US citizens of having access to the product being inspected. FDA’s assessment considers many factors including if the products are innovative breakthrough products or are considered medically necessary. Both for-cause and pre-approval inspections can be deemed mission critical.
Yes, the determination is the same regardless of whether it is domestic or foreign as it is based on an assessment of the drug product and its value to US patients.
During this interim period, we are utilizing additional tools and approaches to ensure the quality of products imported into the U.S. which have proved effective in the past. These include denying entry into the U.S. for unsafe and inferior quality products, physical examinations of products arriving at our borders or product sampling and testing prior to release into commerce, reviewing the compliance histories of facilities, using information shared by trusted foreign regulatory partners through mutual recognition and confidentiality agreements, and requesting records directly from firms “in advance of or in lieu of” on-site drug inspections.
CDER’s Office of Compliance, Office of Pharmaceutical Quality, Office of New Drugs and Office of Generic Drugs are continuing to evaluate applications over the next several months, strategically applying a consistent, holistic approach and decision making to determine if an inspection is warranted using the mission critical definition and additional tools mentioned above. We will continue to work directly with the applicants of those impacted applications. We encourage you to be in communication with all your facilities and sites to ensure timely responses to any inquiries from the Agency to support application assessment.
- If your application is for a drug not related to the treatment of patients with COVID-19 or not on the FDA drug shortage list, please follow the established guidance documents listed below for changing or adding a facility to your application.
- If your drug application relates to the treatment of patients with COVID-19 or is on FDA's drug shortage list, the cover letter to the submission should clearly state “Priority Review Requested” and include supporting information for the request.
- If the product could enter, or is currently in, drug shortage, please also contact CDER DRUG SHORTAGES (DrugShortages@fda.hhs.gov)
- Please refer to the Agency’s existing guidance on making changes to an ANDA, NDA, or BLA, as well as scale-up and postapproval change (SUPAC) guidance documents for specific dosage forms.
- Should circumstances resulting from the COVID-19 pandemic require atypical or flexible submission strategies, please email CDER-OPQ-Inquiries@fda.hhs.gov for further assistance.
Yes, application filing will not be impacted by COVID-19 travel restrictions.
FDA will continue the quality assessment of all applications per normal assessment operations for all disciplines, where all manufacturing facilities will be evaluated using risk-based approach as per existing guidelines. During this interim period, we are utilizing additional tools to determine the need for an on-site inspection to support the application assessment such as reviewing a firm’s previous compliance history, using information sharing from foreign governments as part of mutual recognition and confidentiality agreements, and requesting records “in advance of or in lieu of” on-site drug inspections. If the final determination is an on-site inspection is necessary, an application may receive a Complete Response.
For additional questions about manufacturing changes, please email CDER-OPQ-Inquiries@fda.hhs.gov. Please include “COVID-19 inquiry” in the subject line of the email.
- Guidance for Industry: CMC Postapproval Manufacturing Changes to be documented in annual reports
- Guidance for Industry: Changes to an approved NDA or ANDA
- Guidance for Industry: Changes to an Approved NDA or ANDA: Questions and Answers
- Scale-Up and Postapproval Changes (SUPAC) guidance documents:
- SUPAC-IR: Immediate-Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation
- SUPAC-MR: Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation: Guidance for Industry
- SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation: Guidance for Industry
- SUPAC: Manufacturing Equipment Addendum
- MAPP: OGD Prioritization of the Review of Original ANDAs, Amendments, and Supplements
- Chemistry, Manufacturing, and Controls Changes to an Approved Application: Certain Biological Products
- For more guidances on this topic and a comprehensive list, see COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders.
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