FDA has guidance on how to implement manufacturing process and facility changes, and the process for reporting these types of changes to the application in the references below.
FDA is committed to helping get medical products to market quickly and to helping ensure that these products are safe, effective and high quality. Manufacturers, applicants and sponsors, including those working under U.S. government contracts, must comply with the applicable laws and regulations that govern drug development and manufacturing to protect the public health, including during the COVID-19 outbreak.
As part of this commitment, FDA provides information to stakeholders concerning drug and biologics development and manufacturing, including for products to diagnose, cure, mitigate, treat or prevent COVID-19 and for other critically needed products to treat symptoms of COVID-19 or to provide supportive care to those with COVID-19.
FDA issued a temporary guidance for industry entitled, “Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency Questions and Answers.” FDA recognizes the COVID-19 public health emergency is not only impacting public health, but also drug development programs, ongoing manufacturing operations, and FDA’s ability to conduct inspections. The agency also recognizes sponsors and applicants have many questions related to FDA inspections. FDA developed this guidance to provide answers to a number of frequently asked questions.
The Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, and the Office of Regulatory Affairs remain fully capable of continuing daily activities, such as application assessments, including facility evaluation and certain inspection activities, while responding to public health needs related to the current COVID-19 public health emergency. As this remains an evolving and very dynamic situation, FDA will continue to be flexible and transparent. The questions and answers in this guidance provide information regarding common questions related to inspections for facilities manufacturing pharmaceutical products and sites involved in the conduct of clinical, analytical and nonclinical studies.
FDA is implementing an interim process to communicate issues identified following a review of records or other information requested under section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) in lieu, or in advance, of a Pre-Approval or Pre-License Inspection for CDER regulated products. FDA intends to communicate issues to facility representatives following the completion of its review of records or other information requested under section 704(a)(4) of the FD&C Act. The agency plans to consider any formal responses regarding these issues, including documentation of corrective action, prior to taking an action on a pending application impacted by these issues, as feasible given user fee agreement and internal review program milestones. The interim process will be implemented for the remainder of the COVID-19 public health emergency and evaluated periodically, revised as needed, and may be expanded to record request processes in lieu, or in advance, of other drug inspection programs (e.g., routine surveillance).
Actions FDA May Take on an Application When the Agency Cannot Inspect a Facility Due to Factors Including Travel Restrictions
FDA is providing information to drug manufacturers on circumstances under which the agency plans to approve an application, issue a complete response (CR) letter, or defer action when a site cannot be inspected due to factors including travel restrictions related to the public health emergency, and how FDA plans to prioritize inspections as travel restrictions are lifted.
Decisions regarding applications will be based on the totality of the information available to FDA, including information obtained from use of the alternative tools, which may include remote interactive evaluations as described in FDA’s guidance to industry. Based on an assessment of the product information provided in the application and based on available information about the facility or site, and as further explained in the revised “Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency Questions and Answers" guidance, FDA will take one of the following actions:
Facilities and Sites
Other FDA Drug Assessment Deficiencies
Approve the application
Available information supports the adequacy of the facilities and sites named in a pending application
No deficiencies have been identified and the application otherwise satisfies the requirements for approval.
Issue a CR letter with facility- or site-related deficiencies
Available information from a prior inspection or other source identifies deficiencies about the facility or site, but the required inspection cannot be completed due to factors including travel restrictions.
If any other deficiencies, are identified by the assessment team, the CR letter will include those deficiencies.
Issue a CR letter without facility or site deficiencies
An inspection is necessary because there is a lack of information about the facility or site but cannot be completed due to factors including travel restrictions (a facility or site deficiency will NOT be issued in this case; the facility or site issue will be a comment in the CR letter).
Other deficiencies are identified by the assessment team. The CR letter will contain those deficiencies.
Defer action (i.e., miss the goal date)
An inspection is necessary because there is a lack of information about a facility or site and cannot be completed due to factors including travel restrictions (a facility or site deficiency will NOT be issued in this case).
No deficiencies have been identified, and the application otherwise satisfies the requirements for approval.
Throughout the COVID-19 public health emergency, CDER’s Office of Pharmaceutical Quality has been using all tools at our disposal to continue evaluating facilities to assure drug quality. One of these tools is remote interactive evaluation using livestreamed video of operations and remote, live interactions with operators.
CDER’s Office of Compliance's Use of Remote Interactive Evaluations
FDA adapted to the challenges presented by the COVID-19 public health emergency by using all tools at our disposal to take the compliance and enforcement actions necessary to shield patients from unsafe, ineffective, and poor-quality drugs. Where in-person inspections are not feasible, we use remote interactive evaluations to help ensure product approvals and authorizations are based on valid, reliable data.
For additional questions about manufacturing changes, please email [email protected]. Please include “COVID-19 inquiry” in the subject line of the email.
- CDER’s Work to Meet User Fee Goals During the Pandemic
- Guidance for Industry: Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency
- Guidance for Industry: Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency
- 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
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