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# Alternative Tools Let FDA Slash Preapproval Inspections by 55%
- URL: https://www.fdaweb.com/alternative-tools-let-fda-slash-preapproval-inspections-by-55/
- Published: 2021-10-26T12:00:00.000Z
- Updated: 2026-09-14T17:20:17.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5150444

*\[Report by David McFarland\]* FDA’s need to conduct preapproval inspections was reduced by 55% during the Covid-19 pandemic by the agency’s use of alternative tools, CDER Office of Pharmaceutical Manufacturing Assessment director **Stelios C. Tsinontides** told an online Pharmaceutical Quality Symposium 10/26\. Historically, about 20% of all submitted applications end up requiring a preapproval inspection, he said, which the use of alternative tools cuts to 9% that now get in-person inspections. The alternative tools also helped the agency to meet its user fee review action goals in over 90% of the applications submitted. Tsinontides said the alternative tools frequently used in lieu of an inspection include:

- Relying on a Mutual Recognition Agreement with the EU and UK
- Information from other regulatory authorities through confidentiality agreements
- Information/records requests using 704(a)(4) of the FD&C Act
- Remote Interactive Evaluations (RIEs)

Tsinontides’ presentation touched on the growing interest of RIEs, which include teleconferencing, live-streaming video of a facility/operations, and screen sharing of records/information. Such activities are not considered an inspection by the agency, he said.

A [guidance](https://downloads.regulations.gov/FDA-2020-D-1136-0057/attachment%5F1.pdf?ref=fdaweb.com) was issued in April and it describes how RIEs will be requested and conducted for the duration of the Covid-19 public health emergency at any facility where pharmaceutical products, including biological products, are manufactured, processed, packed or held. FDA says it will use existing risk management methods and related tools to determine when to request a facility’s participation in a remote interactive evaluation. Facilities can choose to decline FDA’s request to perform a remote facility evaluation; however, this may impede the agency’s ability to evaluate the facility or product and to make a timely regulatory decision, it says.

Generally, FDA intends to request records and other information under section 704(a)(4) of the Food, Drug & Cosmetic Act before initiating a remote interactive evaluation, Tsinontides told the symposium. He noted that the agency will not accept requests from applicants or facilities to perform a remote interactive evaluation.

Touching on some key takeaways related to FDA’s experience with RIEs, Tsinontides said live streaming quality is critical to observing facility operations. Firms participating need to ensure “maximum coverage of the facility with adequate WiFi signals to support video streaming.” He said firms should have multiple portable tablets for visits throughout the facility and labs. RIEs do have limitations, he noted, adding that it is difficult to do close-up observations or observe production of the actual product. It is also difficult to do in-depth assessment of data, and equipment use/maintenance. But in general, he said RIEs are valuable in enhancing 704(a)(4) records request assessments.

ORA Office of Pharmaceutical Quality Operations deputy director **Nanci Rolli** addressed for the symposium on what firms should expect during a 704(a)(4) record review. FDA will initiate the records request by email, she said, which will outline the reason for the request and the documents requested (Form 4003). Failure to respond to a request can result in an FDA action (e.g., Warning Letter, import alert, or withholding action on a product application). If records requested are not in English they should be translated into English and firms should certify that the translations are accurate.

“To facilitate the records review, please provide all records requested or provide a reason for any records that are not provided,” Rolli said. “If a record request refers to another SOP or procedure, you may also want to include that record. Also, if an SOP is requested, and your current SOP does not cover that time period in question, please provide the SOP that was in place at the time and or the history page for the SOP. After the initial documents are received, there may be follow-up questions or requests for additional records. Requests for records will include a timeframe for submission to FDA. Typically, the original 704(a)(4) records request has a 30-day time frame and follow-up requests typically have a 15 day time frame.”

If a firm will not be able to meet these timeframes, they should reach out to the investigator and communicate when all records will be received, according to Rolli. “When objectionable conditions are found, the firm will be notified in writing and they will have an opportunity to respond,” she said. “All responses should be received by FDA within 15 days... The results of the records review will be used to prioritize future inspections, inform application decisions, and may be used to take action against products for which there is a public health risk.”

Mission critical inspections re-started in July, Rolli said, and most are preannounced due to Covid. She recommended that discussions be held about any social distancing requirements that have been in place and any requirements for entry into a facility, such as testing requirements, body temperature recordings and vaccination requirements. “During the inspections, social distancing should be practiced whenever feasible,” she said. “You may want to consider having a separate area for reviewing records, computer terminals for reviewing SOPs, and large rooms set up with microphones. During the inspection, or shortly after the inspection, if anyone from the facility has tested positive for Covid and has come in close contact with FDA personnel, please notify the individuals.”