2022-07511. Use of Whole Slide Imaging in Nonclinical Toxicology Studies: Questions and Answers; Draft Guidance for Industry; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice of availability.

SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Use of Whole Slide Imaging in Nonclinical Toxicology Studies: Questions and Answers.” When final, this guidance will represent FDA's current thinking on the use of whole slide images during good laboratory practice (GLP)-compliant toxicology studies using non-human specimens. When whole slide images are used as part of a nonclinical study conducted in compliance with the GLP regulations, adequate documentation is critical. Documentation practices during generation, use, and retention of whole slide images have not been clearly defined and vary among nonclinical testing facilities. This question-and-answer document is intended to clarify FDA's recommendations concerning the management, documentation, and use of whole slide images in histopathology assessment and/or pathology peer review for nonclinical studies conducted in compliance with the GLP regulations.

DATES:

Submit either electronic or written comments on the draft guidance by June 7, 2022 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.

ADDRESSES:

You may submit comments on any guidance at any time as follows:

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.

• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand Delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2021-D-1268 for “Use of Whole Slide Imaging in Nonclinical Toxicology Studies: Questions and Answers.” Received comments will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.govinfo.gov/​content/​pkg/​FR-2015-09-18/​pdf/​2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.

You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)).

Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002 or to the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:

Tahseen Mirza, Office of Study Integrity and Surveillance, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2211, Silver Spring, MD 20993, 301-796-7645; Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993, 240-402-7911; Judy Davis, Office of Device Evaluation, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 2220, Silver Spring, MD 20993, 301-796-6636; Hilary Hoffman, Office of New Animal Drug Evaluation, Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish Pl., Rm. 389, Rockville, MD 20855, 240-402-8406; Yuguang Wang, Office of the Center Director, Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5001 Campus Dr., Rm. 4A012, College Park, MD 20740, 240-402-1757; Hans Rosenfeldt, Office of Science, Center for Tobacco Products, Food and Drug Administration, 11785 Beltsville Dr., Calverton Tower, Rm. 5322, Beltsville, MD 20705, 301-796-2202; Eric S. Myskowski, Division of Operational Policy, Office of Regulatory Affairs, Food and Drug Administration, District Office—Minneapolis, 250 Marquette Ave., Minneapolis, MN 55401, 612-758-7187.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Use of Whole Slide Imaging in Nonclinical Toxicology Studies: Questions and Answers.” The histopathological assessment of tissue samples is one of the key activities conducted during GLP-compliant nonclinical laboratory studies. Commonly, the histopathological assessment includes an initial evaluation of glass histology slides by the study pathologist and a subsequent review (referred to as pathology peer review) by a second pathologist, group of pathologists, or Pathology Working Group. The current regulations include general requirements for histopathology evaluation ( e.g., standard operating procedures), but the use of whole slide images in lieu of glass slides is not specifically addressed. This guidance provides information to sponsors and nonclinical laboratories regarding the management, documentation, and use of whole slide images during histopathology assessment and/or pathology peer review performed for GLP-compliant nonclinical toxicology studies using non-human specimens.

When whole slide images are used in lieu of glass slides as part of a nonclinical study conducted in compliance with the GLP regulations adequate documentation is critical. Documentation practices during whole slide imaging generation and use have not been clearly defined and vary among nonclinical testing facilities. This question-and-answer document is intended to clarify FDA's recommendations concerning the management, documentation, and use of whole slide imaging in histopathology assessment and/or pathology peer review for nonclinical studies conducted in compliance with the GLP regulations. Use of whole slide images in casual consultations, opinion exchanges, and mentoring among pathologists are not covered by this guidance document.

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA on “Use of Whole Slide Imaging in Nonclinical Toxicology Studies: Questions and Answers.” It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

While this guidance contains no collection of information, it does refer to previously approved FDA collections of information. Therefore, clearance by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not required for this guidance. The previously approved collections of information are subject to review by OMB under the PRA. The collections of information in 21 CFR part 58 regarding the good laboratory practice requirements for nonclinical laboratory studies have been approved under OMB control number 0910-0119.

III. Electronic Access

Persons with access to the internet may obtain the draft guidance at either https://www.fda.gov/​drugs/​guidance-compliance-regulatory-information/​guidances-drugs, https://www.fda.gov/​regulatory-information/​search-fda-guidance-documents, https://www.fda.gov/​vaccines-blood-biologics/​guidance-compliance-regulatory-information-biologics/​biologics-guidances, or https://www.regulations.gov.

Dated: April 1, 2022.

Lauren K. Roth,

Associate Commissioner for Policy.