New Drugs Regulatory Program Modernization: Improving Approval Package Documentation and Communication, 30733-30736 [2019-13751]

Download as PDF Federal Register / Vol. 84, No. 124 / Thursday, June 27, 2019 / Notices INFORMATION section for electronic access to the guidance document. FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Brian Booth, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2186, Silver Spring, MD 20993–0002, 301–796–1508; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993–0002, 240– 402–7911. Regarding the ICH: Amanda Roache, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6364, Silver Spring, MD 20993–0002, 301–796–4548. SUPPLEMENTARY INFORMATION: jspears on DSK30JT082PROD with NOTICES I. Background In recent years, regulatory authorities and industry associations from around the world have participated in many important initiatives to promote international harmonization of regulatory requirements under the ICH. FDA has participated in several ICH meetings designed to enhance harmonization, and FDA is committed to seeking scientifically based harmonized technical procedures for pharmaceutical development. One of the goals of harmonization is to identify and reduce differences in technical requirements for drug development among regulatory agencies. ICH was established to provide an opportunity for harmonization initiatives to be developed with input from both regulatory and industry representatives. FDA also seeks input from consumer representatives and others. ICH is concerned with harmonization of technical requirements for the registration of pharmaceutical products for human use among regulators around the world. The six founding members of the ICH are the European Commission; the European Federation of Pharmaceutical Industries Associations; FDA; the Japanese Ministry of Health, Labour, and Welfare; the Japanese Pharmaceutical Manufacturers Association; and the Pharmaceutical Research and Manufacturers of America. The Standing Members of the ICH Association include Health Canada and Swissmedic. Any party eligible as a Member in accordance with the ICH Articles of Association can apply for membership in writing to the ICH Secretariat. The ICH Secretariat, which coordinates the preparation of VerDate Sep<11>2014 20:15 Jun 26, 2019 Jkt 247001 documentation, operates as an international nonprofit organization and is funded by the Members of the ICH Association. The ICH Assembly is the overarching body of the Association and includes representatives from each of the ICH members and observers. The Assembly is responsible for the endorsement of draft guidelines and adoption of final guidelines. FDA publishes ICH guidelines as FDA guidance. In November 2018, the ICH Assembly endorsed the draft guideline entitled ‘‘M10 Bioanalytical Method Validation’’ and agreed that the guideline should be made available for public comment. The draft guideline is the product of the M10 Expert Working Group of the ICH. Comments about this draft will be considered by FDA and the ICH M10 Expert Working Group. The draft guidance provides guidance on the validation of bioanalytical assays that support regulatory submissions. The draft guidance describes the various elements and expectations of method validation for assays in nonclinical and clinical studies of new drugs and generic drugs and applies to chromatographic and ligand-binding assays for parent drug and active metabolites in biological matrices such as plasma, blood, or serum. This draft guidance has been left in the original ICH format. The final guidance will be reformatted and edited to conform with FDA’s good guidance practices regulation (21 CFR 10.115) and style before publication. The draft guidance, when finalized, will represent the current thinking of FDA on ‘‘M10 Bioanalytical Method Validation.’’ 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. This guidance is not subject to Executive Order 12866. II. Electronic Access Persons with access to the internet may obtain the draft guidance at https:// www.regulations.gov, https://www .fda.gov/Drugs/GuidanceCompliance RegulatoryInformation/Guidances/ default.htm, or https://www.fda.gov/ BiologicsBloodVaccines/ GuidanceComplianceRegulatory Information/Guidances/default.htm. Dated: June 24, 2019. Lowell J. Schiller, Principal Associate Commissioner for Policy. [FR Doc. 2019–13698 Filed 6–26–19; 8:45 am] BILLING CODE 4164–01–P PO 00000 Frm 00044 Fmt 4703 Sfmt 4703 30733 DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2019–N–2012] New Drugs Regulatory Program Modernization: Improving Approval Package Documentation and Communication AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. The Food and Drug Administration (FDA or Agency) is seeking public comment on the Clinical Data Summary Report Pilot program as part of the Agency’s continuous assessment of the efficiency and transparency of the clinical data used in the regulatory decision-making process. The Agency is also seeking public feedback on a new integrated review template for the documentation of new drug marketing applications developed as part of the New Drugs Regulatory Program Modernization. The Agency hopes to receive public feedback on both of these efforts and on how FDA might continue supporting our stakeholders’ needs related to the clarity and transparency of drug approval decisions. SUMMARY: Submit either electronic or written comments on the notice by August 26, 2019. ADDRESSES: You may submit comments as follows. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before August 26, 2019. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of August 26, 2019. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date. DATES: 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 E:\FR\FM\27JNN1.SGM 27JNN1 30734 Federal Register / Vol. 84, No. 124 / Thursday, June 27, 2019 / Notices jspears on DSK30JT082PROD with NOTICES 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– 2019–N–2012 for ‘‘New Drugs Regulatory Program Modernization: Improving Approval Package Documentation and Communication.’’ Received comments, those filed in a timely manner (see ADDRESSES), 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. • 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 VerDate Sep<11>2014 20:15 Jun 26, 2019 Jkt 247001 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.gpo.gov/ fdsys/pkg/FR-2015-09-18/pdf/201523389.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. FOR FURTHER INFORMATION CONTACT: Regarding the Clinical Data Summary Pilot Program: Patrick Zhou, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 1148, Silver Spring, MD 20993–0002, 301– 348–1817, Patrick.Zhou@fda.hhs.gov, with the subject line ‘‘Collecting Public Feedback on the Clinical Data Summary Pilot Program.’’ Regarding the Integrated Review: Kevin Bugin, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 5128, Silver Spring, MD 20993–0002, 301–796–2302, Kevin.Bugin@fda.hhs.gov, with the subject line ‘‘Collecting Public Feedback on the Integrated Review.’’ SUPPLEMENTARY INFORMATION: I. Background Currently, FDA’s Center for Drug Evaluation and Research (CDER) provides access to action packages, which include all discipline reviews, for newly approved original new drug applications (NDAs) and biologics license applications (BLAs) by posting these action packages on the FDA website at www.fda.gov/drugs@FDA. FDA posts them regardless of whether there has been a request under the Freedom of Information Act (FOIA), 5 U.S.C. 552. Other approval-related information such as review documents for abbreviated new drug applications (ANDAs) or NDA efficacy supplements are posted on www.fda.gov/drugs@FDA after they have been redacted and PO 00000 Frm 00045 Fmt 4703 Sfmt 4703 disclosed in response to a FOIA request, but they are not routinely posted proactively by the Agency. While the action packages include a significant amount of information from the sponsor’s application, they can reach up to hundreds of pages and include administrative and/or correspondencerelated documentation. As a result, some stakeholders have difficulty navigating the documents and using them to gain an understanding of the basis for FDA drug approvals. To address this, two efforts have been launched: (1) A pilot program referred to as the Clinical Data Summary Pilot Program (Pilot), launched in January 2018, through which parts of a sponsor’s clinical study reports (CSRs) were to be posted and (2) a new integrated template that will be used to document FDA’s review of new drug applications and efficacy supplements. This document seeks public comment on both of these efforts. On January 16, 2018, then-FDA Commissioner Scott Gottlieb announced several efforts to enhance the transparency of the Agency’s drug approval decisions as part of an overall approach to enhance the efficiency and transparency of the Agency’s drug approval decisions. One of those efforts included the Pilot program to evaluate whether publicly disclosing certain summary information included within sponsor-submitted CSRs improves public understanding of the basis of FDA’s approval decisions. The Pilot’s goals included enhancing the understanding of information about drug approvals to improve the accuracy of discussions about drug approvals in scientific publications, increasing stakeholders’ understanding of the basis for FDA’s approval decisions, and informing physicians and other healthcare providers about the clinical trial results on which regulatory decisions are based. For this Pilot, FDA sought voluntary participation from the sponsors of fewer than ten marketing applications selected on the basis of novelty and clinical importance (e.g., products that are novel including drugs that are new molecular entities, products across a range of disease areas, and products of scientific interest). For any approved application whose sponsor agreed to participate, FDA would post, along with the traditional action package, summary portions of the sponsor’s CSRs for the pivotal trials establishing the safety and effectiveness of the drug. One sponsor voluntarily agreed to participate. The subsequent posting can be found on FDA’s Clinical Data Summary Pilot Program web page at https:// E:\FR\FM\27JNN1.SGM 27JNN1 Federal Register / Vol. 84, No. 124 / Thursday, June 27, 2019 / Notices jspears on DSK30JT082PROD with NOTICES www.fda.gov/drugs/development approvalprocess/ucm589210.htm. All other contacted sponsors declined to participate in the Pilot. The recruitment phase of the Pilot is now concluded. FDA recognizes that the needs and expectations of different stakeholders regarding transparency of information relating to drug approval decisions may vary. By opening a public docket, FDA hopes to learn from its stakeholders more about the potential benefits or risks, resource requirements, and challenges of FDA publicly releasing a limited number of sections from certain CSRs at the time of marketing approval. In addition to the Pilot, FDA has other efforts that also seek to provide greater clarity on FDA’s application review and decision-making process. One of those efforts is the new integrated review process and template developed under the New Drugs Regulatory Program Modernization, which is part of a multiyear, multiphase effort to enhance the new drugs regulatory program. The new integrated review process and template are intended to promote more integrated and interdisciplinary assessments, enhance clarity of our assessments regarding the benefits and risks for new drug products, and improve our communication about the basis for new drug approvals. For more information, please see CDER Director Janet Woodcock’s notes of June 4, 2018, available at https://www.fda.gov/newsevents/fda-voices-perspectives-fdaexperts/fda-proposes-processmodernization-support-new-drugdevelopment. II. The Integrated Review Process The new integrated review process and documentation template, currently being implemented, supports reviewers in conducting a scientifically-rigorous review that efficiently documents regulatory decisions. The integrated review process includes the use and public posting, upon approval of a new drug or biologic, of an integrated review document that contains a summary, an integrated assessment, and appendices. This new review template would replace the current documentation where each discipline provides a separate application review document. The updated template would be a collaborative document with input from clinical, clinical pharmacology, biostatistics, toxicology reviewers, and other disciplines based upon the issues raised by the application. FDA believes this program will also meet the goal of effectively communicating the basis for new drug approvals. The Agency is therefore considering whether to focus its efforts to better communicate the VerDate Sep<11>2014 20:15 Jun 26, 2019 Jkt 247001 basis for drug approvals on the development of new integrated review documents, rather than on the release of CSRs. The guiding principles of this initiative are the importance of conducting an issue-focused assessment, enhanced communication both within the review team and with the applicant, and stronger interdisciplinary collaboration. FDA believes that the format and content of the integrated review will provide a clearer description of FDA’s analysis of the scientific issues raised by the application, and will thereby more effectively communicate the basis for the approval decision. As mentioned above, the integrated review template has three main components: • Summary: Æ Contains an executive summary of FDA’s decision and assessment of the application, including FDA’s benefit-risk determination (as currently employed in marketing application reviews) Æ Provides an overall Agency assessment, including an overview of the major decisions made during the review process, and a brief discussion of the basis for the decisions • Integrated Assessment: Æ Promotes succinct, integrated, focused analyses of the evidence of benefit-risk, and therapeutic individualization (e.g., special populations, drug interactions) Æ Highlights key issues in an interdisciplinary manner that the review team thinks are pertinent to the decision-making process • Appendices: Æ Contains assessments and analyses that are supportive or important to key facts/data or conclusions for the overall review Æ Contains work that did not directly impact the overall assessment of benefit-risk, regulatory action, labeling, or risk mitigation plans The target audiences for this document are diverse, and include the lay public with a specific interest in the particular application, drug sponsors, researchers and others who are seeking to understand the basis for FDA’s decision. In general, the first two parts of the integrated document would be expected to provide a complete explanation of FDA’s action, with the third component (the appendices) also available for those looking for additional detail on the comprehensive analyses FDA conducted in its review of the drug application. PO 00000 Frm 00046 Fmt 4703 Sfmt 4703 30735 As part of FDA’s internal assessment for both of these programs, the Agency is interested in receiving responses to the following questions, in addition to any general comments the public might have. For convenience, it would be helpful if commenters refer to the numbered question and subject when submitting responses and comments to the following questions: A. Regarding the Clinical Data Summary Pilot Program Please see the CSR posting available on FDA’s Clinical Data Summary Pilot Program web page at https:// www.fda.gov/drugs/development approvalprocess/ucm589210.htm. 1. How did the CSR posted in this Pilot affect or compare with your understanding of the CSRs submitted to FDA by drug sponsors? 2. How usable and/or accessible was the information in the CSR that was posted for the Pilot? 3. Did the required redactions/ removal of certain information from the posted CSR affect your understanding or use of the posted information? 4. How might the information/content posted from this Pilot be used? What other information/content would have been helpful? 5. Given the other review documents available (e.g., FDA’s action package), how did the posted CSR affect your understanding of FDA’s decisionmaking process regarding drug applications? 6. What do you believe would be the potential advantages and disadvantages of posting this information routinely? 7. Is there any additional information you would like to provide regarding the potential benefits or risks, resource requirements, and international challenges of publicly releasing a limited number of sections from certain CSRs at the time of marketing approval? To illustrate the new integrated review template, the original reviews for NDA 210806 (PIFELTRO (doravirine) tablets, 100 milligrams (mg)) and NDA 210807 (DELSTRIGO (doravirine, lamivudine, and tenofovir disoproxil fumarate) tablets, 100/300/300 milligrams) have been rewritten to provide an example. The original multidisciplinary review for the NDAs and the information provided in the new integrated review template are posted on https://www.fda.gov/ newdrugsmodernization#integrated. B. Regarding the Integrated Review 1. How does the new format of the integrated review inform your knowledge of FDA’s basis for making decisions? E:\FR\FM\27JNN1.SGM 27JNN1 30736 Federal Register / Vol. 84, No. 124 / Thursday, June 27, 2019 / Notices 2. How does the usability and accessibility of information in the new integrated review compare to the original review posted on FDA’s website? 3. How could the information provided in the new integrated review format be used, if at all? 4. What do you believe would be the potential advantages and disadvantages of posting review documents in this format? 5. Based on the integrated review, were the issues that concerned the review team clear and understandable? If so, what helped achieve this? If not, what can be improved? 6. Is there important information in the integrated review that is difficult to locate or should be added? Dated: June 24, 2019. Lowell J. Schiller, Principal Associate Commissioner for Policy. [FR Doc. 2019–13751 Filed 6–26–19; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration National Vaccine Injury Compensation Program; List of Petitions Received Health Resources and Services Administration (HRSA), Department of Health and Human Services (HHS). ACTION: Notice. AGENCY: HRSA is publishing this notice of petitions received under the National Vaccine Injury Compensation Program (the Program), as required by Section 2112(b)(2) of the Public Health Service (PHS) Act, as amended. While the Secretary of HHS is named as the respondent in all proceedings brought by the filing of petitions for compensation under the Program, the United States Court of Federal Claims (the Court) is charged by statute with responsibility for considering and acting upon the petitions. FOR FURTHER INFORMATION CONTACT: For information about requirements for filing petitions, and the Program in general, contact Lisa L. Reyes, Clerk of Court, United States Court of Federal Claims, 717 Madison Place NW, Washington, DC 20005, (202) 357–6400. For information on HRSA’s role in the Program, contact the Director, National Vaccine Injury Compensation Program, 5600 Fishers Lane, Room 08N146B, Rockville, Maryland 20857; (301) 443– 6593, or visit our website at: http:// jspears on DSK30JT082PROD with NOTICES SUMMARY: VerDate Sep<11>2014 20:15 Jun 26, 2019 Jkt 247001 www.hrsa.gov/vaccinecompensation/ index.html. The Program provides a system of no-fault compensation for certain individuals who have been injured by specified childhood vaccines. Subtitle 2 of Title XXI of the PHS Act, 42 U.S.C. 300aa– 10 et seq., provides that those seeking compensation are to file a petition with the United States Court of Federal Claims and to serve a copy of the petition to the Secretary of HHS, who is named as the respondent in each proceeding. The Secretary has delegated this responsibility under the Program to HRSA. The Court is directed by statute to appoint special masters who take evidence, conduct hearings as appropriate, and make initial decisions as to eligibility for, and amount of, compensation. A petition may be filed with respect to injuries, disabilities, illnesses, conditions, and deaths resulting from vaccines described in the Vaccine Injury Table (the Table) set forth at 42 CFR 100.3. This Table lists for each covered childhood vaccine the conditions that may lead to compensation and, for each condition, the time period for occurrence of the first symptom or manifestation of onset or of significant aggravation after vaccine administration. Compensation may also be awarded for conditions not listed in the Table and for conditions that are manifested outside the time periods specified in the Table, but only if the petitioner shows that the condition was caused by one of the listed vaccines. Section 2112(b)(2) of the PHS Act, 42 U.S.C. 300aa–12(b)(2), requires that ‘‘[w]ithin 30 days after the Secretary receives service of any petition filed under section 2111 the Secretary shall publish notice of such petition in the Federal Register.’’ Due to an administrative error, publication of the notice covering February 2019 was delayed. Set forth below is a list of petitions received by HRSA on February 1, 2019, through February 28, 2019. This list provides the name of petitioner, city and state of vaccination (if unknown then city and state of person or attorney filing claim), and case number. In cases where the Court has redacted the name of a petitioner and/or the case number, the list reflects such redaction. Section 2112(b)(2) also provides that the special master ‘‘shall afford all interested persons an opportunity to submit relevant, written information’’ relating to the following: 1. The existence of evidence ‘‘that there is not a preponderance of the evidence that the illness, disability, SUPPLEMENTARY INFORMATION: PO 00000 Frm 00047 Fmt 4703 Sfmt 4703 injury, condition, or death described in the petition is due to factors unrelated to the administration of the vaccine described in the petition,’’ and 2. Any allegation in a petition that the petitioner either: a. ‘‘[S]ustained, or had significantly aggravated, any illness, disability, injury, or condition not set forth in the Vaccine Injury Table but which was caused by’’ one of the vaccines referred to in the Table, or b. ‘‘[S]ustained, or had significantly aggravated, any illness, disability, injury, or condition set forth in the Vaccine Injury Table the first symptom or manifestation of the onset or significant aggravation of which did not occur within the time period set forth in the Table but which was caused by a vaccine’’ referred to in the Table. In accordance with Section 2112(b)(2), all interested persons may submit written information relevant to the issues described above in the case of the petitions listed below. Any person choosing to do so should file an original and three copies of the information with the Clerk of the United States Court of Federal Claims at the address listed above (under the heading FOR FURTHER INFORMATION CONTACT), with a copy to HRSA addressed to Director, Division of Injury Compensation Programs, Healthcare Systems Bureau, 5600 Fishers Lane, 08N146B, Rockville, Maryland 20857. The Court’s caption (Petitioner’s Name v. Secretary of HHS) and the docket number assigned to the petition should be used as the caption for the written submission. Chapter 35 of title 44, United States Code, related to paperwork reduction, does not apply to information required for purposes of carrying out the Program. Dated: June 21, 2019. George Sigounas, Administrator. List of Petitions Filed 1. Tanja Wagner and Scott Wagner on behalf of S.W., Phoenix, Arizona, Court of Federal Claims No: 19– 0188V 2. Rebecca E. Wood, Wenatchee, Washington, Court of Federal Claims No: 19–0189V 3. Julianna Barmasse, Cheektowaga, New York, Court of Federal Claims No: 19–0190V 4. Curtis Devlin, Pittsburgh, Pennsylvania, Court of Federal Claims No: 19–0191V 5. Janell Ward, Reno, Nevada, Court of Federal Claims No: 19–0192V 6. Trudy Schneidermann, Luverne, Minnesota, Court of Federal Claims No: 19–0193V E:\FR\FM\27JNN1.SGM 27JNN1

Agencies

[Federal Register Volume 84, Number 124 (Thursday, June 27, 2019)]
[Notices]
[Pages 30733-30736]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-13751]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-N-2012]


New Drugs Regulatory Program Modernization: Improving Approval 
Package Documentation and Communication

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for comments.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is seeking 
public comment on the Clinical Data Summary Report Pilot program as 
part of the Agency's continuous assessment of the efficiency and 
transparency of the clinical data used in the regulatory decision-
making process. The Agency is also seeking public feedback on a new 
integrated review template for the documentation of new drug marketing 
applications developed as part of the New Drugs Regulatory Program 
Modernization. The Agency hopes to receive public feedback on both of 
these efforts and on how FDA might continue supporting our 
stakeholders' needs related to the clarity and transparency of drug 
approval decisions.

DATES: Submit either electronic or written comments on the notice by 
August 26, 2019.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before August 26, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of August 26, 2019. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.

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

[[Page 30734]]

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-2019-N-2012 for ``New Drugs Regulatory Program Modernization: 
Improving Approval Package Documentation and Communication.'' Received 
comments, those filed in a timely manner (see ADDRESSES), 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.
     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.gpo.gov/fdsys/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.

FOR FURTHER INFORMATION CONTACT: 
    Regarding the Clinical Data Summary Pilot Program: Patrick Zhou, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 51, Rm. 1148, Silver Spring, MD 20993-
0002, 301-348-1817, [email protected], with the subject line 
``Collecting Public Feedback on the Clinical Data Summary Pilot 
Program.''
    Regarding the Integrated Review: Kevin Bugin, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5128, Silver Spring, MD 20993-0002, 301-
796-2302, [email protected], with the subject line ``Collecting 
Public Feedback on the Integrated Review.''

SUPPLEMENTARY INFORMATION: 

I. Background

    Currently, FDA's Center for Drug Evaluation and Research (CDER) 
provides access to action packages, which include all discipline 
reviews, for newly approved original new drug applications (NDAs) and 
biologics license applications (BLAs) by posting these action packages 
on the FDA website at www.fda.gov/[email protected]. FDA posts them regardless 
of whether there has been a request under the Freedom of Information 
Act (FOIA), 5 U.S.C. 552.
    Other approval-related information such as review documents for 
abbreviated new drug applications (ANDAs) or NDA efficacy supplements 
are posted on www.fda.gov/[email protected] after they have been redacted and 
disclosed in response to a FOIA request, but they are not routinely 
posted proactively by the Agency. While the action packages include a 
significant amount of information from the sponsor's application, they 
can reach up to hundreds of pages and include administrative and/or 
correspondence-related documentation. As a result, some stakeholders 
have difficulty navigating the documents and using them to gain an 
understanding of the basis for FDA drug approvals. To address this, two 
efforts have been launched: (1) A pilot program referred to as the 
Clinical Data Summary Pilot Program (Pilot), launched in January 2018, 
through which parts of a sponsor's clinical study reports (CSRs) were 
to be posted and (2) a new integrated template that will be used to 
document FDA's review of new drug applications and efficacy 
supplements. This document seeks public comment on both of these 
efforts.
    On January 16, 2018, then-FDA Commissioner Scott Gottlieb announced 
several efforts to enhance the transparency of the Agency's drug 
approval decisions as part of an overall approach to enhance the 
efficiency and transparency of the Agency's drug approval decisions. 
One of those efforts included the Pilot program to evaluate whether 
publicly disclosing certain summary information included within 
sponsor-submitted CSRs improves public understanding of the basis of 
FDA's approval decisions.
    The Pilot's goals included enhancing the understanding of 
information about drug approvals to improve the accuracy of discussions 
about drug approvals in scientific publications, increasing 
stakeholders' understanding of the basis for FDA's approval decisions, 
and informing physicians and other healthcare providers about the 
clinical trial results on which regulatory decisions are based.
    For this Pilot, FDA sought voluntary participation from the 
sponsors of fewer than ten marketing applications selected on the basis 
of novelty and clinical importance (e.g., products that are novel 
including drugs that are new molecular entities, products across a 
range of disease areas, and products of scientific interest). For any 
approved application whose sponsor agreed to participate, FDA would 
post, along with the traditional action package, summary portions of 
the sponsor's CSRs for the pivotal trials establishing the safety and 
effectiveness of the drug. One sponsor voluntarily agreed to 
participate. The subsequent posting can be found on FDA's Clinical Data 
Summary Pilot Program web page at https://

[[Page 30735]]

www.fda.gov/drugs/developmentapprovalprocess/ucm589210.htm. All other 
contacted sponsors declined to participate in the Pilot. The 
recruitment phase of the Pilot is now concluded.
    FDA recognizes that the needs and expectations of different 
stakeholders regarding transparency of information relating to drug 
approval decisions may vary. By opening a public docket, FDA hopes to 
learn from its stakeholders more about the potential benefits or risks, 
resource requirements, and challenges of FDA publicly releasing a 
limited number of sections from certain CSRs at the time of marketing 
approval.
    In addition to the Pilot, FDA has other efforts that also seek to 
provide greater clarity on FDA's application review and decision-making 
process. One of those efforts is the new integrated review process and 
template developed under the New Drugs Regulatory Program 
Modernization, which is part of a multiyear, multiphase effort to 
enhance the new drugs regulatory program. The new integrated review 
process and template are intended to promote more integrated and 
interdisciplinary assessments, enhance clarity of our assessments 
regarding the benefits and risks for new drug products, and improve our 
communication about the basis for new drug approvals. For more 
information, please see CDER Director Janet Woodcock's notes of June 4, 
2018, available at https://www.fda.gov/news-events/fda-voices-perspectives-fda-experts/fda-proposes-process-modernization-support-new-drug-development.

II. The Integrated Review Process

    The new integrated review process and documentation template, 
currently being implemented, supports reviewers in conducting a 
scientifically-rigorous review that efficiently documents regulatory 
decisions. The integrated review process includes the use and public 
posting, upon approval of a new drug or biologic, of an integrated 
review document that contains a summary, an integrated assessment, and 
appendices. This new review template would replace the current 
documentation where each discipline provides a separate application 
review document. The updated template would be a collaborative document 
with input from clinical, clinical pharmacology, biostatistics, 
toxicology reviewers, and other disciplines based upon the issues 
raised by the application. FDA believes this program will also meet the 
goal of effectively communicating the basis for new drug approvals. The 
Agency is therefore considering whether to focus its efforts to better 
communicate the basis for drug approvals on the development of new 
integrated review documents, rather than on the release of CSRs.
    The guiding principles of this initiative are the importance of 
conducting an issue-focused assessment, enhanced communication both 
within the review team and with the applicant, and stronger 
interdisciplinary collaboration. FDA believes that the format and 
content of the integrated review will provide a clearer description of 
FDA's analysis of the scientific issues raised by the application, and 
will thereby more effectively communicate the basis for the approval 
decision.
    As mentioned above, the integrated review template has three main 
components:

 Summary:

    [cir] Contains an executive summary of FDA's decision and 
assessment of the application, including FDA's benefit-risk 
determination (as currently employed in marketing application reviews)
    [cir] Provides an overall Agency assessment, including an overview 
of the major decisions made during the review process, and a brief 
discussion of the basis for the decisions
 Integrated Assessment:
    [cir] Promotes succinct, integrated, focused analyses of the 
evidence of benefit-risk, and therapeutic individualization (e.g., 
special populations, drug interactions)
    [cir] Highlights key issues in an interdisciplinary manner that the 
review team thinks are pertinent to the decision-making process
 Appendices:
    [cir] Contains assessments and analyses that are supportive or 
important to key facts/data or conclusions for the overall review
    [cir] Contains work that did not directly impact the overall 
assessment of benefit-risk, regulatory action, labeling, or risk 
mitigation plans

    The target audiences for this document are diverse, and include the 
lay public with a specific interest in the particular application, drug 
sponsors, researchers and others who are seeking to understand the 
basis for FDA's decision. In general, the first two parts of the 
integrated document would be expected to provide a complete explanation 
of FDA's action, with the third component (the appendices) also 
available for those looking for additional detail on the comprehensive 
analyses FDA conducted in its review of the drug application.
    As part of FDA's internal assessment for both of these programs, 
the Agency is interested in receiving responses to the following 
questions, in addition to any general comments the public might have. 
For convenience, it would be helpful if commenters refer to the 
numbered question and subject when submitting responses and comments to 
the following questions:

A. Regarding the Clinical Data Summary Pilot Program

    Please see the CSR posting available on FDA's Clinical Data Summary 
Pilot Program web page at https://www.fda.gov/drugs/developmentapprovalprocess/ucm589210.htm.
    1. How did the CSR posted in this Pilot affect or compare with your 
understanding of the CSRs submitted to FDA by drug sponsors?
    2. How usable and/or accessible was the information in the CSR that 
was posted for the Pilot?
    3. Did the required redactions/removal of certain information from 
the posted CSR affect your understanding or use of the posted 
information?
    4. How might the information/content posted from this Pilot be 
used? What other information/content would have been helpful?
    5. Given the other review documents available (e.g., FDA's action 
package), how did the posted CSR affect your understanding of FDA's 
decision-making process regarding drug applications?
    6. What do you believe would be the potential advantages and 
disadvantages of posting this information routinely?
    7. Is there any additional information you would like to provide 
regarding the potential benefits or risks, resource requirements, and 
international challenges of publicly releasing a limited number of 
sections from certain CSRs at the time of marketing approval?
    To illustrate the new integrated review template, the original 
reviews for NDA 210806 (PIFELTRO (doravirine) tablets, 100 milligrams 
(mg)) and NDA 210807 (DELSTRIGO (doravirine, lamivudine, and tenofovir 
disoproxil fumarate) tablets, 100/300/300 milligrams) have been 
rewritten to provide an example. The original multidisciplinary review 
for the NDAs and the information provided in the new integrated review 
template are posted on https://www.fda.gov/newdrugsmodernization#integrated.

B. Regarding the Integrated Review

    1. How does the new format of the integrated review inform your 
knowledge of FDA's basis for making decisions?

[[Page 30736]]

    2. How does the usability and accessibility of information in the 
new integrated review compare to the original review posted on FDA's 
website?
    3. How could the information provided in the new integrated review 
format be used, if at all?
    4. What do you believe would be the potential advantages and 
disadvantages of posting review documents in this format?
    5. Based on the integrated review, were the issues that concerned 
the review team clear and understandable? If so, what helped achieve 
this? If not, what can be improved?
    6. Is there important information in the integrated review that is 
difficult to locate or should be added?

    Dated: June 24, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-13751 Filed 6-26-19; 8:45 am]
 BILLING CODE 4164-01-P