Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings With Food and Drug Administration Staff; Guidance for Industry and Food and Drug Administration Staff; Availability, 9226-9229 [2014-03453]

Download as PDF 9226 Federal Register / Vol. 79, No. 32 / Tuesday, February 18, 2014 / Notices that the drug products listed in this document were not withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not begin procedures to withdraw approval of abbreviated new drug applications (ANDAs) that refer to these drug products, and it will allow FDA to continue to approve ANDAs that refer to the products as long as they meet relevant legal and regulatory requirements. FOR FURTHER INFORMATION CONTACT: Amy Hopkins, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6207, Silver Spring, MD 20993–0002, 301– 796–5418. In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (Public Law 98– 417) (the 1984 amendments), which authorized the approval of duplicate SUPPLEMENTARY INFORMATION: versions of drug products approved under an ANDA procedure. ANDA applicants must, with certain exceptions, show that the drug for which they are seeking approval contains the same active ingredient in the same strength and dosage form as the ‘‘listed drug,’’ which is a version of the drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing otherwise necessary to gain approval of a new drug application (NDA). The 1984 amendments include what is now section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)), which requires FDA to publish a list of all approved drugs. FDA publishes this list as part of the ‘‘Approved Drug Products With Therapeutic Equivalence Evaluations,’’ which is generally known as the ‘‘Orange Book.’’ Under FDA regulations, a drug is removed from the list if the Agency withdraws or suspends approval of the drug’s NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162). Under § 314.161(a) (21 CFR 314.161(a)), the Agency must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness: (1) Before an ANDA that refers to that listed drug may be approved, (2) whenever a listed drug is voluntarily withdrawn from sale and ANDAs that refer to the listed drug have been approved, and (3) when a person petitions for such a determination under 21 CFR 10.25(a) and 10.30. Section 314.161(d) provides that if FDA determines that a listed drug was withdrawn from sale for safety or effectiveness reasons, the Agency will initiate proceedings that could result in the withdrawal of approval of the ANDAs that refer to the listed drug. FDA has become aware that the drug products listed in the table in this document are no longer being marketed. Application no. Drug Applicant NDA 019961 ........................................ GANITE (gallium nitrate) Injectable; Injection, 25 milligrams (mg)/milliliter (mL). SKELID (tiludronate disodium) Tablet; Oral, Equivalent to (EQ) 200 mg Base. EMEND (fosaprepitant dimeglumine) Powder; Intravenous, EQ 115 mg Base/Vial. GARAMYCIN (gentamicin sulfate ophthalmic solution) Solution; Drops, EQ 0.3% Base. JUVISYNC (simvastin; sitagliptin phosphate) Tablet; Oral, 10 mg, EQ 100 mg Base; 20 mg, EQ 100 mg Base; 40 mg, EQ 100 mg Base; 10 mg, EQ 50 mg Base; 20 mg, EQ 50 mg Base; 40 mg, EQ 50 mg Base. TRIMETHOPRIM (trimethoprim) Tablet; Oral, 200 mg. Chapter 7 Trustee of Genta Inc., 1628 John Kennedy Blvd., Philadelphia, PA 19103 Sanofi Aventis US LLC, 55 Corporate Dr., Bridgewater, NJ 08807. Merck and Co Inc., RY33 200, P.O. Box 2000, Rahway, NJ 07065. Schering Plough Corp., 2000 Galloping Hill Rd., Mail Stop K 6 1, Kenilworth, NJ 07033. Merck Sharp and Dohme Corp., 351 North Sumneytown Pike, UG 2CD 015, P.O. Box 1000, North Wales, PA 19454. NDA 020707 ........................................ NDA 022023 ........................................ NDA 050039 ........................................ NDA 202343 ........................................ tkelley on DSK3SPTVN1PROD with NOTICES ANDA 071259 ...................................... FDA has reviewed its records and, under § 314.161, has determined that the drug products listed in this document were not withdrawn from sale for reasons of safety or effectiveness. Accordingly, the Agency will continue to list the drug products listed in this document in the ‘‘Discontinued Drug Product List’’ section of the Orange Book. The ‘‘Discontinued Drug Product List’’ identifies, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness. Approved ANDAs that refer to the NDAs and ANDAs listed in this document are unaffected by the discontinued marketing of the products subject to those NDAs and ANDAs. Additional ANDAs that refer to these products may also be approved by the Agency if they comply with relevant VerDate Mar<15>2010 20:58 Feb 14, 2014 Jkt 232001 TEVA Pharmaceuticals USA Inc., 650 Cathill Rd., Sellersville, PA 18960–1512. legal and regulatory requirements. If FDA determines that labeling for these drug products should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling. DEPARTMENT OF HEALTH AND HUMAN SERVICES Dated: February 12, 2014. Leslie Kux, Assistant Commissioner for Policy. Requests for Feedback on Medical Device Submissions: The PreSubmission Program and Meetings With Food and Drug Administration Staff; Guidance for Industry and Food and Drug Administration Staff; Availability [FR Doc. 2014–03458 Filed 2–14–14; 8:45 am] BILLING CODE 4160–01–P PO 00000 Food and Drug Administration [Docket No. FDA–2012–D–0530] AGENCY: Food and Drug Administration, HHS. ACTION: Notice. The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled ‘‘Requests for Feedback on Medical Device Submissions: The PreSubmission Program and Meetings with SUMMARY: Frm 00070 Fmt 4703 Sfmt 4703 E:\FR\FM\18FEN1.SGM 18FEN1 tkelley on DSK3SPTVN1PROD with NOTICES Federal Register / Vol. 79, No. 32 / Tuesday, February 18, 2014 / Notices FDA Staff.’’ The purpose of this guidance is to provide an overview of the mechanisms available to application sponsors through which to obtain FDA feedback regarding potential or planned medical device submissions reviewed in the Center for Devices and Radiological Health (CDRH) and the Center for Biologics Evaluation and Research (CBER), including the Pre-Submission program (formerly the preInvestigational Device Exemption (preIDE) program). In addition, the guidance provides recommendations regarding information that should be included in a Pre-Submission Package. This guidance also describes the procedures that CDRH and CBER intend to follow when manufacturers, their representatives, or application sponsors request a meeting with review staff. DATES: Submit either electronic or written comments on this guidance at any time. General comments on Agency guidance documents are welcome at any time. ADDRESSES: Submit written requests for single copies of the guidance document entitled ‘‘Requests for Feedback on Medical Device Submissions: The PreSubmission Program and Meetings with FDA Staff’’ to the Division of Small Manufacturers, International and Consumer Assistance, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 4613, Silver Spring, MD 20993–0002. Send one self-addressed adhesive label to assist that office in processing your request, or fax your request to 301–847– 8149. See the SUPPLEMENTARY INFORMATION section for information on electronic access to the guidance. Submit electronic comments on the guidance to https://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA– 305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Identify comments with the docket number found in brackets in the heading of this document. FOR FURTHER INFORMATION CONTACT: Program Operations Staff (IDE), Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993–0002, 301–796–5640; or Elizabeth Hillebrenner, Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5616, Silver Spring, MD 20993–0002, 301–796–6346; or Stephen Ripley, Center for Biologics Evaluation and Research (HFM–17), VerDate Mar<15>2010 20:58 Feb 14, 2014 Jkt 232001 Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852–1448, 301–827–6210. SUPPLEMENTARY INFORMATION: I. Background Since its establishment in 1995, the pre-IDE program has been a successful resource for both medical device applicants and the FDA. Originally, this program was designed to provide applicants a mechanism to obtain FDA feedback on future IDE applications prior to their submission. Over time, the pre-IDE program evolved to include feedback on other device submission program areas, such as Premarket Approval (PMA) applications, Humanitarian Device Exemption applications, Evaluation of Automatic Class III Designations (de novo petitions), Premarket Notification (510(k)) Submissions, and Clinical Laboratory Improvement Amendments Waiver by Application, as well as to address questions related to whether a clinical study requires submission of an IDE. The purpose of this guidance is to update the pre-IDE program to reflect this broader scope and make important modifications to reflect changes in the premarket program areas as a result of the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110– 85). This guidance also further expands the scope of the program to include those devices regulated by CBER, including those that are regulated as biologics under the Public Health Service Act and require submission of an Investigational New Drug Application (IND) and/or a Biologics License Application. Accordingly, FDA is changing the name for this program from the pre-IDE program to the PreSubmission (Pre-Sub) program. Though successful, the Pre-Sub program has faced challenges, and the guidance is intended to address them and improve the Pre-Sub program by: (1) Describing the types of information that FDA would recommend submitting in order to get the best possible feedback from FDA; (2) outlining the process by which FDA meetings should be scheduled; and (3) explaining the Agency’s expectations regarding advice given during the Pre-Sub process. This guidance outlines clear recommendations for sponsors and FDA staff. In addition to the Pre-Sub program, the guidance addresses other types of FDA feedback already available to applicants through other mechanisms. The Food and Drug Administration Modernization Act of 1997 (FDAMA) (Pub. L. 105–115) established two types PO 00000 Frm 00071 Fmt 4703 Sfmt 4703 9227 of formal early collaboration meetings (‘‘determination meetings’’ as described in section 513(a)(3)(D) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and ‘‘agreement meetings’’ as described in section 520(g)(7) of the FD&C Act) to provide clear direction for testing and development of devices requiring clinical investigations to support marketing. FDAMA also requires that FDA, upon written request, must meet with a PMA applicant no later than 100 days after the receipt of a PMA application that has been filed to discuss the review status of the application (referred to as a ‘‘day-100 meeting’’ and described in section 515(d)(3) of the FD&C Act). For other premarket submissions under review, FDA will also grant meetings on an informal basis to discuss our requests for additional information to better ensure that the formal response to FDA’s request will fully address the outstanding questions (these meetings are referred to as ‘‘submission issue meetings’’). FDA will respond to requests for a determination (called ‘‘study risk determinations’’) whether a proposed device study is exempt from or subject to the IDE regulation (21 CFR part 812). For device studies that are subject to the IDE regulations, FDA will also provide its determination whether the study is a significant risk or nonsignificant risk study in response to a voluntary request for this information. In some cases, sponsors may wish to inform or educate FDA about ongoing device development or planned submissions without a specific request for feedback. FDA will, as resources allow, grant requests for such ‘‘informational meetings.’’ As part of the Medical Device User Fee Amendments of 2012 (MDUFA III), FDA committed to instituting a structured process for managing PreSubs. This final guidance establishes such a structured process for submission and management of PreSubs as well as other types of requests for feedback. In addition, the guidance describes how FDA will internally track these requests as ‘‘Q-Submissions,’’ or ‘‘Q-Subs,’’ including what types of submissions will be handled as supplements and amendments to an initial Q-Sub. FDA has also revised the optional CDRH Cover Sheet (Form FDA 3514) to include submission types that more closely track with the types of feedback requests discussed in the guidance. FDA intends to provide the best possible advice in accordance with the information provided by the sponsor, to ensure it is captured accurately in the meeting minutes drafted by the sponsor, E:\FR\FM\18FEN1.SGM 18FEN1 tkelley on DSK3SPTVN1PROD with NOTICES 9228 Federal Register / Vol. 79, No. 32 / Tuesday, February 18, 2014 / Notices and commit to that advice unless the circumstances sufficiently change such that our advice is no longer applicable, such as when a sponsor changes the intended use of their device after we provide feedback. It is also our intention to hold timely meetings with appropriate staff and managers present, as resources permit. However, both our ability to provide advice and to hold timely meetings are dependent on our receiving the necessary information from the sponsor in advance of the meeting. Finally, the guidance describes the procedures that CDRH and CBER intend to follow when manufacturers, their representatives, or application sponsors request a meeting with review staff as the preferred method of feedback in response to a Pre-Sub, as an early collaboration meeting, or to discuss an existing regulatory submission. This guidance also recommends how to prepare for meetings with FDA staff. In the Federal Register of July 13, 2012 (77 FR 41413), FDA announced the availability of the draft guidance document. Interested persons were invited to comment by October 11, 2012. Seventeen sets of comments were received with multiple recommendations pertaining to the administrative processes and policies regarding the Pre-Sub program and meetings with FDA staff. The guidance was revised to provide a broader overview of available mechanisms for FDA feedback prior to a planned submission, with references to other existing guidance documents for those mechanisms where available. The guidance was also reorganized to discuss the various feedback mechanisms first, with a second section including specifics about meeting procedures that apply to all types of FDA feedback mechanisms where a meeting or teleconference is requested. Finally, an acceptance checklist for these submissions has been added as an appendix to clearly outline how FDA intends to determine if a Q-Sub meets the definition of the identified Q-Sub type, and to determine if a qualifying request is administratively complete. It is not necessary for each element in the checklist to be present for the submission to be accepted. Instead, the acceptance checklist is intended to ensure only that the submission includes sufficient information for FDA to provide the requested feedback and/ or identify the appropriate FDA attendees so that the meeting or teleconference can be scheduled. FDA received comments regarding the proposed timeframes for feedback to be provided to the applicant. Specifically, VerDate Mar<15>2010 20:58 Feb 14, 2014 Jkt 232001 the guidance outlines a proposed target of 75 days, but generally no longer than 90 days, for feedback in response to a Pre-Sub. Comments requested that FDA modify the guidance to include a timeframe of 60 days for response to a Pre-Sub. As part of the MDUFA III Commitment Letter (Ref. 1), FDA agreed to improve the Pre-Sub process ‘‘as resources permit,’’ but, because there were no additional resources provided for this program as part of the overall MDUFA III program, the recommended timeframe for FDA feedback in a PreSub represents the time in which FDA believes that feedback generally can be provided without the application of additional resources to this specific program. Some comments expressed concern regarding FDA’s recommendation that if more than 1 year has passed since our last feedback on key clinical trial design elements without a submission to the Agency, the sponsor should contact the review branch to confirm that the previous advice is still valid. The guidance has clarified that the reason for this recommendation is because clinical practice (including available alternative therapies or diagnostics) is rapidly evolving. The guidance has been further modified to clarify that a new Pre-Sub to the Agency is no longer recommended. Instead, confirmation that prior feedback is still valid can be accomplished through a phone call to the lead reviewer or branch chief. In response to other minor substantive and editorial comments, FDA revised the guidance document to clarify the processes and policies as appropriate. II. Significance of Guidance This guidance is being issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115). The guidance represents the Agency’s current thinking on requests for FDA feedback, including the Pre-Sub program, and meetings with FDA staff. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute and regulations. III. Electronic Access Persons interested in obtaining a copy of the guidance may do so by using the Internet. A search capability for all CDRH guidance documents is available at https://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/ GuidanceDocuments/default.htm. Guidance documents are also available at https://www.regulations.gov. To PO 00000 Frm 00072 Fmt 4703 Sfmt 4703 receive ‘‘Requests for Feedback on Medical Device Submissions: The PreSubmission Program and Meetings with FDA Staff,’’ you may either send an email request to dsmica@fda.hhs.gov to receive an electronic copy of the document or send a fax request to 301– 847–8149 to receive a hard copy. Please use the document number 1677 to identify the guidance you are requesting. IV. Paperwork Reduction Act of 1995 This guidance also refers to previously approved information collections found in FDA regulations. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501–3520). The collections of information in 21 CFR part 803 are approved under OMB control number 0910–0437; the collections of information in 21 CFR part 807, subpart E are approved under OMB control number 0910–0120; the collections of information in 21 CFR part 812 are approved under OMB control number 0910–0078; the collections of information in 21 CFR part 814 are approved under OMB control number 0910–0231; and the collections of information for Request for Feedback on Medical Device Submissions are approved under OMB control number 0910–0756. V. Comments Interested persons may submit either electronic comments to https:// www.regulations.gov or written comments regarding this document to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify comments with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to the docket at https:// www.regulations.gov. VI. Reference The following reference is available electronically at https:// www.regulations.gov. (FDA has verified the Web site address in this reference section, but we are not responsible for any subsequent changes to the Web site after this document publishes in the Federal Register.) 1. MDUFA III Commitment Letter, April 18, 2012, available at https://www.fda.gov/ downloads/MedicalDevices/NewsEvents/ WorkshopsConferences/UCM295454.pdf. E:\FR\FM\18FEN1.SGM 18FEN1 Federal Register / Vol. 79, No. 32 / Tuesday, February 18, 2014 / Notices Dated: February 12, 2014. Leslie Kux, Assistant Commissioner for Policy. BILLING CODE 4160–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA–2014–N–0001] Food and Drug Administration/Xavier University PharmaLink Conference— Leadership in a Global Supply Chain Food and Drug Administration, HHS. tkelley on DSK3SPTVN1PROD with NOTICES ACTION: Notice of public conference. The Food and Drug Administration (FDA) Cincinnati District, in cosponsorship with Xavier University, is announcing a public conference entitled ‘‘FDA/Xavier University PharmaLink Conference: Leadership in a Global Supply Chain.’’ The public conference seeks solutions to important and complicated issues by aligning with the strategic priorities of FDA, and includes presentations from key FDA officials, global regulators, and industry experts. Each presentation challenges the status quo and conventional wisdom to create synergies focused on finding solutions which make a difference. The experience level of the audience has fostered engaged dialog that has led to innovative initiatives. Dates and Times: The public conference will be held on March 19 and 20, 2014, from 8:30 a.m. to 5 p.m. and March 21, 2014, from 8:30 a.m. to 12:15 p.m. Location: The public conference will be held on the campus of Xavier University, 3800 Victory Pkwy., Cincinnati, OH 45207, 513–745–3073 or 513–745–3020. Contact Persons: For information regarding this notice: Steven Eastham, Food and Drug Administration, Cincinnati South Office, 36 East 7th Street, Cincinnati, OH, 45202, 513–246–4134, email: steven.eastham@fda.hhs.gov. For information regarding the conference and registration: Marla Phillips, Xavier University, 3800 Victory Pkwy., Cincinnati, OH 45207, 513–745–3073, email: phillipsm4@ xavier.edu. Registration: There is a registration fee. The conference registration fees cover the cost of the presentations, training materials, receptions, breakfasts, lunches, and dinners for the 2 1/2 days of the conference. There will VerDate Mar<15>2010 20:58 Feb 14, 2014 Jkt 232001 • Operationalizing Effective Contract Partnerships • Comparing Metrics with Other TABLE1.—REGISTRATION FEES 1 Companies—is There a Way? Why is it Vital? Registration • Complex Supply Chain Attendee type fees Development • The FDA Safety and Innovation Act Industry ................................. $1,895 (FDASIA): The New Frontier Small Business (<100 employees) ............................. $1,295 • Why Your Incoming Supply is Not Startup Manufacturer ............ $300 Reliable—Shifting Paradigms Academic .............................. $300 • Innovation Versus Safety—The Media .................................... Free Government .......................... Free Impact of the Center for Drug Evaluation and Research’s Restructure 1 The fourth registration from the same com• MHRA Perspective on Global pany is free—all four attendees must register Supply Chain Challenges at the same time. • How Did They Do That? Learn from The following forms of payment will Other Industries! be accepted: American Express, Visa, The conference includes: Mastercard, and company checks. • Networking by topic To register online for the public • Case studies conference, please visit the • Small group discussions ‘‘Registration’’ link on the conference • Action plans Web site at https:// • Keynote dinner at the Cincinnati www.XavierPharmaLink.com. FDA has Reds Baseball Stadium with the Chief verified the Web site address, but is not Executive Officer of Patheon, James responsible for subsequent changes to Mullen the Web site after this document The most pressing challenges of the publishes in the Federal Register. global pharmaceutical industry require To register by mail, please send your solutions which are inspired by name, title, firm name, address, collaboration to ensure the ongoing telephone and fax numbers, email, and health and safety of patients. These payment information for the fee to challenges include designing products Xavier University, Attention: Matty Toomb, 3800 Victory Pkwy., Cincinnati, with the patient in mind, building quality into the product from the onset, OH 45207. An email will be sent selecting the right suppliers, and confirming your registration. considering total product life-cycle Attendees are responsible for their systems. Meeting these challenges own accommodations. The conference requires vigilance, innovation, supply headquarter hotel is the Downtown Cincinnati Hilton Netherlands Plaza, 35 chain strategy, relationship management, proactive change West 5th Street, Cincinnati, OH 45202, management, and a commitment to 513–421–9100. To make reservations doing the job right the first time. FDA online, please visit the ‘‘Venue & has made education of the drug and Logistics’’ link at https:// www.XavierPharmaLink.com. The hotel device manufacturing community a high priority to help ensure the quality of is expected to sellout during this FDA-regulated drugs and devices. timeframe, so early reservation in the The conference helps to achieve conference room-block is encouraged. objectives set forth in section 406 of the If you need special accommodations due to a disability, please contact Marla Food and Drug Administration Modernization Act of 1997 (21 U.S.C. Phillips (see Contact Persons) at least 7 393), which includes working closely days in advance of the conference. with stakeholders and maximizing the SUPPLEMENTARY INFORMATION: The availability and clarity of information to public conference helps fulfill the stakeholders and the public. The Department of Health and Human conference also is consistent with the Services and FDA’s important mission Small Business Regulatory Enforcement to protect the public health. The Fairness Act of 1996 (Pub. L. 104–121) conference will engage those involved by providing outreach activities by in FDA-regulated global supply chain Government Agencies to small quality and management through the businesses. following topics: be onsite registration. The cost of registration is as follows: [FR Doc. 2014–03453 Filed 2–14–14; 8:45 am] AGENCY: 9229 • The Impact of ‘‘The CDER Challenge’’ to Industry • FDA and the Medicines and Healthcare Products Regulatory Agency (MHRA) Investigator Insights PO 00000 Frm 00073 Fmt 4703 Sfmt 9990 Dated: February 12, 2014. Leslie Kux, Assistant Commissioner for Policy. [FR Doc. 2014–03454 Filed 2–14–14; 8:45 am] BILLING CODE 4160–01–P E:\FR\FM\18FEN1.SGM 18FEN1

Agencies

[Federal Register Volume 79, Number 32 (Tuesday, February 18, 2014)]
[Notices]
[Pages 9226-9229]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-03453]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0530]


Requests for Feedback on Medical Device Submissions: The Pre-
Submission Program and Meetings With Food and Drug Administration 
Staff; Guidance for Industry and Food and Drug Administration Staff; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of the guidance entitled ``Requests for Feedback on 
Medical Device Submissions: The Pre-Submission Program and Meetings 
with

[[Page 9227]]

FDA Staff.'' The purpose of this guidance is to provide an overview of 
the mechanisms available to application sponsors through which to 
obtain FDA feedback regarding potential or planned medical device 
submissions reviewed in the Center for Devices and Radiological Health 
(CDRH) and the Center for Biologics Evaluation and Research (CBER), 
including the Pre-Submission program (formerly the pre-Investigational 
Device Exemption (pre-IDE) program). In addition, the guidance provides 
recommendations regarding information that should be included in a Pre-
Submission Package. This guidance also describes the procedures that 
CDRH and CBER intend to follow when manufacturers, their 
representatives, or application sponsors request a meeting with review 
staff.

DATES: Submit either electronic or written comments on this guidance at 
any time. General comments on Agency guidance documents are welcome at 
any time.

ADDRESSES: Submit written requests for single copies of the guidance 
document entitled ``Requests for Feedback on Medical Device 
Submissions: The Pre-Submission Program and Meetings with FDA Staff'' 
to the Division of Small Manufacturers, International and Consumer 
Assistance, Center for Devices and Radiological Health, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 4613, Silver 
Spring, MD 20993-0002. Send one self-addressed adhesive label to assist 
that office in processing your request, or fax your request to 301-847-
8149. See the SUPPLEMENTARY INFORMATION section for information on 
electronic access to the guidance.
    Submit electronic comments on the guidance to https://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852. Identify comments with the docket number 
found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Program Operations Staff (IDE), Center 
for Devices and Radiological Health, Food and Drug Administration, 
10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-5640; 
or Elizabeth Hillebrenner, Office of In Vitro Diagnostics and 
Radiological Health, Center for Devices and Radiological Health, Food 
and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5616, 
Silver Spring, MD 20993-0002, 301-796-6346; or Stephen Ripley, Center 
for Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-
1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

    Since its establishment in 1995, the pre-IDE program has been a 
successful resource for both medical device applicants and the FDA. 
Originally, this program was designed to provide applicants a mechanism 
to obtain FDA feedback on future IDE applications prior to their 
submission. Over time, the pre-IDE program evolved to include feedback 
on other device submission program areas, such as Premarket Approval 
(PMA) applications, Humanitarian Device Exemption applications, 
Evaluation of Automatic Class III Designations (de novo petitions), 
Premarket Notification (510(k)) Submissions, and Clinical Laboratory 
Improvement Amendments Waiver by Application, as well as to address 
questions related to whether a clinical study requires submission of an 
IDE.
    The purpose of this guidance is to update the pre-IDE program to 
reflect this broader scope and make important modifications to reflect 
changes in the premarket program areas as a result of the Food and Drug 
Administration Amendments Act of 2007 (Pub. L. 110-85). This guidance 
also further expands the scope of the program to include those devices 
regulated by CBER, including those that are regulated as biologics 
under the Public Health Service Act and require submission of an 
Investigational New Drug Application (IND) and/or a Biologics License 
Application. Accordingly, FDA is changing the name for this program 
from the pre-IDE program to the Pre-Submission (Pre-Sub) program.
    Though successful, the Pre-Sub program has faced challenges, and 
the guidance is intended to address them and improve the Pre-Sub 
program by: (1) Describing the types of information that FDA would 
recommend submitting in order to get the best possible feedback from 
FDA; (2) outlining the process by which FDA meetings should be 
scheduled; and (3) explaining the Agency's expectations regarding 
advice given during the Pre-Sub process. This guidance outlines clear 
recommendations for sponsors and FDA staff.
    In addition to the Pre-Sub program, the guidance addresses other 
types of FDA feedback already available to applicants through other 
mechanisms. The Food and Drug Administration Modernization Act of 1997 
(FDAMA) (Pub. L. 105-115) established two types of formal early 
collaboration meetings (``determination meetings'' as described in 
section 513(a)(3)(D) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) and ``agreement meetings'' as described in section 520(g)(7) of 
the FD&C Act) to provide clear direction for testing and development of 
devices requiring clinical investigations to support marketing. FDAMA 
also requires that FDA, upon written request, must meet with a PMA 
applicant no later than 100 days after the receipt of a PMA application 
that has been filed to discuss the review status of the application 
(referred to as a ``day-100 meeting'' and described in section 
515(d)(3) of the FD&C Act). For other premarket submissions under 
review, FDA will also grant meetings on an informal basis to discuss 
our requests for additional information to better ensure that the 
formal response to FDA's request will fully address the outstanding 
questions (these meetings are referred to as ``submission issue 
meetings''). FDA will respond to requests for a determination (called 
``study risk determinations'') whether a proposed device study is 
exempt from or subject to the IDE regulation (21 CFR part 812). For 
device studies that are subject to the IDE regulations, FDA will also 
provide its determination whether the study is a significant risk or 
nonsignificant risk study in response to a voluntary request for this 
information. In some cases, sponsors may wish to inform or educate FDA 
about ongoing device development or planned submissions without a 
specific request for feedback. FDA will, as resources allow, grant 
requests for such ``informational meetings.''
    As part of the Medical Device User Fee Amendments of 2012 (MDUFA 
III), FDA committed to instituting a structured process for managing 
Pre-Subs. This final guidance establishes such a structured process for 
submission and management of Pre-Subs as well as other types of 
requests for feedback. In addition, the guidance describes how FDA will 
internally track these requests as ``Q-Submissions,'' or ``Q-Subs,'' 
including what types of submissions will be handled as supplements and 
amendments to an initial Q-Sub. FDA has also revised the optional CDRH 
Cover Sheet (Form FDA 3514) to include submission types that more 
closely track with the types of feedback requests discussed in the 
guidance.
    FDA intends to provide the best possible advice in accordance with 
the information provided by the sponsor, to ensure it is captured 
accurately in the meeting minutes drafted by the sponsor,

[[Page 9228]]

and commit to that advice unless the circumstances sufficiently change 
such that our advice is no longer applicable, such as when a sponsor 
changes the intended use of their device after we provide feedback. It 
is also our intention to hold timely meetings with appropriate staff 
and managers present, as resources permit. However, both our ability to 
provide advice and to hold timely meetings are dependent on our 
receiving the necessary information from the sponsor in advance of the 
meeting.
    Finally, the guidance describes the procedures that CDRH and CBER 
intend to follow when manufacturers, their representatives, or 
application sponsors request a meeting with review staff as the 
preferred method of feedback in response to a Pre-Sub, as an early 
collaboration meeting, or to discuss an existing regulatory submission. 
This guidance also recommends how to prepare for meetings with FDA 
staff.
    In the Federal Register of July 13, 2012 (77 FR 41413), FDA 
announced the availability of the draft guidance document. Interested 
persons were invited to comment by October 11, 2012. Seventeen sets of 
comments were received with multiple recommendations pertaining to the 
administrative processes and policies regarding the Pre-Sub program and 
meetings with FDA staff. The guidance was revised to provide a broader 
overview of available mechanisms for FDA feedback prior to a planned 
submission, with references to other existing guidance documents for 
those mechanisms where available. The guidance was also reorganized to 
discuss the various feedback mechanisms first, with a second section 
including specifics about meeting procedures that apply to all types of 
FDA feedback mechanisms where a meeting or teleconference is requested. 
Finally, an acceptance checklist for these submissions has been added 
as an appendix to clearly outline how FDA intends to determine if a Q-
Sub meets the definition of the identified Q-Sub type, and to determine 
if a qualifying request is administratively complete. It is not 
necessary for each element in the checklist to be present for the 
submission to be accepted. Instead, the acceptance checklist is 
intended to ensure only that the submission includes sufficient 
information for FDA to provide the requested feedback and/or identify 
the appropriate FDA attendees so that the meeting or teleconference can 
be scheduled.
    FDA received comments regarding the proposed timeframes for 
feedback to be provided to the applicant. Specifically, the guidance 
outlines a proposed target of 75 days, but generally no longer than 90 
days, for feedback in response to a Pre-Sub. Comments requested that 
FDA modify the guidance to include a timeframe of 60 days for response 
to a Pre-Sub. As part of the MDUFA III Commitment Letter (Ref. 1), FDA 
agreed to improve the Pre-Sub process ``as resources permit,'' but, 
because there were no additional resources provided for this program as 
part of the overall MDUFA III program, the recommended timeframe for 
FDA feedback in a Pre-Sub represents the time in which FDA believes 
that feedback generally can be provided without the application of 
additional resources to this specific program.
    Some comments expressed concern regarding FDA's recommendation that 
if more than 1 year has passed since our last feedback on key clinical 
trial design elements without a submission to the Agency, the sponsor 
should contact the review branch to confirm that the previous advice is 
still valid. The guidance has clarified that the reason for this 
recommendation is because clinical practice (including available 
alternative therapies or diagnostics) is rapidly evolving. The guidance 
has been further modified to clarify that a new Pre-Sub to the Agency 
is no longer recommended. Instead, confirmation that prior feedback is 
still valid can be accomplished through a phone call to the lead 
reviewer or branch chief.
    In response to other minor substantive and editorial comments, FDA 
revised the guidance document to clarify the processes and policies as 
appropriate.

II. Significance of Guidance

    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
Agency's current thinking on requests for FDA feedback, including the 
Pre-Sub program, and meetings with FDA staff. It does not create or 
confer any rights for or on any person and does not operate to bind FDA 
or the public. An alternative approach may be used if such approach 
satisfies the requirements of the applicable statute and regulations.

III. Electronic Access

    Persons interested in obtaining a copy of the guidance may do so by 
using the Internet. A search capability for all CDRH guidance documents 
is available at https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. Guidance 
documents are also available at https://www.regulations.gov. To receive 
``Requests for Feedback on Medical Device Submissions: The Pre-
Submission Program and Meetings with FDA Staff,'' you may either send 
an email request to dsmica@fda.hhs.gov to receive an electronic copy of 
the document or send a fax request to 301-847-8149 to receive a hard 
copy. Please use the document number 1677 to identify the guidance you 
are requesting.

IV. Paperwork Reduction Act of 1995

    This guidance also refers to previously approved information 
collections found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information in 21 CFR part 803 are approved under OMB 
control number 0910-0437; the collections of information in 21 CFR part 
807, subpart E are approved under OMB control number 0910-0120; the 
collections of information in 21 CFR part 812 are approved under OMB 
control number 0910-0078; the collections of information in 21 CFR part 
814 are approved under OMB control number 0910-0231; and the 
collections of information for Request for Feedback on Medical Device 
Submissions are approved under OMB control number 0910-0756.

V. Comments

    Interested persons may submit either electronic comments to https://www.regulations.gov or written comments regarding this document to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at https://www.regulations.gov.

VI. Reference

    The following reference is available electronically at https://www.regulations.gov. (FDA has verified the Web site address in this 
reference section, but we are not responsible for any subsequent 
changes to the Web site after this document publishes in the Federal 
Register.)

    1. MDUFA III Commitment Letter, April 18, 2012, available at 
https://www.fda.gov/downloads/MedicalDevices/NewsEvents/WorkshopsConferences/UCM295454.pdf.



[[Page 9229]]


    Dated: February 12, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-03453 Filed 2-14-14; 8:45 am]
BILLING CODE 4160-01-P
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