
[Federal Register Volume 82, Number 175 (Tuesday, September 12, 2017)]
[Notices]
[Pages 42815-42818]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-19258]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-4765]


Center for Devices and Radiological Health Premarket Approval 
Application Critical to Quality Pilot Program

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration's (FDA or Agency or we) 
Center for Devices and Radiological Health (CDRH or Center), Office of 
Compliance (OC) and Office of In Vitro Diagnostics and Radiological 
Health (OIR) is announcing its Premarket Approval Application Critical 
to Quality (PMA CtQ) pilot program. Participation in the PMA CtQ pilot 
program is voluntary and the program aims to evaluate device design and 
manufacturing process quality information early on to assist FDA in its 
review of the PMA manufacturing section and post-approval inspections. 
This voluntary pilot program is part of the FDA's ongoing Case for 
Quality effort to apply innovative strategies that promote medical 
device quality and is a joint effort between the FDA's CDRH and Office 
of Regulatory Affairs (ORA). The pilot program is intended to provide 
qualifying PMA applicants with the option to engage FDA on development 
of CtQ controls for their device and forego the standard PMA 
preapproval inspection. FDA would in turn, focus on the PMA applicant's 
implementation of the CtQ controls during a postmarket inspection.

DATES: FDA is seeking participation in the voluntary PMA CtQ pilot 
program starting from September 29, 2017. See the ``Participation'' 
section for instructions on how to submit a request to participate. 
This pilot program will run from September 29, 2017, to December 31, 
2018. The voluntary PMA CtQ pilot program will accept the first nine 
participants with submissions that meet the acceptance criteria.

ADDRESSES: You may submit comments 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-

[[Page 42816]]

2017-N-4765 for ``Center for Devices and Radiological Health Premarket 
Approval Application Critical to Quality Pilot Program.'' 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.
     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: Bleta Vuniqi, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 3463, Silver Spring, MD 20993, 301-796-5497, 
Bleta.Vuniqi@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    CDRH believes that proactive engagement with PMA applicants and a 
focused inspectional approach will promote quality in device design and 
manufacturing. CDRH plans to initiate the voluntary PMA CtQ pilot 
program focusing on activities critical to product and process quality 
starting September 29, 2017. The Center intends to work collaboratively 
with PMA applicants identified to participate in the PMA CtQ pilot 
program to define characteristics of the PMA device that are critical 
to product quality and how these characteristics are controlled in 
design and manufacturing prior to the postmarket inspection. PMA 
applicants can expect discussions during the inspection to relate to 
those factors most likely to impact device quality by working with FDA, 
before PMA approval, on defining activities critical to product and 
process quality. Improvements in overall device quality may reduce 
device failures and recalls, and translate into more efficient 
utilization of resources for CDRH, ORA, and the device industry. 
Previously, CDRH's OC completed the implantable devices containing 
batteries Critical to Quality Inspection pilot which established a 
collaborative framework for determining specific operations, design 
considerations, and controls that most impact the quality and safety of 
these devices (Ref. 1). Post-inspection feedback from ORA and CDRH's OC 
indicated that FDA can improve its approach for medical device 
inspections by focusing on areas critical to quality of the device, 
which in turn will change the compliance focus to influence better 
device quality. In addition, feedback received from industry 
participants indicated that many of the risks for devices reside in 
product and process design and post-production activities.
    Whether firms are appropriate candidates for participation in this 
voluntary PMA CtQ pilot program is determined based on the factors 
listed in Section A. Participation Criteria. Upon applicant's pre-PMA 
q-submission meeting request, FDA will identify appropriate candidates 
to participate in this voluntary pilot program. Due to resource 
constraints, we intend to limit this voluntary pilot program to a 
maximum of nine participants. FDA intends to work with each 
participating applicant to identify characteristics of its device and 
its manufacture that are critical to its quality, which may include 
specific device features or quality control practices. The identified 
CtQ characteristics and controls will help focus FDA's post-approval 
inspectional approach.
    The aim of the voluntary PMA CtQ pilot program is to have the 
applicant discuss device design and manufacturing process quality 
information with FDA early on to assist FDA in its review of the PMA 
manufacturing section and post-approval inspections. The goal of this 
voluntary pilot program is to streamline the premarket approval process 
while assuring that a firm's quality system includes rigorous controls 
for features and characteristics considered critical to the safety and 
effectiveness of the device. FDA believes that focusing on these 
activities may also lead to fewer device failures, a decrease in device 
recalls, and improved device innovation and efficiencies. For 
participants in the voluntary PMA CtQ pilot program, FDA intends to 
forego conducting a preapproval inspection, which it would usually 
conduct, and instead conduct a more focused post-approval inspection. 
That post-approval inspection would focus on the design, manufacturing, 
and quality assurance practices identified by the applicant in its PMA. 
In addition, this voluntary pilot program is part of the FDA's ongoing 
Case for Quality effort to apply innovative strategies that promote 
medical device quality instead of focusing only on compliance with the 
Quality System regulation (Ref. 2). This voluntary PMA CtQ pilot 
program does not represent a new requirement; instead, it is an 
opportunity to promote quality in device manufacturing, timely review 
of the PMA manufacturing section and more effective use of inspectional 
resources, and an enhanced opportunity to engage with firms regarding 
device quality prior to marketing of the device. This voluntary PMA CtQ 
pilot program augments the FDA's traditional Quality System Inspection 
Technique (QSIT) inspectional approach, and does not replace it (Ref. 
3).
    Combination products, products regulated by the Center for 
Biologics Evaluation and Research, and companion diagnostic In Vitro 
Diagnostic devices that require coordination with the Center for Drug 
Evaluation and Research are not within the scope of this voluntary PMA 
CtQ pilot program.

A. Participation Criteria

    Firms that are appropriate to participate in this voluntary PMA CtQ 
pilot program are those firms submitting an original PMA who follow the 
procedures set out in Section B and who also:

[[Page 42817]]

    1. Submit a request for a pre-PMA q-submission meeting, and
    a. Provide the recommended information identified in the guidance 
document, ``Requests for Feedback on Medical Device Submissions: The 
Pre-Submission Program and Meetings with Food and Drug Administration 
Staff'' dated February 18, 2014 (Ref. 4), along with a statement of 
interest for participation in this voluntary PMA CtQ pilot program in 
the applicant's cover letter.
    b. Provide a list of PMA-related facilities responsible for the 
manufacture, processing, packing, or installation with the applicant's 
pre-PMA q-submission submission package.
    c. If available, submit a draft list of critical characteristics 
for the device which is the subject of the PMA application.
    2. As part of the PMA application, include the proposed list of 
critical characteristics as well as their associated controls for the 
device which is the subject of the PMA. The list should include 
characteristics where failure in meeting the characteristic would have 
a reasonable likelihood or a remote likelihood of causing a death or 
serious injury.
    3. Have their PMA application accepted and filed for review by FDA 
(Ref. 5).
    4. Have not had Quality System deficiencies identified in FDA's 
review of the manufacturing section of the applicant's PMA (Ref. 6).
    5. Have had an FDA inspection of the PMA-related facilities 
conducted at least once within the last 5 years.
    6. An FDA inspection of the PMA-related facilities has not been 
classified as Official Action Indicated or been subject to a judicial 
action (e.g., seizure or injunction, including consent decrees) within 
the last 5 years (Ref. 7).

B. Procedures

    Postmarket inspections under this proposed voluntary PMA CtQ pilot 
program will be conducted in accordance with FDA's general 
establishment inspection authority in section 704(a) of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 374(a)). FDA intends for the 
investigator to follow the current medical device inspection model as 
outlined in the 2017 FDA Investigations Operations Manual (IOM) Chapter 
5 and FDA Compliance Program 7383.001 ``Medical Device Premarket 
Approval and Postmarket Inspections'' dated March 5, 2012, with the 
following exceptions: (1) The inspection is conducted in the postmarket 
setting and (2) the postmarket inspection includes an evaluation of 
critical control measures for the production of the device are 
implemented (Ref. 8-10). Section 5.1.2 of the IOM provides the 
inspection may be directed for ``obtaining specific information on new 
technologies, good commercial practices, or data for establishing food 
standards or other regulations.''
    Additionally, FDA intends on soliciting feedback from ORA, industry 
participants, and CDRH's OC/OIR staff during the voluntary PMA CtQ 
pilot program. Feedback from participants will be gathered through 
meetings and questions proposed in Appendices A and B (Ref. 11).
    The following captures FDA's expected process for the voluntary PMA 
CtQ pilot program:
    1. A firm submits a pre-PMA q-submission meeting request at least 
75-90 days in advance of submission of the PMA application following 
the recommendations outlined in the guidance document ``Requests for 
Feedback on Medical Device Submissions: The Pre-Submission Program and 
Meetings with Food and Drug Administration Staff'' (Ref. 4) dated 
February 18, 2014. Additional expectations, include:
    a. Providing a statement in the pre-PMA q-submission to support 
being considered for participation in the voluntary PMA CtQ pilot 
program.
    b. Providing a list of PMA-related facilities responsible for the 
manufacture, processing, packing, or installation for the device which 
is the subject of the PMA as part of the applicant's pre-PMA q-
submission package.
    c. If available, submitting a draft list of critical 
characteristics for the device which is the subject of the PMA 
application.
    2. During the pre-PMA q-submission meeting, FDA clearly 
communicates the voluntary PMA CtQ pilot program expectations and 
discusses and provides the applicant's proposed draft list of critical 
characteristics for the PMA device and provide feedback.
    3. Once a firm has expressed interest in participating in the 
voluntary PMA CtQ pilot program, CDRH determines whether:
    a. all PMA-related facilities have been inspected within the last 5 
years, and
    b. all of the inspections of the PMA-related facilities have not 
been classified as Official Action Indicated and have not been subject 
to a judicial action (e.g., a seizure or injunction action, including a 
consent decree) within the last 5 years.
    4. The PMA application:
    a. Is accepted and filed for review by FDA.
    b. Includes as part of the manufacturing section the proposed list 
of device critical characteristics as well as their associated 
controls, which may include certain design, manufacturing, or quality 
assurance practices. The list of critical characteristics identified in 
4(b) is based on risk to the patient or user, including whether failure 
in meeting the characteristic can have a reasonable likelihood or a 
remote likelihood of causing a death or serious injury.
    c. Is accompanied by a streamlined process validation report to 
CDRH OC or OIR no later than day 45 within the PMA application process.
    5. CDRH OC/OIR completes the following during review of the PMA 
application:
    a. Checks the CtQ information for clarity, completeness, and 
relevance to the Quality System regulation within days 1-45, with the 
goal to have the list of device critical characteristics as well as 
their associated controls finalized by day 60 of the 180-day clock.
    b. Reviews the manufacturing section of the PMA application within 
the first 30 days of the 180-day clock. If Quality System deficiencies 
are identified during this review, then the PMA application would no 
longer be appropriate for inclusion in this voluntary PMA CtQ pilot 
program. The reviewer would follow the current established procedures 
and place the PMA application on ``hold'' pending correction of the 
deficiencies.
    c. Reviews the validation report identified in section B.4(c) 
within 30 calendar days of receipt. Any concerns raised by the 
validation report review may result in the issuance of a deficiency 
letter that will place the PMA on ``hold'' pending Good Manufacturing 
Practices corrections.
    d. Provides an inspectional assignment to the investigator and 
makes necessary technical expertise available to the ORA. The critical 
characteristics and controls will help guide the investigator and 
appropriately focus their activities during the postmarket inspection. 
In addition, CDRH intends to include CtQ and control information in an 
inspectional assignment and contact the investigator(s) to discuss 
critical control measures and expectations prior to the inspection.
    6. Following an approval decision, FDA conducts the postmarket 
inspection in accordance with the 2017 FDA IOM, Compliance Program 
7382.845, and Compliance Program 7383.001 (Ref. 8-10) utilizing 
elements

[[Page 42818]]

of QSIT, and informed by the PMA CtQ information developed jointly by 
FDA and the PMA applicant.
    7. Following completion of the inspection, participating FDA 
Offices and applicants provide the information/data needed to assess 
the voluntary PMA CtQ pilot program's impact on resource utilization 
and quality focus, utilizing the evaluation forms provided in 
Appendices A and B (Ref. 11).
    During this voluntary PMA CtQ pilot program, CDRH staff intends to 
be available to answer questions or concerns that may arise. The 
voluntary PMA CtQ pilot program participants will be asked to comment 
on and discuss their experiences with the PMA CtQ pilot submission 
process. Comments and discussions may assist FDA in determining whether 
the goals of this voluntary PMA CtQ pilot program goal are clearly 
communicated and attainable.

II. Duration of the Premarket Approval Application Critical to Quality 
Pilot Program

    FDA intends to accept requests for participation in the voluntary 
PMA CtQ pilot program from September 29, 2017, to December 31, 2018, or 
until such time as when a total of nine PMAs have been enrolled.

III. Paperwork Reduction Act of 1995

    This notice refers to previously approved collections of 
information 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 814, subparts A through E 
have been approved under OMB control number 0910-0231; the collections 
of information in 21 CFR part 820 have been approved under OMB control 
number 0910-0073; and the collections of information in ``Requests for 
Feedback on Medical Device Submissions: The Pre-Submission Program and 
Meetings with Food and Drug Administration Staff'' have been approved 
under OMB control number 0910-0756.

IV. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES), and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and are available electronically at https://www.regulations.gov. (FDA 
has verified the Web site addresses, but we are not responsible for any 
subsequent changes to the Web sites after this document publishes in 
the Federal Register.)

1. Implantable Devices that Contain Batteries Critical to Quality 
Inspection Pilot. Available at https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/MedicalDeviceQualityandCompliance/UCM469128.pdf.
2. FDA's Case for Quality, available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/MedicalDeviceQualityandCompliance/ucm378185.htm.
3. FDA's Guide to Inspections of Quality Systems, Quality System 
Inspection Technique, available at http://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074883.htm.
4. FDA Guidance for Industry and FDA Staff ``Requests for Feedback 
on Medical Device Submissions: The Pre-Submission Program and 
Meetings with Food and Drug Administration Staff'' dated February 
18, 2014. Available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm311176.pdf.
5. FDA's Guidance for Industry and FDA Staff: Acceptance and Filing 
Reviews for Premarket Approval Applications (PMAs) at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-gen/documents/document/ucm313368.pdf.
6. FDA's Guidance for Industry and FDA Staff: Quality System 
Information for Certain Premarket Application Reviews, available at 
http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm070897.htm.
7. FDA's Official Action Indicated, available at http://www.fda.gov/downloads/AboutFDA/Transparency/PublicDisclosure/GlossaryofAcronymsandAbbreviations/UCM212061.pdf.
8. 2017 FDA Investigations Operations Manual (IOM) Chapter 5 at 
https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-afda-ice/documents/document/ucm123522.pdf.
9. FDA Compliance Program 7383.001 at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/MedicalDeviceQualityandCompliance/UCM295570.pdf.
10. FDA Compliance Program 7382.845 at https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM244277.pdf.
11. Appendices A and B.

    Dated: September 5, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-19258 Filed 9-11-17; 8:45 am]
 BILLING CODE 4164-01-P


