Post on 04-May-2018
2015 GPhA
CMC Workshop
Ted Sherwood
Acting Director
Office of Regulatory Operations
Office of Generic Drugs
June 9, 2015
1
Office of Generic Drugs Update
Today’s Discussion
• Collaborations with the Office of
Pharmaceutical Quality (OPQ)
• Communications Update
• Tips for Industry
• Sources of Information
2
• Collaborations with the Office of
Pharmaceutical Quality (OPQ)
Joint OPQ/OGD Activities
• Application review priorities including:
– Target Action Dates (TADs)
– Drug shortages, 1st generics, PIVs*
• Managing complex ANDAs
• IT / platform enhancements
• Operations updates
• Backlog performance 3
* paragraph IV
• GDUFA I performance
• GDUFA II planning
• Memorandums of Understanding for
review responsibilities
• Joint SOPs*
• Use of same training and facilitation teams
• Research collaborations
4
Joint OPQ/OGD Activities (cont.)
* Standard Operating Procedures
Joint OPQ/OGD Forums
• OGD-OPQ GDUFA Coordinating Committee
• GDUFA Steering Committee
• Workload Planning Forums
– Year 3 applications
– Pre-Year 3 applications
• Weekly Check-ins 5
• Platform User Groups
• GDUFA Status Check-in, Co-Chair
• OPQ-OGD Biweekly Directors 1:1
• ORO*/OGD : OPRO**/OPQ Interactions
• Others from IT to Lifecycle Management
6
Joint OPQ/OGD Forums (cont.)
* Office of Regulatory Operations; ** Office of Program and Regulatory Operations
Today’s Discussion
• Collaborations with the Office of
Pharmaceutical Quality (OPQ)
• Communications Update
• Tips for Industry
• Sources of Information 7
Industry
Generic Drug Program
8
Available
Communications
• Filing Decision
• ANDA assigned to an RPM – introductory
• ANDA reassigned to another RPM
• Target Action Dates (TADs)
9
Communications (cont.)
• No Go
• Pre-action communication
• Complete Responses (CR)
• Post CR meetings
10
Communications (cont.)
• Pre-Information Request (IR) notification
• IRs (a.k.a. Real Time Communications)
• Easily Correctable Deficiencies (ECDs)
• Telephone Information Requests
11
Communications (cont.)
• Launch Planning (a.k.a. Health of the
Application)
• Go / Action Letter Expected
• Approvals / Tentative Approvals
12
• Notification of a Target Action Date does
not constitute a commitment or guarantee
that FDA will take action on the application
by the Target Action Date.
• Any amendments submitted after the
notification may affect whether FDA will
take action on the application by the
Target Action Date. 13
Caveats
• When contacted for an additional status update
3 or 6 months prior to the Target Action Date,
the RPM will provide the total number of
discipline reviews needed for the application and
the number of reviews pending.
• All outstanding ECDs and IRs must be
addressed before an action can be taken.
14
Caveats (cont.)
• When an application is in the clearance phase,
the RPM will notify the applicant by phone
that FDA is on track to provide an action.
– The RPM may request assurance
that the application’s labeling, information,
Type II DMFs, and inspections are up-to-date.
– The RPM cannot provide additional information
other than that the application is on track to
receive an action.
– Not a guarantee of approval. 15
Caveats (cont.)
Filing Time Frames
• Typical assessment time
– Current/GDUFA Year 3 submissions: 31 days
– Prior submissions/backlog <400, but <40 with
the primary filing reviewer
• Check-list: http://www.fda.gov/downloads/Drugs/DevelopmentApprov
alProcess/HowDrugsareDevelopedandApproved/Approval
Applications/AbbreviatedNewDrugApplicationANDAGeneri
cs/UCM320405.pdf
16
Filing Time Frames (cont.)
• Guidance on Refuse-to-Receive
Standards: http://www.fda.gov/downloads/Drugs/GuidanceComplia
nceRegulatoryInformation/Guidances/UCM370352.pdf
• Electronic format:
• “highly recommend”
• GDUFA review goals only apply to
electronic ANDA submissions
17
43
28 29 26 27
19
49 47 42
73
92
100 100
81
93
61
2 3 4 4 8
12
22
35
10 7 5 5
13 6
20 13 68 84
129
260
324 334
724
583
0
100
200
300
400
500
600
700
800
0
20
40
60
80
100
120
Oct-2014 Nov-2014 Dec-2014 Jan-2015 Feb-2015 Mar-2015 Apr-2015 May-15
Approved Complete Response
Complete Response Pending Inspections Tentative Approval
Withdrawn ECD/IR
ANDA Originals – Actions Taken
18
Oct 2014 Nov 2014 Dec 2014 Jan 2015 Feb 2015 Mar 2015 Apr 2015 May 2015 Grand Total
AP 43 28 29 26 27 19 49 47 266 CR 42 73 92 100 100 81 93 61 642 CR –
Pending
Inspections 2 3 4 4 8 12 22 35 90
TA 10 7 5 5 13 6 20 13 79 WD 2 1 1 4
ECD/IR 68 84 129 260 324 334 724 583 2506
CR
AP
ECD/IR
*excludes filing
26
54
29
49
55 53
66
40
9
14
8
14 14 15 17
13
4 7
2 4
2 1
16 13
21
34 33
39
32 34
0
10
20
30
40
50
60
70
Oct-2014 Nov-2014 Dec-2014 Jan-2015 Feb-2015 Mar-2015 Apr-2015 May-15
Approved Complete Response Withdrawn ECD/IR
ANDA PAS – Actions Taken
19
CR
AP
WD
Oct-2014 Nov-2014 Dec-2014 Jan-2015 Feb-2015 Mar-2015 Apr-2015 May-2015 Grand Total
Approved 26 54 29 49 55 53 66 40 372 Complete Response 9 14 8 14 14 15 17 13 104
Withdrawn 4 7 2 4 2 1 20 Tentative Approval 1 1 ECD/IR 16 13 21 34 33 39 32 34 222
ECD/IR
*excludes filing
Controlled Correspondence
• GDUFA Goals
– Year 3: 70% within 4 months (exceeding)
– Year 4: 70% within 2 months
– Year 5: 90% within 2 months
– Extra month for clinical issues
20
21
Control Correspondence (cont.)
22
1299
871
704
579
512 468
429 411 363
328
0
200
400
600
800
1000
1200
1400
Grand TotalBacklog
September October November December January February March April May
Total Controls Pending at End of Month
Controlled Correspondence Pre-FY15 GDUFA
(submitted prior to 10/1/14)
Today’s Discussion
• Collaborations with the Office of
Pharmaceutical Quality (OPQ)
• Communications Update
• Tips for Industry
• Sources of Information 23
Tips
• Submit a complete application – avoid
“Refuse-to-Receive.”
• Submit electronically.
• Assure Drug Master Files (DMFs) have
undergone Completeness Assessments.
• Assure facilities are ready for inspection.
• Respond completely and timely to IRs from
the Division of Filing Review (DFR).
24
Tips (cont.)
• When correcting communicated eCTD
deficiencies, check all documents for the
identified deficiencies & correct where
needed.
• Place information in the proper sections of the
ANDA hierarchy.
– Comparative dissolution data should be
placed in modules 2.7 and 5.3.1.3
25
Tips (cont.)
• Know the quality of your contractor.
• Integrate contractor data into your
submission.
• Submit labels and labeling in final print in
your original submission (reduces cycles).
• Requirement for “same” labeling is the
NDA reference listed drug (RLD) product,
and not the current ANDA reference
standard reflected in the Orange Book.
26
Tips (cont.)
• Watch for guidance updates.
• Watch for compendia changes and update
your application accordingly.
• Make sure OGD has all legal documents
and update as needed.
• Submit a new 356h when reg. contact
changes.
27
Tips (cont.) • Provide complete and timely responses.
• Goal dates are important to FDA too.
• No response to IR triggers a CR
(consumes Agency resources).
• When correcting communicated eCTD
deficiencies, check all documents for the
identified deficiencies & correct where
needed.
28
Tips (cont.)
• Work with your Regulatory Project Manager
(RPM). (If you cannot reach the RPM,
contact the Team Leader then Supervisor.)
• Contact the RPM, not the discipline unless
specifically requested.
• Contact the Discipline PM for your delays in
responding to IRs.
• Provide ANDA number when communicating
• OGD cannot rescue ANDAs.
29
Tips (cont.)
• If Tentatively Approved*, make sure any
changes are reported in a timely manner
• For supplements that provide for alternate
manufacturing facility, revised labeling and
labeling to reflect the new manufacturer
may be submitted in the annual report.
• Properly and clearly identify the types of
changes in a supplement.
30 * meets FDA’s requirements, but patent and/or exclusivity protection exists
Tips (cont.)
• When submitted Controlled
Correspondence, include relevant RLD(s),
as applicable, including application
number, proprietary (brand) name, 278
manufacturer, active ingredient, dosage
form, and strength(s).
• Link:
http://www.fda.gov/downloads/drugs/guida
ncecomplianceregulatoryinformation/guida
nces/ucm411478.pdf
31
Response to Filing Concerns
• New review practices will prevent
inappropriate application of guidance
standards.
• Rescissions have been primarily a result of
old review practices that have since been
corrected by the first bullet.
• Enhanced RTR standards have been
developed and implemented, along with the
necessary training to evaluate and enforce
such standards.
Response to a Labeling Concern
• Many generic sponsors do not realize that
the RLD designation in the Orange Book is
only for bioequivalence purposes.
• If there was a NDA RLD and that NDA
RLD is no longer marketed because it was
discontinued or withdrawn, it still remains
to be the RLD for labeling purposes.
Today’s Discussion
• Collaborations with the Office of
Pharmaceutical Quality (OPQ)
• Communications Update
• Tips for Industry
• Sources of Information
34
Office of Generic Drugs - Information
• Your RPM http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm119463.htm
• Web page: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm119100.htm
• Submission Requirements: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ucm120955.htm
35
Public Meetings
• FY 2015 Regulatory Science Initiatives -
June 5, 2015
– Overview of regulatory science initiatives.
– Opportunity for public input on research
priorities.
– http://www.fda.gov/ForIndustry/UserFees/Gene
ricDrugUserFees/ucm436485.htm
– Watch for future meetings.
36
Public Meetings (cont.)
• GDUFA II June 15, 2015
– Seeking participation (i.e., attendance and oral
presentations)
– Link:
http://www.fda.gov/ForIndustry/UserFees/Gener
icDrugUserFees/ucm444958.htm
37
Webinar with GPhA
• Date: June 30, 2015
• Time: 2:00 pm - 3:00 pm
38
Questions?
39
Ted Sherwood
Phone: 301-796-1605 (Direct)
Fax: 301-595-1271
E-mail: edward.sherwood@fda.hhs.gov