FDA s ectd Mandate for 2017: Latest Developments Phillip DeNoble, PharmD, B.Sc. 5
2 Nothing to disclose Disclosure
3 Presentation Overview Introduction/Background Good Review Practices Refuse to Receive Best Practices PDF/Scanned Documents First Hand Experiences Summary
4 Brief Intro/Review 5 5
5 Good Review Practices (GRPs) A documented best practice within CDER that discusses any aspect related to the process, format, content and/or management of a product review. GRPs are 1 : developed over time as superior practices based on experience, and provide consistency to the overall review process of new products 1 developed to improve the quality of reviews and review management. GRPs improve efficiency, clarity, and transparency of the review process and review management 1 adopted by review staff as standard processes through supervisor mentoring, implementation teams and formal training when necessary 1
6 Refuse to Receive (RTR) A Refuse to Receive is a GRP policy designed for ANDAs and Prior Approval Supplements ANDAs An RTR decision indicates that FDA determined that an ANDA is not substantially complete 2. The agency will evaluate each application submitted (prior to content review). The agency must deem the application as substantially complete to permit a review 2
7 Background on RTR Generic Drug User Fee Amendments of 2012 (GDUFA). The legislation was enacted to accomplish several tasks; one being: enhanced refusal to receive standards for ANDAs and other related submissions by the end of year 1 of the program. 3 Intended to increase agency efficacy by reducing time spent correcting improperly prepared applications 3
8 RTR Figures Between Fiscal Years (FY) 2013 to 2015, FDA refused to receive 379 ANDAs for reasons other than failure to pay a GDUFA fee. Of all original ANDA submissions, FDA refused to receive 4 : 14% in FY 2013 10% in FY 2014 14% in FY 2015
9 Major Deficiencies A deficiency found in 21 CFR 314.101(d)(e) or discussed in the December 2016 guidance ANDA Submissions Refuse-to-Receive Standards 6 Examples...
10 Major Deficiencies Examples Related to PET ANDAs 6 Form 356h* Format & Organization Sterility Assurance Data Inadequate Stability Executed Batch Record Method Validation Reports
11 Minor Deficiencies The agency deems the deficiency as easily remedied 6 The agency will allow the applicant with 7 calendar days to amend the ANDA 6 Only occurs if the application contains 10 or less minor deficiencies 6
12 What Happens After RTR? If an applicant decides to amend to application: The resultant application will be considered new and dated as such 6 The applicant will be required to pay a new ANDA Fee 6 Bear in mind PET drug exemptions
13 What Happens After RTR? If the applicant decided to take no action, the agency will consider the application withdrawn after one year 6 The applicant may appeal the decision 6 : Submit concerns to the e-mail listed on the RTR letter If applicant is still unsatisfied, a formal dispute resolution may be conducted in accordance with 21 CFR 314.103 and the Formal Dispute Resolution: Appeals Above the Division Level guidance
14 Guidelines for PDFs and Scanned Documents FDA guidelines for PDFs and Scanned documents align with ICH Requirements Guidance's have been around since 2008, with revisions up to 2016
15 Guidelines for PDFs and Scanned Documents: Best Practices Use fonts that are known to be available on the reviewers computer 7 : Use font sizes ranging from 9 to 12 point. Times New Roman 12-point font is recommended for narrative text 7
16 Guidelines for PDFs and Scanned Documents: Best Practices Page Orientation: In summation; never have the reviewer flip the page 7 *** Scanning Resolution 7 : Handwritten Notes/Chromatographs: 300dpi Photos: 600dpi
17 Guidelines for PDFs and Scanned Documents: Best Practices All PDFs and Scanned documents should have searchable text 7 PDFs over 5 pages 7 : Indexed with a Table of Contents Hyperlinked Text
18 First Hand Account ANDA for 18F-FDG (post 2012 deadline) Option to submit (full ectd/hybrid/paper) Submitted September, 2015 Refuse to Receive Committee comments in October, 2015
19 First Hand Account Minor deficiencies found: 7 comments in total Minor changes to 356h requested (add USP or language in proposed indications) Mass and concentration of excipients listed CofAs for all components requested Minor Corrections to impurities tables include all potential impurities in the recommended tabular format with the following column headers: IUPAC Chemical Name, Code #, Chemical Structure, Degradation Impurity and Source/ Mechanism. You may refer to the OGD website for further clarification.
20 PDF/Scan Issues: First Hand Account Inadequate bookmarks for file entitled 1-14-1-3- draft-labeling-text-pdf.pdf in section 1.14.1.3 An example of an unacceptable file in your submission is the PTS printout for batch number FDG-063015 in section 3.2.P.5.4 and 3.2.R.
21 PDF Scan ectd Issue First Hand Account
22 Practical Experiences with ectd What type of model should you implement? Institution Bears Full Responsibility Hybrid (Consultant and Institution Share Responsibility) Consultant Bears Responsibility
23 Practical Experiences with ectd Personal Opinion: The hybrid model makes the most sense (both practically and financially) Outsource work that is overly burdensome or technical in detail Avoid software implementation costs and compliance issues Develop and prepare bulk of the application to save consultant time/fees
24 Miscellaneous Information Is ectd Actually Required for PET? Electronic copy of requested documents during PAI/cGMP inspections
25 Acknowledgments/Thanks Memorial Sloan Kettering Cancer Center Ariel Brown, Serge lyashchenko, Jason Lewis New York University CAI 2 R Dr. Yokell and the MGH PET Center
26 References 1. Good Review Practices (GRPs). Updated 02/13/2017. https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/ucm118777.htm 2. 21 CFR 314.101(b)(1). Applications for FDA Approval to Market a New Drug. Revised April 1, 2016. 3. Generic Drug User Fee Act Performance Goals and Procedures. https://www.fda.gov/downloads/forindustry/userfees/genericdruguserfees/ucm282505.pdf 4. Performace Report to Congress for the Generic Drug User Fee Amendments. FY 2015. https://www.fda.gov/downloads/aboutfda/reportsmanualsforms/reports/userfeereports/performancereports/ucm493026.pdf 5. Providing Regulatory Submissions in Electronic Format Certain Human Pharmaceutical Product Applications and Related Submissions Using the ectd Specifications Guidance for Industry. Revision 4. April 2017. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm333969.pdf 6. ANDA Submissions Refuse-to-Receive Standards Guidance for Industry. December 2016. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm370352.pdf 7. Portable Document Formart (PDF) Specifications Guidance for Industry. September 2016. https://www.fda.gov/downloads/drugs/ucm163565.pdf