Data Presentation for FDA Submission ppt.pptx

The ideas in this chapter for improving the text and the tables in NDA submissions (or other regulatory submissions) will be representative rather than comprehensive and will focus more on general methods for improving the quality of the text and the tables than on specific styling conventions.

1. CHHATRAPATI SHAHU JI MAHARAJ UNIVERSITY, KANPUR SCHOOL OF PHARMACEUTICAL SCIENCES, CSJMU PRESENTED BY :- SIDDHARTH TIWARI M.PHARM (PHARMACEUTICS) ROLL NO. - 22077000014 P resentation on DATA PRESENTATION FOR FDA SUBMISSIONS

2. CONTENTS INTRODUCTION TEXT EXPOSITION TABULAR PRESENTATION CONCLUSION REFERENCES

3. INTRODUCTION Over the years, representatives of both the FDA and the pharmaceutical industry have published in pharmaceutical journals or presented at work-shops many helpful suggestions to facilitate NDA review. Several authors and presenters have expressed the FDA reviewers’ frustration at having to review a submission that is incoherently assembled or confusing in its presentation.

4. The ideas in this chapter for improving the text and the tables in NDA submissions (or other regulatory submissions) will be representative rather than comprehensive and will focus more on general methods for improving the quality of the text and the tables than on specific styling conventions.

5. TEXT EXPOSITION Content : Most NDA submissions contain an enormous amount of data, which cannot be presented entirely within the body of a document. Data necessary for the development of a specific thesis should be presented within the body of the document rather than placed into a remote appendix, which will impede the review. Less important data can be summarized briefly, clearly referenced in text, and placed in appendices.

6. 2. Tone: The tone of the text should be formal without being stilted. Avoid legal language on the one hand and colloquial or informal language on the other. 3. Conciseness : Be mindful that FDA reviewers must read through many volumes of an NDA to make a report on their conclusions. Having to pour through dense, inflated, entangled text to ascertain the point being made will slow the review process. Keep the language simple and straightforward. Use acronyms and initialisms to speed up the flow of text if they are easily recognized and have been spelled out at first mention. Eliminate redundancies.

7. 4. Correctness: The textual presentation should agree with the tabular data in the document; in turn, the tabular data should agree with the data source (which agrees with the case report form and other clinical documentation). 5. Consistency: Consistent punctuation, capitalization, abbreviations, and other styling conventions are much desired in any document, but use judgment before applying the consistency rule unquestioningly. Does the adherence to consistency improve the document or confound it?

8. 6. Clarity: The FDA reviewer should be able to read through an application expeditiously and not have to stop to try to discern the meaning of a textual presentation. The sponsor of the application should have someone who is familiar with the material in general, but not with the specific document, read it for clarity before submission. Clarity is facilitated by careful attention to the following: Punctuation Sentence structure and length Misplaced modifiers Parallelism

9. 7. Outline of Sections and Subsections: The clear relationship of one section to another is critical to the review of a document. If no definite structure is apparent, the reviewer will become lost. The decimal system is a very popular outlining system; it is easy to use and can be set up automatically in most current word processing software applications. This author strongly advises against going beyond three or four levels in the decimal system, because it is difficult to figure out by then which level you are reading.

10. 8. Indenting: Avoid indenting large sections of text. Most text should be flush to the left margin with appropriate headers to identify the section. Multiple and sequential indenting wastes space and is confusing. 9. Global to Specific: For any section, begin with global statements or data and then discuss the specifics. For example, in the discussion of adverse events, the overall presentation of the events should precede the presentation by severity, by relationship, by subgroup, etc. It is particularly important in the discussion of the populations evaluated in a particular document. Begin with the allinclusive population first, then define the subpopulations.

11. TABULAR PRESENTATION In-text tables should be used whenever they simplify the presentation and allow for substantial reduction in text. Comprehensive multipage tables that interrupt text should be avoided, if possible, unless they are critical to the development of the thesis of the section. If the tables are very important, they can be placed in the same volume in an appendix. Usually, data can be collapsed to be included in the in-text table, with reference to the full table in an easy-to-locate appendix. It should be mentioned here that any tables, figures, or graphs in the appendices must have in-text references.

12. Title: All tables require concise but descriptive titles. Sequences of tables that are similar should identify their differences very conspicuously in the title, such as at the end of the title after a colon (e.g., Treatment-Related Adverse Events: by Age;…by Sex…by Race) . 2. Data Source: Every table should identify the source of the data contained in it. This is usually done in a footnote to the table (e.g., Data source: Statistical Table 23, Volume XX, p. xx). The volume and page numbers will be inserted at the end of the project. Exact referencing of in-text tables will facilitate the review process.

13. 3. Footnotes: Footnotes should be assigned letters (superscripted), not symbols or numbers, which can be confused with the data. Asterisks (*, **, ***) are generally reserved for levels of statistical significance. In multipage tables, footnotes should be assigned letters in the order in which they appear on the specific page of the table. A

14. 4. Orientation : Portrait tables are always preferable to landscape tables. Remember that the volumes in a submission will be about 2 inches thick. It is cumbersome, annoying, and disruptive for an FDA reviewer to have to move the volume around repeatedly to coordinate the text presentation with the tabular data. If data appear not to fit in the portrait orientation, try changing the axes of the table, so that the axis with more individual descriptors is vertical, whereas the axis with fewer items is horizontal (column headings).

15. 7. Order of Data Presentation: In multiple tables with similar data, present the data in the same order as much as possible. If the first column always has the active drug and the second column the placebo or comparative agent, then keep this order throughout the tables. 8. Present Meaningful Data Together: Try to present the data that will be evaluated and compared as close together as possible rather than scattered around the table. For example, if the tabular data represent both evaluable and nonevaluable patients who have been either previously treated or previously untreated, place the evaluable patients together rather than present them by previous treatment.

16. CONCLUSION The suggestions presented is for improving text and tables are meant to be neither complete nor sacrosanct, but simply considered. Indeed, the suggestions may be countermanded by particular constrictions and style conventions of the company sponsoring an NDA or other submission. However, the ability of the writer to look at a document through the eyes of an NDA reviewer will reinforce the suggestions. The goal is to speed up the review process and obtain fast approval for a new drug entity

17. REFERENCES Blaine Patricia.“ Data Presentation for FDA Submissions: Text and Tabular Exposition”.New Drug Approval Process. Drugs and the Pharmaceutical Sciences. Chapter 15. Volume 139.Edition 4. Pg 340-350. Buday PV. Manufacturing controls sections of new drug applications. Drug Cosmet Ind 1976; 119:62; 126–127; 129–131; 133–135. Reports 1981; 43:T&G\4, December 14. Washington D.C.: F-D-C Reports. Code of Federal Regulations. Food and Drug Administration. Guidelines: Manufacturing and Controls for INDs and NDAs. FDA Papers 1971; 5:4–14. https://www.fda.gov/drugs/electronic-regulatory-submission-and-review/electronic-submissions-presentations https://www.iptsalipur.org/wpcontent/uploads/2020/08/BP702T_IP_III.pdf