ANDA CHECKLIST FOR CTD or eCTD FORMAT

**[FOR COMPLETENESS and ACCEPTABILITY of an APPLICATION FOR
FILING]{.underline}**

**For More Information on Submission of an ANDA in Electronic Common
Technical Document (eCTD) Format please go to:
<http://www.fda.gov/cder/regulatory/ersr/ectd.htm>**

**\*For a Comprehensive Table of Contents Headings and Hierarchy please
go to: <http://www.fda.gov/cder/regulatory/ersr/5640CTOC-v1.2.pdf>**

**\*\* For more** CTD and eCTD informational links **see the final page
of the ANDA Checklist**

\*\*\* **A model Quality Overall Summary for an immediate release tablet
and an extended release capsule can be found on the OGD webpage**
<http://www.fda.gov/cder/ogd/>

**ANDA #:**       **FIRM NAME**:      

**PIV:**       **ELECTRONIC OR PAPER SUBMISSION:**      

**RELATED APPLICATION(S):**      

**First Generic Product Received?**

**DRUG NAME:**      

**DOSAGE FORM:**      

**Random Queue:**

Chem Team Leader:       PM:       Labeling Reviewer:      

+-----------------------------------------------------------------------+
| **Letter Date**:       **Received Date**:                             |
+-----------------------------------------------------------------------+
| **Comments:**       **On Cards:**                                     |
|                                                                       |
| **Therapeutic Code:**                                                 |
+-----------------------------------------------------------------------+
| > **Archival copy:**       **Sections**                               |
| >                                                                     |
| > **Review copy**:       E-Media Disposition:                         |
| >                                                                     |
| > Not applicable to electronic sections                               |
+-----------------------------------------------------------------------+
| > PART 3 Combination Product Category                                 |
| >                                                                     |
| > (Must be completed for ALL Original Applications) Refer to the Part |
| > 3 Combination Algorithm                                             |
+-----------------------------------------------------------------------+

+--------------------------------------+-------------------------------+
| **Reg. Support Reviewer**            | **Recommendation:**           |
|                                      |                               |
|                                      | **FILE** **REFUSE to          |
|                                      | RECEIVE**                     |
+--------------------------------------+-------------------------------+
|                                      |                               |
+--------------------------------------+-------------------------------+
| **ADDITIONAL COMMENTS REGARDING THE  |                               |
| ANDA:**                              |                               |
|                                      |                               |
| **     **                            |                               |
+--------------------------------------+-------------------------------+

**MODULE 1**

**ADMINISTRATIVE** ACCEPTABLE

+-------+----------------------------------------------------------+---+
| 1.1   | **1.1.2 Signed and Completed Application Form (356h)     |   |
|       | (original signature)**                                   |   |
|       |                                                          |   |
|       | (Check Rx/OTC Status)                                    |   |
+-------+----------------------------------------------------------+---+
| > **  | **Cover Letter**                                         |   |
| 1.2** |                                                          |   |
+-------+----------------------------------------------------------+---+
| >     | **Form FDA 3674                                          |   |
|  **1. | [(PDF)](http://www                                       |   |
| 2.1** | .fda.gov/opacom/morechoices/fdaforms/FDA-3674_508.pdf)** |   |
+-------+----------------------------------------------------------+---+
| \*    | **Table of Contents (paper submission only)**            |   |
+-------+----------------------------------------------------------+---+
| **1.  | **Field Copy Certification (original signature)**        |   |
| 3.2** |                                                          |   |
|       | **(N/A for E-Submissions)**                              |   |
+-------+----------------------------------------------------------+---+
| **1.  | **Debarment Certification-GDEA (Generic Drug Enforcement |   |
| 3.3** | Act)/Other:**                                            |   |
|       |                                                          |   |
|       | 1\. Debarment Certification (original signature)         |   |
|       |                                                          |   |
|       | 2\. List of Convictions statement (original signature)   |   |
|       |                                                          |   |
+-------+----------------------------------------------------------+---+
| **1.  | **Financial Certifications**                             |   |
| 3.4** |                                                          |   |
|       | Bioavailability/Bioequivalence Financial Certification   |   |
|       | (Form FDA 3454)                                          |   |
|       |                                                          |   |
|       | Disclosure Statement (Form FDA 3455, submit copy to      |   |
|       | Regulatory Branch Chief)                                 |   |
+-------+----------------------------------------------------------+---+
| **1.  | **1.3.5.1 Patent Information**                           |   |
| 3.5** |                                                          |   |
|       | Patents listed for the RLD in the Electronic Orange Book |   |
|       | Approved Drug Products with                              |   |
|       |                                                          |   |
|       | Therapeutic Equivalence Evaluations                      |   |
|       |                                                          |   |
|       | **1.3.5.2 Patent Certification**                         |   |
|       |                                                          |   |
|       | 1\. Patent number(s)                                     |   |
|       |                                                          |   |
|       | 2\. Paragraph: (Check all certifications that apply)     |   |
|       |                                                          |   |
|       | MOU       PI       PII       PIII                        |   |
|       |                                                          |   |
|       | PIV       (Statement of Notification)                    |   |
|       |                                                          |   |
|       | 3\. Expiration of Patent(s):                             |   |
|       |                                                          |   |
|       | a\. Pediatric exclusivity submitted?                     |   |
|       |                                                          |   |
|       | b\. Expiration of Pediatric Exclusivity?                 |   |
|       |                                                          |   |
|       | 4\. Exclusivity Statement:                               |   |
+-------+----------------------------------------------------------+---+
| **1.  | **References**                                           |   |
| 4.1** |                                                          |   |
|       | Letters of Authorization                                 |   |
|       |                                                          |   |
|       | 1\. DMF letters of authorization                         |   |
|       |                                                          |   |
|       | a\. Type II DMF authorization letter(s) or synthesis for |   |
|       | Active Pharmaceutical                                    |   |
|       |                                                          |   |
|       | Ingredient                                               |   |
|       |                                                          |   |
|       | > b\. Type III DMF authorization letter(s) for container |   |
|       | > closure                                                |   |
|       |                                                          |   |
|       | 2\. US Agent Letter of Authorization (U.S. Agent \[if    |   |
|       | needed, countersignature on                              |   |
|       |                                                          |   |
|       | > 356h\])                                                |   |
+-------+----------------------------------------------------------+---+
| *     | **Basis for Submission**                                 |   |
| *1.12 |                                                          |   |
| .11** | NDA# : **     **                                         |   |
|       |                                                          |   |
|       | Ref Listed Drug:                                         |   |
|       |                                                          |   |
|       | Firm:                                                    |   |
|       |                                                          |   |
|       | ANDA suitability petition required?                      |   |
|       |                                                          |   |
|       | If Yes, then is change subject to PREA (change in dosage |   |
|       | form, route or active ingredient) see section 1.9.1      |   |
+-------+----------------------------------------------------------+---+

**MODULE 1 (Continued)**

**ADMINISTRATIVE**

**ACCEPTABLE**

+------+-----------------------------------------------------------+---+
|      |                                                           |   |
+------+-----------------------------------------------------------+---+
| **1  | **Comparison between Generic Drug and RLD-505(j)(2)(A)**  |   |
| .12. |                                                           |   |
| 12** | 1\. Conditions of use                                     |   |
|      |                                                           |   |
|      | 2\. Active ingredients                                    |   |
|      |                                                           |   |
|      | 3\. Inactive ingredients                                  |   |
|      |                                                           |   |
|      | 4\. Route of administration                               |   |
|      |                                                           |   |
|      | 5\. Dosage Form                                           |   |
|      |                                                           |   |
|      | 6\. Strength                                              |   |
+------+-----------------------------------------------------------+---+
| **1  | **Environmental Impact Analysis Statement**               |   |
| .12. |                                                           |   |
| 14** |                                                           |   |
+------+-----------------------------------------------------------+---+
| **1  | **Request for Waiver**                                    |   |
| .12. |                                                           |   |
| 15** | Request for Waiver of In-Vivo BA/BE Study(ies):           |   |
+------+-----------------------------------------------------------+---+
| **   | **Draft Labeling (Mult Copies N/A for E-Submissions)**    |   |
| 1.14 |                                                           |   |
| .1** | **1.14.1.1**                                              |   |
|      |                                                           |   |
|      | 4 copies of draft (each strength and container)           |   |
|      |                                                           |   |
|      | **1.14.1.2**                                              |   |
|      |                                                           |   |
|      | 1 side by side labeling comparison of containers and      |   |
|      | carton with all differences                               |   |
|      |                                                           |   |
|      | annotated and explained                                   |   |
|      |                                                           |   |
|      | **1.14.1.3**                                              |   |
|      |                                                           |   |
|      | 1 package insert (content of labeling) submitted          |   |
|      | electronically                                            |   |
|      |                                                           |   |
|      | \*\*\*Was a proprietary name request submitted?           |   |
|      |                                                           |   |
|      | (If yes, send email to Labeling Reviewer indicating such) |   |
+------+-----------------------------------------------------------+---+
| **   | **Listed Drug Labeling**                                  |   |
| 1.14 |                                                           |   |
| .3** | **1.14.3.1**                                              |   |
|      |                                                           |   |
|      | 1 side by side labeling (package and patient insert)      |   |
|      | comparison with all differences                           |   |
|      |                                                           |   |
|      | annotated and explained                                   |   |
|      |                                                           |   |
|      | **1.14.3.3**                                              |   |
|      |                                                           |   |
|      | 1 RLD label and 1 RLD container label                     |   |
+------+-----------------------------------------------------------+---+

**MODULE 2**

**SUMMARIES ACCEPTABLE**

+-------+----------------------------------------------------------+---+
| 2.3   | **Quality Overall Summary (QOS)**                        |   |
|       |                                                          |   |
|       | **E-Submission: PDF**                                    |   |
|       |                                                          |   |
|       | **Word Processed e.g., MS Word**                         |   |
|       |                                                          |   |
|       | A model Quality Overall Summary for an immediate release |   |
|       | tablet and an extended release capsule can be found on   |   |
|       | the OGD webpage                                          |   |
|       | [[http://www.fda.g                                       |   |
|       | ov/cder/ogd/]{.underline}](http://www.fda.gov/cder/ogd/) |   |
|       |                                                          |   |
|       | **Question based Review (QbR)**                          |   |
|       |                                                          |   |
|       | **2.3.S**                                                |   |
|       |                                                          |   |
|       | **Drug Substance (Active Pharmaceutical Ingredient)**    |   |
|       |                                                          |   |
|       |                                                          |   |
|       | **2.3.S.1 General Information**                          |   |
|       |                                                          |   |
|       | **2.3.S.2 Manufacture**                                  |   |
|       |                                                          |   |
|       | **2.3.S.3 Characterization**                             |   |
|       |                                                          |   |
|       | **2.3.S.4 Control of Drug Substance**                    |   |
|       |                                                          |   |
|       | **2.3.S.5 Reference Standards or Materials**             |   |
|       |                                                          |   |
|       | **2.3.S.6 Container Closure System**                     |   |
|       |                                                          |   |
|       | **2.3.S.7 Stability**                                    |   |
|       |                                                          |   |
|       | **2.3.P**                                                |   |
|       |                                                          |   |
|       | **Drug Product**                                         |   |
|       |                                                          |   |
|       | **2.3.P.1 Description and Composition of the Drug        |   |
|       | Product**                                                |   |
|       |                                                          |   |
|       | **2.3.P.2 Pharmaceutical Development**                   |   |
|       |                                                          |   |
|       | **2.3.P.2.1 Components of the Drug Product**             |   |
|       |                                                          |   |
|       | **2.3.P.2.1.1 Drug Substance**                           |   |
|       |                                                          |   |
|       | **2.3.P.2.1.2 Excipients**                               |   |
|       |                                                          |   |
|       | **2.3.P.2.2 Drug Product**                               |   |
|       |                                                          |   |
|       | **2.3.P.2.3 Manufacturing Process Development**          |   |
|       |                                                          |   |
|       | **2.3.P.2.4 Container Closure System**                   |   |
|       |                                                          |   |
|       | **2.3.P.3 Manufacture**                                  |   |
|       |                                                          |   |
|       | **2.3.P.4 Control of Excipients**                        |   |
|       |                                                          |   |
|       | **2.3.P.5 Control of Drug Product**                      |   |
|       |                                                          |   |
|       | **2.3.P.6 Reference Standards or Materials**             |   |
|       |                                                          |   |
|       | **2.3.P.7 Container Closure System**                     |   |
|       |                                                          |   |
|       | **2.3.P.8 Stability**                                    |   |
+-------+----------------------------------------------------------+---+
| **    | **Clinical Summary (Bioequivalence)**                    |   |
| 2.7** |                                                          |   |
|       | **Model Bioequivalence Data Summary Tables**             |   |
|       |                                                          |   |
|       | **E-Submission: PDF**                                    |   |
|       |                                                          |   |
|       | **Word Processed e.g., MS Word**                         |   |
|       |                                                          |   |
|       | **2.7.1 Summary of Biopharmaceutic Studies and           |   |
|       | Associated Analytical Methods**                          |   |
|       |                                                          |   |
|       | **2.7.1.1 Background and Overview**                      |   |
|       |                                                          |   |
|       | Table 1. Submission Summary                              |   |
|       |                                                          |   |
|       | Table 4. Bioanalytical Method Validation                 |   |
|       |                                                          |   |
|       | Table 6. Formulation Data                                |   |
|       |                                                          |   |
|       | **2.7.1.2 Summary of Results of Individual Studies**     |   |
|       |                                                          |   |
|       | Table 5. Summary of In Vitro Dissolution                 |   |
|       |                                                          |   |
|       | **2.7.1.3 Comparison and Analyses of Results Across      |   |
|       | Studies**                                                |   |
|       |                                                          |   |
|       | Table 2. Summary of []{.mark}Bioavailability (BA)        |   |
|       | Studies                                                  |   |
|       |                                                          |   |
|       | Table 3. Statistical Summary of the Comparative BA Data  |   |
|       |                                                          |   |
|       |                                                          |   |
|       | **2.7.1.4 Appendix**                                     |   |
|       |                                                          |   |
|       | **2.7.4.1.3 Demographic and Other Characteristics of     |   |
|       | Study Population**                                       |   |
|       |                                                          |   |
|       | Table 7. Demographic Profile of Subjects Completing the  |   |
|       | Bioequivalence Study                                     |   |
|       |                                                          |   |
|       | **2.7.4.2.1.1 Common Adverse Events**                    |   |
|       |                                                          |   |
|       | Table 8. Incidence of Adverse Events in Individual       |   |
|       | Studies                                                  |   |
+-------+----------------------------------------------------------+---+

**MODULE 3**

**3.2.S DRUG SUBSTANCE** ACCEPTABLE

+-------+----------------------------------------------------------+---+
| 3.    | **General Information**                                  |   |
| 2.S.1 |                                                          |   |
|       | **3.2.S.1.1 Nomenclature**                               |   |
|       |                                                          |   |
|       | **3.2.S.1.2 Structure**                                  |   |
|       |                                                          |   |
|       | **3.2.S.1.3 General Properties**                         |   |
+-------+----------------------------------------------------------+---+
| 3.    | **Manufacturer**                                         |   |
| 2.S.2 |                                                          |   |
|       | **3.2.S.2.1**                                            |   |
|       |                                                          |   |
|       | **Manufacturer(s) (This section includes contract        |   |
|       | manufacturers and testing labs)**                        |   |
|       |                                                          |   |
|       | **Drug Substance (Active Pharmaceutical Ingredient)**    |   |
|       |                                                          |   |
|       | 1\. Name and Full Address(es)of the Facility(ies)        |   |
|       |                                                          |   |
|       | 2\. Function or Responsibility                           |   |
|       |                                                          |   |
|       | 3\. Type II DMF number for API                           |   |
|       |                                                          |   |
|       | 4\. CFN or FEI numbers                                   |   |
+-------+----------------------------------------------------------+---+
| 3.    | **Characterization**                                     |   |
| 2.S.3 |                                                          |   |
+-------+----------------------------------------------------------+---+
| *     | **Control of Drug Substance (Active Pharmaceutical       |   |
| *3.2. | Ingredient)**                                            |   |
| S.4** |                                                          |   |
|       | **3.2.S.4.1 Specification**                              |   |
|       |                                                          |   |
|       | Testing specifications and data from drug substance      |   |
|       | manufacturer(s)                                          |   |
|       |                                                          |   |
|       | **3.2.S.4.2 Analytical Procedures**                      |   |
|       |                                                          |   |
|       | **3.2.S.4.3 Validation of Analytical Procedures**        |   |
|       |                                                          |   |
|       | 1\. Spectra and chromatograms for reference standards    |   |
|       | and test samples                                         |   |
|       |                                                          |   |
|       | 2\. Samples-Statement of Availability and Identification |   |
|       | of:                                                      |   |
|       |                                                          |   |
|       | a\. Drug Substance                                       |   |
|       |                                                          |   |
|       | b\. Same lot number(s)                                   |   |
|       |                                                          |   |
|       | **3.2.S.4.4 Batch Analysis**                             |   |
|       |                                                          |   |
|       | 1\. COA(s) specifications and test results from drug     |   |
|       | substance mfgr(s)                                        |   |
|       |                                                          |   |
|       | 2\. Applicant certificate of analysis                    |   |
|       |                                                          |   |
|       | **3.2.S.4.5 Justification of Specification**             |   |
+-------+----------------------------------------------------------+---+
| *     | **Reference Standards or Materials**                     |   |
| *3.2. |                                                          |   |
| S.5** |                                                          |   |
+-------+----------------------------------------------------------+---+
| *     | **Container Closure Systems**                            |   |
| *3.2. |                                                          |   |
| S.6** |                                                          |   |
+-------+----------------------------------------------------------+---+
| *     | **Stability**                                            |   |
| *3.2. |                                                          |   |
| S.7** |                                                          |   |
+-------+----------------------------------------------------------+---+

**MODULE 3**

**3.2.P DRUG PRODUCT ACCEPTABLE**

+-------+----------------------------------------------------------+---+
| *     | **Description and Composition of the Drug Product**      |   |
| *3.2. |                                                          |   |
| P.1** | 1\. Unit composition                                     |   |
|       |                                                          |   |
|       | 2\. Inactive ingredients and amounts are appropriate per |   |
|       | IIG                                                      |   |
+-------+----------------------------------------------------------+---+
| *     | **Pharmaceutical Development**                           |   |
| *3.2. |                                                          |   |
| P.2** | Pharmaceutical Development Report                        |   |
+-------+----------------------------------------------------------+---+
| *     | **Manufacture**                                          |   |
| *3.2. |                                                          |   |
| P.3** | **3.2.P.3.1 Manufacture(s)** (Finished Dosage            |   |
|       | Manufacturer and Outside Contract Testing Laboratories)  |   |
|       |                                                          |   |
|       | 1\. Name and Full Address(es)of the Facility(ies)        |   |
|       |                                                          |   |
|       | 2\. CGMP Certification:                                  |   |
|       |                                                          |   |
|       | 3\. Function or Responsibility                           |   |
|       |                                                          |   |
|       | 4\. CFN or FEI numbers                                   |   |
|       |                                                          |   |
|       | **3.2.P.3.2 Batch Formula**                              |   |
|       |                                                          |   |
|       | **3.2.P.3.3 Description of Manufacturing Process and     |   |
|       | Process Controls**                                       |   |
|       |                                                          |   |
|       | 1\. Description of the Manufacturing Process             |   |
|       |                                                          |   |
|       | 2\. Master Production Batch Record(s) for largest        |   |
|       | intended production runs                                 |   |
|       |                                                          |   |
|       | (no more than 10x pilot batch) with equipment specified  |   |
|       |                                                          |   |
|       |                                                          |   |
|       | 3\. If sterile product: Aseptic fill / Terminal          |   |
|       | sterilization                                            |   |
|       |                                                          |   |
|       | 4\. Reprocessing Statement                               |   |
|       |                                                          |   |
|       | **3.2.P.3.4 Controls of Critical Steps and               |   |
|       | Intermediates**                                          |   |
|       |                                                          |   |
|       | **3.2.P.3.5 Process Validation and/or Evaluation**       |   |
|       |                                                          |   |
|       | 1\. Microbiological sterilization validation             |   |
|       |                                                          |   |
|       | 2\. Filter validation (if aseptic fill)                  |   |
+-------+----------------------------------------------------------+---+
| *     | **Controls of Excipients (Inactive Ingredients)**        |   |
| *3.2. |                                                          |   |
| P.4** | Source of inactive ingredients identified                |   |
|       |                                                          |   |
|       | **3.2.P.4.1 Specifications**                             |   |
|       |                                                          |   |
|       | 1\. Testing specifications (including identification and |   |
|       | characterization)                                        |   |
|       |                                                          |   |
|       | 2\. Suppliers\' COA (specifications and test results)    |   |
|       |                                                          |   |
|       |                                                          |   |
|       | **3.2.P.4.2 Analytical Procedures**                      |   |
|       |                                                          |   |
|       | **3.2.P.4.3 Validation of Analytical Procedures**        |   |
|       |                                                          |   |
|       | **3.2.P.4.4 Justification of Specifications**            |   |
|       |                                                          |   |
|       | Applicant COA                                            |   |
+-------+----------------------------------------------------------+---+

**MODULE 3**

**3.2.P DRUG PRODUCT**

ACCEPTABLE

+-------+----------------------------------------------------------+---+
| 3.    | **Controls of Drug Product**                             |   |
| 2.P.5 |                                                          |   |
|       | **3.2.P.5.1 Specification(s)**                           |   |
|       |                                                          |   |
|       | **3.2.P.5.2 Analytical Procedures**                      |   |
|       |                                                          |   |
|       | **3.2.P.5.3 Validation of Analytical Procedures**        |   |
|       |                                                          |   |
|       | Samples - Statement of Availability and Identification   |   |
|       | of:                                                      |   |
|       |                                                          |   |
|       | 1\. Finished Dosage Form                                 |   |
|       |                                                          |   |
|       | 2\. Same lot numbers                                     |   |
|       |                                                          |   |
|       | **3.2.P.5.4 Batch Analysis**                             |   |
|       |                                                          |   |
|       | Certificate of Analysis for Finished Dosage Form         |   |
|       |                                                          |   |
|       | **3.2.P.5.5 Characterization of Impurities**             |   |
|       |                                                          |   |
|       | **3.2.P.5.6 Justification of Specifications**            |   |
+-------+----------------------------------------------------------+---+
| *     | **Container Closure System**                             |   |
| *3.2. |                                                          |   |
| P.7** | 1\. Summary of Container/Closure System (if new resin,   |   |
|       | provide data)                                            |   |
|       |                                                          |   |
|       | 2\. Components Specification and Test Data               |   |
|       |                                                          |   |
|       | 3\. Packaging Configuration and Sizes                    |   |
|       |                                                          |   |
|       | 4\. Container/Closure Testing                            |   |
|       |                                                          |   |
|       | 5\. Source of supply and suppliers address               |   |
+-------+----------------------------------------------------------+---+
| *     | **3.2.P.8.1 Stability (Finished Dosage Form)**           |   |
| *3.2. |                                                          |   |
| P.8** | 1\. Stability Protocol submitted                         |   |
|       |                                                          |   |
|       | 2\. Expiration Dating Period                             |   |
|       |                                                          |   |
|       | **3.2.P.8.2 Post-approval Stability and Conclusion**     |   |
|       |                                                          |   |
|       | Post Approval Stability Protocol and Commitments         |   |
|       |                                                          |   |
|       | **3.2.P.8.3 Stability Data**                             |   |
|       |                                                          |   |
|       | 1\. 3 month accelerated stability data                   |   |
|       |                                                          |   |
|       | 2\. Batch numbers on stability records the same as the   |   |
|       | test batch **     **                                     |   |
+-------+----------------------------------------------------------+---+

**MODULE 3**

**3.2.R Regional Information**

ACCEPTABLE

+-------+----------------------------------------------------------+---+
| **3.  | **3.2.R.1.S Executed Batch Records for drug substance    |   |
| 2.R** | (if available)      **                                   |   |
|       |                                                          |   |
| **    | **3.2.R.2.S Comparability Protocols      **              |   |
| (Drug |                                                          |   |
| Su    | **3.2.R.3.S Methods Validation Package      **           |   |
| bstan |                                                          |   |
| ce)** | Methods Validation Package (3 copies) (Mult Copies N/A   |   |
|       | for E-Submissions)                                       |   |
|       |                                                          |   |
|       | (Required for Non-USP drugs)                             |   |
+-------+----------------------------------------------------------+---+

+-------+----------------------------------------------------------+---+
| **3.  | **3.2.R.1.P.1**                                          |   |
| 2.R** |                                                          |   |
|       | **Executed Batch Records**                               |   |
| **    |                                                          |   |
| (Drug | Copy of Executed Batch Record with Equipment Specified,  |   |
| Produ | including Packaging Records                              |   |
| ct)** |                                                          |   |
|       | (Packaging and Labeling Procedures)                      |   |
|       |                                                          |   |
|       | Batch Reconciliation and Label Reconciliation            |   |
|       |                                                          |   |
|       | Theoretical Yield                                        |   |
|       |                                                          |   |
|       | Actual Yield                                             |   |
|       |                                                          |   |
|       | Packaged Yield                                           |   |
|       |                                                          |   |
|       | **3.2.R.1.P.2 Information on Components**                |   |
|       |                                                          |   |
|       | **3.2.R.2.P Comparability Protocols**                    |   |
|       |                                                          |   |
|       | **3.2.R.3.P Methods Validation Package**                 |   |
|       |                                                          |   |
|       | Methods Validation Package (3 copies) (Mult Copies N/A   |   |
|       | for E-Submissions)                                       |   |
|       |                                                          |   |
|       | (Required for Non-USP drugs)                             |   |
+-------+----------------------------------------------------------+---+

**MODULE 5**

**CLINICAL STUDY REPORTS ACCEPTABLE**

+-------+-----------------------------------------------------------+---+
| **    | **Tabular Listing of Clinical Studies**                   |   |
| 5.2** |                                                           |   |
+-------+-----------------------------------------------------------+---+
| **5.  | **Bioavailability/Bioequivalence**                        |   |
| 3.1** |                                                           |   |
|       | **1. Formulation data same?**                             |   |
| (com  |                                                           |   |
| plete | a\. Comparison of all Strengths (check proportionality of |   |
| study | multiple strengths)                                       |   |
| data) |                                                           |   |
|       | b\. Parenterals, Ophthalmics, Otics and Topicals          |   |
|       |                                                           |   |
|       | per 21 CFR 314.94 (a)(9)(iii)-(v)                         |   |
|       |                                                           |   |
|       | **2. Lot Numbers of Products used in BE Study(ies):**     |   |
|       |                                                           |   |
|       |                                                           |   |
|       | **3. Study Type:** (Continue with the appropriate study   |   |
|       | type box below)                                           |   |
+-------+-----------------------------------------------------------+---+
|       | **5.3.1.2 Comparative BA/BE Study Reports**               |   |
|       |                                                           |   |
|       | 1\. Study(ies) meets BE criteria (90% CI of 80-125, C     |   |
|       | max, AUC)                                                 |   |
|       |                                                           |   |
|       | 2\. Summary Bioequivalence tables:                        |   |
|       |                                                           |   |
|       | Table 10. Study Information                               |   |
|       |                                                           |   |
|       | Table 12. Dropout Information                             |   |
|       |                                                           |   |
|       | Table 13. Protocol Deviations                             |   |
|       |                                                           |   |
|       | **5.3.1.3**                                               |   |
|       |                                                           |   |
|       | **In Vitro-In-Vivo Correlation Study Reports**            |   |
|       |                                                           |   |
|       | 1\. Summary Bioequivalence tables:                        |   |
|       |                                                           |   |
|       | Table 11. Product Information                             |   |
|       |                                                           |   |
|       | Table 16. Composition of Meal Used in Fed Bioequivalence  |   |
|       | Study                                                     |   |
|       |                                                           |   |
|       | **5.3.1.4**                                               |   |
|       |                                                           |   |
|       | **Reports of Bioanalytical and Analytical Methods for     |   |
|       | Human Studies**                                           |   |
|       |                                                           |   |
|       | 1\. Summary Bioequivalence table:                         |   |
|       |                                                           |   |
|       | Table 9. Reanalysis of Study Samples                      |   |
|       |                                                           |   |
|       | Table 14. Summary of Standard Curve and QC Data for       |   |
|       | Bioequivalence Sample                                     |   |
|       |                                                           |   |
|       | Analyses                                                  |   |
|       |                                                           |   |
|       | Table 15. SOPs Dealing with Bioanalytical Repeats of      |   |
|       | Study Samples                                             |   |
|       |                                                           |   |
|       | **5.3.7**                                                 |   |
|       |                                                           |   |
|       | **Case Report Forms and Individual Patient Listing**      |   |
|       |                                                           |   |
+-------+-----------------------------------------------------------+---+
| **    | **Literature References**                                 |   |
| 5.4** |                                                           |   |
+-------+-----------------------------------------------------------+---+
|       | **Possible Study Types:**                                 |   |
+-------+-----------------------------------------------------------+---+
| Study | **IN-VIVO BE STUDY(IES) with PK ENDPOINTS (**i.e.,        |   |
| Type  | fasting/fed/sprinkle)                                     |   |
|       |                                                           |   |
|       | 1. Study(ies) meets BE criteria (90% CI of 80-125, C max, |   |
|       | AUC)                                                      |   |
|       |                                                           |   |
|       | 2\. EDR Email: Data Files Submitted: YES SENT TO EDR      |   |
|       |                                                           |   |
|       |                                                           |   |
|       | 3\. In-Vitro Dissolution:                                 |   |
+-------+-----------------------------------------------------------+---+
| Study | **IN-VIVO BE STUDY with CLINICAL ENDPOINTS**              |   |
| Type  |                                                           |   |
|       | 1\. Properly defined BE endpoints (eval. by Clinical      |   |
|       | Team)                                                     |   |
|       |                                                           |   |
|       | 2\. Summary results meet BE criteria: 90% CI of the       |   |
|       | proportional difference in success rate between test and  |   |
|       |                                                           |   |
|       | reference must be within (-0.20, +0.20) for a             |   |
|       | binary/dichotomous endpoint. For a continuous endpoint,   |   |
|       | the                                                       |   |
|       |                                                           |   |
|       | test/reference ratio of the mean result must be within    |   |
|       | (0.80, 1.25).                                             |   |
|       |                                                           |   |
|       | 3\. Summary results indicate superiority of active        |   |
|       | treatments (test & reference) over vehicle/placebo        |   |
|       |                                                           |   |
|       | (p\<0.05) (eval. by Clinical Team)                        |   |
|       |                                                           |   |
|       | 4\. EDR Email: Data Files Submitted                       |   |
+-------+-----------------------------------------------------------+---+
| Study | **IN-VITRO BE STUDY(IES) (**i.e., in vitro binding        |   |
| Type  | assays)                                                   |   |
|       |                                                           |   |
|       | 1\. Study(ies) meets BE criteria (90% CI of               |   |
|       | 80-125)                                                   |   |
|       |                                                           |   |
|       | 2\. EDR Email: Data Files Submitted:                      |   |
|       |                                                           |   |
|       | 3\. In-Vitro Dissolution:                                 |   |
+-------+-----------------------------------------------------------+---+
| Study | **NASALLY ADMINISTERED DRUG PRODUCTS**                    |   |
| Type  |                                                           |   |
|       | 1\. [Solutions]{.underline} (Q1/Q2 sameness):             |   |
|       |                                                           |   |
|       | a\. In-Vitro Studies (Dose/Spray Content Uniformity,      |   |
|       | Droplet/Drug Particle Size Distrib., Spray Pattern,       |   |
|       |                                                           |   |
|       | Plume Geometry, Priming & Repriming)                      |   |
|       |                                                           |   |
|       | 2\. [Suspensions]{.underline} (Q1/Q2 sameness):           |   |
|       |                                                           |   |
|       | a\. In-Vivo PK Study                                      |   |
|       |                                                           |   |
|       | 1\. Study(ies) meets BE Criteria (90% CI of 80-125, C     |   |
|       | max, AUC)                                                 |   |
|       |                                                           |   |
|       | 2\. EDR Email: Data Files Submitted                       |   |
|       |                                                           |   |
|       | b\. In-Vivo BE Study with Clinical End Points             |   |
|       |                                                           |   |
|       | 1\. Properly defined BE endpoints (eval. by Clinical      |   |
|       | Team)                                                     |   |
|       |                                                           |   |
|       | 2\. Summary results meet BE criteria (90% CI within +/-   |   |
|       | 20% of 80-125)                                            |   |
|       |                                                           |   |
|       | 3\. Summary results indicate superiority of active        |   |
|       | treatments (test & reference) over                        |   |
|       |                                                           |   |
|       | vehicle/placebo (p\<0.05) (eval. by Clinical Team)        |   |
|       |                                                           |   |
|       | 4\. EDR Email: Data Files Submitted                       |   |
|       |                                                           |   |
|       | c\. In-Vitro Studies (Dose/Spray Content Uniformity,      |   |
|       | Droplet/Drug Particle Size Distrib., Spray Pattern,       |   |
|       |                                                           |   |
|       | Plume Geometry, Priming & Repriming)                      |   |
+-------+-----------------------------------------------------------+---+
| Study | **IN-VIVO BE STUDY(IES) with PD ENDPOINTS** (e.g.,        |   |
| Type  | topical corticosteroid vasoconstrictor                    |   |
|       |                                                           |   |
|       | studies)                                                  |   |
|       |                                                           |   |
|       | 1\. Pilot Study (determination of ED50)                   |   |
|       |                                                           |   |
|       | 2\. Pivotal Study (study meets BE criteria 90%CI of       |   |
|       | 80-125)                                                   |   |
+-------+-----------------------------------------------------------+---+
| Study | **TRANSDERMAL DELIVERY SYSTEMS**                          |   |
| Type  |                                                           |   |
|       | 1\. [In-Vivo PK Study]{.underline}                        |   |
|       |                                                           |   |
|       | 1\. Study(ies) meet BE Criteria (90% CI of 80-125, C max, |   |
|       | AUC)                                                      |   |
|       |                                                           |   |
|       | 2\. In-Vitro Dissolution                                  |   |
|       |                                                           |   |
|       | 3\. EDR Email: Data Files Submitted                       |   |
|       |                                                           |   |
|       | 2\. [Adhesion Study]{.underline}                          |   |
|       |                                                           |   |
|       | 3\. [Skin Irritation/Sensitization Study]{.underline}     |   |
|       |                                                           |   |
+-------+-----------------------------------------------------------+---+

Updated 5/28/2008