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**[Major Issues:]{.underline}**

+-------------------+--------------------------------------------------+
| **[Page 50 Line   | **[Lilly Comment:]{.underline}** The cited CFR   |
| 1793-1795         | requirement for executed production records      |
| Executed          | states: "(b) Unless provided by paragraph        |
| Production        | (d)(1)(ii)(a) of this section, for each batch of |
| Reco              | the drug product used to conduct a               |
| rds]{.underline}: | **bioavailability or bioequivalence study**      |
| "**Executed       | described in Sec. 320.38 or Sec. 320.63 of this  |
| Production        | chapter or used to conduct a **primary stability |
| Records (EPRs)    | study**: The batch production record; the        |
| for               | specifications and test procedures for each      |
| representative    | component and for the drug product; the names    |
| batches used in   | and addresses of the sources of the active and   |
| **Phase III       | noncompendial inactive components and of the     |
| clinical**,       | container and closure system for the drug        |
| bioavailability,  | product; the name and address of each contract   |
| bioequivalence,   | facility involved in the manufacture,            |
| or primary        | processing, packaging, or testing of the drug    |
| stability studies | product and identification of the operation      |
| and supporting    | performed by each contract facility; and the     |
| production        | results of any test performed on the components  |
| information must  | used in the manufacture of the drug product as   |
| be provided (21   | required by Sec. 211.84(d) of this chapter and   |
| CFR               | on the drug product as required by Sec. 211.165  |
| 314.5             | of this chapter."                                |
| 0(d)(1)(ii)(b))." |                                                  |
|                   | **The expansion of the current CFR requirement   |
| **[Page 50 Lines  | to representative Phase III clinical batches is  |
| 1799-1801         | inconsistent with current regulation and will    |
| Executed          | add no value to the review process. Information  |
| Production        | on formulation development is provided in the    |
| Reco              | Pharmaceutical Development Section. We support   |
| rds:]{.underline} | providing adequate information to thoroughly     |
| "**For NDA        | explain and justify the development of the       |
| submissions, an   | product, but that information is more            |
| EPR for a batch   | appropriately summarized within the application, |
| manufactured on   | not in providing additional volumes of batch     |
| at least a pilot  | records.**                                       |
| scale should be   |                                                  |
| submitted. In     |                                                  |
| cases where       |                                                  |
| clinical batches  |                                                  |
| used in Phase III |                                                  |
| trials were less  |                                                  |
| than pilot scale, |                                                  |
| submission of the |                                                  |
| EPR for the       |                                                  |
| largest scale     |                                                  |
| clinical batch is |                                                  |
| also              |                                                  |
| recommended."     |                                                  |
+-------------------+--------------------------------------------------+

+-----------------+----------------------------------------------------+
| **Pages 27-28   | **[Lilly Comment]{.underline}**: Several citations |
| (Excipients)**  | require distinctions to be made for whether the    |
|                 | applicant or the excipient supplier performs the   |
|                 | monograph testing for compendial excipients. Only  |
|                 | if the applicant performs full testing on each     |
|                 | batch can they simply list the excipient (Lines    |
|                 | 982-983). Otherwise, the FDA is requesting in this |
|                 | guidance that the applicant designate what results |
|                 | will be accepted on the basis of a COA.            |
|                 |                                                    |
|                 | Reliability of vendor testing is a GMP issue, and  |
|                 | the information being requested is more            |
|                 | appropriately handled under established GMP        |
|                 | programs.                                          |
|                 |                                                    |
|                 | CFR 211.84(d)(2) states that \"a report of         |
|                 | analysis may be accepted from the supplier of a    |
|                 | component, provided that at least one specific     |
|                 | identity test is conducted on such component by    |
|                 | the manufacturer, and provided that the            |
|                 | manufacturer establishes the reliability of the    |
|                 | supplier\'s analysis through appropriate           |
|                 | validation of the supplier\'s test results at      |
|                 | appropriate intervals.\"                           |
|                 |                                                    |
|                 | As long as the standard the excipient will meet is |
|                 | submitted (e.g. NF, USP), the delineation of who   |
|                 | does what specific test is unnecessary. It is the  |
|                 | responsibility of the applicant, as required by    |
|                 | cGMP's, to verify the acceptability of the vendor  |
|                 | testing, and to determine what tests they may      |
|                 | choose to conduct in-house.                        |
+-----------------+----------------------------------------------------+
| **Pages 27-28   | **[Lilly Comment]{.underline}**: An applicant will |
| (Excipients)**  | often perform additional tests on an excipient in  |
|                 | order to meet requirements for compendia other     |
|                 | than USP in order to support global supplies.      |
|                 | These types of additional tests should be outside  |
|                 | the scope of "additional tests" required to be     |
|                 | submitted.                                         |
|                 |                                                    |
|                 | Additionally, in order to support global           |
|                 | submissions and reduce redundant testing, an       |
|                 | applicant may utilize a modified testing protocol  |
|                 | which is equivalent to the USP, but not identical. |
|                 | These modifications provide a harmonized test      |
|                 | scheme which ensures full compliance with two or   |
|                 | more compendia. These harmonized test procedures   |
|                 | used for routine testing which ensure compliance   |
|                 | with the USP need not be submitted as long as the  |
|                 | requirements of the USP are met. It is clearly     |
|                 | stated in the General Notices to the USP that "it  |
|                 | is not to be inferred that application of every    |
|                 | analytical procedure in the monograph to samples   |
|                 | from every production batch is necessarily a       |
|                 | prerequisite for assuring compliance with          |
|                 | Pharmacopeial standards before the batch is        |
|                 | released for distribution.... Compliance may be    |
|                 | determined also by the use of alternative methods, |
|                 | chosen for advantages in accuracy, sensitivity,    |
|                 | precision, selectivity, or adaptability to         |
|                 | automation or computerized data reduction or in    |
|                 | other special circumstances."                      |
|                 |                                                    |
|                 | Reference to the USP requirement is sufficient,    |
|                 | when compliance with the current USP requirements  |
|                 | is in fact met by the modified testing program     |
|                 | utilized by the applicant. This provides an        |
|                 | acceptable risk approach for the pharmaceutical    |
|                 | industry and minimizes numerous and burdensome     |
|                 | submissions to product applications. One excipient |
|                 | may be utilized in many products owned by the      |
|                 | applicant, and minor and insignificant changes to  |
|                 | a testing scheme for one excipient could trigger   |
|                 | numerous modifications to applications, creating a |
|                 | non-value added activity for both the applicant    |
|                 | and the FDA.                                       |
+-----------------+----------------------------------------------------+

+-----------------+----------------------------------------------------+
| **[Page 30      | **[Lilly Comment]{.underline}**: As noted above,   |
| Lines 1089-1092 | the request for both vendor COA results and drug   |
| Justification   | product manufacturers results for components used  |
| for Proposed    | in lots provided in the executed batch record(s)   |
| Excipient       | is an encroachment into the GMP responsibility of  |
| Specifications  | the applicant to establish the reliability of the  |
| and Page 50     | supplier\'s analysis. The applicant may choose to  |
| Lines 1817-1819 | perform comparative testing to establish vendor    |
| Executed        | reliability for excipient lots other than those    |
| Production      | presented in the executed production records and   |
| Records:        | at a time after submission or approval of the      |
| ]{.underline}** | application. The results used to accept the        |
| "1089-1092- A   | material, regardless of who performed the testing, |
| certificate of  | are available in the executed production record.   |
| analysis (COA)  | As such, we do not support submission of the       |
| from the        | information in the noted section.                  |
| manufacturer    |                                                    |
| and the test    |                                                    |
| results for the |                                                    |
| same batch from |                                                    |
| the drug        |                                                    |
| product         |                                                    |
| manufacturer    |                                                    |
| should be       |                                                    |
| provided for    |                                                    |
| the components  |                                                    |
| described in    |                                                    |
| P.4. The        |                                                    |
| information     |                                                    |
| should be for   |                                                    |
| the materials   |                                                    |
| used to produce |                                                    |
| the batch       |                                                    |
| described in    |                                                    |
| the executed    |                                                    |
| production      |                                                    |
| record          |                                                    |
| (R.1.P)."       |                                                    |
|                 |                                                    |
| "1817-1819-     |                                                    |
| Results of any  |                                                    |
| test performed  |                                                    |
| on the          |                                                    |
| components.     |                                                    |
| This should     |                                                    |
| include a       |                                                    |
| certificate of  |                                                    |
| analysis (COA)  |                                                    |
| from the        |                                                    |
| component       |                                                    |
| manufacturer    |                                                    |
| and the test    |                                                    |
| results for the |                                                    |
| same batch from |                                                    |
| the drug        |                                                    |
| product         |                                                    |
| manufacturer."  |                                                    |
+-----------------+----------------------------------------------------+

+-----------------+----------------------------------------------------+
| **[Page 13      | **[Lilly Comment:]{.underline}** As we have stated |
| Lines           | previously, we strongly support providing adequate |
| 495-503:        | information to thoroughly explain and justify the  |
| ]{.underline}** | development of the product. We suggest caution in  |
|                 | providing too much extraneous information as could |
| A summary of    | occur in a strict interpretation of the noted      |
| all             | section. The detailed comparison of batches and    |
| formulations    | supporting rationale for changes should be limited |
| used in         | to the clinical efficacy, bioequivalence and       |
| clinical trials | primary stability batches (in comparison to the    |
| should be       | proposed commercial formulation). We suggest the   |
| provided. The   | following wording:                                 |
| differences     |                                                    |
| between         | "*Any significant changes between the proposed     |
| clinical        | commercial formulation and those formulations used |
| formulations    | in clinical efficacy, bioequivalence and primary   |
| and the         | stability batches (pivotal batches) should be      |
| proposed        | clearly described and the rationale for the        |
| commercial      | changes provided. Results from comparative in      |
| formulation     | vitro studies (e.g., bioequivalence) that link     |
| described in    | pivotal batch formulations to the proposed         |
| P.1 (i.e.,      | commercial formulation described in P.1 should be  |
| composition     | summarized and a cross-reference to the studies    |
| statement)      | (with study numbers) should be provided."*         |
| should be       |                                                    |
| discussed. Any  |                                                    |
| changes between |                                                    |
| the proposed    |                                                    |
| commercial      |                                                    |
| formulation and |                                                    |
| those           |                                                    |
| formulations    |                                                    |
| used in         |                                                    |
| clinical        |                                                    |
| batches and     |                                                    |
| primary         |                                                    |
|                 |                                                    |
| stability       |                                                    |
| batches should  |                                                    |
| be clearly      |                                                    |
| described and   |                                                    |
| the rationale   |                                                    |
| for the changes |                                                    |
| provided.       |                                                    |
+-----------------+----------------------------------------------------+

**[Minor Comments and Clarifications:]{.underline}**

+------------------------------------------+---------------------------+
| **[Page 6 (Drug Master                   | [Lilly                    |
| Files):]{.underline}** "Under FDA\'s     | Comment:]{.underline} We  |
| regulations, an application may          | suggest for the           |
| incorporate by reference all or part of  | convenience of the FDA    |
| the contents of any drug master file     | and the applicant, a more |
| (DMF) to address particular drug product | efficient place to        |
| issues if the DMF holder provides        | include the letters of    |
| written authorization to the applicant   | authorization for DMF's   |
| and the authorization is included in the | is within Module 3 in a   |
| application (Module 1)."                 | Regional Appendix.        |
|                                          | Reference would be made   |
|                                          | from the relevant section |
|                                          | in the body of Module 3   |
|                                          | to the Appendix.          |
+------------------------------------------+---------------------------+
| [Page 8 Lines 326-328]{.underline}       | [Lilly                    |
|                                          | Comment:]{.underline} For |
| The target amount of each component by   | lyophilized vials,        |
| definite weight or other measure should  | providing component       |
| be provided on a per unit basis. The     | amounts on a per vial     |
| amount of weight per unit volume should  | basis may be more         |
| be on the                                | appropriate.              |
|                                          |                           |
| per milliliter (mL) basis regardless of  |                           |
| the size of the container.               |                           |
+------------------------------------------+---------------------------+
| # Page 9 Line 337                        | **[Lilly                  |
|                                          | Comment]{.underline}**:   |
|                                          | For clarification, we     |
|                                          | suggest adding            |
|                                          | dimethicone used for      |
|                                          | processing stoppers as an |
|                                          | example of a processing   |
|                                          | agent for parenteral      |
|                                          | products                  |
+------------------------------------------+---------------------------+

+------------------------------------------+---------------------------+
| [Page 9 Lines 341-342 (Unit              | [Lilly                    |
| Formula):]{.underline}                   | Comment:]{.underline}     |
|                                          | Distinction should be     |
| "The amount of drug substance in the     | made between "overage" to |
| specified unit, including any overages,  | compensate for            |
| should be listed. An explanatory note    | manufacturing losses,     |
| should identify any justified overages." | "overage" to compensate   |
|                                          | for degradation, and      |
| [Page 14 Lines 529-539 Pharmaceutical    | "overfill" to ensure      |
| Development; Overages:]{.underline}      | proper dose delivery.     |
|                                          | Inclusion of associated   |
| "An overage is a fixed amount of the     | definitions in the        |
| drug substance in the dosage form that   | glossary would be useful. |
| is added in excess of the label claim.   | Manufacturing overages    |
| Any overages included in the             | are utilized to achieve   |
| formulations described in P.1 should be  | the target amount         |
| justified. Information should be         | reflected in the unit     |
| provided on the: (1) amount of overage,  | formula and label, and    |
| (2) reason for overage (e.g., compensate | therefore could not be    |
| for expected and documented              | reflected in the unit     |
| manufacturing losses, ensure proper dose | formula. It is unclear    |
| delivery), and (3) justification for the | how, and for what reason, |
| amount of the overage. The overage       | an overfill would be      |
| should be included in the amount of drug | reflected in the unit     |
| substance listed in the composition      | formula. We suggest       |
| statement (P.1) and the representative   | removing the example of   |
| batch formula (P.3.2). In general, use   | "ensure proper dose       |
| of an overage of a drug substance to     | delivery" from this       |
| compensate for degradation during        | section.                  |
| manufacture or a product's shelf life,   |                           |
| or to extend the expiration dating       |                           |
| period, is not appropriate."             |                           |
+------------------------------------------+---------------------------+
| # Page 15 M                              | **[Lilly                  |
| anufacturing Process Development (P 2.3) | Comment:]{.underline}**   |
|                                          | We suggest including the  |
|                                          | following statement       |
|                                          | within this section:      |
|                                          |                           |
|                                          | *"The rationale for the   |
|                                          | selected method of        |
|                                          | sterilization should be   |
|                                          | explained and             |
|                                          | justified."*              |
+------------------------------------------+---------------------------+
| # Page 16 Lines 610-611                  | **[Lilly                  |
|                                          | Comment:]{.underline}**   |
|                                          | Change to read:           |
|                                          |                           |
|                                          | ". . .are more readily    |
|                                          | leached into              |
|                                          | *lipid-containing         |
|                                          | systems* such as          |
|                                          | blood..."                 |
+------------------------------------------+---------------------------+

+------------------------------------------+---------------------------+
| # Page 19 (Addresses) Lines 692-697 and  | **[Lilly                  |
|                                          | Comment:]{.underline}**   |
| # Lines 710-713:                         | Contact names, addresses, |
|                                          | phone numbers, e-mail     |
| "Building numbers or other specific      | addresses etc. are        |
| identifying information should be        | provided in the 356H      |
| provided for multifacility campuses. For | form. Maintenance of this |
| sites processing sterile drug            | type of information       |
| substances, drug products, or packaging  | within the application is |
| components, the sterile processing area  | redundant and will result |
| (e.g., room, filling line) should also   | in unnecessary            |
| be included. Addresses for foreign sites | application updates.      |
| should be provided in comparable detail, |                           |
| and the name, address, and phone number  |                           |
| of the U.S. agent for each foreign drug  |                           |
| establishment,                           |                           |
|                                          |                           |
| as required under 21 CFR 207.40(c),      |                           |
| should be included."                     |                           |
|                                          |                           |
| "To facilitate preapproval inspection    |                           |
| related activities, it is recommended    |                           |
| that the name, telephone number, fax     |                           |
| number and e-mail address of a contact   |                           |
| person be provided for each site listed  |                           |
| in the application. Facilities should be |                           |
| ready for inspection when the            |                           |
| application is submitted to FDA."        |                           |
+------------------------------------------+---------------------------+
| **[Page 22 Lines 826-828:]{.underline}** | [Lilly                    |
|                                          | Comment:]{.underline}     |
|                                          | Clarification should be   |
|                                          | provided that the         |
|                                          | facility information      |
|                                          | requested for multi-use   |
|                                          | facilities is applicable  |
|                                          | only to                   |
|                                          | biotechnology-derived     |
|                                          | drug products.            |
+------------------------------------------+---------------------------+

  ------------------------------------------- ---------------------------
  **Page 24 Lines 887- 901 Reprocessing and   [Lilly
  Reworking**                                 Comment:]{.underline}
                                              Additional clarification
                                              and examples regarding
                                              reprocessing which is not
                                              required to be described in
                                              the application and that
                                              which is required to be
                                              described in the
                                              application needs to be
                                              provided. It is unclear if
                                              the distinction is intended
                                              to be based on the type of
                                              drug product, or the type
                                              of reprocessing. The very
                                              general criteria given
                                              provides insufficient
                                              guidance to determine the
                                              expected reporting
                                              requirement.

  **[Page 26 Lines 958-960 Process            [Lilly
  Validation:]{.underline}** "Validation      Comment:]{.underline} We
  information relating to the adequacy and    suggest that reference may
  efficacy of any sterilization process       be made in this section of
  (e.g., drug product, packaging components)  the application to an
  should be submitted in this section of the  Appendix which contains
  application."                               stand-alone information on
                                              Sterilization Validation as
                                              outlined in the FDA
                                              Guidance: *Submission of
                                              Documentation for
                                              Sterilization Process
                                              Validation in Applications
                                              for Human and Veterinary
                                              Drug Products.*
  ------------------------------------------- ---------------------------

+------------------------------------------+---------------------------+
| **[Page 37 Lines 1329 -- 1334: Collated  | [Lilly                    |
| Batch Analyses Data:]{.underline}**      | Comment:]{.underline}     |
|                                          |                           |
| "Presentation of results from all        | This is a repetition of   |
| batches for a particular test in tabular | information already       |
| and/or graphical format is often helpful | provided in other         |
| in justifying the acceptance criteria.   | sections of the           |
| Collated batch analyses data are not     | application. We suggest   |
| warranted for all tests. However,        | removing this paragraph.  |
| collated data should be provided for     |                           |
| assay and impurities (e.g., degradation  |                           |
| products, residual solvents) and should  |                           |
| be considered for other tests such as    |                           |
| water content."                          |                           |
+------------------------------------------+---------------------------+

+-----------------------------------+-----------------------------------+
| **[Page 37 Lines                  | [**Lilly Comment:**]{.underline}  |
| 1317-1326]{.underline}**          | Analytical method changes that    |
|                                   | have no significant potential to  |
| A summary of any changes in the   | impact the results need not be    |
| analytical procedures should be   | summarized in the batch analysis  |
| provided if the analytical        | or stability data reports. To aid |
| procedures (1) changed over the   | in interpretation of the batch or |
| course of generating the batch    | stability results, only those     |
| analyses data and/or (2) are      | method changes which have         |
| different from the analytical     | impacted the results need be      |
| procedure included in P.5.2. The  | described.                        |
| summary should identify when an   |                                   |
| analytical procedure changed, the | While we strongly support         |
| differences between the           | providing sufficient information  |
| analytical procedures, and the    | to thoroughly explain the         |
| impact of the differences with    | development of the process and    |
| respect to the data being         | methods, providing extraneous     |
| reported. For example, a summary  | data which does not aid in the    |
| could state that the solvent      | interpretation of results         |
| system for the assay was changed  | undermines the ability to present |
| on December 15, 1999, from A to B | information clearly. We suggest   |
| so that impurities Y and Z that   | the section be revised to read:   |
| co-elute using System A could be  |                                   |
| quantitated separately. If there  | "A summary of **significant**     |
| are significant differences in    | changes in the analytical         |
| the analytical procedures (e.g.,  | procedures **which impact the     |
| different fundamental principles  | data being reported** should be   |
| such as titration and HPLC), a    | provided if the analytical        |
| more detailed summary describing  | procedures (1) changed over the   |
| the changes may be warranted.     | course of generating the batch    |
|                                   | analyses data and/or (2) are      |
| # And Page 44 Lines 1584-1593     | different from the analytical     |
|                                   | procedure included in P.5.2. The  |
| A summary of any changes in the   | summary should identify when an   |
| analytical procedures should be   | analytical procedure changed, the |
| provided if the analytical        | differences between the           |
| procedure was changed over the    | analytical procedures, and the    |
| course of generating the          | impact of the differences with    |
| stability data.                   | respect to the data being         |
|                                   | reported. For example, a summary  |
| The summary should identify when  | could state that the solvent      |
| an analytical procedure changed,  | system for the assay was changed  |
| the differences between the       | on December 15, 1999, from A to B |
| analytical procedures, and the    | so that impurities Y and Z that   |
| impact of the differences with    | co-elute using System A could be  |
| respect to                        | quantitated separately. ~~If      |
|                                   | there are significant differences |
| the data being reported. For      | in the analytical procedures      |
| example, a summary could state    | (e.g., different fundamental      |
| that the solvent system for the   | principles such as titration and  |
| assay was changed on December 15, | HPLC), a more detailed summary    |
| 1999, from A to B so that         | describing the changes may be     |
| impurities Y and Z that co-elute  | warranted."~~                     |
| using System A could be           |                                   |
| quantitated separately. If there  |                                   |
| are significant differences in    |                                   |
| the analytical procedures (e.g.,  |                                   |
| different fundamental principles  |                                   |
| such as titration and HPLC), a    |                                   |
| more detailed summary describing  |                                   |
| the changes may be warranted.     |                                   |
+-----------------------------------+-----------------------------------+

+-----------------------+----------------------------------------------+
| **[Page 38 Lines      | [Lilly Comment:]{.underline} The replication |
| 1341-1358 List of     | of drug substance impurity information here  |
| Expected (Drug        | is unnecessary. Reference to the relevant    |
| Product)              | portion of the drug substance section should |
| Impur                 | be sufficient unless additional impurities   |
| ities:]{.underline}** | result from the drug product manufacturing   |
|                       | or from interaction of the drug substance    |
| "All expected drug    | with the excipients.                         |
| product impurities    |                                              |
| (e.g., degradation    |                                              |
| products of the       |                                              |
| active ingredient,    |                                              |
| residual solvents,    |                                              |
| enantiomeric          |                                              |
| impurities, excipient |                                              |
| degradants,           |                                              |
| leachables from the   |                                              |
| container closure     |                                              |
| system) should be     |                                              |
| listed in this        |                                              |
| section of the        |                                              |
| application whether   |                                              |
| or not                |                                              |
|                       |                                              |
| the impurities are    |                                              |
| included in the drug  |                                              |
| product               |                                              |
| specification. For    |                                              |
| example, drug         |                                              |
| substance process     |                                              |
| impurities that could |                                              |
| carry over to the     |                                              |
| drug product should   |                                              |
| be listed             |                                              |
|                       |                                              |
| here even if they are |                                              |
| normally controlled   |                                              |
| during drug substance |                                              |
| testing and will not  |                                              |
| be                    |                                              |
|                       |                                              |
| included in the drug  |                                              |
| product               |                                              |
| specification. When   |                                              |
| qualified, the        |                                              |
| qualified level of an |                                              |
|                       |                                              |
| expected impurity     |                                              |
| with a cross          |                                              |
| reference to the      |                                              |
| appropriate studies   |                                              |
| (include study        |                                              |
|                       |                                              |
| numbers) should be    |                                              |
| provided."            |                                              |
+-----------------------+----------------------------------------------+
| [Page 44 Line 1567:   | [Lilly Comment:]{.underline} We suggest the  |
| Formal Stability      | title of this section read "Primary          |
| Studies]{.underline}: | Stability Studies" for consistency with      |
|                       | accepted terminology.                        |
+-----------------------+----------------------------------------------+
| [Page 46 Lines 1636   | [Lilly Comment:]{.underline} The             |
| -- 1678 Appendix      | organization of the guidance for Appendix I  |
| I:]{.underline}       | is confusing. The ICH CTD guidance clearly   |
|                       | specifies Appendix I (Facilities and         |
|                       | Equipment) as applicable to Biotech products |
|                       | only. It is unclear if the FDA is expanding  |
|                       | the scope of this section to encompass other |
|                       | product types, which would be unwarranted.   |
+-----------------------+----------------------------------------------+

**[General Comments:]{.underline}**

1\. In order to improve the clarity of the guidance, we suggest a closer
alignment with the format provided in the ICH Common Technical Document
Guidance. Also, in many sections of the guidance, it is unclear if the
subheadings used for the detailed content guidance are intended as
format guidance to applicants or simply to organize the guidance.

2\. Location of Information on Devices for Combination Products: We
suggest that the FDA specify the preferred location for information on
devices when part of a Combination Product. We propose that a
stand-alone section such as an Appendix to the drug product section
would provide the best submission approach.