# Presentation: 404449

## Part 15 Public Hearing  FDA Regulation of Combination ProductsNovember 25, 2002Rockville, MD

- Michael Gross, Ph.D., RAC
- Vice-President Worldwide Compliance
- Aventis Behring
- King of Prussia, PA
- michael.gross@aventis.com

**Notes:**
Title of my talk

## PERSONAL EXPERIENCE

**Inhalation device [510(k)]**
**Passive transdermal patches [ANDA]**
**Medicated tooth paste [IND]**
**Iontophoretic drug delivery systems [RFD, IND, *****510(k)–NDA*****]**
**Prefillable syringes [DMF]**
**Pens, liquid- and liquid-dry [****RFD, 510(k), MAF]**** **
**Autoinjector [****RFD****, 510(k)]**
**Nasal delivery syringe [B****MF]**** **
**Diluent syringes [RFD, 510(k)]**
**Flush syringes [510(k)]**
**Disposable syringes, needles [*****510(k)*****]**
**Surgical kits [*****NDA, 510(k)*****]**
**Surgical scrubs [NDA]**
**Infusion ****Pumps [510(k)]**
***Jet and powder injectors *****[*****510(k)*****]**
***Inhalation delivery systems *****[*****510(k)-NDA*****]**

## DOWNSTREAM ISSUES

- _User Fees _
- PDUFA, MDUFMA_ _
- _Quality Systems: _
-  	21CFR 210, 211, 820
- _Manufacturing/Design Changes: _
- 21CFR 314.70, 601.12, 807.81 814.39
-  _Adverse Events/Experiences: _
- 21CFR 314.80, 600.8, 803
- _Toxicology/Biocompatibility: _
- 21CFR 312.23, ISO-10993-
-  _Orphan Drug/Humanitarian Device: _
- 21CFR316, 814.100
- _Applications: _
- 21CFR 312, 314, 600, 807.81 812, 814

## 1. What guiding principles should be used when revising the existing Inter-center Agreements?

**Guidance level documents, subject to comment period**
**Consistent format, clear language and content; examples**
**Distinguish between combination products (Combination Products Office) and products of unclear designation (Product Jurisdiction Office)**
** ****For a combination product do not say, “it’s a drug” or “it’s a device”, or “it’s regulated as a ...” ;these statements pertain to a product of unclear designation.**
**Address only jurisdiction and application of investigational exemptions and pre-market regulatory authorities; address “downstream issues” in separate guidance(s)**
**Describe and diagram designation and dispute resolution processes**
**Reaffirm that reviews are consultative and not collaborative**
**Virtual Combination Products are created **_**only**_** when brand names are specified and labeling is mutually conforming**

## 2. What factors should be considered in determining primary mode of action?

**Primary Jurisdiction established according to primary mode of action**
** **
**In special cases ****where the effects are synergistic or mechanism is unclear also consider**** :**
**Risk**
**Toxic or adverse mode of action **
** **
**Intended use **
** **
**Center capability to assess safety and effectiveness**
**Must have foundation in FD&CA, fit drug or device definitions**
**Describe/diagram determination/dispute resolution processes in Inter-center Agreement rewrites**

## 3. Is one pre-market review (notification) mechanism more suitable than another?

**Is it appropriate to regulate combination products under 510(k)?**
**Can there be “substantial equivalence” for a combination product?**
**Should a consistent level of regulatory approval be applied to all components [i.e., 510(k) is not pre-market approval]?  **
**Consider a new (unique) application (CPAA) for combination products? This would require legislation. **

## 4. What criteria should be used in determining if single or multiple applications are necessary? Should the need to use a mixed regulatory approach influence this?5., 6. What principles should be followed in determining the quality system and adverse event reporting requirements for a combination product?

**Each Guidance should include descriptions/diagrams of determination/dispute resolution processes.**
**Guidance should be predictable and consistent on application formatting (e.g., single application, imbedded pull-out, linked or stand-alone). **
**For quality systems, design control may be useful for managing combination products; perhaps design reviews throughout development and post-marketing should be required for **_**all**_** combination products, as it will help to identify and manage interactions between the components. **
**For adverse events:**
**Reports should be sent to both Centers indicating the report is for a combination product**
**FDA must sort out duplicate reporting**** **

## 7. Other comments?

**Virtual Combination Products are created **_**only**_** when brand names are specified and labeling is mutually conforming**
**Certain combination product examples cited in **
**	****the CDER-CDRH Inter-center Agreement (which are not composed of finished medical devices) should be reconsidered; if these pharmaceutical dosage forms are combination products then capsules, ointments, implants, depots, and suppositories would also be combination products. **
**passive transdermal patches **
**drug eluting disks**

## Slide 9