# Presentation: 372286

## Practical Issues in Combination ProductsCross LabelingAdvaMed MTLI ConferenceMay 25, 2006

- Suzanne O’Shea
- Product Classification Officer
- Office of Combination Products
- Food and Drug Administration

## What is Cross Labeling?

*Combination product *includes:
- A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g. to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose....
- 21 CFR 3.2(e)(3)

## What’s so hard about that?

- Hypothetical
- Company A is the sponsor of approved drug product A.
- Company B wants to obtain premarket approval for device B which will administer product A in a new dosage form, strength,  route of administration, or intended use.
- Company A does not want to cooperate with Company B in this venture.
- Can FDA approve / clear device B?
- Note:  Approved product A may also be a device; new product B may also be a drug.

## 

Many Questions

Few Answers

- Many Questions
- Few Answers

## 
What does individually specified mean?  

What if product B has other approved intended uses?  

When does label of Product A “need to be changed?”

If labeling of Product A does need to be changed, but Company A does not want to submit a supplement to its marketing application, does that mean that Product B cannot be approved?

- What does individually specified mean?
- What if product B has other approved intended uses?
- When does label of Product A “need to be changed?”
- If labeling of Product A does need to be changed, but Company A does not want to submit a supplement to its marketing application, does that mean that Product B cannot be approved?

**Some of the questions...**

## Public Workshop

- May 10, 2005
- Transcript and presentations accessible on OCP website:  _[http://www.fda.gov/oc/combination/](http://www.fda.gov/oc/combination/)_
- Comments available on docket

## Why is a cross labeling policy important?

- Confusion about whether Company A must participate may deter product development
- Greater clarity may be more efficient

## A note on terminology

- Cross labeling
- Mutually conforming labeling
- Is there any difference?

## Situations where cross labeling issues arise

- Product B enhances safety or effectiveness of Product A
- Product B uses Product A in a new route of administration

## More cross labeling situations....

- Product B uses Product A for new indication, new patient population
- Product B is a new component of an already approved combination product
- a. originally approved under two applications
- b. originally approved under one application

## And still more...

- Labeling of Product B and Product A will be inconsistent in some way
- Labeling of Product B and Product A will be contradictory

## Categories of Issues

- Labeling issues – possible end user confusion
- No ongoing relationship between manufacturers issues – what if product A is reformulated or redesigned
- Will reviewing application covering Product B necessarily rely on proprietary information in application covering Product A?
- Pathway issues

## What’s NOT an issue

- A conclusion that cross labeling is not required is not a data shortcut
- Differences in types of marketing application
- Active consultation / collaboration within FDA

## Why is this so challenging?

- Company A’s proprietary interests
- FDA’s core beliefs about labeling
- Company B’s commitment to Product B

## Protect and Promote the Public Health

- FDA prefers cooperation
- In the absence of cooperation, our goal is to identify a regulatory pathway for Product B while ensuring adequate regulatory oversight.
- What should be FDA’s default position?

## What can Company B do in the meantime?

**Call OCP to discuss!**
- Is Product A “individually specified?”
- Is Product B intended for use “only” with Product A?

## 
Consider whether labeling of Product A “needs to be changed”
Would Product A be intended to be used for a new intended use, dosage form, strength, or route of administration, 
Is end user confusion likely?
What would happen if Product A is reformulated or redesigned without notice to Company B?
Would Company B rely on proprietary information in application covering Product A?

- Consider whether labeling of Product A “needs to be changed”
- Would Product A be intended to be used for a new intended use, dosage form, strength, or route of administration,
- Is end user confusion likely?
- What would happen if Product A is reformulated or redesigned without notice to Company B?
- Would Company B rely on proprietary information in application covering Product A?

**Points to Consider**

## Contact Us!  

- Office of Combination Products
- 15800 Crabbs Branch Way
- Suite 200, HFG-3
- Rockville, Maryland 20855

## Contact Us!  

**301-427-1934**
**combination@fda.gov**

## Slide 20