# Presentation: 264477

## Target Product Profile (TPP) DIA Annual Meeting – June 2004

- _Speakers_:
- Janice Soreth, FDA
- Jennifer Stotka, Eli Lilly and Company
- Steven Linberg, Chiesi

## TPP: History of this Initiative and FDA PerspectiveDIA Annual Meeting – June 2004

- Janice Soreth, MD
- Director
- Division of Anti-Infective Drug Products
- FDA
- June 2004

##  FDA Working Group Members:
Janice Soreth, ODE IV (co-chair)
Laurie Burke (OND)
Jamie Cross (OND)
Beth Duvall-Miller (OND)
Shirley Murphy (DPDD)

Pharmaceutical Working Group Members: 
Jennifer Stotka, Eli Lilly and Company (co-chair)
Donald Black, Merck
Linda Carter, Novartis
David Cocchetto, GlaxoSmithKline
David Goldberger, Johnson & Johnson 
Steven Linberg, Chiesi 
Sharon Olmstead, Schering Plough 

- Janice Soreth, ODE IV (co-chair)
- Laurie Burke (OND)
- Jamie Cross (OND)
- Beth Duvall-Miller (OND)
- Shirley Murphy (DPDD)
_**Pharmaceutical Working Group Members**_**: **
- Jennifer Stotka, Eli Lilly and Company (co-chair)
- Donald Black, Merck
- Linda Carter, Novartis
- David Cocchetto, GlaxoSmithKline
- David Goldberger, Johnson & Johnson
- Steven Linberg, Chiesi
- Sharon Olmstead, Schering Plough

- TPP Working Group

## TPP History 

**TPP was previously called TPI (Target Product Information).**
**In 1997, the Clinical Development Working Group in the Office of Drug Evaluation IV (ODE IV) began discussions with PhRMA on ways of improving sponsor / FDA interactions in the drug development process.**
**Mechanism identified was the development of a TPP – an  evolving version of the proposed package labeling which can be used during all phases of drug development.**
**The pilot was conducted between 1997 and 2003, and was  determined to be beneficial – both by FDA and PhRMA.**
**In January 2004, FDA and PhRMA decided to **_**expand**_** the pilot to full utilization.  The working group was expanded, renamed the initiative, updated templates / website / links to other development initiatives . . . and we’re ready to implement!**

***The new TPP will ******be ready****** for you to use ******soon******!!***

## TPP Intent

**The sponsor writes the TPP to guide the design, conduct, and analysis of clinical trials.  At the end of the development program, the data would support the sponsor’s **_**desired outcome**_**, i.e.,  the approval and appropriate labeling of the drug under development.**
**Over time, the **_**TPP evolves**_** and can serve as the basis for an ongoing dialogue between the FDA and the sponsor to **_**facilitate a shared understanding**_** of the goals of the drug development program, and the specific studies designed to achieve those goals.  **
**Useful at **_**key meetings**_** with the FDA during drug development **
**Pre-IND**
**End of Phase 1  (EOP 1)**
**End of Phase 2  (EOP 2)**
**Pre-NDA **
**Discussions about efficacy supplements**

***Start with the end in mind!***

## TPP:  What it is!

- Presents the overall development goals and goals for proposed claims for a prescription drug product, with annotations to the sources of data that will ultimately support the key sections and statements in the final label.
- Provides a statement of the _overall intent_ of the drug development program, given the totality of knowledge about the compound *at that point in development.*
- Is _multidisciplinary_ . . . and within each technical discipline, the TPP should summarize the specific studies that will supply the evidence for each major claim about the drug.
- Can be used as _a tool_ for _facilitating early discussions and achieving a clear, shared understanding_, with the review team at the FDA, of the evidence necessary to support desired labeling statements.

- TPP:  What it is!

## TPP:  What it is not!

***The TPP. . . ***
- _Is not_ a required component of any regulatory submission, but it may be provided by a sponsor – strictly on a voluntary basis.
- _Should not_ be a long, burdensome document!!
- _Should not_ be considered to represent an implicit or explicit obligation on the sponsor’s part to pursue all stated claims.
- _Does not_ comprise a commitment by the sponsor of FDA that the nature of evidence to support a specific claim will not change over time.
- _Should not_ be construed to represent an agreement on the part of the FDA that the proposed development plan will be adequate to support each proposed indication or claim.

## TPP:  How to Access Templates

***Current FDA website***
- _[www.fda.gov/cder/tpi](http://www.fda.gov/cder/tpi)_
*** “******new and improved” website coming soon***
***User-friendly templates***
***If questions, contact review division.  For additional support from OND, contact:***
***301-594-3937***
***ONDEIO@cder.fda.gov***

## TPP:  Part of a Briefing Document

- Regulatory procedures at the FDA provide sponsors with standardized mechanisms to prepare sound drug development proposals
- Guidance for Industry on Formal Meetings with Sponsors and Applicants for PDUFA Products
- MaPP on Formal Meetings between CDER and CBER’s External Constituents
- Guidance Document on Special Protocol Assessment
- Guidance Documents state:
- The sponsor must prepare a Briefing Document
- FDA will review and discuss the background information, as well as the sponsors questions, in advance of the meeting
- The meeting will focus its dialogue on the questions posed to the FDA
- TPP
- Can facilitate shared understanding
- Addresses the fundamental question of whether the development plan, if completed successfully, can support a given claim or statement.

## TPP: Ideal Linkages with Other Initiatives

- Good Review Practices
- End of Phase 2a Meetings
- Continuous Marketing Application (Pilot)
- Critical Path Initiative (Innovation or Stagnation?)

## TPP Experience – FDA Vignette

*TPP Experience – FDA Vignette*

-  _**Experience With TPP During Development of an Antibacterial Drug**_
- DAIDP successfully collaborated with the sponsor beginning during Phase 2 in the development program of an antibacterial drug product that was already under clinical development.   DAIDP held a face-to-face meeting with the sponsor solely to discuss the TPP.
- The drug development was complex, encompassing 3 formulations that were submitted and thereby being reviewed simultaneously.  The drug product was an NME seeking multiple indications, including infections due to drug-resistant pathogens.
- Ultimately the applications were reviewed under a priority clock with an Advisory Committee meeting.  Labeling negotiations were challenging, particularly with the shortened PDUFA clock.
- Both DAIDP reviewers and the sponsor agreed that the use of the TPP was integral for the successful introduction of the new drug under a 6-month PDUFA clock!

## TPP: Next Steps

**Milestone today with DIA Presentations**
**Availability of White Paper Summary **
**Availability of FAQs**
**2.    Implementation of updated website and tools **
_***www.fda.gov/cder/tpi***_
**Implementation of TPP workgroup communication plans**
**FDA-PhRMA collaborations at professional meetings**
**FDA updates within OND Management Meetings and Review Division Meetings**
**Will be presented at the FDA’s Project Manager Forum this Fall**
**Other PhRMA initiatives  (covered in next talk)**
**Utilization of this process by all of you!**

## TPP:  Summary

**Use of a TPP should enable a sponsor to be explicit and clear about the number and type of adequate and well-controlled studies that are planned to support an indication.**
**The TPP should help focus the sponsor’s development team and the FDA’s review team on a multidisciplinary product development plan.**
**A well-written TPP can serve as an excellent component of a Briefing Document. **
**If questions, contact review division.  OND can also provide information and support:**
***	****** *****301-594-3937*****  ******	******ONDEIO@cder.fda.gov***

## Target Product Profile (TPP) DIA Annual Meeting – June 2004

- _Speakers_:
- Janice Soreth, FDA
- Jennifer Stotka, Eli Lilly and Company
- Steven Linberg, Chiesi

## Target Product Profile (TPP): PhRMA PerspectiveDIA Annual Meeting – June 2004

**Jennifer L. Stotka, MD**
**Eli Lilly and Company**
**June 2004**

## TPP:  What it is!

- Was formerly called TPI (Targeted Product Information)
- Is an _evolving_ document, prepared by the sponsor to facilitate clinical drug development and enhance constructive dialogue between the sponsor and reviewing Division at the FDA
- A TPP is written and updated _by the sponsor_ during the investigational phases of development in order to capture the goals of clinical drug development as statements of proposed claims for a prescription drug or biologic product
- In the TPP, each proposed claim should be _annotated_ to the specific study or other sources of data intended to support the key sections and statements in the TPP
- In essence, the TPP embodies the notion of “_beginning drug development with the end in mind_”

- TPP:  What it _is_!

## TPP:  What it is not!

- _Is not_ a required component of any regulatory submission.  It is voluntary.
- _Should not_ be a long, burdensome document!!
- _Should not_ be considered to represent an implicit or explicit obligation on the sponsor’s part to pursue all stated claims.
- _Does not_ comprise a commitment by the _sponsor_ _or_ _FDA_ that the nature of evidence to support a specific claim will not change over time.
- _Should not_ be construed to represent an agreement on the part of the FDA that the proposed development plan will be adequate to support each proposed indication or claim.

- TPP:  What it _is_ _not_!

## TPP:  Sample Template Page

_**Optional Comments**_**: The proposed biomarkers included in  the protocols BBBB and CCCC are acceptable to DMEDP (discussed 12 Dec2002).  Protocol CCCC will be submitted for a  Special Protocol Assessment in 1Q04.**

## TPP: Aligned with PhRMA’s Goals

_***Key PhRMA Goal   ***_
***Structuring clinical development requirements to ***_***efficiently***_*** provide the most ***_***important information***_***, in the shortest time, using the most appropriate methods.***

## 4Q’03 PhRMA Survey:TPP Pilot (TPI) Experience

**Did you use TPP for any product since the pilot was introduced?  **
**What FDA Division(s) used this in conjunction with you?**
**Was it a useful tool overall?**
**What phase did you start using the tool?**
**Was it used at most or every FDA meeting?  **
**Was it used at key meetings (EOP 2, Pre-NDA, etc.)**
**Did it drive alignment of the development program?**
**Did it help with decision-making?**
**Did it help to yield more accurate meeting minutes with FDA?**
**Did it help to prevent surprises?**
**Would you use it again in a development program?**
**Please provide other comments about the TPP initiative.**
**If your TPP was rejected by a FDA, what were the reasons given?**

## A 13-question survey was sent out by PhRMA in October 2003
Ten companies responded to the PhRMA survey  
Responses represented work done with 6 divisions of the FDA, including:
Division of Anti-Infective Drug Products (5) 
Division of Anesthetic, Critical Care, Addictive Drug Products (1)
Division of Metabolic and Endocrine Drug Products (1)
 Division of Oncology Drug Products (1)
Division of Reproductive and Urologic Drug Products (1)
Division of Pulmonary and Allergy Drug Products (attempted, unsuccessfully)
Results of the survey were presented at the December 2003 – PhRMA Clinical and Regulatory Conclave

*TPP PhRMA Survey Process / Results*

**A 13-question survey was sent out by PhRMA in October 2003**
**Ten companies responded to the PhRMA survey  **
**Responses represented work done with 6 divisions of the FDA, including:**
**Division of Anti-Infective Drug Products (5) **
**Division of Anesthetic, Critical Care, Addictive Drug Products (1)**
**Division of Metabolic and Endocrine Drug Products (1)**
** ****Division of Oncology Drug Products (1)**
**Division of Reproductive and Urologic Drug Products (1)**
**Division of Pulmonary and Allergy Drug Products (*****attempted, unsuccessfully*****)**
**Results of the survey were presented at the December 2003 – PhRMA Clinical and Regulatory Conclave**

## 1.  Most TPP pilot utilization has been with the DAIDP, but other divisions have participated in the pilot program
2.  Most companies used it at and after the EOP 2 meeting
3.  The companies that responded to the survey, for the most part, found the TPP process to be helpful in focusing discussion and explaining their development plans
4.  Most said that it helped with decision-making
5.  It did not seem to make a difference to the quality or clarity of meeting minutes.
6.  Unanimously, sponsors said that they would use it again in  another development program   

**1.  Most TPP pilot utilization has been with the **_**DAIDP**_**, but other divisions have participated in the pilot program**
**2.  Most companies used it **_**at and after**_** the **_**EOP 2**_** meeting**
**3.  The companies that responded to the survey, for the most part, found the TPP process to be **_**helpfu**_**l in focusing discussion and explaining their development plans**
**4.  Most said that it **_**helped with decision-making**_
**5.  It did not seem to make a difference to the quality or clarity of meeting minutes.**
**6.  **_**Unanimously**_**, sponsors said that they **_**would use it again**_** in  another development program   **

## TPP - Typical Survey Comments

***The TPP . . . ***
- “Was useful in strategy planning with the agency . . ”
- “Was useful in guiding important discussions with the FDA . . .”
- “Ensured that the agency had a good understanding of our development  plan.”
- “Was valuable in forging alignment . . .”
- “Assisted in the clarification of issues . . .”
- “Was a particularly useful tool to bring clarity to FDA and sponsor expectations regarding the clinical development plans. . .”
- “Should be adopted more uniformly across FDA divisions . . .”

*TPP - Typical Survey Comments*

## TPP – Typical PhRMA Vignette

*TPP – Typical PhRMA Vignette*

_**Experience With TPP During Development of an Antibacterial Drug**_
** **
- As part of a 1999-2001 partnership with the Division of Anti-Infective Drug
- Products (DAIDP) to develop an antibacterial compound, the TPP process
- was employed.
- DAIDP and the sponsor agreed to begin using the TPP in support of the
- Briefing Document at an End of Phase 2 meeting.  The TPP proved to be:
- _Very useful_ because it served as a discussion tool to help _clarify_ the sponsor’s proposed clinical development plan and targeted label claims
- b)    Served as valuable “_anchor document_” to ensure appropriate communication and understanding between the sponsor and FDA
_**Comment by PhRMA survey participant**_**: **
*“**We sincerely hope that other divisions within FDA adopt the TPP process!”*

## TPP:  Some Anticipated FAQs

**Q: Why will TPP be better and/or more successful than the TPI pilot?**
**A: The TPI Pilot was recently assessed by PhRMA and the FDA and deemed to be value added.  The TPP program has captured the “lessons learned” from the pilot.  The website will be enhanced and the communication plan is more broad-sweeping.  The new TPP program is supported by senior management in the OND.**
**Q: When is the best time to submit a TPP?**
**A: The TPP is voluntary and may be used throughout drug development.  We can submit a TPP starting **_**as early as the pre-IND**_** meeting.**
**Q: Is the TPP FOI-able?**
**A: No.  Documents submitted to the IND are not FOI-able**

## TPP: Anticipated FAQs (cont.)

**Q: Is the TPP a final document?**
**A:  No.  It is a **_**dynamic**_** document that provides the overall intent  of drug development; it changes as the knowledge of the compound increases. **
**Q: How will TPP be integrated into new labeling initiatives? **
**A: Ideally, the TPP will be linked to the Critical Path Initiative, Continuous Marketing Applications pilots, etc.  This is a work-in-progress that the workgroup will continue to shepherd.**
**Q: What if someone is unfamiliar with the TPP process or initiative?**
**A:  Sponsors should work with the review divisions, but OND will be willing to provide background and support if necessary.**

## TPP:  Summary

**Use of a TPP should enable a sponsor to be **_**explicit and clear**_** about the number and type of adequate and well-controlled studies that are planned to **_**support a labeling claim**_**.**
**The TPP should help to **_**focus**_** a sponsor’s drug development team and the FDA’s review team on the multidisciplinary drug development plan.**
**A well-written TPP can serve as an excellent **_**component**_** of a Briefing Document **

## TPP: Next Steps

**Milestone today with DIA Presentations**
- Availability of White Paper Summary
**2.   Implementation of new website and tools *****(Coming Soon!)***
**Implementation of TPP Workgroup communication plans**
- FDA-PhRMA collaborations at DIA, RAPS, and other professional meetings
- PhRMA announcement on PhRMA’s home page on the web.
-  Updates at key PhRMA meetings
- Communications in various newsletters (DIA, RAPs, etc.)
**Utilization of this process by all of you!**

## Acknowledgement: TPP FDA-PhRMA Working Group

- Laurie Burke (OND)
- Jamie Cross (OND)
- Beth Duvall-Miller (OND)
- Shirley Murphy (DPDD)
*Janice Soreth, ODE IV (co-chair)*
_**Pharmaceutical Working Group Members**_**: **
- Donald Black, Merck
- Linda Carter, Novartis
- David Cocchetto, GlaxoSmithKline
- David Goldberger, Johnson & Johnson
- Steven Linberg, Chiesi
- Sharon Olmstead, Schering Plough
*Jen Stotka, Eli Lilly and Company (co-chair)*

*Acknowledgement: *TPP FDA-PhRMA Working Group

## Implement!

## Target Product Profile (TPP) DIA Annual Meeting – June 2004

- _Speakers_:
- Janice Soreth, FDA
- Jennifer Stotka, Eli Lilly and Company
- Steven Linberg, Chiesi

## Target Product Profile (TPP): Implementation DIA Annual Meeting – June 2004

- Steven E. Linberg, PhD
- Chiesi Pharmaceuticals Inc.
- June 2004

## The Setting:

**Feedback from the FDA on a detailed development program - priceless (and free!)**
**IND recently submitted, program at End-of-Phase 1**
**Based on the TPP PhRMA Survey, there was some question as to whether or not the DPADP was going to be an enthusiastic “partner”.**

*The Setting:*

***Start with the end in mind!***

## Survey was sent out by PhRMA in October 2003
Ten companies responded to the PhRMA survey  
Responses represented work done with 6 divisions of the FDA, including:
Division of Anti-Infectives (5) 
Division of Anesthetic, Critical Care, Addictive Drugs (1)
Division of Metabolic and Endocrine Drug Products (1)
Division of Oncology Drug Products (1)
Division of Reproductive and Urologic Drug Products (1)
Division of Pulmonary and Allergy Drug Products (attempted, unsuccessfully)
...

*TPP PhRMA Survey Results*

**Survey was sent out by PhRMA in October 2003**
**Ten companies responded to the PhRMA survey  **
**Responses represented work done with 6 divisions of the FDA, including:**
- Division of Anti-Infectives (5)
- Division of Anesthetic, Critical Care, Addictive Drugs (1)
- Division of Metabolic and Endocrine Drug Products (1)
- Division of Oncology Drug Products (1)
- Division of Reproductive and Urologic Drug Products (1)
**Division of Pulmonary and Allergy Drug Products (attempted, unsuccessfully)**
**...**

## The decision:

**Introduce the concept as a Target and not as an attempt to pre-define the label.**

*The decision:*

## The “Flavors” of a TPP

**Excellent template – no need to “re-create the wheel”**
**However, “modification” is always an option**
**The format of the TPP should fit the situation**

## The “Flavors” of a TPP

## The “Flavors” of a TPP

## The “Flavors” of a TPP

## Sections to consider for Pre-IND

**Clinical Pharmacology**
**b)(2)****	****Clinical Studies (proposed and/or completed)**
**Indications and Usage**
**Precautions (based on preclinical toxicology, if applicable)**
**Dosage and Administration**
**l)****	****Animal Pharmacology and/or Toxicology**

*Sections to consider for Pre-IND*

## Sections to consider for EOP2

**Clinical Pharmacology**
**b)(2)****	****Clinical Studies (proposed and/or completed)**
**b)(3)****	****Patient-Reported Outcomes**
**Indications and Usage**
**d-i)****	****(Depending on Toxicology, Phase 1-2 studies)**
**Dosage and Administration**
**l)****	****Animal Pharmacology and/or Toxicology**

*Sections to consider for EOP2*

## Approach to the Division

**TPP submitted as part of an FDA Meeting Package**
**TPP abbreviated  to accommodate EOP-1 status, contained essential aspects of development program at that point:**
**a)****	****  Description**
**c)****	****  Indications and Usage**
** ****j)****	****  Dosage and Administration**
**m)  Clinical Studies (Trial Outlines)**

*Approach to the Division*

## TPP:  Sample Template Page

_**Comments**_**: *****Italics***** represent text that is not yet supported by data.  ****Color**** is used for emphasis (internal and/or FDA).**

- TPP:  Sample Template Page

## TPP:  Sample Template Page

- TPP:  Sample Template Page

## TPP:  Sample Template Page

- TPP:  Sample Template Page

## Clinical Trials

_**CT-11: Adult Dose-Ranging Study (to be conducted as Protocol EU-CT-07)**_
**Randomized, double-blind, placebo-controlled, single-dose 5-way crossover**
**Balderdash pMDI: 20 pg, 40 pg, q.d.**
**Active control pMDI: 100 and 200 ****μ****g, q.d.**
**N = 46 (Powered for ****equivalence**** hypothesis)**
**Inclusion criteria:**
**FEV****1**** = ****50**** to 80% of predicted ****(60-80% recommended for the US)**
**Ages = ****18**** to 70 years ****(12 years minimum age recommended for the US)**
**Nocturnal asthma**
**Regular use of inhaled short-term beta****2**** agonists**
**Primary Endpoint: **
**FEV****1****-AUC****0-12**** from same-day, pre-treatment baseline**
**Secondary Endpoints:**
**FVC, FEV****1****/ FVC, PEFR, FEF****25%****, FEF****25-75%**** and flow volume curve at T0 (just before drug inhalation) and T3’, T5’, T10’, T15’, T20’, T30’, T1h, T2h, T4h, T6h, T8h, T10h, T12h after drug inhalation.**

## Summary of Experience to Date

- PDADP freely offered advice on the appropriateness of the program to address the targets presented.
- Types of question used: “Does the overall program appear adequate at this point to address the targeted program?”
- Type of question NOT used: “Will the successful completion of this program support the indicated labeling?”
- Seeing clearly what was intended, the DPADP was able to offer welcome advice on a number of issues.

## The TPP makes sense
All Divisions approached so far appear to welcome the use of the TPP
Greater use of the TPP will help Sponsors internally in their development strategy and execution
Greater use of the TPP will allow the FDA to more clearly understand the intentions of Sponsors and provide valuable feedback
The TPP makes sense

- The TPP makes sense
- All Divisions approached so far appear to welcome the use of the TPP
- Greater use of the TPP will help Sponsors internally in their development strategy and execution
- Greater use of the TPP will allow the FDA to more clearly understand the intentions of Sponsors and provide valuable feedback
- The TPP makes sense

## Target Product Profile (TPP) DIA Annual Meeting – June 2004Thank you

- _Speakers_:
- Janice Soreth, FDA
- Jen Stotka, Eli Lilly and Company
- Steven Linberg, Chiesi