The Draft PI or Target Product Profile (TPP)
Drug development is expensive and time consuming. In 2014, the Tufts Center for the Study of Drug Development estimated that approval of a new prescription drug can take 10 years or longer and cost an average of 2.5 billion dollars ( $1.4 for out-of-pocket development costs and $1.1 billion in lost opportunity costs for the money that might have been made with alternative investments). To justify these costs, it is critical to choose a drug or biologic that provides sufficient clinical benefit that it will be successful in the market to can repay these expenses.
Planning is key -- key to selecting the right drug for development, key to designing an efficient development program, and key to making the tough Go/No Go decisions that may be needed to avoid wasting money on projects that will not be successful.
Many companies use a document called a “Draft PI” or “Target Product Profile” (TPP) to guide development. This is now so commonplace that the FDA has issued a Guidance Document for industry and FDA review staff called “Target Product Profile--A Strategic Development Process Tool.” You can find a link to this Guidance in the Resource section. The Guidance defines a TPP as “a format for a summary of a drug development program described in terms of labeling concepts.” What does this mean? A Draft PI or TPP is a document that describes what the prescribing information will look like if the proposed studies are successful and the drug is approved. It’s a “wish list” that outlines the attributes you hope your drug will have and explains what studies you will do to confirm these attributes. In addition to labeling concepts, the FDA Guidance states that the TPP can serve as a tool for discussing proposed promotional claims for your drug and defining what development activities would be used to support these claims.
Preparation of the Draft PI requires input from a multidisciplinary Project Team which usually includes representatives from Discovery, Manufacturing, Regulatory Affairs, Clinical Development and a Commercial representative who provides marketing projections and information about competition. The Draft PI must identify the indication being sought for the product. A broad indication such as “for treatment of bacterial pneumonia” would allow the drug to be marketed to a larger group than a more restrictive indication such as “for treatment of hospital-acquired pneumonia caused by aerobic gram-negative bacilli” but the drug and the clinical studies might not be able to support such a broad claim. The dosing regimen, the safety profile, etc. outlined in the prescribing information will all influence how often physicians will choose to prescribe it and how well the product will be reimbursed.
The Draft PI should be used to design the Phase 2 and Phase 3 protocols. If you want a label that says that the drug is indicated for “treatment of adults with Type 2 diabetes mellitus who have failed to respond adequately to metformin,” your protocols will have to define clearly what it means to “fail to respond adequately to metformin” and then you will have to recruit subjects that fit that definition. Nowadays, this type of specificity is critical for drugs or biologics that target specific tumor markers.
The development team can also use the draft PI to set Go/No Go decision points throughout the development process. The investigational compound must perform well enough to get past these decision points and “earn” further investment of time, money and staff. For example, one early hurdle might be a review of the side effects in Phase 1 studies. If these early studies show an adverse event profile that would be unacceptable for a drug with the proposed indication, that might trigger a No Go decision. The indication is important, side effects that might be acceptable for an oncology drug might make an antihypertensive non competitive. Similarly, Phase 1 results that show that the formulation being tested would require twice daily dosing might trigger a No Go decision if competitive drugs are dosed once a day. If your drug substance is very expensive and the Phase 1 or Phase 2 studies show that a higher than expected dose of drug will be necessary to show efficacy, that might lead to a decision to stop development or a decision to devote additional efforts to find ways to cut drug costs.
Your draft PI and the primary endpoints of your studies will define the indications and the risk/benefit of your proposed product. It is important that the marketing team and the clinical development team are in agreement here. Usually a commercial person is a key member of the development team. Let’s imagine you are developing a new antiviral for hepatitis C. If your sales projections are based on being able to say that the drug is better than Brand X, everyone needs to know what “better” means. Is it safety, efficacy, duration of treatment, or exactly what? Then you need to decide if you will include Brand X as a comparator in the Phase 3 studies or just hope to show that your drug efficacy is superior without conducting a direct comparison. If you don't have head to head comparisons, you will have to limit your claims. If you decide to use Brand X as a comparator in your Phase 3 studies, will you have to provide Brand X for the subjects in that arm of the study? Have you considered those costs?
At first, your Draft PI will have more holes than data. What are the pharmacokinetics? What are the most common adverse events. How frequent are they? Does the drug do what we expect it to do? These holes have to be filled with the results of preclinical and clinical studies. Some companies do not develop a Draft PI until Phase 2 when they have some information. When you start to use the PI is not as important as making sure all the disciplines are working together to draft and use the document during development.
Drug development is expensive and time consuming. In 2014, the Tufts Center for the Study of Drug Development estimated that approval of a new prescription drug can take 10 years or longer and cost an average of 2.5 billion dollars ( $1.4 for out-of-pocket development costs and $1.1 billion in lost opportunity costs for the money that might have been made with alternative investments). To justify these costs, it is critical to choose a drug or biologic that provides sufficient clinical benefit that it will be successful in the market to can repay these expenses.
Planning is key -- key to selecting the right drug for development, key to designing an efficient development program, and key to making the tough Go/No Go decisions that may be needed to avoid wasting money on projects that will not be successful.
Many companies use a document called a “Draft PI” or “Target Product Profile” (TPP) to guide development. This is now so commonplace that the FDA has issued a Guidance Document for industry and FDA review staff called “Target Product Profile--A Strategic Development Process Tool.” You can find a link to this Guidance in the Resource section. The Guidance defines a TPP as “a format for a summary of a drug development program described in terms of labeling concepts.” What does this mean? A Draft PI or TPP is a document that describes what the prescribing information will look like if the proposed studies are successful and the drug is approved. It’s a “wish list” that outlines the attributes you hope your drug will have and explains what studies you will do to confirm these attributes. In addition to labeling concepts, the FDA Guidance states that the TPP can serve as a tool for discussing proposed promotional claims for your drug and defining what development activities would be used to support these claims.
Preparation of the Draft PI requires input from a multidisciplinary Project Team which usually includes representatives from Discovery, Manufacturing, Regulatory Affairs, Clinical Development and a Commercial representative who provides marketing projections and information about competition. The Draft PI must identify the indication being sought for the product. A broad indication such as “for treatment of bacterial pneumonia” would allow the drug to be marketed to a larger group than a more restrictive indication such as “for treatment of hospital-acquired pneumonia caused by aerobic gram-negative bacilli” but the drug and the clinical studies might not be able to support such a broad claim. The dosing regimen, the safety profile, etc. outlined in the prescribing information will all influence how often physicians will choose to prescribe it and how well the product will be reimbursed.
The Draft PI should be used to design the Phase 2 and Phase 3 protocols. If you want a label that says that the drug is indicated for “treatment of adults with Type 2 diabetes mellitus who have failed to respond adequately to metformin,” your protocols will have to define clearly what it means to “fail to respond adequately to metformin” and then you will have to recruit subjects that fit that definition. Nowadays, this type of specificity is critical for drugs or biologics that target specific tumor markers.
The development team can also use the draft PI to set Go/No Go decision points throughout the development process. The investigational compound must perform well enough to get past these decision points and “earn” further investment of time, money and staff. For example, one early hurdle might be a review of the side effects in Phase 1 studies. If these early studies show an adverse event profile that would be unacceptable for a drug with the proposed indication, that might trigger a No Go decision. The indication is important, side effects that might be acceptable for an oncology drug might make an antihypertensive non competitive. Similarly, Phase 1 results that show that the formulation being tested would require twice daily dosing might trigger a No Go decision if competitive drugs are dosed once a day. If your drug substance is very expensive and the Phase 1 or Phase 2 studies show that a higher than expected dose of drug will be necessary to show efficacy, that might lead to a decision to stop development or a decision to devote additional efforts to find ways to cut drug costs.
Your draft PI and the primary endpoints of your studies will define the indications and the risk/benefit of your proposed product. It is important that the marketing team and the clinical development team are in agreement here. Usually a commercial person is a key member of the development team. Let’s imagine you are developing a new antiviral for hepatitis C. If your sales projections are based on being able to say that the drug is better than Brand X, everyone needs to know what “better” means. Is it safety, efficacy, duration of treatment, or exactly what? Then you need to decide if you will include Brand X as a comparator in the Phase 3 studies or just hope to show that your drug efficacy is superior without conducting a direct comparison. If you don't have head to head comparisons, you will have to limit your claims. If you decide to use Brand X as a comparator in your Phase 3 studies, will you have to provide Brand X for the subjects in that arm of the study? Have you considered those costs?
At first, your Draft PI will have more holes than data. What are the pharmacokinetics? What are the most common adverse events. How frequent are they? Does the drug do what we expect it to do? These holes have to be filled with the results of preclinical and clinical studies. Some companies do not develop a Draft PI until Phase 2 when they have some information. When you start to use the PI is not as important as making sure all the disciplines are working together to draft and use the document during development.
