Medical and Regulatory Affairs

The First Step for Streamlined CMC Development: Optimize the Target Product Profile

The ultimate goal of any drug development program is to obtain regulatory approval with the desired prescribing information. Beyond that, developers hope to obtain this approval in the shortest amount of time and with the most efficient use of resources.

In an article published in Trends in Biotechnology,1 researchers found that the approved drugs and biologics that mentioned target product profiles (TPPs) had a more efficient review process through the FDA. This may mean the agency sees the use of TPPs as indicative of a more thoughtful approach to the clinical and drug development process.

Developing the TPP to meet patient needs and achieve marketplace success

The path to approval becomes more efficient from both a time and resource perspective by beginning the development cycle with the end in mind. The first step along the way is the TPP.

The TPP is an evolutionary document describing the mechanism of action, clinical pharmacology, indication for use, and primary and secondary efficacy endpoints of a drug. A TPP should be used and modified based on the current knowledge from the pre-investigational new drug application (pre-IND) phase through post-marketing programs to expand the approved indication. It establishes the goals for the drug development program, lays out the nonclinical and clinical trial strategy intended to support the labeling concepts, and provides a tool for use in communication with regulatory agencies.

It is key to prepare the TPP from a patient safety and efficacy perspective to ensure that the product ultimately developed meets the patient’s needs and is successful in the marketplace.

Building in quality to guide CMC development

The quality target product profile (QTPP) focuses the concepts established in the TPP to guide chemistry, manufacturing, and controls (CMC) development. According to the ICH guidance Q8(R2) [PDF] on pharmaceutical development, a QTPP is a prospective summary of quality characteristics that ideally will be achieved to ensure the desired quality, factoring in the safety and efficacy of the drug product. Based on the requirements delineated in the TPP, the QTPP establishes:

  • Intended use in clinical setting, route of administration, dosage form, delivery systems
  • Dosage strength(s)
  • Container closure system
  • Therapeutic moiety release or delivery and attributes affecting pharmacokinetic characteristics (e.g., dissolution, aerodynamic performance) appropriate to the drug product dosage form being developed
  • Drug product quality criteria (e.g., sterility, purity, stability, and drug release) appropriate for the intended marketed product

The product quality attributes established in the QTPP can then be incorporated into the CMC development plan. The development of the drug substance and drug product processes is executed to deliver the quality attributes described in the QTPP. These attributes will also drive the analytical development program to ensure that appropriate assays are developed and qualified to meet the quality requirements for nonclinical and clinical trial materials.

Defining process parameters and strategy with a risk-based approach

As the CMC development program matures, the quality attributes established in the QTPP are evaluated through a risk-based quality management approach to determine their criticality. These critical quality attributes are essential in determining the critical process parameters, process validation strategy, and the establishment of the process control strategy.

When the goals of the development cycle align with the product characteristics established in the TPP and the quality attributes in the QTPP, the result is a robust formulation and manufacturing process with an acceptable control strategy that ensures the performance of the drug product.

1 Breder, Christopher; Du, Wenny; & Tyndall, Adria (2017). What’s the Regulatory Value of a Target Product Profile? Trends in Biotechnology,35(7), 576-579. doi:10.1016/j.tibtech.2017.02.011.