The lack of attention when it comes to sufficient planning, developing and verifying of the actual CMC section of any pharmaceutical project is most common during the very early development phase; from pre-clinical to clinical phase 2A.
To gain a competitive clinical edge, pharmaceutical companies may look to do the most minimal CMC work required while still maintaining an acceptable level of control, as required by the competent authority. However, the question that arises is whether such decisions truly accelerate the overall development project.
Drugs and biopharmaceuticals approved by the FDA, where Target Product Profiles (TPPs) are mentioned, are associated with more efficient regulatory review times, perhaps because of increased planning or the TPP promotes well-organised regulatory dialogue. A well-defined Quality Target Product Profile (QTPP) that considers key CMC issues is one potential way to obtain early regulatory approval.
CMC activities during development
CMC activities include establishing manufacturing processes and product characteristics, defining product testing methods to ensure the drug product’s safety and efficacy, and consistency between batches.
The regulators expect that there is consistency between the product tested during the clinical trials and commercialised batches produced years later. To minimise the risk of later-stage failure, several key CMC activities must be considered during the development of biopharmaceuticals, see Figure 1.
The main part of the CMC activities defining the quality characteristics of the commercial product is performed during early development, that is in the pre-clinical phase and further developed until Phase 2AB. It is during these phases of development that the quality characteristics of a drug product ideally will be achieved to ensure the desired quality, considering the safety and efficacy of the drug product.
Establishing the design criteria for the different CMC activities in a structured and strategic way minimises the risk of repeating studies or delaying product development.
The value of a Quality Target Product Profile (QTTP) in early development
The QTPP is an overview of all the elements during the product development process that have an impact on the quality, safety and efficacy of a product in a given clinical indication. The QTPP does not only focus on CMC issues but should also cover the specific product design, mode of action of the product, intended clinical use, dosing, route of administration, and so on.
The QTPP is part of the ICH Q8 (R2) enhanced approach as a more systematic approach to development including, for example, incorporation of prior knowledge, results of experimental studies using design of experiments or multivariate data analysis, establishment of a control strategy, use of quality risk management, and use of knowledge management throughout the lifecycle of the product, see Figure 2.
