ACTIVE SUBSTANCE AND DOSAGE FORM ARE DESCRIBED IN THIS DOCUMENT formalizing STATE OF KNOWLEDGE OF ITS FUTURE DRUG DEVELOPMENT STAGE.
Described in ICH Q8 guide (R2) published in 2009 as “A prospective summary of the quality characteristics of a drug product […]”, the Quality Target Product Profile (QTPP) is based on the approach of Quality by Design (QbD). The QTPP is a product description that summarizes the characteristics expected during the development to respond to the therapeutic drug target.
It is established from the elements relating to the active molecule, its identity, purity or stability, highlighted during the early stages of research and development but also from the scientific data studies of pharmaco-toxicology, pharmacokinetics and clinics. The QTPP concerns not only the active substance itself, based on the activity of the product, but also the dosage form chosen which allows to bring the product to its therapeutic target with the desired concentration.
This document formalizes the state of knowledge of the future stage of drug development.
Summary document should allow the QTPP ultimately justify the choice of the dose, the nature of the packaging, the track and the delivery device. The different characteristics of the product should provide an answer on the fate of the product after its administration to ensure its bioavailability necessary for its effectiveness and safety.
For the active substance, a molecule and the characterization of the impurities is expected. The structure of the drug substance (conformation, molecular weight …), its physicochemical properties (pH, melting point, solubility, polymorphism …) must be entered in the QTPP. The impurities present in the active substance, the potential toxicity of which must be evaluated, need to be studied in order to elucidate their structure and to send the quantification by suitable analytical methods.
Impurities can be obtained from the processing or degradation of the active molecule itself ( product related Impurities ) but also come from components and materials used in the process ( process related Impurities ).Specifications must be specified for each identified and a description of quality control methods used attribute. In view of these different quality attributes, the results of studies of pharmaco-toxicology in vitro and in vivo provide rational needed to provide evidence of their impact on the activity and safety of the product. Functional testing, supporting the mechanism of action of the product, require to be described.
Some characteristics of the finished to meet the required efficiency and safety of the drug product are required in QTPP. The selected dosage form, which may be different during the phases of clinical evaluation of the product and at the time of marketing, must ensure the stability of the molecule and allow its distribution in the body with the desired concentration in order to act on the biological target .
As such, the composition of the final product, unit concentration of active substance and components, as well as its physicochemical characteristics may affect its bioavailability and tolerance (pH, osmolality, disintegration, dissolution …) need to be specified in QTPP. Rational selection of excipients, their function and compatibility will justify both a qualitative and quantitative point of view, their presence in the final dosage form.
Toxicology studies and animal and human pharmacokinetics as well as the results of clinical studies will reinforce these choices. Related to the route of drug administration, specific features can be highlighted. This is the case, for example, injectable products for which sterility and pyrogen are essential requirements to ensure patient safety.
The package is taken into account to ensure product stability and integrity. Interactions container / content supported by studies highlight the presence or absence in the future drug leachables from materials in contact with the product. The identification of these substances, the evaluation of their potential toxicity but their quantification by suitable methods are part of the document. The QTPP should include criteria to justify the integrity of packaging and storage conditions necessary to ensure the quality of the product.
The QTPP is an essential document that enables the formalization and tracing the evolution of the knowledge acquired throughout the lifecycle of the drug. Established during the early stages of development in addition to the Target Product Profile (TPP), it should be updated following the changes in the manufacturing process, a change in the dosage form or in function of the evolution of knowledge Product.
This is a reference element of the expected quality of the product during transfer and scale-up or during comparability studies. The characteristics mentioned in the document must be justified to meet the required efficiency and safety. In this respect, the rational present in QTPP must be clearly expressed and information contained deserve crossed with those described in the literature on products of the same family.
Its establishment and update require the pooling of skills and multidisciplinary knowledge, scientific, medical, technical and regulatory, making it a useful communication tool for the understanding of the product in relation to the claimed therapeutic target.