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ment, the earlier studies should be carried out in a manner that allows us to justify our later decisions and assessments. This article discusses the types of supporting activities and scale of operations that will help get the new product filing accepted and eventually approved by the regulatory authorities. Application of QbD QbD can be applied to all commercial formulations, regardless of whether they are formulations for innovator tablets or capsules, or for generic ones. QbD requires that the applicant demonstrate enhanced understanding of the critical material attributes (CMAs) of their active pharmaceutical ingredient (API) and excipients and of the critical process parameters (CPPs) that have the potential to affect the critical qual- ity attributes (CQAs) of the finished drug product. It also requires that the applicant establish an appropriate design space and control strategy to ensure that the finished drug product is consistently produced while meeting specifications, and is fit for its purpose. It is important to remember that a drug product's per- formance can relate to manufacturability, stability, and in vivo performance after administration to a patient. Can the drug product be manufactured consistently batch after batch? Will it be stable for the required shelf-life? Will it perform in vivo as intended? Necessary activities and investigations So where do we start? The first step is to define the objectives in the Quality Target Product Profile (QTPP). This document should clearly state the desired outcomes, such as the route of administration, type of dosage form(s), dosage strength(s), and desired pharmacokinetic profile. This information should be available for any com- mercial project, whether for an innovator drug product or for a generic. For an innovator project, clinical studies will have been performed, both Phase I and Phase II, to iden- tify the parameters for the QTPP. For a generic project, a match for the reference-listed drug (RLD) is required. Given a route of administration and a type of dosage form to develop, the next step is to examine the proper- ties of the API and determine likely and preferred formu- lation approaches. In that respect, the requirements of a QbD development project are no different from those of a more traditional formulation project. The foundation for formulation design and development of a successful tablet or capsule will be the pre-formulation studies. If the relevant properties of the API are not fully understood, it is likely that the formulation project will not succeed. Does that require a Design of Experiments (DoE) for your pre-formulation work? No! Good data from sound scientific studies are required so that the best decisions can be made. For the purposes of this discussion, the pre-formulation screen should include, but not be limited to, API stability and degradation pathways, excipient compatibilities, pH solubility, and an estimate of intestinal permeability and efflux, e.g., using Caco-2 cell monolayers. For drug products with poor water solubility, the choice of a processing methodology may not be so straightforward. There is a preliminary question to be answered: What is needed to get the API into a form that medical practitioners can successfully administer to a patient, can be manufactured at commercial scale, is sta- ble, and provides the necessary therapeutic effect? 16 September 2017 Tablets & Capsules Establish Quality Target Product Profile Route of administration Type of dosage form Release characteristics Pre-formulation API pH solubility API intestinal permeability and efflux API stability and degradation Excipient compatibilities Other studies as necessary Formulation and process design (0.1-0.5 × ) Formulation and process development Initial scale-up: 1× a Design of Experiments Establish Design Space and Control Strategy Scale-up Pilot/intermediate scale: 10× Confirm Design Space and Control Strategy are still appropriate Full scale: 100× Confirm Design Space and Control Strategy are still appropriate Technical transfer, process qualification, and continued verification a Depending on the critical scale for the unit operations Table 1 Stages in a QbD formulation development project