Module 9 2024

03/09/2024

What

What is PC? •

Process characterisation (also referred to as Stage 1 of process validation) is the activity of defining the commercial manufacturing process that will be reflected in master production document and batch protocols. The goal of this stage is to design a process suitable for routine commercial manufacturing that can consistently deliver an active substance that meets its quality attributes. • Process characterization identifies relations between process parameters (PPs) and critical quality attributes (CQAs), to deliver or justify manufacturing operating ranges within which consistent quality is achieved. The relationship between PPs and CQAs can be studied e.g. through a combination of design of experiments (DoE), mathematical models, or studies. (ICH Q8)

What is PV? •

Documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an active substance or intermediate meeting its predetermined specifications and quality attributes (ICH Q7).

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Why

Why is PC needed? • In order to define the manufacturing process parameters and controls the manufacturing process has to be characterised. On the basis of this information a commercial process can be proposed. Why is PV needed ? • Once a process has been characterised, evidence must be generated to confirm the proposed commercial process performs consistently and is robust. MAA/BLA Dossier review and upon Pre-Approval Inspection • Module 3 sections include: • 3.2.S.2.2, 3.2.S.2.4, 3.2.P.3.3 and 3.2.P.3.4 Commercial process and control descriptions • 3.2.S.2.5 and 3.2.P.3.5 Process validation studies, data and commitments • 3.2.S.2.6 and 3.2.P.2.3 Process development, characterisation studies and outcomes (including scale down model (SDM) qualification) • During dossier review, the EMA/FDA will issue questions regarding the PV if they have any concerns that the process is not appropriately controlled and validated • They may request further justification of CQAs, CPPs, PAR and NOR. • They may ask for repeat/redesign of process performance qualification (PPQ) if it is not considered acceptable. Commercial Launch • If a manufacturing process is not well controlled (due to poor PC and PV), there may be an increased fail rate • Post approval change may be required prior to launch (launch delays)

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