The European Medicines Agency (EMA) has finalized guidance intended to help sponsors meet the data requirements for process validation for biotechnology-derived active substances.
The guidance, which goes into effect in November 2016, covers process validation for a host of biological active ingredients, such as recombinant proteins and recombinant polypeptides, and may be applicable to other biological products such as vaccines or plasma-derived products.
The scope of the guideline is to provide guidance on the data to be included in a regulatory submission to demonstrate that the active substance manufacturing process is in a validated state. The guideline focuses on recombinant proteins and polypeptides, their derivates, and products of which they are components (e.g. conjugates). But it is explicitly mentioned that the principles could also be applied to vaccines or plasma-derived products and other biological products, as appropriate.
Process validation is defined in International Conference for Harmonization’s (ICH) Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients as, “The documented evidence that the process, operated within establish parameters, can perform effectively and reproducibly to produce an intermediate or API [active pharmaceutical ingredient] meeting its predetermined specifications and quality attributes.”
EMA breaks process validation up into two main components: process characterization and process verification.
Process characterization is further divided into process development and process evaluation, and involves a sponsor defining its manufacturing process for an active ingredient and evaluating the process to ensure it is adequately designed.
Process verification involves studies done at manufacturing scale to confirm the performance of the processes the manufacturer has specified.
According to EMA, “Process validation should not be viewed as a one-time event. Process validation incorporates a lifecycle approach linking product and process development, validation of the commercial manufacturing process and maintenance of the process in a state of control during routine commercial production.”
Process validation is divided into two parts:
process characterisation, where the commercial manufacturing process is defined
process verification, where the final manufacturing process as established based on process evaluation studies performs effectively in routine manufacturing.
Process characterization it self is also divided into two parts:
process development, which includes studies to reach a potential design of a future manufacturing process
process evaluation which includes studies on small and/or commercial scales, providing evidence that the complete manufacturing process has been appropriately designed to design the full operating ranges of the manufacturing process.
Guidance: Process Development and Evaluation
When evaluating a manufacturing process, EMA recommends that sponsors focus the “potential criticality” of the inputs and outputs identified during process development.