Standard Guide for Application of Continuous Manufacturing (BioCM) in the Biopharmaceutical Industry

Importancia y uso:

4.1 This guide focuses on upstream and downstream processes for biopharmaceutical products with a particular focus on antibody production processes. For further information, see Appendix X1 and Refs (1-3).

4.2 Bioprocesses traditionally consist of discrete unit operations labeled as upstream, downstream, and fill/finish operations. The objectives at each stage are significantly different, as are the operating parameters and control processes, that can make complete integration impractical initially (Appendix X1). This guide does not imply that complete integration is a prerequisite. A higher degree of integration may be possible over time as a better understanding of the dynamics of processes become established.

4.2.1 Upstream Processes—The purpose of upstream processes is to generate sufficient product to meet patient requirements preferably in the fewest number of batches. This starts with increasing biomass (cell-line expansion from working cell bank to production inoculation) to a production bioreactor in which the focus shifts to producing product. The material within a bioreactor during extended growth is heterogenous, for example, cells will differ in age, there may be genetic drift, secreted product can differ in the residence time spent in the bioreactor, and cell debris accumulates throughout the process.

4.2.2 Downstream Processes—The purpose of downstream processes is to harvest product and purify it from process- and product-related impurities (for example, cell debris, nucleic acids, and misfolds) to the desired level. Solids are first separated from solutes; solutes are then separated from each other in the process of purification. Certain processes may at best be semi-continuous, and some steps may be prone to fouling, which may require manual intervention.

4.2.3 Fill/Finish Operations—The purpose of fill/finish operations is to formulate the purified product in a form that ensures stability and sterility and provides a dosage form consistent with the desired product profile. Operations may also include inclusion in a delivery system as a combination product. In this guide, operations up to and including final bulk fill for final drugs substance are addressed. Fill/finish operations for drug product and combination products are out of scope for this guide.

4.3 This guide does not advocate the following:

4.3.1 CM is suitable for the manufacture of all biopharmaceutical products and processes;

4.3.2 Guidance on issues related to the safe operation of a CM process or continuous biomanufacturing equipment. It is the responsibility of the user of this guide to establish appropriate health and safety practices and determine the applicability of regulatory limitations before use; and

4.3.3 Specific designs or operating regimes for CM.

Subcomité:

E55.12

Volúmen:

14.01

Número ICS:

11.120.01 (Pharmaceutics in general)

Palabras clave:

application; bioprocess; continuous manufacturing; continuous processing; pharmaceutical industry; process control;