ICH je objavio draft nove Q13 smjernice Continuous manufacturing of drug substances and drug products. Dok opći dio dokumenta donosi generalne smjernice za kontinuiranU proizvodnju (npr. kako definirati seriju, nadzor procesa, pristup validaciji kontinuiranog procesa, reference na specifična poglavlja CTD dokumentacije s obzirom na kontinuirani proces i sl.), dodaci pokrivaju različite operativne i praktične aspekte kontinuirane proizvodnje.

Pogledajmo u nastavku nekoliko zanimljivih izvadaka iz drafta nove ICH Q13 smjernice.

Što draft ICH Q13 smatra kontinuiranom proizvodnjom?

CM (Continuous Manufacturing) involves the continuous feeding of input materials into, the transformation of in-process materials within, and the concomitant removal of output materials from a manufacturing process. While this description may apply to an individual unit operation (e.g., tableting, perfusion bioreactors), this guideline focuses on the integrated aspects of a CM system in which two or more unit operations are directly connected. In this context, any changes made in a unit operation of CM may have a direct and often immediate impact on downstream and upstream (e.g., via a feedback control) unit operations.

Kako se definira serija u slučaju kontinuirane proizvodnje?

… the size of a batch produced by CM can be defined in terms of one of the following:

• Quantity of output material

• Quantity of input material

• Run time at a defined mass flow rate

Other approaches to define batch size can also be considered, if scientifically justified based on the characteristics of the CM process. A batch size can also be defined as a range. For example, a batch size range can be established by defining a minimum and maximum run time.

Koje smjernice vezano za validaciju procesa predlaže draft ICH Q13?

The use of a continuous process verification approach should be justified based on the product and process understanding, system design, and overall control strategy. When continuous process verification is used, the CM system performance and material quality should be continuously monitored, such that the real-time data collected demonstrate the maintenance of a state of control and production of output material with the desired quality for the run time duration.

When a continuous process verification approach is used to support initial product launch, applicants should define when validation activities are considered sufficient to provide confidence in the commercial manufacturing process.

Koji su principi nadzora kontinuiranog procesa?

In CM, frequent process monitoring and control can be achieved through use of PAT tools, such as in-line/online/at-line monitoring and control, soft sensors and models. These tools allow real time data collection for parameters relevant to process dynamics and material quality, and hence ensure the state of control for every batch.

Što treba uzeti u obzir vezano za uzorak i uzorkovanje?

… the sampling strategy (e.g., location, sample size, frequency, statistical approach and criteria, and their relevance to the intended use) …

Pogledajte draft ICH Q13