Industry organizations recommend that ICH reduce the supervision and supervision of manufacturing models in order to reduce the burden of model change reporting

Recently, several industry organizations have jointly formulated a proposal to manage the supervision and supervision of models used in the pharmaceutical production process, suggesting that even for those models that have a significant impact on pharmaceutical production, the supervision and use of minor changes can be used.

If the proposal is successfully accepted by ICH, these organizations will establish a consistent approach among many regulatory agencies around the world, allowing changes to the manufacturing model to be managed within the enterprise as much as possible, and appropriately restricting the supervision of other changes by the regulatory agencies.

According to the definition of the industry proposal, the “model” mentioned here is a method that uses multiple variables as input (for example, data or spectrum) and uses mathematical transformations to predict the output (for example, process and product attributes).

Reduce regulatory complexity

Isabelle Lequeux of BioPhorum said, “Manufacturing models are the key driving force for continuous manufacturing and part of the new method of analysis and testing.

The initiative began a few years ago, when PPAR's process analysis technology professionals from different companies held an annual meeting to discuss topics of mutual interest and mutual benefit, and explore the need for consensus methods in PAT model registration and life cycle management.

Doddridge explained, “What we are looking for is a standard path for initial registration and life cycle management.

This work is a solution developed on the basis of the experience of using models in the manufacture of small molecule drugs.

Plan based on model influence

The proposal is based on the framework of the ICH Guidelines for the Implementation of Q8 Drug Development, Q9 Quality Risk Management and Q10 Drug Quality System Guidelines in November 2011.

Low-impact models to support product and/or process development (for example, formulation optimization).

The medium-impact model is used to ensure product quality, but it is not the only product quality indicator (for example, most design spaces, many intermediate process controls).

High-impact model.

The key considerations guide also discusses model development, implementation, verification, and life cycle verification.

Regulatory concerns for high-impact models

The industry recommends further distinguishing high-impact models from low-impact models and medium-impact models.

However, according to industry recommendations, low-impact and medium-impact models should be recorded in the sponsor’s drug quality system, not in regulatory documents, and model information can be obtained at the inspection site.

Given that under the proposed method, all low-impact and medium-impact models are managed within the company's drug quality system, changes to these models will also be managed within the company.

Industry organizations continue to propose that certain changes to the high-impact model do not need to be considered particularly influential.
Some changes to the high-impact model will not have an impact (no impact changes), others will only have a small impact (low-impact changes), and only a few changes will have a large impact and need to be re-verified.
According to the proposal, there is no need to report non-impact changes to the high-impact model to the regulator, while low-impact changes to the high-impact model only need to be notified to the regulator.

As far as possible changes that have a significant impact on the high-impact model require prior approval.
Even so, if such changes have been submitted in the comparability agreement or the post-approval change management plan, a lower reporting category can be used for such changes.