It is common to release compendial waters (Purified Water and Water for Injection) continuously based on the online testing for its chemical attributes (TOC and conductivity).

 However, the release of this water would be “at risk” since its microbial attributes would not have been evaluated due to the time required to grow and enumerate microbial colonies.

 As an example, during the monitoring of the microbial attributes of our water system by traditional growth-based methods, we observed inconsistent and sometimes failing results from week-to-week.

 Although the water system in question is a product development tool, not a water system for use with a pharmaceutical product, the maintenance of the chemical and microbial control is paramount.

 Instead of increasing the frequency of the traditional sampling with more samples per week, we employed an at-line, real-time, fluorescence-based microbial detection technology.

 These periodic test failures, which later turned out to be the result of purification process failures, were occurring every 24-30 hours, and traditional growth-based microbial detection methods could not have easily detected these failures.

 By examining the continuous data, we correlated the auto-fluorescent count to a tank-filling process, then correlated the tank filling process to an exhaustion of mixed-bed ion-exchange resin.

 The observation was a sudden increase in microbial counts followed by a subsequent decay over hours as the recirculation loop reduced the microbial counts.

 By measuring continuously (every second), we observed periodic and serious purification failures.

 We corrected those failures, thereby producing consistent and compliant water quality, and now have a predictive tool to identify maintenance needs of key purification processes, i.e., processes that are consumed over time such as carbon bed and ion-exchange resin.

This article describes the drafting process and key points of ICH Q2(R2)(Analytical Validation) and ICH Q14(Analytical Development). The harmonization effort started in 2018 and the two documents are being drafted by one Expert Working Group. The drafts for public consultation will be published in early 2022. The revised Q2 will include spectroscopic procedures, procedures used for biologics, multivariate analysis based procedures, etc. The new Q14 will cover Enhanced (Quality by Design) development approach. Q14 emphasizes that the enhanced knowledge supports robust analytical procedures and their effective lifecycle management.

 As the technology recently advances in healthcare industries, combination product composed of drug and medical device will be expected to be increasingly launched.

 To ensure the effectiveness and safety of such combination products, risk management is important.

 However, integrated consideration on risks from both drug and medical device perspective is not necessarily simple because risks derived from interactions between drug and medical device or usage (“how to use”) need to be considered comprehensibly.

 This paper discussed the inherent differences between drug and medical device from the viewpoints of their properties, applicable regulations and product realization processes along quality management system. Based on the discussion, this paper has demonstrated how to conduct integrated risk management as combination products by taking pre-filled syringe product as an example.

 As a result, this paper concluded the importance to recognize the difference between drug and medical device in terms of inherent product properties, their development processes, approach for risk and risk management in product realization process.

 Also, this paper suggested the usefulness of hazard frameworks in ISO14971 to list drug-related hazards comprehensibly and the effectiveness to consider “usage” hazard for listing hazards of combination products.