On October 26, 2020, a business plan was endorsed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) that eventually resulted in a holistic revision to ICH Q9, “Quality Risk Management,” the “R1” of the framework. The four areas of concern were identified as:

    1. High levels of subjectivity in risk assessments and QRM outputs, leading to a lack of good science;
    2. Challenges in the management of product availability risks, resulting in continued shortages of important medicines for patients;
    3. A lack of understanding of what constitutes formality in QRM and how to apply varying degrees of formality in QRM activities so that better use of resources can be made; and
    4. A lack of clarity on what constitutes good risk-based decision-making.

 

As ICH Q9(R1) developed, other guidances evolved in parallel. However, in practice, many firms fail to treat risk maturity as an iterative process. A self-reflective question for any firm is “how are we applying the impact and learnings of ICH Q9(R1) into our assessments of other regulatory developments?” A previous Lachman blog (Update! 49th International GMP Conference) highlights how Lachman has presented the integration of Q9 and Q10 concepts to address ICH objective #2, complementing the call to action stated in the ICH Q9 business case.

The ICH Q9 revision came on the heels of the formalization of many Data Integrity (DI) guidelines issued by regulatory agencies such as the FDA (2018), MHRA (2018), and PIC/S (2021), just to name a few. Thematically, these DI guidelines are based on the ICH Q9 principles that encourage critical thinking based on an analysis of data criticality. This underscores the need to understand the interdependence of these guidelines now as well as when new regulations and guidelines are published.

The European Commission’s Annex 1, “Manufacture of Sterile Medicinal Products,” came into effect in August 2023. From a process standpoint, it has strong alignment with ICH Q10, “Pharmaceutical Quality System,” and ICH Q9. It states, “[t]he new guideline [Annex 1] should clarify how manufacturers can take advantage of new possibilities deriving from the application of an enhanced process understanding by using innovative tools as described in the ICH Q9 and Q10 guidelines.” In order to achieve this, a next level of integration should be performed to understand the impact of Q9, Q10, AND Annex 1.

Annex 1 states as a principle that “[t]he manufacture of sterile products is subject to special requirements in order to minimize risks of microbial, particulate, and endotoxin/pyrogen contamination.” In considering this statement and the DI guidelines mentioned above, industry needs to review the data to support control of contaminants. In doing so, companies may develop a blind spot if they focus only on Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs). Ignoring key areas, such as viable and non-viable data, WFI data, HEPA filter certifications, visual inspections, and other key facility services, can have substantial impact to a firm’s ability to demonstrate that its contamination and control strategy is effective in design and monitoring.

To integrate these guidelines effectively, Lachman has been providing expert and independent reviews by cross-functional subject matter experts to discover any blind spots. Our experts, combined with novel technologies, such as artificial intelligence, can accelerate a company’s Annex 1 compliance. Additionally, appropriate contamination control can only be ensured with high-integrity data. Reach out to Lachman today at LCS@LachmanConsultants.com if you are data curious and need to test whether your Contamination Control Strategy (CCS) has blind spots.