n today’s increasingly complex and intricate pharmaceutical landscape, industry and regulators alike frequently state the same core aim: to ensure that pharmaceutical products offer significant benefit to patients. This concept is captured via varied phrasing including reference to the voice of the patient, benefit/risk analysis, confidence in the next dose, and patient centricity, among many others. However, in all cases, fundamental benefit to patients is essential and is broken down into three pillars: efficacy, safety, and quality. Accordingly, in the pharmaceutical quality landscape, it is critical to develop common ground among regulators and industry when discussing patient centricity.

ICH defines quality as “The suitability of either a drug substance or drug product for its intended use.” During development, benefits of a medicine’s intended use are established through successful pivotal clinical studies that are designed to demonstrate safety and efficacy in a target patient population. Often, regional differences in clinical practice as well as dependences on race, ethnicity, weight, disease state, etc., may contribute to potential regional differences in a clinical dossier. While such clinical practice may differ by region, the intended use, target population, and proposed product remain unchanged, as should the appropriate quality requirements for that product. In an ideal global environment, this would hold true; however, in today’s pharmaceutical landscape, this ideal case is not fully realized and remains an area of opportunity in our service to patients worldwide.

Typically, if a product is manufactured to a single quality standard at a manufacturing site and then distributed globally, a single global quality dossier would be achievable. Unfortunately, realization of a single global quality dossier has proven elusive as regional or health authority interpretations of a proposed control strategy (reference to ICH Q8 and Q10) can result in many region-specific control strategy requirements. This presents a collective and broad challenge in the CMC space, which is then compounded by differing post-approval change requirements across the globe, and also, large and often very complex pharmaceutical portfolios.

Quality by Design (QbD) as described in ICH Q8, in combination with ICH Q9, Q10, and Q11, committed to improving confidence in quality through a product’s lifecycle and enabling global regulatory convergence for new marketing applications and post-approval variations. Collectively, the guidelines reference the control strategy as a fundamental concept in QbD implementation. In turn, this concept could be considered a significant shared opportunity for regulators and industry, as the holistic, total, or overall control strategy could easily be envisioned as a tangible link to the patient in the CMC space.

Unfortunately, industry has observed global regulatory divergence regarding the interpretation and implementation of ICH guidelines (including the acceptance of a proposed control strategy) across various geographic regions. Accordingly, strong and strategic leadership from industry and global regulators is needed to address differing control-strategy requirements and to adopt standards and assessment practices that more significantly focus on patient needs and expectations.

A specific case study includes patient-centered quality standards (PCQS). As described in a global dossier, PCQS would identify specific safety or efficacy risks to the patient from the proposed design and control of manufacturing process or product. Correspondingly, the content of a global dossier would then demonstrate an understanding of how the proposed “overall” control strategy controls and/or mitigates identified risks to the patient. However, in the current state, the variation of interpretations of control strategy often results in a “one size fits all” approach to quality requirements based upon historical and/or local norms, which challenges the concept of patient centricity. In addition, the “one size fits all” approach does not allow for the consideration of numerous factors present when developing and communicating a holistic/overall control strategy, including but not limited to the intended therapeutic use of the drug product, the breadth of the therapeutic index, its onset of action, the intended duration of treatment, and the efficacy and safety profile of the drug. Furthermore with experience, a manufacturer’s knowledge of the product will grow and allow for continued improvement in the holistic/overall control strategy, which can be factored in throughout the product’s lifecycle.

In the CMC landscape, it can be attractive to focus patient-centricity discussions on specific technical topics (e.g., specifications, post-approval variations). Certainly, there is no question as to the general link of CMC to serving patients and putting them first. There is also no question that specific technical topics can be linked to service to and supply for patients. More specifically though, debates often circulate regarding exactly how the link between CMC data/submissions and patient centricity can be realized. Given the broad perspectives needed to explore this debate, it is critical to develop common ground among regulators and industry when discussing patient centricity in the CMC space. Based on multiple ICH guidelines (e.g., Q8, Q10, and Q11), this common ground remains the overall control strategy, and it represents a significant opportunity in propelling patient centricity forward in the coming years.

While the importance of the specific technical conversations cannot be overstated, it remains critical to consider patient centricity as a much larger picture that incorporates numerous technical and strategic topics in the CMC space (e.g., advanced manufacturing, accelerated submissions/assessments). This larger picture of patient centricity remains critical to the future of one global dossier, and it incorporates a direct need for strategic, visionary, and bold leadership to drive truly transformative and collaborative efforts among industry and regulators. The exploration of these opportunities, using this larger frame of patient centricity and a focus on the holistic/overall control strategy, remains critical to our collective ability to effectively serve patients worldwide.