Drug development programs are no exception to the rising importance of quality for pharmacos. Increasing demands by regulators and business partners have made it imperative for quality functions to have scientifically sound processes for review and assurance, rather than solely fulfilling the requirements set out in regulatory guidelines. Regulators have increased enforcement of compliance, especially for vendors and other third parties and for trials conducted outside the European Union and U.S. used for EMA or FDA registration. Indeed, the number of warning letters relating to GCP and GLP has more than doubled in the past five years. At the same time demand is increasing for an evidence-based approach to development activities. This means pharmacos must focus on establishing and verifying a clear, measureable, and objective quality standard and account for the risk-benefit tradeoffs of a particular product or treatment.
Moreover, as margin pressure forces pharmacos to demand greater effectiveness and efficiency (such as by outsourcing clinical trials), there is a greater need for stronger quality oversight. The complexity increases given the ample spectrum of regulations that Quality organizations have to oversee during the drug development process. These regulations range from GLP of some discovery areas and pre-clinical trials to the GCP, GMP, GVP and GDP of the clinical and post-clinical phases. As the FDA has stated, “improving the science of drug development is challenging and requires collaboration”
from each of the diverse stakeholders involved.
A robust approach to quality in development programs is also required to proactively address and minimize vulnerabilities (such as those relating to clinical sites’ compliance and protocol integrity) that could lead to unexpected delays or regulatory interventions.
Pharmacos seeking to improve quality in development programs will find there is no “quick fix.” First and foremost, they will need to raise the organization’s awareness of quality’s importance in development and its potential impact on the successful commercialization and launch of products. They should ensure that the development function regards quality as a core capability and that the quality function proactively addresses issues and aligns its strategy with the development strategy.
Beyond raising awareness of quality’s importance, pharmacos need to strengthen four pillars to build lasting excellence for quality in development: organizational structure; process ownership and improvement responsibilities; skills, capabilities and tools; and quality metrics.
Achieving excellence in four pillars: What are the challenges/opportunities?
We have observed a common set of challenges and opportunities for each of the four pillars of quality in development:
1. Organizational structure. Pharmacos need to address the challenge of optimizing the quality organization’s structure given the varied activities that comprise the development value chain. Activities and oversight are fragmented not only among different parts of the R&D value chain (for example, pre-clinical, clinical and technical development), but also within the same step of the value chain (such as activities related to clinical trials from phase I to phase IV). Quality often has limited oversight of critical areas, such as the commercial function (including registries and education material) and vendors. Further complicating oversight, the quality function’s support services are typically fragmented across different units, such as regulatory QA and quality systems and training. Quality performance is also undermined by the absence of adequate interfaces between the quality function and various parts of the development value chain, including pre-clinical and clinical
development, pharmacovigilance (PV), technical development and national affiliates.
2. Process ownership and improvement responsibilities. In many cases, it is unclear whether the development function or the quality function is responsible for ensuring that a process is implemented and appropriately simplified. This can lead to the existence of several independent quality systems, each with its own set of standard operating procedures (SOPs) that are not well harmonized (for example, clinical SOPs, preclinical SOPs, and technical development SOPs). Multiple SOPs, each
entailing a number of process steps and roles, increase the complexity of quality assurance and often are not adequately supported by IT systems that facilitate access, use and efficient updating. The existence of multiple quality systems also means that quality support may not be scalable at the right stages of the development process, such as clinical, PV or business development and licensing.
3. Skills, capabilities and tools. Many quality functions lack the skills, capabilities and tools to engage effectively and efficiently with the development side and influence its decisions. For example, the interaction style of personnel in the quality function is often not well aligned with development personnel’s expectations (see Exhibit 1). Development personnel perceive quality personnel as acting like policemen or auditors and having a manufacturing mindset focused on GMPs, whereas they are
looking for solutions-oriented business partners with a clinical mindset focused on GCPs. Among all development personnel, pharmacos need to raise the appreciation of and adherence to evidence-based decision making.