Document Type

Theses, Ph.D

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

1.4 CHEMICAL SCIENCES, 3. MEDICAL AND HEALTH SCIENCES, Pharmacology and pharmacy

Publication Details

A thesis submitted to Technological University Dublin in fulfilment of the requirements for the award of Doctor of Philosophy (PhD), September 2021,

Abstract

Patients deserve their medicines on time every time. Regulators safeguard public health by ensuring availability of safe, effective, high-quality medicines. Pharmaceutical companies must continually improve and innovate to deliver such medicines. In spite of these patient-centric objectives, drug shortages have continued to grow as a global public health concern. The drug shortage problem has existed for decades though there has been no shortage of effort, recommendations, papers, and expectations to resolve it. During the ongoing COVID-19 pandemic even exceptional measures were rapidly implemented to prevent shortages, yet no long-term solutions have been found.

This research hypothesis was that due to the high global regulatory complexity of making post-approval changes (PACs), pharmaceutical companies are slow in implementing new knowledge to continually improve and innovate their products and processes – even when this reduces risk to patients or improves the state-of-control. This results in sub-optimal operations, and eventually drug shortages.

To date, most efforts and solutions to tackle drug shortages by the industry or regulatory authorities have been from their individual respective perspectives. This research concluded that no one stakeholder can solve this ‘wicked problem’, and that its resolution lies in practical standard solutions collaboratively developed and globally implemented across the pharmaceutical industry and its regulatory authorities.

This research explored how an enhanced science and risk basis which considers current product and process knowledge within the framework of an effective Pharmaceutical Quality System (PQS) – could provide a clear pathway to overcome the global regulatory complexity, accelerate continual improvement and innovation, and help reduce drug shortages. It proposed that any PAC which can be demonstrated to not increase risk to product quality or patient safety should be implemented immediately within the construct of an effective PQS, without requiring prior regulatory approval; such changes would still remain under regulatory oversight through routine inspections that assess effectiveness of a company’s PQS.

The research resulted in the development of standard practical solutions for the pharmaceutical sector - to enable regulatory flexibility, faster decision-making and implementation of PACs by allowing more changes to be managed in the PQS without requiring prior-approval. The research also defined what constitutes an effective PQS for PAC management, and how companies could demonstrate this during inspections, thereby shifting the regulatory oversight from review of individual PACs by assessors, to evaluation of the PQS effectiveness for PAC management by inspectors.

A portion of this research occurred during the COVID-19 pandemic. Given the pandemic is still ongoing, it did not assess implications or consequences of the “new normal” state that will emerge post-pandemic. However, the thesis touches on anticipatory considerations and poses relevant questions on how faster risk-based decision-making and collaborative models that emerged during the pandemic could and should continue as part of the “new normal”.

DOI

https://doi.org/10.21427/960f-8s69

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