Risk-based asset management policies and practices for physical assets are valuable additions to operations within the pharmaceutical industry. These practices have strong parallels to commonly used quality risk management (QRM) concepts, and have specific benefits related to preventing drug shortages. Specifically, risk-based asset management programs are intended to control risks associated with product manufacturing, packaging, facilities/utilities infrastructure, and supply chain inventory management within controlled environments.
Quality Risk Management Background
The pharmaceutical industry has been focused on the benefits of risk-based strategies for the past decade, with large-scale guidance on the topic published under ICH Q9¹. Currently, there are multiple recognized international standards that incorporate these concepts such as ASTM E2500² and the ISPE Baseline Guide for Commissioning and Qualification³. The primary purpose of these standards is to provide requirements and guidance for balancing product quality, patient safety and financial cost. This focus has combined into the overarching concept of quality risk management (QRM) for the pharmaceutical industry.
The driving force for QRM is the need to alleviate the immense burden of validation, qualification and commissioning of systems associated with the development, manufacture and distribution of pharmaceutical products. Traditional methods of paper-based process and equipment validation efforts utilized prior to QRM required pharmaceutical companies to make large investments in time and labor for asset installations and modifications. While these costs are still significant for the industry, they have been reduced. Through QRM, processes that are critical to product quality and patient safety receive the most rigorous validation and care, while other non-critical systems may only require commissioning to ensure basic desired functionality.
While QRM has been a great advancement for maintaining product quality and alleviating some business burdens, it does not expand guidance to other critical aspects of the business such as production reliability and market delivery. To maintain a focus on patient safety but also ensure reliable delivery of products when they are needed, companies need to combine their current QRM policies with risk-based asset management principles. This combination provides the foundation for stabilizing production and supply chain operations, which allows for clear understanding of market delivery capabilities and early warning signs for drug shortages.
In October of 2013, FDA published a Strategic Plan for Preventing and Mitigating Drug Shortages in response to a new requirement within the Food and Drug Administration Safety and Innovation Act (FDASIA)⁴. Due to ongoing drug shortage events reported to FDA and the associated risk to patients, the Agency has been analyzing all facets of reliably delivering pharmaceutical products to the public.
Under the specific goals listed within the Strategic Plan, several tasks were identified to prevent and mitigate drug shortages. The following is an abbreviated list of those tasks that can benefit from risk-based asset management practices:
• Task 1.2: Improve Agency databases related to shortages and the tracking procedures FDA uses to manage shortages. Improved tracking will enable FDA to better assess progress on preventing and mitigating shortages.
• Task 1.3: Clarify roles/responsibilities of manufacturers by finalizing the proposed rule explaining when and how to notify FDA of a discontinuance or interruption in manufacturing, working with manufacturers on remediation efforts, and encouraging manufacturers to engage in best practices to avoid or mitigate shortages.
• Task 2.1: Identify ways FDA can implement positive incentives to promote and sustain manufacturing and product quality improvements.
• Task 2.2: Continue to develop risk-based approaches to identify early warning signals for manufacturing and quality problems to prevent supply disruptions.
The following figure is from the Strategic Plan:
The data indicates that 66% of disruptions are due to product-specific quality failures (31%) and issues with manufacturing processes or facilities (35%). Risk-based asset management practices can directly address these types of disruptions, and provide a better understanding of production demand concerns.
To further develop information regarding drug shortages, ISPE has developed a Drug Shortage Initiative Task Force to work closely with regulatory agencies and the pharmaceutical business community. The Task Force is comprised of industry representatives and they have been working on ways to better understand the root causes and possible mitigations for drug shortages⁵. One example of this work is the Drug Shortages Survey issued in February of 2013 to professionals within different sectors of the pharmaceutical industry to collect more specific data regarding contributing factors to drug shortages. The results of this survey have been published by ISPE, and respondents identified that manufacturing quality issues were among the most prevalent causes leading to drug shortages, which is consistent with the information published by FDA⁶.
Risk-based Asset Management
There are two primary recognized international standards regarding physical asset management: BSI PAS 557 and ISO 550008. The current version of BSI PAS 55 was published in 2008, and ISO 55000 is currently in the final approval stage with expected publication in early 2014. These two standards are providing much-needed structure to the practice of managing physical assets, which is often loosely organized by ad hoc procedures, manufacturer-recommended maintenance practices, and a reactive culture where risks are not proactively analyzed or mitigated.