On the precipice of an impending avalanche of regulatory compliance activity: Are you prepared?

On the precipice of an impending avalanche of regulatory compliance activity: Are you prepared?

BY Lynne Ensor, PhD, Head of Global Regulatory Compliance - 3.15.21 -

The COVID-19 pandemic brought into sharp focus the vulnerabilities in supply chains for medical products and the importance of ensuring their integrity to provide patient access to critical products. This historical event has also engendered an unprecedented pace in developing, testing, and producing COVID-19 tests, treatments, and vaccines – and triggered extraordinary flexibility among regulatory authorities. However, this flexibility could have unintended consequences for medical product manufacturing and testing facilities. Let’s explore five key developments.

1. Measures taken to mitigate viral spread at manufacturing facilities. Most companies took steps to mitigate the virus’s risk of spreading among their employees, directing many to work off-site, including those responsible for oversight of compliant manufacturing and quality management. While risk-based decisions were doubtless prudent, off-site support does not enable the same robust level of monitoring. Gaps likely occurred that might not be recognized until more normal operations are resumed with uninterrupted on-site oversight.

2. Inability to perform on-site regulatory inspections. The pandemic significantly impacted regulatory authorities’ ability to conduct on-site inspections, including the U.S. Food and Drug Administration (FDA). For example, the U.S. Government Accountability Office (GAO) recently reported that “the total number of FDA inspections of foreign and domestic establishments was 56% lower in fiscal year 2020 than during each of the previous two fiscal years.”1

The FDA is continuing to monitor the global situation and assess the feasibility of performing foreign and domestic surveillance inspections.1 In certain regions, the FDA has already resumed or is preparing to resume on-site inspections using staff at their local offices, such as in China and India. The agency also intends to resume domestic inspections beyond those deemed mission-critical, as geographic risk and safety guidelines allow. However, on-site inspections will probably not return to standard frequency for some time, leading to a significant backlog adding to the looming backlog caused by the pandemic. Risk-based indicators will likely be used to determine sites’ priority to receive on-site inspection as conditions improve.1

3. Virtual facility assessment and other tools. Some regulatory health authorities pivoted to alternative methods to perform facility assessment. For example, the FDA expanded its use of its authority granted under Section 704(a)(4) of the Food, Drug and Cosmetic Act to allow the request for records in lieu of or in advance of inspections. The virtual record review allows for the assessment of information related to a facility’s good manufacturing practice (GMP) compliance and quality management systems but typically are not equivalent to an on-site inspection.1

Some FDA requests using this method were considered to make drug application approval decisions2, and some companies performed virtual assessments of their vendors’ facilities. For example, Parexel recently performed over 80 virtual facility assessments for clients, including due diligence audits. The FDA noted that most of the record reviews performed by regulators during the pandemic have had positive outcomes.1 However, the agency issued its first warning letter based on a virtual facility record review in late January 2021.3 This could set a precedent for more regulatory enforcement using this authority as the pandemic continues.

4. Emergency Use Authorization (EUA). To allow for the fastest possible production and distribution of COVID-related products, some regulators are using EUA more broadly than ever before. The industry’s willingness to support critical COVID-related products in a timely manner under EUAs was desperately needed to combat the pandemic’s global impact. Many facilities associated with applications requesting EUA were granted GMP waivers, some stemming from lack of inspections due to travel restrictions. But as the pandemic abates, these facilities might well be candidates for an on-site inspection. Since most of the products granted EUA approval were developed at lightning speed, compliance challenges might emerge.

From a legal perspective, the Public Readiness and Emergency Preparedness Act Declaration for COVID-19 provides immunity from liability suits for companies with EUA approvals. However, these companies are still expected to maintain regulatory compliance for their manufacturing facilities, supply chains, and products or risk enforcement actions, which could include revoking their product authorization. Further, whistleblowers could emerge, exposing questionable activities during this period of stressed conditions.

5. Improved tracking of facility quality-management maturity (QMM). The FDA is currently developing programs to closely track the maturity of companies’ and manufacturing facilities’ quality management. These tools are intended to inform timely decision-making by regulators about facility records assessment versus a virtual or on-site inspection during application/license approval or facility assessment, based on data compiled from a variety of available sources. A QMM rating could be an important consideration in the future, both for regulatory decision-making and as a quality assessment measure used by biopharmaceutical companies or consumers.

 

The need for proactive compliance

As the saying goes, “You have only one opportunity to make a first impression.” Now more than ever, proactive compliance is well worth the investment. As their ability to monitor facilities and share information improves, regulators will have a basis for future decisions about on-site versus virtual inspection or facility record review assessment. Facilities that maintain high-quality standards and demonstrate a strong quality culture will likely be better positioned for virtual inspection or compliance assessment by facility record review. The others might have to invest significant resources to address areas of non-compliance that surface during an on-site inspection. Demonstrating a robust, mature quality-management system could be a gift that keeps on giving as regulators continue to depend on compliance history as the basis of decision-making.

 

When your production line is someone else’s lifeline, we’re here to help

Breaches in compliance can impact everyone in the supply chain, including patients waiting for the treatments they need. Our regulatory consulting group includes over 80 former regulators and inspectors alongside seasoned industry experts who help companies mitigate compliance risks, manage remediations and restore confidence. To find out more, visit parexel.com/compliance


References:

  1. www.gao.gov/reports/GAO-21-265 (COVID-19: Critical Vaccine Distribution, Supply Chain, Program Integrity, and Other Challenges Require Focused Federal Attention (gao.gov) .
  2. Miller, Elizabeth. 2020. ORA Updates. 2020 Parenteral Drug Association (PDA)/FDA Joint Regulatory Conference. Sept. 16, 2020.
  3. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/yuyao-yijia-daily-chemical-co-ltd-610487-01222021.

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