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Siegfried Schmitt, PhD, is principal consultant withÂ PAREXEL, Siegfried.Schmitt@parexel.com.
Siegfried Schmitt, vice president, Technical at Parexel, offers insight into FDA’s guidance on performing operations during COVID-19.
Q. We are a manufacturer of prescription pharmaceuticals, and we experienced many disruptions to our operations because of the COVID-19 restrictions. This made it difficult to fully comply with current good manufacturing practices (CGMPs). Is there a regulatory agency expectation by when we need to be back in compliance?
A. During the current pandemic, manufacturers have encountered difficulties in continuing operations while staying in compliance with regulations. Although there is a lot of talk about the “new normal”, when it comes to CGMP, there is no such thing, because the regulations have not changed, nor were they suspended. So, the question is not when you need to be back in compliance, but when you can resume normal operations in compliance.
In September 2020, FDA published the Guidance for Industry, Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency (1), in which FDA acknowledges that deviations from established CGMP activities have likely happened and provides guidance on how to address these issues. FDA writes, “This guidance describes how to evaluate and prioritize the remediation of CGMP activities that were necessarily delayed, reduced, or otherwise modified during the public health emergency in order to maintain production and the drug supply” (1).
A risk-based approach to remediating is necessary, as resources are strained, be it for employee illness and absenteeism, travel restrictions, site closures, social distancing measures, or supply chain disruptions (including services). Despite these difficulties, FDA reminds industry of their obligation to provide necessary medicines to patients and to maintain compliance with the regulations (i.e., to prevent disruptions to the supply chain, especially of medically necessary products) (2), or the release of products that would be considered adulterated. FDA emphasizes that, “CGMP requirements remain in effect during the COVID-19 public health emergency” (1).
With the COVID-19 pandemic, the supply of any type of drug, not just medically necessary drug products, is at risk. FDA therefore requests that, “A drug manufacturer whose manufacturing operations have been disrupted by the COVID-19 public health emergency should follow an established plan, which includes returning to normal CGMP operations, with consideration given to when there is a reasonable expectation that normal operations will be maintainable for an extended period of time” [emphasis added by author] (1). In other words, companies must have a plan (e.g., based on a business continuity plan) on how to get back to normal operations on a continuous basis.
Before companies reach that situation, they may have departed from established CGMP activities. FDA requests that in these circumstances drug manufacturers perform the following (1):
FDA explains that, “Where critical CGMP activities were delayed, interrupted, or reduced in frequency, the batch should be quarantined and the decision to approve the batch delayed until remediation activities ensuring drug quality are completed. Such activities include, for example, critical quality attribute testing, investigations of critical deviations, and evaluation of unapproved changes to critical operations or materials. Drugs not manufactured in a manner that ensures their quality must not be distributed” (1).
The guidance document includes examples of areas where remediation may be needed. This section reminds drug manufacturers to be extra vigilant with regards to the supply chain (e.g., look out for economically motivated adulteration or changes to established logistics or transportation systems).
FDA points out in the guidance that a resumption plan, preferably in conjunction with an emergency plan, requires management leadership for successful execution and that such a plan should be based on a risk management approach. The concern must be the patient (i.e., the assurance of supply of drugs of the right quality). To come back to your question, this guidance document provides a wealth of information for manufacturers like yourself and you are well-advised to study it carefully.
1. FDA, Guidance for Industry, Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency (September 2020).
2. FDA,Guidance for Industry, Planning for the Effects of High Absenteeism to Ensure Availability of Medically Necessary Drug Products (March 2011).
Siegfried Schmitt is vice president, Technical at Parexel.
Volume 33, Number 11
Pages: 58, 57
When referring to this article, please cite it as S. Schmitt, "Resuming Operations During a Pandemic," BioPharm International 33 (11) 2020.