Regulators discuss concerns, sustainable GMP compliance at ISPE Europe

Officials from the US Food and Drug Administration (FDA) and prominent European regulators said that supply chain oversight, inadequate compendial methods to test for unsafe ingredients, aging facilities and poor quality management are some of their top global compliance concerns. Multinational companies were also criticized for “not operating in a global environment” and not sharing information across their networks.

These assertions were made by regulators during a 9 May panel discussion at the International Society for Pharmaceutical Engineering’s (ISPE) Europe Annual Conference in Amsterdam and virtual.

At the meeting, regulatory officials from the US, UK, EU and Spain were asked to address their top global concerns, discuss how manufacturers can achieve sustainable GMP compliance, and how they can bring innovative technologies to market. The moderator of the discussion was Mark Birse of Parexel, who used to work at the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

Panelists included Roberto Conocchia and Evdokia Korakianiti of the European Medicines Agency (EMA), James Pound of MHRA, Rick Friedman and Carmelo Rosa of FDA and Manuel Ibarra Lorente of the Spanish Agency of Medicines and Medical Devices (AEMPS).

Raw materials, test method adequacy, aging facilities

In response to a question on the regulators’ top concerns, Friedman, deputy director of FDA’s Office of Manufacturing Quality (OMQ) at the Center for Drug Evaluation and Research (CDER), said that raw material quality and safety, inadequate monographs to test for unsafe drug ingredients, and aging facilities are major problem areas.

He pointed to recent poisonings related to diethylene glycol (DEG) and ethylene glycol (EG) contamination in pharmaceutical ingredients as a major source of concern. This issue was also raised by FDA’s Francis Godwin, director of the OMQ at a recent meeting, and FDA issued immediately effective guidance on testing high-risk drug components for these contaminants. (RELATED: FDA official cites concerns with benzene and DEG contamination, Regulatory Focus 8 May 2023; Amid DEG/EG contamination concerns, FDA issues guidance on testing high-risk drug components, Regulatory Focus 10 May 2023)

“Vulnerable test methods” are another problem, he said. “There is a risk that substitutions can occur, like what happened with heparin, and we need to be thinking of what is the next risk on the horizon? What is the next material that can be vulnerable to such tragic poisoning and adulteration … This is an area that really needs special attention.”

There is also a need to update and modernize certain pharmacopeial monographs. He noted that “some compendia do not have good monographs for glycerin, propylene glycol and other at-risk excipients, so that is an area that needs improvement.”

Another issue of concern: insufficient quality systems at aging facilities. He said that such facilities are “unreliable with low capability and are not appropriate for new product demand.”

“The question is, will senior management keep an aging facility operating at the edge of failure or will they invest in more reliable facilities,” said Friedman. “Are you designed for quality are not? Design is one of the biggest parts of the quality system.”

Better communication needed at multinational firms

Regulators were also asked to address what role multinational companies can play to support global harmonization efforts for inspections.

Rosa, who directs the Division of Drug Quality I in FDA’s OMQ, said multinational companies are not always the best models of global harmonization because these companies “are not operating in a global environment.”

Rosa said “one of the things that we are seeing, and it is a little bit unfortunate, is that many global companies have multiple facilities around the world are not operating in a global environment. We are still seeing a lot of silos. Companies are implementing corrections at their own facilities and not necessarily sharing this information across their networks.”

He added that such firms need to strengthen their internal audit programs and share the results of audits across the network to learn from their quality mistakes.

“What is happening over the past four or five years is that the regulators are serving as a quality control unit for these companies. And it is challenging for us.”

Achieving sustainable GMP compliance

The panel was asked to describe how firms can ensure sustainable GMP compliance and what skills industry needs to achieve this level of compliance.

Friedman said that one way to achieve such compliance is for firms to automate their manufacturing processes, including the pharmaceutical labs.

Friedman said that when he goes into pharmaceutical labs, he still sees staff use manual pipetting, which he called “ridiculous.” He said that “everyone should be doing automated pipetting” as well as automate their sample preparations.” He added that “there are some labs that are fully automated and use digitized photos of the microbiology lab so that way you don’t question whether someone fudged the results for your petri dish.”

Encouraging new technologies

Panelists were asked to address how regulators can support a “safe space” for industry to develop new and novel technologies without the fear of regulatory delays.

Korakianiti, who heads EMA’s Quality and Safety of Medicines department, said the EU’s recently established Quality Innovations Group (QIG) is such a space in the EU and is designed to help translate new ideas into reality. (RELATED: EMA’s quality innovation group helps to propel regulatory path for novel technologies, Regulatory Focus 30 March 2023).

“It is very important to learn together, to have a space where we can hear the successes of what you’re trying to do as well as the failures and find a solution,” she said.

She added that continuous manufacturing was discussed at the first meeting in March. A second meeting on decentralized trials will be held later this year.

To ease the process of converting these innovations into applications, it is also important for industry to meet early with regulators on these technologies, asserted James Pound, the deputy director of standards and compliance at MHRA.

Pound added that a “sandboxing approach,” which is used in the UK to test new regulatory approaches in the financial sector, could also be leveraged in the pharmaceutical space.

Ibarra Lorente, head of the pharmaceutical inspections and enforcement for AEMPS, said that industry should also engage with academia on bringing new technologies to market.

ISPE meeting

Regulators discuss concerns, sustainable GMP compliance at ISPE Europe

Related topics

Recommended content

Welcome to the new RAPS Digital Experience