In August, long-awaited drug manufacturing regulations took effect with the implementation of the European Commission’s updated “Manufacture of Sterile Medicinal Products.”
Known as the Annex 1 revision, the updated rules will impact manufacturers across the globe, says Marcia Baroni, VP, Enterprise GxP Compliance & Systems with Emergent. “Some significant change is going to be required for everyone,” says Baroni, who sits on the scientific advisory board of the Parenteral Drug Association (PDA), which provided comments throughout the Annex revising process.
The revision, which was a joint effort among teams from the European Union, Pharmaceutical Inspection Co-operation Scheme (PIC/S) and the World Health Organization, with involvement from the U.S. Food and Drug Administration, was an involved process that took seven years and broadened a 16-page document to 59 pages.
The current regulations are more prescriptive than in the past, says Baroni, and demand more responsibility and accountability from manufacturers. “With the Annex 1 revision, regulators are saying they want employees involved in pharmaceutical manufacturing to have both the experience and demonstrated capability,” she says. “It isn’t good enough to have just read the procedure and know what to do. You have to be able to show that you can do it.”
As biopharmaceutical organizations around the globe adjust to the new guidelines, Baroni shared insights on three things they need to know about Annex 1.
- Barrier technology is critical.
In the latest regulations, Restricted Access Barrier Systems (RABS) or isolators are repeatedly mentioned as beneficial in assuring required conditions and minimizing microbial contamination , says Baroni. “The standard—the expectation—is a RABS or isolator. And if you have anything that’s not a RABS or an isolator, then you need to justify why it’s okay for you to manufacture,” she says. “That is truly a significant change.” Baroni believes that this emphasis is meant to try and push the industry towards implementing new technology, which will provide greater sterility assurance.
- Organizations may need to update—and document—their contamination control strategy.
In a similar vein, Baroni says the new regulations focus more intently on contamination control strategy than previously. “The 2008 version referred to potential sources of contamination but did not specifically reference a contamination control strategy. In the 2022 version, contamination control strategy is mentioned over 50 times,” she says, adding that it includes detailed requirements of what a single contamination control document should have and how it should address manufacturing at the facility. “They’re really forcing the manufacturers to understand and defend their process end to end, in order to identify how a failure in one area could impact the overall system.” In doing so, she says, she hopes that this change will help resolve problems such as drug shortages.
- Training is more important than ever.
Education and training are key to competency and quality, and the new regulations make that clear. This is an area that has seen increased focus,, with multiple requirements around qualifications and training. “I’m a microbiologist by training and I keep saying that the Annex 1 was the biggest boost for the job market for microbiologists,” she says. “It speaks in so many parts about the need for microbiology and the need for qualified personnel, and it explains how it needs to be done.”
These additions are important, says Baroni, because they push the industry to understand their process and the impact and consequences those processes can have. “This is not like putting furniture together. It’s not like reading the instructions on a piece of paper,” she says. “You need competency. Every phase of manufacturing pharmaceutical products requires education, training and qualification.”
Guidance and support are available.
Adapting to the new guidelines could pose challenges to biopharmaceutical companies of all sizes, whether they’re updating their processes, facing timeline pressures, dealing with added costs, or all the above. Collaborating with an experienced Contract Development and Manufacturing Organization (CDMO) partner, such as Emergent, could prove to be invaluable, says Baroni, because these organizations understand an array of different processes from end-to-end, and can offer expert guidance as well as a long-term partnership.
Baroni believes that Annex 1 is raising the bar so that manufacturers everywhere are even more focused on quality and consistency through current good manufacturing practices. And that, she says, is a win for all involved.
“It’s a benefit to the industry. It’s a benefit to the regulators. And, bottom line, it’s a benefit to patients,” she says. “Because they’ll have greater assurance around the quality of products, and they’ll have greater assurance that the products they need will be available when they need it.”
To connect with an Annex 1-compliant manufacturing partner, visit Emergent Bioservices.