Annex 1 Changes go into effect in August 2023, are you prepared?
EudraLex - Volume 4 - Good Manufacturing Practice (GMP) guidelines, Annex 1 provides guidance on the minimum controls that are required to protect sterile medicinal products and certain low bioburden products during manufacturing to minimize the risk of microbial, particulate and pyrogen contamination in the final product.
Annex 1 - Implications
- Expectation that the manufacturing process and associated activities, equipment and facilities are managed proactively using quality risk management -QRM- principles to identify potential risks to quality, based on scientific knowledge and data.
- Requires documentation, including the Contamination Control Strategy (CCS), regarding why practices employed are adequate for guaranteeing product, and therefore patient safety.
- Evaluate an acceptable level of residual risk and it is expected that this evaluation is always kept current through ongoing review and re-assessment of process risk.
IPS has anticipated these changes and is actively involved in developing compliant solutions.
Reaching Annex 1 Compliance Starts Here.
IPS doesn’t simply find gaps in compliance; we work alongside our clients every step of the way to provide comprehensive solutions.
Our expertise is relied upon to move the industry forward and our experts have been involved in every step in the process of updating guideline since the opening of the revision period. Actively leading industry reviews of the pending revisions gave IPS the insight to assess our clients’ facilities and prospective designs with an eye toward the future.
All manufacturers that sell product to the European Union must be compliant by August of 2023. Many companies have already started the journey to compliance, but if you haven’t, it’s not too late. Get in touch with the experts that helped to develop the guidance.
Meet our Annex 1 Experts
No Room for Contamination: How thorough is your Contamination Control Strategy (CCS)?
The focus of Annex 1 is heavily weighted on contamination control strategies, with a focus on provable processes that minimize the risk to patients. Each facility – and all the controls and processes put in place – is accountable for ensuring the product is not compromised. A thorough strategy should not only be in place, but it should also be verifiable, testable, and provable.
To meet contamination control goals, many solutions are a matter of human behavior – improving procedures to mitigate risk effectively. Others might require investment in new manufacturing technologies, with the knowledge that changes to a manufacturing line will require re-validation and product testing procedures to prove there is no contamination in the interim.
PUPSIT
One manufacturing technology involves PUPSIT or pre-use, post-sterilization integrity testing. When putting drug products into a vial or syringe, you have two options: heating or filtering. Most drug products denature at sterilizing temperatures, so filtering becomes required. This filtering is an expected practice.
Currently, testing the filter before use in the US is not standard practice. Under the PUPSIT norms of Annex 1, however, the integrity of the filter must be verified before and after the filtration process. A manufacturing line that has yet to put PUPSIT in place before August 2023 is at risk, particularly if the manufacturers cannot demonstrate they have a plan to mitigate potential contamination while the desired changes to the manufacturing line occur.
IPS’ Expertise on Annex 1 has been Published Worldwide.
Three Steps All Companies Should Take to Reach Annex 1 Compliance
The clock is ticking.
In August 2023, the EU GMP Annex 1 Revision will take effect. Facilities that do not comply with the new standards risk shutting down their manufacturing lines or losing market share in the EU. Their inability to take basic steps now will guarantee the immobility of the process lines very soon.
To comply with Annex 1, organizations should immediately perform these three tasks.
Annex 1 - The Brave New World of Regulatory Compliance
After six years in draft form and through various consultations with Industry, the revision to Annex 1 was finally released in August 2022 and will become effective in August 2023. It is the greatest single change to the regulatory approach in decades.
Those following the journey of the draft Annex 1 through to fruition have already identified and largely anticipated the changes to the previous Annex 1. Indeed for many pharmaceutical manufacturers, Annex 1 now aligns closely with the technologies and processes they have already built into their manufacturing facilities over the last few years.
Changes Are Coming: Annex 1 Manufacturing of Sterile Products and Staying Ahead of the Curve
INTERPHEX Live presents Aaron Weinstein and Russ Somma. In recent years, the EU has been planning to update Annex 1 and, based on the drafts that have circulated, their intent is to create regulations and guidance that provide more detail.
Annex 1 - How We've Helped Our Clients
After six years in review, the final emergence of Annex 1 in August 2022 has either been a consolidation of accepted practice and wisdom, or a rude awakening for many! However, it is universally accepted that it is the greatest single change to the regulatory approach in decades. As Annex 1 deals with products made in Europe, or products intended for Europe, it is likely to have a significant international reach.
Annex 1 - How the Changes to Regulatory Compliance Could Affect your Facility
In an interview with Pharmaceutical Technology, Aaron Weinstein, Director of Validation at IPS-Integrated Project Services, guides you through the new requirements, revisions, and any challenges manufacturers may face in implementing this new guidance.
In this video, you’ll learn:
- New expectations for contamination control.
- Updated requirements for environmental monitoring.
- What has expanded in the sterilization section.
- Updated requirements for barrier systems.
- Overall, what has been most impacted by changes.
Aaron Weinstein discusses some of the expectations of EU regulatory bodies.
Get the IPS Advantage
We are Leading the Way
The IPS team of technologists, scientists, architects, engineers, and compliance experts have been consistently engaged with industry committees on consolidating industry comments for Annex 1 revisions. Every project we have worked on in the past few years has had the Annex 1 revisions in mind. We have helped our clients become compliant – even before the final version was released. Intelligently anticipating the future regulatory expectations are important when our facilities have such a long life span, and still remains integral to our thinking.
Easy-to-Use Gap Analysis Tool
Our team of experts developed a unique Annex 1 Gap Analysis Tool that assists in systematically analyzing all aspects of a facility, including operational processes, against the new requirements. This tool is structured to provide a single source of knowledge related to the facility’s state of readiness.
End-to-End Support
Once the gaps have been identified using this tool, our team works alongside you throughout the entire process of meeting compliance. This could include utilizing IPS resources to provide assistance with sourcing and procurement of new equipment. Our goal is to serve as a trusted advisor from start to finish.
We’ve Been in Your Shoes
IPS brings a unique blend of operational expertise, regulatory understanding, and technical knowledge to provide real support in not just identifying gaps, but closing them. Many of our team members have worked in and managed manufacturing facilities across the world. We understand the challenges you face from first-hand experience, allowing us to add value on day 1.
Let's Talk!
Contact us to talk to an Annex 1 Expert.
