iSpeak Blog

New Trends & Requirements from Digitalization, Annex 1, Continuous Manufacturing & High Potent Manufacturing

Natalia Nikolaevna Vtyurina, PhD
Dany Shami
Richard Denk
Automation Pyramid. Courtesy SKAN

The pharmaceutical industry is rapidly evolving. The major trends in the recent years are (1) fully automated production such as continuous manufacturing and (2) the adoption of digitalized processes for paperless production. Both approaches have significant implications for Annex 1 compliance and the role of Contract Manufacturing Organizations (CMOs) in production facilitating these trends.

In this blog, we will briefly explore the challenges and opportunities of digitalized aseptic production, fully contained and automated production and collaborative work with CMOs. We will also address the ways in which these approaches can help to improve adherence to new Annex 1 and the overall quality and safety of pharmaceutical products.

During the 2023 ISPE Europe Annual Conference, you will have the opportunity to explore all these topics in details. This track will be divided into 4 main parts, which are then split into various segments:

1. Annex 1 - Supplementary guidelines to the EC-GMP Guide with specific requirements for the manufacture of sterile medicinal products

Annex 1 of the EU-GMP Guide provides detailed guidance for the manufacture of sterile medicinal products and contains specific requirements. The guidelines are intended to ensure the safety, quality, and efficacy of sterile products and cover all aspects of manufacturing, from facility design and environmental control to personnel training and validation.

One of the key changes in the latest revision of Annex 1 is a focus on Contamination Control Strategy (CCS) and Quality Risk Management (QRM). Manufacturers are required to identify potential risks in the manufacturing process and implement appropriate control measures to minimize the risk of contamination. The guidelines also emphasize the importance of process understanding, which requires manufacturers to have a thorough analysis of the factors that can impact product quality.

Annex 1 also places a greater emphasis on the use of isolators and restricted access barrier systems (RABS) which provide a physical barrier between the operator and the product that can help reduce the risk of contamination.

Environmental monitoring is another important aspect of Annex 1. Manufacturers are required to monitor the manufacturing environment for airborne and surface contamination. The document provides specific guidance on the sampling and testing procedures for environmental monitoring, as well as the limits for particular and microbial contamination.

This part of the track will include the following segments:

  • Annex 1 overview- What is new? Does retrofitting of existing production make sense or better invest in new equipment/ production?
  • CCS and QRM requirements for aseptic filling – a CDMO perspective
  • Digitalization in cleanrooms from a hardware and Annex 1 viewpoint.

Fully automated, gloveless, robotic aseptic filling
Courtesy PSM – CDMO - Germany

2. Annex 1 - Digitalized Aseptic Production

Digitalized aseptic production offers significant advantages over traditional aseptic manufacturing processes in the pharmaceutical industry and can have a positive effect on the entire manufacturing process. By using advanced digital technologies and automated processes, manufacturers can achieve greater accuracy and precision, which translates into higher quality products. Real-time monitoring and data collection allows for rapid identification and correction of quality issues, reducing the risk of contamination or other manufacturing errors.

2023 ISPE Europe Annual Conference

By implementing flexible and adaptable digital systems, manufacturers can more easily adjust production processes in response to changes in demand or new regulations, allowing them to remain competitive and compliant.

Overall, digitalized aseptic production is an innovative and promising approach that can have a positive impact on the entire pharmaceutical manufacturing process, from production and quality control to waste reduction and regulatory compliance.

This part of the track will include the following segments:

  • Pharma 4.0TM at the CDMO PSM: Digitalized aseptic GMP production with paperless production for 100% traceability
  • Risk-based human factor control strategy: How to combine in-depth analysis of human errors with high-end simulators – A case study with J&J
  • Landscape on digitalization for aseptic production

Automation Pyramid
Courtesy SKAN

3. Fully Contained and Automated Production

In the recent years, the pharmaceutical industry has seen a shift towards fully contained and automated production processes. This approach to manufacturing has the potential to improve safety and quality in the production of pharmaceuticals. By removing the need for manual handling and reducing the risk of contamination, pharmaceutical manufacturers can produce products that meet the highest standards of quality. This also results in significant cost savings and increased efficiency.

Automated systems offer a range of options for pharmaceutical companies. Examples include fully contained and automated production lines for small molecules, advanced automation for cell therapies and personalized medicine, and continuous manufacturing for high-potency drug manufacturing. These options are customizable and adaptable to the specific requirements of each company.

However, it is important to note that these systems require significant initial investment, both in terms of infrastructure and training. Careful planning and consideration are essential to ensure that the right system is chosen for each company and that the benefits of automation are fully realized.

This part of the track will include the following segments:

  • New ISPE containment good practice guide – GMP and occupational safety requirements working with high potent substances
  • High potent continuous manufacturing
  • OSD continuous manufacturing platform to technology. Current and future good practices from an owner’s & engineer’s perspective.

ISPE Good Practice Guide on Containment for Potent Compounds
ISPE Good Practice Guide on Containment for Potent Compounds

4. Annex 1 - Challenges and Contribution of CMOs

There are several challenges that can arise during a product transfer to a CMO. Some of these challenges include for example regulatory compliance, quality control and effective communication between the original manufacturer and the CMO.

Product transfer to a CMO is typically used to take advantage of cost savings, access specialized expertise or equipment, or increase manufacturing capacity. The transfer process is complex and involves several steps, including the selection of the appropriate CMO, the preparation and transfer of documentation, and the validation of the manufacturing process to ensure that the product is manufactured consistently and complies with regulatory requirements, such as those set by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

The final step of full-scale manufacturing is also critical, requiring compliance with cGMP, maintenance of quality systems, and the oversight of the process to ensure that the product is manufactured to the required standards.

As the pharmaceutical industry continues to evolve, the use of CMOs for product transfer is likely to become increasingly common, as companies seek to streamline their operations and increase their competitiveness in the marketplace. By partnering with a CMO, pharmaceutical companies can focus on their core competencies, such as research and development, marketing, and sales, while leaving the manufacturing and regulatory aspects to the CMO. This can allow pharmaceutical companies to bring their products to market faster and more efficiently.

This part of the track will include the following segments:

  • Pharma – a 40-year globalization journey
  • Is re-shoring of APIs and finished dosage forms to Europe still possible?
  • CMO as a platform for geographic flexibility

It’s exciting to see the industry's progress and to bring together experts to share knowledge and insights on these important topics. By fostering collaboration and knowledge-sharing, we can continue to drive innovation and improvement in the pharmaceutical industry.

As emerging leaders (Dany Shami and Natalia Vtyurina) at ISPE we are very excited to be able to support Richard Denk and Amjad Wahbeh with Track 2 – Annex 1. We are especially looking forward to spending the 3 days during the conference in the beautiful city of Amsterdam. Our goal is to gain new knowledge and connect with different leaders from various companies across Europe.

We are confident that the conference will be a great success and hope that you will join us for this exciting event. We look forward to welcoming you to the conference!

Learn More & Register