Annex 1

The update to Annex 1 is perhaps the biggest change to the manufacture of sterile medicinal products in recent times and possibly the most important topic for many in the biomanufacturing industry now.

BioPhorum workstreams are facilitating discussions among industry leaders about the challenges they face with Annex 1, along with those that are held to Annex 2 requirements.

The Annex will be updated to reflect current best practices and new technologies for the manufacture of sterile medicinal products. It also places a greater emphasis on the use of quality risk management (QRM) and encourages the use of QRM throughout the manufacturing process to ensure that potential risks are identified and mitigated.

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1992

Annex 1 is first issued by the European Medicines Agency (EMA) regarding the guidance of the manufacture of sterile medicinal products.
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2009

First major update of Annex 1
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2017

The EU Commission presents a new draft and BioPhorum starts work on comments
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2022

BioPhorum starts facilitating dedicated workstreams early in the year. The updated Annex is published in August.
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2023

New update comes into force and Annex 1 will increase in length significantly from 16 to 59 pages.
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2024

Loading of lyophilizers comes into force

BioPhorum Annex 1

Although the updated Annex 1 was published in August 2022, drafts were available to the industry prior to this.

BioPhorum has been working on several details in these drafts since the first updated draft publication in 2017.

Many BioPhorum workstream topics are relevant to Annex 1, and we have teams working on industry priorities that cover;

Sterile filtration, QRM and PUPSIT

BioPhorum and the Parenteral Drug Association (PDA) formed the Sterile Filtration Quality Risk Management (SFQRM) consortium in 2017. The consortium aimed to fill existing gaps in scientific data with studies and industry guidance that provide professionals and license holders with the ability to make informed decisions about appropriate risk management strategies. The BioPhorum Team are on working to determining best approaches to risk assessment and influencing regulatory expectations

Alternative and Rapid Micro Methods

The purpose of this workstream is removing internal and external barriers to implementation of ‘ready now’ systems by defining systematic best practices for evaluation (business case), validation and deployment of these systems: Rapid Sterility, fluorescent particle counters for air (and water) and automated colony counters.

Container Closure Integrity (CCI)

This workstream which started in 2014 provides open, transparent and collaborative discussion on technical and scientific exchange related to CCI methods, technologies and testing strategies between companies; share best practices and regulatory driven questions/demands. Seeking to lead industry towards a ‘quality built-in’ approach rather than a ‘testing into compliance’ paradigm for CCI through a comprehensive series of papers.

Visual Inspection

Missioned in 2015 After publication of a proof-of-concept level guidance on the risk classification of particles, the team has updated the methodology. Version 2 includes a tools for a risk-based approach to classifying visible particles and decision-making in particulate investigations

Annex 1 in Drug Substance facilities

Most biologic products are ultimately sterile products, and Annex 1 is about the manufacture of sterile medicinal products. However, it also states that the guidance pertaining to sterile manufacturing operations and products could also be applied to low bioburden manufacturing facilities.

To address this, BioPhorum has been running Annex 1 Applied in Drug Substance, a workstream dedicated to applying Annex 1 to the biological (low bioburden) drug substance manufacturing facilities which are governed by Annex 2 – manufacture of biological active substances and medicinal products for human use.

Annex 1
The workstream are working to provide additional clarity be provided as to the relevancy and applicability of Annex 1 to manufacturers that are held to Annex 2 requirements. Alignment on this topic is essential to ensure consistency across low bioburden manufacturers and provide all, including regulators, with a risk-based “road map”.

The workstream is planning a series of documents on how to apply the new Annex 1 guidance to DS facilities which will be available during 2023

Fill Finish Annex 1 workstream will addressing the practicalities of implementation of the updated Annex 1. This activity will give the opportunity to share know-how and experiences and benchmark on the day-to-day challenges of implementation.

To find out more and get involved please register your interest using the form below :

Annex 1 interest form

Sign up form for the Annex 1 specific E-Mail list.

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Phorums

Cell & Gene Therapy
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Development Group
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Drug Substance
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Fill Finish
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Information Technology
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Regulatory-CMC
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Supply Chain to Patient
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Supply Partner
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Sustainability
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Technology Strategy
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Cell & Gene Therapy

Maximizing the impact of the many advanced therapies under development requires that the industry comes together to improve understanding of how to develop, control and manufacture these life changing therapies.

We connect strategic thinkers in drug development and contract manufacturing organizations with the aim of ensuring harmonization and alignment around issues such as potency assays, phase-appropriate guidance for critical quality attributes, operator safety, regulatory guidelines, and C&GT-specific validation issues, as well as working toward resolving the current challenges to commercializing C&GT products. Discover more and learn about the outputs here.

Development Group

The ever-increasing need to reduce product development lead times and the opportunities to exploit innovative technologies in development are two key industry themes that remain at the forefront of our work. The Phorum successfully connects process development organizations and provides a space where subject matter experts can work on issues such as quality by design and process characterization, cell line technologies, and molecule selection. Read some of the outputs and discover how you could benefit by getting involved.

Drug Substance

Accelerating improvement, exploiting opportunities offered by innovation, and identifying best practice approaches across all aspects of the manufacturing process – these are the essential objectives

Data and digital capabilities are at the core of many of these industry challenges. Work in BioPhorum Drug Substance is informed by BioPhorum Technology Strategy, which has summarized our industry’s market drivers and trends. Capacity, flexibility, sustainability and pace all feature as requirements to succeed in a rapidly changing environment.

Find out more about what our members are currently discussing and learn about some of the successful implementations of our output.

Fill Finish

Quality and demonstrating compliance are two priorities of BioPhorum Fill Finish. Representatives of the world’s top sterile filling operations come together to develop solutions to some of the most intractable technical and regulatory challenges. To address these challenges in drug product aseptic filling (‘fill’) and secondary packaging (‘finish’) operations, our community of industry experts is working relentlessly to continually improve the pharmaceutical quality system (PQS). Together they continue to strive towards developing and implementing safe, predictable, lean, and agile processes in drug product operations. Find out more about the Phorum output here. 

Information Technology

IT and digital advances are crucial in responding to the pharmaceutical industry’s challenges around speed, cost, quality, flexibility, and sustainability. Unlocking and realizing the value in the industry’s IT opportunities is the core mission of the IT Phorum. 

The digital manufacturing facility of the future needs to consider technology advances alongside organizational perspectives while maintaining foundational security requirements. All elements must be considered in the long term to deliver systemic change toward the digital factory vision. Our members collaborate in a format that stimulates and supports industry innovation and implementation. 

Regulatory-CMC

BioPhorum Regulatory CMC is affording professionals the opportunity to shape their own collaboration program focused on challenges and opportunities across strategy, science, operations, submissions and compliance. Following a discovery program of work with Heads of Regulatory CMC, in which we identified some key topics of collaboration, we are giving you the opportunity to participate and help us to shape the final collaboration program. This will focus on, filing and review, interactions with Health Authorities, and harmonization. Our mission is not just to discuss, but to deliver applicable outputs and publications that will have an impact – learn more about how you can get involved.

Supply Chain to Patient

The pharmaceutical outbound supply chain was built on a blockbuster model and doesn’t fit the needs of the changing pipeline and new modalities currently being developed. The geopolitical challenges of recent years have shown that the outbound supply chain needs to evolve to become more agile, and resilient, and address a more expectant end-user bying on patient-centricity. Industry collaboration can accelerate improvements and transform performance in a way not possible when working independently. This Phorum is founded on the belief that learning from each other and challenging current thinking to re-imagine the supply chain can reduce costs and increase efficiency.

Supply Partner

BioPhorum SP members want the inbound supply chain for the biomanufacturing industry to be recognized as one of the best-understood and managed global supply chains. They intend to be not only a trusted advisory group but also the engine that drives change for the industry. Working together, we aim to achieve supply chain transformation that provides:

  • an enhanced robustness and resilience
  • accelerated capability and capacity to effect technology adoption
  • reduced cost of quality, and
  • industry-wide alignment on operational implementation

There’s an extensive list of Phorum successes and tangible benefits that have been delivered to define industry best practise.

Sustainability

The BioPhorum Sustainability program is jointly designed, governed, and delivered by a membership drawn from licence holders, contract manufacturers, major suppliers and niche suppliers. This dynamic partnership means that we can quickly focus on the areas that have the greatest industry impact, and we can leverage learning from each other and other sectors – the chemical industry and the built environment for example.

BioPhorum’s unique ability to build a strong coalition for change for an entire industry is now being applied to the greatest challenge of our generation. Driven by evident industry needs, Phorum members are working to develop agreed industry benchmarks, establish the ROI of sustainability investments and to increase the efficacy of implementation of members’ sustainability strategies.

Technology Strategy

With a mission to define strategies to accelerate technology transformation and support the adoption of innovative technologies, BioPhorum Technology Strategy evolved from BioPhorum Technology Roadmapping, strives to realize the technology roadmap vision 2.0.

This is being achieved through a multi-stakeholder team of member companies with collective capability and influence who are committed to driving forth industry goals associated with: Speed to market, Quality, Value, Agility and On-Demand Supply and Sustainability.

Building on industry feedback to standardize plasmid release specifications
Plasmids release specifications are critical to the manufacture of many cell and gene therapy (CGT) products, but current regulatory... read more

How to predict, optimize and analyze high-concentration biologic therapeutic formulations
Developing high-dose biologic drugs for subcutaneous injection often requires high-concentration formulations. It also needs to optimize... read more

A media fingerprinting toolbox that comes with a host of benefits
Cell culture media raw materials can contain many chemical substances, each with its own properties. While simple substances can be... read more

Why 100% visual inspection does not mean 100% defect detection
There is a common misunderstanding that 100% visual inspection (VI) of biopharmaceutical products should mean 100% detection of defects.... read more

How to bridge the data integration gap between sponsors and contract organizations
... read more

Bringing BioPhorum’s unique perspective to continuous manufacturing in biologics
Continuous manufacturing (CM) has been a goal for the pharmaceutical industry for several years. While small molecule drug substances and... read more

Supply Chain to Patient has launched!
Have your outbound supply chain costs increased? Do you want to leverage data and digital technologies more effectively to reduce... read more

Electronic data exchange – the foundation for an efficient, resilient inbound supply chain
The COVID-19 pandemic, geopolitical unrest, and military action across the world have fundamentally disrupted the assumption and practice... read more

How are you improving your environmental sustainability performance?
Climate change and global warming resulting from greenhouse gas emissions are widely recognized as the biggest threats to global health.... read more

Adding value for analytical instrument partners
Analytical instrument vendors have been integral to developing and publishing our technology roadmaps and developing product... read more

MediPhorum

Introducing MediPhorum
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Advanced Wound Care and Wound Management
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Drug Delivery
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Introducing MediPhorum

The medical technology (MedTech) industry is a critical and complex sector. As highlighted during the Covid-19 pandemic, the MedTech industry provides a wide array of products and technologies that are vital to the safe and effective provision of care to many. Also, as seen over recent years, there is often the requirement for flexibility in supply, rapid development, and the introduction of new products to keep pace with global public health demands.

Advanced Wound Care and Wound Management

Advanced wound care (AWC) is the medical treatment for wounds that have not healed properly using conventional wound care products such as gauze, bandages, plasters, and wadding.

AWC involves treating chronic or complex wounds using products that are not as easily obtained over the counter. AWC can be divided into three main categories: wound healing, infection prevention, and restoration.

Drug Delivery

Drug delivery products are therapeutic and diagnostic products combining drugs, devices, and/or biological products, which enable safer and more efficient treatment due to careful and precise drug targeting, local administration, and tailored treatment.

Introducing the new MediPhorum
MediPhorum by BioPhorum has been launched to bring together senior business leaders and subject matter experts across multiple MedTech... read more

Introducing the new MediPhorum
MediPhorum by BioPhorum has been launched to bring together senior business leaders and subject matter experts across multiple MedTech... read more

Introducing the new MediPhorum
MediPhorum by BioPhorum has been launched to bring together senior business leaders and subject matter experts across multiple MedTech... read more

Deliverables

Deliverables Report
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Industry Priorities
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Downloads
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Case Studies
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Webinars and Podcasts
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BioPhorum Deliverables Report
BioPhorum brings you the latest Deliverables Report, an informative and inspiring consolidation of the benchmarks, position papers, guidance documents, assessment tools, industry user requirements, study results, and roadmaps produced in the last twelve months.
Technology Strategy
Buffer stock blending system
Knowledge management
Technology adoption
Operations
Change notification
Closure playbook
Extractables and leachables
In-Line Monitoring and Real-Time Release
Raw materials
Regulatory Governance and External Partners
Single-use systems
Annex 1
Information Technology
Digital integration of sponsor and contract organizations
Digital plant maturity model
IT for cell and gene therapies
Lab of the future
BioPhorum Downloads
Access a variety of free tools and papers and other resources designed to provide you with up-to-date information and insights to help you make informed decisions and maximize your success. Access our resources today and start making improving and streamlining your business processes.
Case Studies
Welcome to the BioPhorum case studies page, where you can learn how our clients have used our service to discover innovative solutions and save money. Here you can read real-life stories of how various organizations have used our unique data-driven approach to streamline their processes and make the most of their resources. Whether you're looking for inspiration or want to learn more about the potential benefits of our service, you'll find it here.
Webinars and podcasts
Welcome to BioPhorum Connect, the podcast series that keeps you up to date with the latest news and trends in the biopharmaceutical industry. From experienced professionals to thought leaders, this podcast brings you the insights and perspectives of experts from around the world. We'll discuss all aspects of the biopharmaceutical industry, from digitization and knowledge management to raw materials, supply chain, sustainability and more. So, join us on our journey as we explore the world of biopharmaceuticals and learn from the perspectives of those at the forefront of the industry.