Trends, challenges and priorities

Markets are growing and the range of new product types is expanding. To prepare for these exciting opportunities, drug product and secondary packaging processes will need to develop excellent operations and quality management systems (QMS) and develop new capabilities. New markets continue to emerge for existing medicines that will require lean supply chains and more in-region manufacturing. New product types will include non-mAbs, cell and gene therapies, and more complex devices. Also, patients and clinicians are understandably demanding more convenient modes of delivery, such as longer-lasting formats and better electronic patient information.

The industry will need to invest to realize the opportunities, adding pressure on current CAPEX and OPEX costs. Another challenge, more acute in the Covid-19 world, is the uncertainties of inbound supply where there are shortages of quality, vital, raw materials, such as vials and single use systems (SUS).

In a competitive multi-opportunity market, it is essential fill finish does not impede speed to supply clinical trials and speed to supply the market.  Industry’s relentless drive for quality is matched by the expectations from health authorities that continue to expect higher standards or quality, for example in demonstrating sterility assurance and product serialization. Of course, the industry must also contribute to environmental sustainability and reduce material waste generated by its operations and products.

Biophorum fill finish programme pack 2022

The costs of quality and compliance are high.  It is a complex and time-consuming task to minimise the risk of harm to patient, batch loss and challenges by inspectors.  Even the most experienced companies face challenges in designing processes and using equipment which will meet ever more stringent regulatory requirements.  Quality and demonstrating compliance will remain the priority of BioPhorum Fill Finish.  To address these challenges, drug product aseptic filling (‘fill’) and secondary packaging (‘finish’) operations are working relentlessly to continually improve the pharmaceutical quality system (PQS). BioPhorum Fill Finish has recently made progress in best practices in several key areas: sterile filtration quality risk management (SFQRM), environmental monitoring (EM), container closure integrity (CCI), visual inspection (VI) and isolator gloves management. The seminal work of the SFQRM consortium provides a risk-based approach to the sterilization of filters has been very well-received by industry and health agencies.

In these areas, major improvements with currently available technologies are also being evaluated and the barriers to adoption being cleared. For example, the Alternative and Rapid Micro Methods (ARMM) team is working to remove settle plates in grade A areas with direct-detection systems (i.e., bio-fluorescent particle counters (BFPCs) that can detect viable and non-viable particles in real-time). The Isolator of the Future team is developing best practices for automation that will reduce the need for human beings, which is the primary contamination risk. In 2022, the Phorum’s Visual Inspection team provided a user requirement specification for testing technologies and wrote a paper providing much needed clarity on misunderstandings about 100% testing.   

The Phorum members are also wanting to create space to support each other with the implementation of Annex 1, a key driver for changes to filling operations.

An essential element to successfully meet challenges is the need for a single industry voice. The Phorum will utilize BioPhorum’s collaboration with the ASTM and USP and continues to form partnerships to add value for members, which include: the SFQRM consortium with the Parenteral Drug Association (PDA); the ARMM team’s partnership with thought leaders in the PEMM group and OWBA; and discussions with EDQM’s Expert Group 1 EDQM; the EM team and the team revising the PDA’s TR13; and the Phorum’s Robotic team coordination with the ISPE–DACH’s Robotics Special Interest Group.  The Secondary Packaging team are also working with experts from GS1 on ePI (electronic patient information). The Lyophilization team in 2022 partnered with the University of Purdue’s Advanced Lyophilization Technology Hub to work on a paper on technology transfer best practices with case studies.

In 2022 a set of manufacturing scenarios were defined by our members, that are required to address the opportunities and challenges mentioned above. The emerging goals are shown in the figure below. In the final months of 2022, we are developing a plan to work collaboratively towards a future set of priorities. Including an ambitious workstream accelerate progress towards commercial lines of the future.

BioPhorum High Level Goals Fill Finish infographic

Demand for FF capacity exceeds supply, and there is demand for new more complex to make product types and flexible manufacturing.  FF capacity is expensive and takes time to build.  So, our work on commercial facilities of the future will accelerate availability of next generation filling and process control technology and make it simpler for members to make smart CapEx choices.  Here, BioPhorum FF is also leveraging supplier expertise in the Technology Roadmap and Supply Partner Phorums.

Many of the Phorum members depend greatly for fill finish capacity on contract manufacturing companies. While several contract manufacturers are valued members of the Phorum, we continue to encourage non-members to collaborate and keep pace with  views on best practices; in turn contract manufacturers could connect with their clients to eliminate variation in practices which add no value. Potential topics for collaboration include tech transfer and deviation management. 

The Phorum’s ethos is very much about declaring success only when best practices are implemented. All workstreams are chartered to both deliver best practices and provide stewardship and support for wide-scale implementation.   Perhaps the most important feature of the Phorums is that the work is done in positive atmosphere in which problems are discussed openly, advice shared generously.  Subject matter experts find-like minded scientists and engineers to work with and learn from.  Our professional facilitation is about creating this vibe of mutual trust and joy in developing robust solutions to tough problems together.

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Fill Finish deliverables November 2021 to November 2022

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Milestones

Alternative and Rapid Micro Methods (ARMM)

The ARMM program is working to support the use of three ready-to-implement and high-value applications, which are pivotal to achieving the ambitions for in-line monitoring/ real time release (ILM/RTR):

  • Bio-fluorescent particle counters (BFPCs) for routine direct-detection air monitoring
  • Rapid sterility testing systems
  • Automated colony counters

The validation strategies for the technologies have been discussed with key opinion leaders from the EMA, FDA, USP, EP and national inspectorates. In July and August respectively, best practices papers were submitted to the PDA journal describing best practices for the evaluation and validation or rapid sterility systems and automated colony counters. The methods in these papers have stood up to the scrutiny of several health authorities in post approval change submissions.

In August 2021, the BFPC team partnered with key opinion leaders accelerating progress on key empirical work and five seminal papers designed to remove barriers to BFPC adoption (a vital enabler for gloveless isolators).

Clean Room Automation Pathfinder

This is a pathfinder activity started in August 2021  to find collaborative opportunities for automation in the wider clean room environment, sample transport, co-bots, cleaning robots etc. The pathfinder will work with the TR automation pathfinder team to share learning and experiences where appropriate. This team and the Isolator of the Future team formerly know as the FF Robotics team.

Container Closure Integrity (CCI)

With more than 50 active SMEs from 25 member companies at 30 international sites, this team forms the most representative group of biopharma CCI practitioners globally. In 2021 the team provided a scientific approach to sampling and sample size selection , and provided to vendors an industry view of user requirements for optimized container closure integrity testing equipment.

An holistic approach to CCI overing product lifecycle is the primary work of the CCI team. This work will result in a guidance paper which will enable the industry to harmonize on a ‘quality built-in’ approach rather than a ‘testing into compliance’ paradigm for CCI. A thorough review process is in progress of this comprehensive paper, although the challenges of the pandemic has slowed paced, the planned publication is due in Q1 2022.

Following publication  the team will turn their attention to two supplemental papers: the first covering special considerations for devices, and the second paper will cover considerations when 100% CCI testing is justified.

Enabling In-Line Monitoring and Real-Time Release (RTR) in Fill Finish – a path forward

The workstream has served as a pathfinder group to define the route to RTR with the target to accelerate product release to one to two days. The team have completed initial work on the criteria to define the RTR roadmap:

  1. Identification of technologies that can enable ILM/ RTR in the fill finish manufacturing process
  2. Development of strategies
  3. Provision of guidance for a QMS that supports ILM/RTR.

The Fill Finish ILM/RTR FF team is part of the cross-phorum adoption of ILM/RTR program, which focuses on the operational requirements for the implementation of ILM/RTR in a GMP environment across all manufacturing operations. The recommendations of the FF ILM/RTR will discussed and actioned in November 2021 by the FF leadership team.

Harmonized Risk-based approach to routine Environmental Monitoring (EM)

The EM team have continued to drive home adoption of the best practice guidance on routine EM risk assessments. The majority of member companies have adopted this work as their own standard and feedback indicates fewer questions from inspectors.

An open webinar in September 2021 attracted 105 participants from around the globe. The BioPhorum risk assessment is recommended in the 2020 update to the PDA TR13.

In August 2021 started dialogue with the with USP about the potential of a link in USP<1116>. In January the team started work on defining best practices for EMPQ in new facilities and then existing facilities, due to complete in Q1 2022 and end of 2022 respectively.

Isolators and Commercial Lines of the Future

The focus of this teams is developing the practical application of technology to ensure that  outputs serve to further develop the route from restricted access barrier systems (RABS) to a gloveless isolator. The URS will be published in 2022 and the team will focus on collaborative work to facilitate the realization of technology in line with the URS.

In September, the Phorum leadership decided to start a pathfinder which will broaden the vision to commercial lines of the future. The objective is accelerated progress towards the next generation aseptic filling lines. A consortium project is envisioned, comprizing biomanufacturers, vendors, technology hubs, and Health Agency representatives. Phase one will start in 2022 to create a ‘theoretical designs rendered in computer simulations; then Phase two will deliver a physical prototype; and Phase three a full proof of concept. As with other BioPhorum proof of concept projects, a consortium approach will help to maximise value from capital expenditure, reduce investment and risk and foster innovative approaches.

Isolator good operating practices

Since publishing the glove management paper at the beginning of 2020  the team have been reviewing the adoption of the paper’s recommendations both internally within member companies as well as by the wider industry. A report of this adoption review will be available early 2022. ​

The new recommendations in the recent Annex 1 update are pertaining to isolator sterility. The team have discussed the impact of these new regulations and in particular the issues it highlights regarding the perceived fragility of vaporized hydrogen peroxide (VHP) as an effective method for decontamination. This remains a hot topic for the team and has been the subject of a number of case studies shared across the team.

Lyophilization community of practice: productively addressing today’s pain points

The Lyophilization Community of Practice continues to be productive forum for discussion and debate within the lyophilization community. In Nov 2020 the CoP delivered a paper on modelling of the primary drying phase and in May 2021 the team delivered a opinion piece advocating a better approach to aseptic process simulation for lyophilized products. In September 2021 their paper on standards for leak rates was submitted for pre-publication company legal review. And in October  the BioPhorum team were pleased to start a collaboration with the University of Purdue’s Advanced Lyophilization Technology Hub on a paper on technology transfer best practices with case studies.

Pre-filled syringes: launch of community of practice

Pre-filled syringes (PFS) are of growing interest to the industry and a community of practice was launched in March 2021. The subject matter experts are sharing the unique challenges of PFS manufacturing; for example, challenges experienced with silicone particles; control and measure of air bubble size; and plunger movement.

Process Validation (PV): launch of community of practice

A community of practice was started in Spring 2022 to share know-how on process validation. After collecting topics of interest, a call series has been set up which started at the end of August working through the schedule of discussion topics. Recorded case-studies are available on request to Phorum members covering for example, overview of PV readiness and execution for a new liquid product; application of QbD principles in process validation: learning from drug substance; statistics in process validation; and, sampling plan and acceptance criteria.

Secondary Packaging – delivering an ambitious program

The Secondary Packaging Workstream’s goal is to help member companies transition from large batch manufacture to small-batch, high-value packaging runs. The workstream has organized four sub-teams, each has delivered the first part of their mission in 2021. The Electronic Product Information (ePI) complete their work with key stakeholder organizations, including GS1 HealthCare, toward a commonly accepted ePI packaging operations implementation strategy that will help shape future regulations by providing the packaging perspective on broader ePI. 

The Line Clearance/Change Over sub-team completed their work best practices on the implementation of Rhythm Wheel, change over and the implementation of global OEE standards.

The team have a final draft of a tool to support a risk-based approach to line clearance.

The Serialization sub-team delivered points to consider document. This will broaden the industry knowledge of best practices and capabilities and highlight the risks of a lack of standardization. Topics included in the paper are operational (training, technical limitations, OEE and the decommissioning of serial numbers) and regulatory/strategic (primary pack serialization, print grading and non-standard requirements). 

The Vision Systems sub-team  developed a tool to help set limits on specifications for vision systems. The protocol covers the readability of single characters to establish a data background, showing how much of each character can be missing before it is not perceived as the correct character aimed at reducing labelling errors. 

By October 2021 the team had completed their work on a vision and five+ year strategy for secondary packaging. Currently in member consultation phase and due for publication in Q2 2022.

SFQRM Community of Practice (CoP): Supporting Adoption

On completing their primary mission in establishing a framework for a risk-based approach to pre-use post-sterilization filter integrity testing (PUPSIT), in 2021 the BioPhorum SFQRM team worked as a CoP to support and drive home adoption. The CoP addressed the following key topics:

  1. Case study sharing of completed risk assessments that have led to effective risk mitigations
  2. Case study sharing of interactions with inspectors
  3. Filter user questionnaire for the assessment of masking risk
  4. Single-use systems in regard to PUPSIT
  5. React to other projects and studies related to filtration and continue engagement with the regulatory agencies.

In August the team completed the 2021 The PUPSIT failure survey (updating the 2017 and 2019 survey). The initial conclusions from the data comparison was presented at the 2021 PDA Pharmaceutical Manufacturing and Quality Symposium in September and a publication is due to be published in Q1 2022.

Visual Inspection (VI)

Risk-based tool for classification and investigations

The VI team are near to completing their work on an update to this common methodology guidance on the risk classification of particles . Version two provides a tool and several cases studies on a risk-based approach to classifying visible particles and a tool to help with decision-making in particulate investigations. The much-anticipated update went through a comprehensive technical review in the Summary of 2021 and the paper is now  in pre-publication company legal review .

Test kits

The team has completed a survey and current practices around test kits. After further scoping work, the team have started writing a ‘good practice’ paper on the development, use, and maintenance of test kits for VI will help to add clarity to an essential topic.

Technology

Taking a closer look at how technology is applied for VI across the industry, and future trends and opportunities, was another major topic for the team in 2021. The link between VI and CCI (container closure integrity) is just one of the avenues to be explored, with a possible mindset shift from a ‘silo’ mentality towards a more holistic ‘inspection’ paradigm. A survey seeking to understand the trajectory of technology in the VI space was completed in March 2021.

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

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.

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A media fingerprinting toolbox that comes with a host of benefits

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Why 100% visual inspection does not mean 100% defect detection

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Bringing BioPhorum’s unique perspective to continuous manufacturing in biologics

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Supply Chain to Patient has launched!

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Electronic data exchange – the foundation for an efficient, resilient inbound supply chain

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How are you improving your environmental sustainability performance?

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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
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