NEWS

The four steps for registering innovative and complex raw materials

1 February 2022
Drug Substance
BioPhorum

The Covid-19 pandemic has put extra strain on an already stretched biopharmaceutical supply chain. As industry has grown exponentially over the last couple of years, there has been an increased demand for materials and many existing products share these with the new Covid-19 vaccines, testing kits and therapies. As a result, these materials have been diverted to this high-priority use. 

The pandemic has therefore demonstrated that reliance on sole sources of supplies is not a commercially valid strategy.

When a raw material has a compendial status, changing to a second source of supply does not lead to a regulatory change – the material from the second source will comply with the same registered specification.

However, when a raw material is not compendial, defined and registered through its name, supplier, and part number, the registered details change – leading to a post-approval regulatory notification and review before implementation. Depending on the regulatory authority, the review period and implementation can vary from 6–14 months and more (for a major change).

This situation has led to the publication of the BioPhorum approach to the registration of innovative raw materials using quality by design principles, which contains a best practice approach to registering innovative and complex raw materials. This allows future changes to be notified as minor and can be documented in the license holder’s pharmaceutical quality system or notified to the agency in the product annual report for immediate implementation (with no review required).

The approach provides license holders with a pragmatic, simple and regulatory-acceptable solution to mitigate the regulatory challenges associated with a second source of supply for non-compendial materials.

Quality by design

The BioPhorum approach is based on ‘quality by design’ (QbD) principles and consists of four steps:

  1. Defining the target material profile
  1. Describing the material attributes
  1. Reviewing the product summary control strategy
  1. Identifying the critical material attributes (CMAs).

The proposal allows the systematic identification of CMAs, defined as those impacting product quality and process performance. These CMAs are then used to register the raw materials as part of the product control strategy.

It then allows flexibility of supply – if the same CMAs are met for the two materials (current and second source), the change is considered minor as it will have no impact on product quality.

It is important to note that the BioPhorum approach only allows regulatory relief, not relief from the qualifying work required to assess that the change has no impact on product quality. The scientific approach to reach that conclusion is unchanged – it is just notified to the regulatory agencies differently.

The proposal is aligned with the QbD principles defined in ICH Q8, Q9, and Q10. It is also aligned with Q12 Technical and regulatory considerations for pharmaceutical product lifecycle management as CMAs are likely to be defined as Established Conditions.

The approach can be applied to different families of non-compendial raw materials used when manufacturing biologics – such as ancillary raw materials, CGT starting materials, and excipients – making it very powerful for the industry. BioPhorum member organizations have already used it.

In this first version of the approach, a virus-retentive filter used to manufacture monoclonal antibodies is shown as an example.

This paper is intended to be the start of a transformational change in the registration of raw materials for the biologics industry. Implementing the recommendations will bring a different approach to registering product control strategies – through well-defined critical attributes of the raw materials.

The approach has many benefits for the biomanufacturing industry. These include increased flexibility of supply, enhanced quality of regulatory submissions, and potentially improved product and process robustness through the definition and control of the CMAs.

There are also benefits for the agencies when reviewing and approving manufacturing authorizations. These include fewer notifications/supplements if the post-approval change can be documented in the biomanufacturer’s pharmaceutical quality system or the product annual report.

Ultimately, a continuity of the supply chain will mean patients have better access to medicines that, in the case of biologics, are often a matter of life and death.

Arrow On Colourful Background
NEWS
Do you want to influence the future of long-range planning?
Raw Material Logo On Colourful Background
NEWS
Why BioPhorum’s trace element approach will save you time, money and wasted batches
Digital Lines On Blue Bckground
NEWS
A media fingerprinting toolbox that comes with a host of benefits
BioPhorum Raw Material Logo
NEWS
BioPhorum’s strategic framework shines a light on raw material management
Microscopic Bacteria
NEWS
Collaborating with USP on its Bacterial Endotoxin Test Protocol and Bioreactivity Draft Monographs

Advanced Therapy Medicinal Products

Advanced Therapy Medicinal Products support the quest for better and faster development of cell, gene and RNA therapies​ through connecting therapy developers, contract manufacturing, and testing organizations to gain an understanding and respond to the challenges faced by the advanced therapeutics industry.

Development Group

Development Group accelerates and improves the development process of biopharmaceutical medicines for the benefit of the patient. Replacing isolation with collaboration by providing a “safe” space where subject matter experts can work on sharing solutions and best practice on emerging industry trends, implementation of new technologies and common issues whilst ensuring their intellectual property and confidentiality is protected.

Drug Substance

Drug Substance advances excellence in drug substance manufacturing and testing, acting as an industry voice to accelerate technology adoption, implement post-approval change more rapidly and increase confidence in maintaining compliance.

Fill Finish

Fill Finish accelerates development and acceptance of sustainable world-class filling and packaging operations for drug product which meets the future needs of patients. Through innovative solutions resulting from the sharing of expertise, we can overcome common performance challenges and deliver on quality and regulatory compliance.

Information Technology

Information Technology accelerates digital maturity across the ​global pharmaceutical manufacturing industry.

Quality

BioPhorum Quality provides a dedicated, safe space for quality professionals from biomanufacturers and contract organizations to coalesce and enhance effective collaboration to address shared industry challenges.

Regulatory-CMC

Regulatory CMC brings leaders together who have a common goal – to improve access to medicines through innovation in the Regulatory ecosystem. It provides a dedicated space for strategic leadership and a coordinated industry voice, to move from divergence to convergence.

Supply Chain to Patient

Supply Chain to Patient transforms the performance of global pharmaceutical clinical and commercial outbound supply chains through industry collaboration by creating transparent patient-centric, resilient and agile E2E supply chains, that consistently deliver high-quality medicines ensuring an uninterrupted supply to patients.

Supply Partner

Supply Partner is a trusted advisory group and collaboration that is the engine for driving change across the global industry for all things relevant to the inbound supply chain. Addressing the challenges of complexity, resilience, cost, sustainability, and innovation.

Sustainability

Sustainability enables the industry’s transition to a low carbon, circular future – supporting members to improve patient health while respecting the planet. We activate multi-disciplinary teams drawn from our network to deliver environmental sustainability improvements across the value chain.

Technology Strategy

Technology Strategy acts as one voice of the industry to define strategy, accelerate technology transformation and support technology translation and adoption. With a purpose of enabling the future state of flexible, resilient, sustainable end-to-end biomanufacturing.

DOWNLOAD
An industry perspective on understanding AAV capsid content variants
Needle On Yellow Background
EXTERNAL-RESOURCE
An intercompany perspective on practical experiences of predicting, optimizing and analyzing high concentration biologic therapeutic formulations
DOWNLOAD
The Drug Substance 2.0 Strategic Value Framework
Coloured dots on teal, next to vial
DOWNLOAD
BioPhorum’s holistic approach to container closure integrity
Magnifying glass over a tablet all coloured blue
DOWNLOAD
Digital Plant Maturity Model 3.0
NEWS
Inaugural BioPhorum Quality face to face – get involved
PODCAST
The next step in building regulatory as a capability to enable strategic innovation across the BioPhorum community
PODCAST
Delivering a Cell and Gene Therapy Outbound Supply Chain Pathway for the Industry
DNA and Earth on blue background
DOWNLOAD
A vision for the biopharmaceutical industry’s inbound supply chain
NEWS
A major milestone – a harmonized approach to product carbon footprint data
Technology Roadmap V 2.0
DOWNLOAD
BioPhorum Technology Roadmapping roadmap vision 2.0

Publications

Documents including best practices, vision statements and peer reviewed papers to help you take value back to your business.

Webinars

Discussing all aspects of the biopharmaceutical industry, from digitization and knowledge management to raw materials, supply chain, sustainability and more. Learn from the perspectives of those at the forefront of the industry.

Podcasts

BioPhorum Connect is our podcast series that keeps you up to date with the latest news and trends in the biopharmaceutical industry. From experienced professionals to thought leaders, these podcasts bring you the insights and perspectives of experts from around the world.

Tools

A variety of resources including design tools and user requirement specifications to help you improve and streamline your business processes.

Benchmarks and Surveys

Research conducted among the BioPhorum membership providing evidence to support change and identify best practice.

Browse all

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.

WEBINAR
Bioreactivity testing in single-use system biomanufacturing
WEBINAR
Bioreactivity testing in single-use system biomanufacturing
WEBINAR
Bioreactivity testing in single-use system biomanufacturing
Magnifying glass over a tablet all coloured blue
DOWNLOAD
Digital Plant Maturity Model 3.0
WEBINAR
Bioreactivity testing in single-use system biomanufacturing