Platform Technology: How to Reference Prior Knowledge

The term’ platform’ or ‘platform technologies’ has appeared in several recently published regulatory guidelines. Each offers its own definition. The concept is not new, but the range of interpretations can make it difficult to implement in global medicine development.

Platform Technology Definitions

ICH Q11, published in 2012, defines ‘Platform Manufacturing’ as

“The approach of developing a production strategy for a new drug starting from manufacturing processes similar to those used by the same applicant to manufacture other drugs of the same type (e.g., as in the production of monoclonal antibodies using predefined host cell, cell culture, and purification processes, for which there already exists considerable experience).”

 ‘Platform Technology’ is defined by WHO in the 2022 Technical Report on mRNA vaccines as

“a group of technologies used as a base upon which other applications, processes or technologies are developed.”

The recently published draft guideline from the FDA on the Platform Technology Designation Program for Drug Development provides a more comprehensive definition:

“a well-understood and reproducible technology, which can include a nucleic acid sequence, molecular structure, mechanism of action, delivery method, vector, or a combination of any such technologies that the Secretary determines to be appropriate, that the sponsor demonstrates (1) is incorporated in or used by a drug and is essential to the structure or function of such drug; (2) can be adapted for, incorporated into, or used by, more than one drug sharing common structural elements; and (3) facilitates the manufacture or development of more than one drug through a standardized production or manufacturing process or processes.”

Platform Technology in Formulation and Analysis

It is worth noting that the concept of ‘platforms’ is not restricted to manufacturing. It applies to other areas in the pharmaceutical development of a medicinal product. For example, formulation and analytical methods. ICH Q2 (R2) and ICH Q14 published in 2023, introduced ‘Platform Analytical Procedure’ as “An analytical procedure that is suitable to test quality attributes of different products without significant change to its operational conditions, system suitability and reporting structure. This type of analytical procedure can be used to analyse molecules that are sufficiently alike with respect to the attributes that the platform analytical procedure is intended to measure.”

How is Platform Technology Adopted Currently?

The pharmaceutical industry already embraces ‘platforms’ to some extent by leveraging knowledge from existing medicinal products. This approach accelerates new drug development. For example established pharmaceutical companies developing monoclonal antibodies (mAbs) can employ similar manufacturing processes and facilities. Companies occasionally quote prior knowledge in regulatory dossiers to support submissions. However, no formal regulatory framework yet officially incorporates ‘platform technology’. Industry leaders increasingly recognise the need for faster drug development and regulatory approval. Platform technology offers significant potential to streamline these processes.

This Article: Where Next for Platform Technologies?

This article examines how companies currently use tools and procedures in the US and EU to reference existing data in regulatory submissions. We provide updates on ongoing efforts in both regions to revise regulatory guidance and legislation to include ‘platform technology’. We explore whether regulators will adapt existing tools or establish new processes to reference this technology.

The US Landscape

US DMFs

In the US, Drug Master Files (DMFs) are commonly used to support Investigational New Drug (IND) applications, New Drug Applications (NDAs), and Abbreviated New Drug Applications (ANDAs). The use of DMFs covering biological active substances for Biologics License Applications (BLAs) is theoretically also possible but excluded in practice.

Submitted separately and directly to the FDA, DMFs allow applicants to reference the materials described in the DMF in their regulatory submission without requiring the DMF holder to disclose the content directly to the applicant. Currently, there are four types of DMF, each depending on the content included:

• Type II:  Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation; or Drug Product.
• Type III: Packaging Material
• Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation
• Type V: FDA-Accepted Reference Information

A DMF is a valuable tool for leveraging and protecting proprietary information while meeting regulatory requirements. It facilitates collaboration between applicants and manufacturers. This supports the development of innovative medicinal products. In the context of ‘platform technology,’ the US ’Type V’ DMF has potential applications. These include contract manufacturing facilities and sterilisation processes.

Platform Technology Designation Program for Drug Development

However, in May 2024, the FDA published a draft regulatory guideline detailing implementation of a new platform technology designation program. This was established under Section 506K of the FD&C Act. It enables industries to finally put the more extensive concept of ‘platform technology’ into practice. This guideline clarifies the eligibility criteria for a formalised platform technology designation. It also offers process guidance. Eligibility criteria include the platform technology being well-understood and reproducible, already incorporated in or utilised by an approved drug or licensed biological product,  and likely to bring significant efficiencies to drug development, manufacturing, and review processes.

A platform technology designation allows data leverage in subsequent applications (IND, NDA or BLA) using the same platform technology. A sponsor can use a cross-reference mechanism between their own products, or may grant right of reference  to a different sponsor. For a BLA, however, the sponsor should include full information from the technology platform in the application. Examples of platform technology include lipid nanoparticle (LNP) platforms for mRNAs and gene therapy products, CRISPR gene-editing technology, and monoclonal antibody platform technologies. The program currently stops short of including delivery devices.  In addition, other technologies may not be suitable for designation because they do not bring sufficient efficiency or streamlining benefits compared to current processes.

Sponsors can request the designation via an eCTD submission at any time concurrent with or after the submission of an IND that uses the platform technology. For designation holders, it may provide the benefit of early and enhanced FDA interactions.

This program introduces a useful new regulatory tool that formally leverages prior knowledge from a ‘platform technology’ for new applications. It aims to improve the efficiency of drug development and regulatory assessment.

The Current European Landscape

Cross-reference to existing data to support Marketing Authorisations Applications (MAA) is also established practice in the EU. This is done by using Master Files (MF) or Certificates of Suitability to the Monographs of the European Pharmacopoeia (CEP). As a result, there is no need to include full details in the MAA dossier.

Certificates of Suitability

The CEP procedure is widely used by manufacturers of well-established substances described in the European Pharmacopoeia (EP) monographs, who can apply for a CEP. The CEP demonstrates compliance of the relevant substance with the rules in the EP monograph. When using the substance in a medicinal product, the CEP can be included in the MAA dossier. This is instead of presenting full information on the related active substance, thus avoiding reassessment of the data.

Active Substance Master Files (ASMF)

The ASMF procedure allows the manufacturer to protect confidential information related to the chemical active substance. It still provides health authorities full access to information necessary to evaluate the suitability of the drug substance (DS) for use in the medicinal product. Confidential drug substance information is included in the Restricted Part (RP) of the ASMF. Non-confidential information is included in the Applicant’s Part (AP). The AP is submitted as part of the MAA. Whereas the RP is submitted separately and in parallel to the health authority.

This way, the established technology of one manufacturer can be efficiently used for multiple products. This protects the intellectual property of the DS developer. Recent (May 2024) updates to the EU Worksharing Procedure for the assessment of the ASMF are expected to improve efficiency further. Under current legislation, however, the ASMF procedure does not apply to biological medicinal products. It only applies to active substances of chemical origin.

Vaccine Antigen and Plasma Master Files

Additionally, applicants can use master files for vaccine antigen and plasma (Vaccine Antigen Master Files [VAMF] and Plasma Master Files [PMF]). For medicinal products derived from plasma, applicants can include one or more PMF certificates in the MAA instead of providing full plasma information. The VAMF procedure, rarely used, allows the same vaccine antigen to be used in several vaccines from the same applicant.

These regulatory procedures have been used in the EU for decades. However, efforts to expand or develop new regulatory processes to accelerate pharmaceutical development, regulatory assessment, and approvals have recently increased.

Future Legislation in Europe

During the COVID-19 pandemic, the urgent need for accelerated development and regulatory assessment of new candidate vaccines became a pressing reality. The European Commission also recently acknowledged this need. The proposed revisions to the Pharmaceutical Directive recognise the need for specific provisions for new platform technologies, which will facilitate the development and authorisation of such innovations to benefit patients.

Updates of Interest in the Pharmaceutical Directive

1. Introduction of Platform Technologies concept: Article 15 of the proposed new Directive highlights that, in exceptional circumstances, a more flexible approach to granting an MAA can be used where the medicinal product is defined as comprising a fixed component and a variable component (‘Platform Technologies’). This is particularly foreseen for different variants of an infectious agent or personalised medicines.
2. Introduction of ASMF Certificates: The proposed directive also recognises the necessity of simplifying cross-reference to other manufacturers’ data in MAA, with the inclusion of ASMF Certificates, which may be used instead of submitting the relevant data of a medicinal product’s chemical active substance (Article 25).
3. Introduction of Quality Master Files covering other substances: Additional Quality Master Files (and corresponding Quality Master File Certificates) have also been proposed. These are intended for active substances other than chemical substances and other substances used in the manufacture of medicinal products (Article 26).

Building on the proposal, the European Parliament introduced amendments to include cell therapies and gene therapies within the scope of the proposed additional Quality Master Files. They also suggested adding a specific Quality Master File for platform technology. This is outlined in Article 26a of the European Parliament report on the current draft Regulation. It would establish a formal regulatory pathway for filing platform technology.

How will this Support Innovation?

The recognition of platform technology concepts and the introduction of Master File certificates represent significant advancements. Master File certificates will facilitate collaboration between manufacturers and developers without disclosing proprietary information. They also add, for the first time, a route to obtaining standalone regulatory approvals for manufacturers of novel substances not associated with a finished medicinal product. This new regulatory tool will also optimise resources for marketing authorisation applicants and competent authorities. This will reduce duplication of assessments and streamline the MAA approval process.

Platform Technology Through the Medicinal Product Lifecycle

The platform technology concept is also reflected in the proposed amendments to the European Commission’s guidelines on variation categories and procedures, with the introduction of variation category B.I.a.6. This category specifically targets vaccines that have the potential to address a public health emergency. It also allows for the registration of a change in the approved active substance (such as a different strain or coding sequence) as a Type II variation. This recognises that when some major elements of the medicinal products remain unchanged, resubmission of a full MAA dossier might not be required.

Room for Learning from the EU Veterinary Medicines Sector?

Lastly, we note with interest that the EMA already has a program for vaccine platform technology for veterinary products. They recently issued the first certificate for a vaccine platform technology master file (vPTMF). This was based on a turkey herpesvirus vector backbone already used in vaccines for chicks and embryonated chicken eggs. The recently published guidelines on data requirements and procedural advice include a system description. In this context, ‘platform technology’ is defined as a collection of technologies that share a common ‘backbone’ carrier or vector, which is modified with a different active substance or set of active substances for each vaccine derived from the platform.

The EMA approved this vPTMF based on established technology. However, developers can also use the scheme for new vaccine platforms. This is by submitting it alongside the application for the new vaccine. The EMA could apply what it has learned from the veterinary program when developing human medicine regulations in the future.

Summary

The COVID-19 pandemic highlighted that regulatory processes need room for flexibility so that product development can be accelerated. ‘Platform technology’ emerged as a potential approach to address these challenges. Until recently, regulatory submissions made limited references to prior knowledge. And there was no specific regulatory tool for utilising ‘platform technology.’

The US already provided a helpful framework for referencing data through Type II-V DMFs. The FDA has added a new draft guideline implementing the “platform technology” designation program. The EU currently offers more limited data referencing procedures. However, the proposed new EU Regulatory Directive significantly expands the Master Files concept beyond active substances to include ATMPs and ‘platform technology.’

Regulators and industry must still work to harmonise terminology, processes, and eligibility criteria. Once implemented, this will be a better-defined and wider-ranging framework for leveraging prior knowledge. Platform technology will substantially change Quality sections in regulatory dossiers, enhance manufacturer collaboration, and accelerate pharmaceutical development and regulatory approval.