The FDA has issued much-awaited draft guidance that details how it plans to implement its new platform technology designation program. What does it mean for manufacturing overall and in specific sectors—biologics and advanced therapies?

By Patricia Van Arnum, Editorial Director, DCAT, pvanarnum@dcat.org 

Scope of platform technology designation
The US Food and Drug Administration has issued draft guidance, Platform Technology Designation Program for Drug Development, to provide details about the implementation of the Platform Technology Designation Program, which is intended to result in efficiencies in drug development, manufacturing, and review processes for applications that incorporate designated platform technologies. The program is applicable to development of all drugs, biologics, and drug or biologic constituents of combination products, including cell- and gene-therapy products.

The draft guidance outlines eligibility factors for receiving a platform technology designation, potential benefits of receiving a designation, how to leverage data from designated platform technologies, how to discuss the planned designation request as part of a milestone meeting with FDA, the recommended content of a designation request submission, and the review timelines for a designation request. FDA is seeking input on the draft guidance through July 29, 2024.

FDA issued the draft guidance to help clarify what is meant by a platform technology, which it says may differ from common industry convention on the term. In its draft guidance, FDA acknowledged that the term “platform technology” has been used by both industry and  FDA to describe technologies in ways that differ from the definitions of platform technology and designated platform technology that are outlined in statute and this draft guidance. FDA noted in its draft guidance that some technologies that industry and FDA have historically considered to be platform technologies might not meet the statutory definition and statutory eligibility factors and, therefore, would not be eligible for the designation program. Ineligibility for designation, however, does not preclude a sponsor from leveraging prior knowledge across applications. FDA has allowed sponsors to leverage prior knowledge from previously submitted applications when authorizing or approving drugs in an application submitted by the same sponsor.

What is a platform technology?
As specified in the draft guidance, the FDA will first determine eligibility for designation as a designated platform technology. Under section 506K(h)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), a platform technology is a well understood and reproducible technology, which can may include a nucleic acid sequence, molecular structure, mechanism of action, delivery method, vector, or a combination of any such technologies that FDA determines to be appropriate, where it: (1) is incorporated in or utilized by a drug and is essential to the structure or function of such drug; (2) can be adapted for, incorporated into, or utilized 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. A platform technology designation does not affect product eligibility for any expedited approval pathways if it is otherwise eligible. Sponsors of applications or emergency use authorization requests will also be allowed under certain circumstances to leverage data related to designated platform technologies previously submitted to FDA.

More specifically, under section 506K(b) of the FD&C Act, a platform technology is eligible for designation by FDA if: (1) it is incorporated in, or utilized by, an approved drug; (2) preliminary evidence demonstrates that the platform technology has the potential to be incorporated in, or utilized by, more than one drug without an adverse effect on quality, manufacturing, or safety; and (3) data or information submitted by the same party indicates that incorporation or utilization of the platform technology has a reasonable likelihood to bring significant efficiencies to the drug development or manufacturing process and to the review process.

For the platform technology designation program, section 506K of the FD&C Act establishes criteria outlining who can request designations and who, once that platform technology has been designated, can leverage them. The draft guidance describes those categories and provides  recommendations for the types of platform technologies that may be eligible for consideration for designation. This guidance also gives recommendations for what should be included in  submission requests to designate a platform technology, how to update a designated platform technology and, when appropriate, the process for revoking a designation.

Examples of platform technologies
Platform technologies that are appropriate for the designation program are those that meet the definition of a platform technology and the eligibility factors for designation as described in the draft guidance. Examples of potential platform technologies include: lipid nanoparticle (LNP) platforms for mRNA vaccines or gene therapies; LNP platforms encapsulating different short, single-stranded or double-stranded oligonucleotides: monoclonal antibodies platform technologies; and platforms using a chemically defined targeting moiety in conjugation with a well-characterized synthetic small interfering RNA (siRNA).

Within these platform technologies, FDA further provides examples of key elements of each technology as outlined below. 

LNP platforms for mRNA vaccine or gene-therapy products:

• Composition, including type, amount, and manufacture of the lipids;
• Manufacturing process unit operations (e.g., transcribing RNA, synthesizing lipid moieties, and formation of the lipid nanoparticles) that are not sensitive to inputs (e.g., template sequences), and yield consistent outputs across multiple products, and where sequence differences of the mRNA have no effect on product quality;
• Manufacturing process parameters, in-process controls, and equipment critical to manufacture of the mRNA LNP vaccine or gene therapy; and
• Process-related impurity clearance across a defined downstream purification process.

Lipid nanoparticle platforms encapsulating different short, single stranded or double-stranded oligonucleotides:

• Composition, including type and amount of the lipids;
• Demonstration that, within a narrow range of double-stranded or single-stranded  oligonucleotide length, there is no effect on product quality arising from sequence differences of the oligonucleotides; and
• Manufacturing process parameters, in-process controls, and equipment critical to the formation of the lipid nanoparticles.

Monoclonal antibody platform technologies:

• Approaches for cell substrate and expression construct engineering that can be used with multiple products with the same upstream manufacturing process  developed for the specific cell substrate and expression construct backbone; and
• Process-related impurity clearance evaluated across a defined downstream purification process that can be used for multiple products with little modification.

Platforms using a chemically defined targeting moiety in conjugation with a well-characterized synthetic siRNA:

• Identification of the targeting moiety, including its synthesis, incorporation into the final drug substance, and quality control;
• Modification of synthetic siRNA sequence has no biological effect on the product quality or safety arising from the differences such that some pharmacology/toxicology and CMC (chemistry, manufacturing and control) data are potentially appropriate to be leveraged;
• Safety of the targeting moiety is not altered when used with multiple different siRNA moieties such that some pharmacology/toxicology data are potentially appropriate to be leveraged; and
• Use of a unique method of manufacturing, purification approach, or purification strategies that simplify downstream characterization of the drug product and that can be used for multiple products with little modification.

What is not eligible for a platform technology designation
FDA’s draft guidance specifies that for a technology to be designated as a platform technology, it must not only meet the platform technology definition in the statute, but it must also meet the eligibility factors for designation. It is possible, therefore, for a technology to meet the definition of a platform technology, but not be designated by FDA as a designated platform technology. For example, technology that meets the definition of a platform technology might be inappropriate for the designation program because current review processes already reflect the use of the well-understood technology or there is a public standard. Therefore, FDA would not consider such technologies to meet the criterion of bringing significant efficiencies to the drug development, manufacturing, and review processes for the purposes of the designated platform technology program.

In its draft guidance, FDA provides examples of technologies that could be inappropriate for the designation program because the technologies do not meet the definition, criteria, or both as outlined below:

• Approaches to viral clearance for certain unit operations;
• Manufacturing unit operations that are sensitive to inputs (e.g., the general use of roller compaction that might be sensitive to material properties);
• Technologies that rely on established manufacturing unit operations (e.g., blending, compressing, or film-coating operations);
• Established formulation technologies that have been traditionally used for immediate-release and extended-release solid oral dosage forms (e.g., matrix, osmotic pump), established formulation technologies for oral and parenteral dosage forms, and other established drug-delivery systems; and
• Near-infrared technologies for monitoring in-process material attributes.

Requesting a platform technology designation
A specified in the draft guidance, if FDA has approved an abbreviated new drug application (ANDA), new drug application (NDA), or biologics license application (BLA) for a drug that incorporates or uses a platform technology, a sponsor of a subsequent investigational new drug (IND) application, NDA, or BLA can request designation of that platform technology to enable leveraging of the technology in new or future applications. FDA recommends requesting the designation of a platform technology during the IND phase of drug development for a planned subsequent NDA or BLA because by this stage of development, the sponsor should have sufficient knowledge to outline for FDA how the proposed platform technology would meet the eligibility factors. FDA says this should facilitate a more complete request and its timely review by FDA.

The draft guidance specifies that designation of a platform technology does not give third parties additional rights to reference  information from an approved product application containing that platform technology if they do not own or have full rights of reference to it. In addition, a BLA holder is generally expected to  have knowledge of and control over the manufacturing process for the biological product for which it has a license. Any referencing of data or information by an application based on a platform technology designation should be consistent with this general expectation, as outlined in the draft guidance.

Potential benefits of a platform technology designation
As specified in the draft guidance, information about a designated platform technology may be leveraged in a subsequent application when supported by sufficient preliminary evidence. The application should be from the sponsor that was originally granted the platform technology designation. Alternatively, it can be from a sponsor that has full rights of reference to that information. Potential benefits to a sponsor that is granted a platform technology designation for a subsequent application may  generally include one or more of the following, as deemed appropriate by FDA, as outlined below.

• Engaging in early interactions with FDA to discuss the use of a platform technology, including information relevant to establishing, as applicable, safety, purity, potency, or quality.
•  Receiving timely advice from and having additional engagement with FDA during the  development program, such as additional interactions and/or meetings on the use of the  platform technology. Depending on resources, FDA might prioritize interactions or additional engagements regarding a designated platform technology for those products  where the agency has determined that there is the most significant public health benefit or impact.
• Leveraging data from a prior product that used the designated platform technology, such as leveraging batch and stability data from a related product as prior knowledge that can supplement product development studies (e.g., in-use stability studies to define administration conditions and/or light exposure studies to inform the design of the container closure system), or support shelf-life extrapolation and determination for structurally alike products.
•  Leveraging certain nonclinical safety data from prior products that used the designated platform technology such that a product-specific assessment for specific, designated endpoints might not be warranted.
• Considering previous inspectional findings by FDA for subsequent marketing applications related to the manufacture of a drug that incorporates or uses the designated platform technology.