Quick recap on platform technologies
- As part of the 2023 Consolidated Appropriations Act (Section 2503), Congress directed FDA to establish a new “Platform Technologies Designation” program. The law describes a system by which sponsors of applicable, eligible technologies could seek a request for designation from the agency that would allow for “expedite[d] development and review” by the agency.
- The legislation described platform technologies as “a well-understood and reproducible technology, which may include a nucleic acid sequence, molecular structure, mechanism of action, delivery method, vector, or a combination of any such technologies […].” Put more simply, the term refers to approaches utilized within or by drug and biological products that have potential to be used in subsequent products without an adverse effect on quality, manufacturing, or safety. The legislation further explained that for a certain method to qualify as a “platform technology,” it must demonstrate “reasonable likelihood to bring significant efficiencies to drug development and review processes.”
- The intended benefit for sponsors of this approach is that products making use of designated platforms would be eligible to receive expedited development benefits from the FDA, including access to early-stage development meetings with regulators. Companies could also ask the FDA to “reference or rely upon data and information … that incorporates or utilizes the same or a substantially similar advanced platform technology.” However, there are conditions on this right of reference, including that the data must be from an application controlled by the same sponsor or for which the right of access has been granted.
- The bill mandated that FDA initiate a program to designate these technologies as of one year following the passage of the Consolidated Appropriations Act, or December 28, 2023. FDA had the same deadline to issue a draft guidance regarding the implementation of the program, to include specifics about what would be required by sponsors hoping to leverage this approach, examples of products that can use platform technologies, and information about the FDA’s review process. However, both deadlines came and went without any official action by the FDA.
FDA’s Platform Technologies Designation Program and Guidance are finally here
- Today, the FDA announced the launch of the highly-anticipated platform designation program and released a draft guidance containing further detail on what the program entails and how sponsors can utilize it. As FDA explains in its Federal Register notice, FDA’s new 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, the recommended content of a designation request submission, and the review timelines for a designation request.”
- Indeed, the 18-page draft guidance document offers a more-than-perfunctory overview of the program with ample detail on how it will work in practice. Aside from the first section of the guidance, which offers some background on the origin of the designation and its envisioned benefit to sponsors, the document is grouped into four additional sections: requests, revocation of designation, post-approval changes and “general considerations” for eligibility. Most of the content is focused on designation requests (Section II): what technologies are eligible, when requests should be submitted, how sponsors can ask FDA questions about their submission, and what information should be included in the request itself.
- However, the last section ( Section V) provides a list of technologies that the FDA has already determined would meet the statutory and regulatory criteria for platform technology designation eligibility. As the list offers examples of potential platform technologies, it is not all-inclusive. Therefore, additional technologies may be eligible for the new designation as long as they meet the key criteria for eligibility provided in Section II.
- The examples include: lipid nanoparticle (LNP) platforms for mRNA vaccine or gene therapy products, monoclonal antibody platform technologies, platforms using a chemically defined targeting moiety in conjugation with a well-characterized synthetic siRNA, and lipid nanoparticle platforms encapsulating different short, single stranded or double-stranded oligonucleotides.
Proving eligibility
- First, the guidance explains that the term “platform technology” has been used broadly by both industry and FDA in ways that likely differ from how the term is defined in statute and is used in the guidance. For this reason, the guidance advises sponsors 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, if not, would not be eligible for the designation program.” However, it emphasizes that ineligibility for designation does not preclude sponsors from leveraging “prior knowledge across applications,” a practice which the FDA has long recognized. For example, states a footnote, sponsors can already “leverage their own data previously submitted in an [investigational new drug] IND, [new drug application] NDA, or [biologic license application] BLA” while other applicants can “leverage certain information in an approved NDA or BLA (e.g., based on a letter of authorization from the application holder).”
- Speaking of terminology, the guidance explicitly describes and separates two distinct concepts: platform technology and designated platform technology. Though the guidance underscores the importance of correcting applying the recommendations provided by the FDA to the proper term, neither definition is actually new. The definitions provided in the guidance’s glossary are—for all intents and purposes—identical to those contained in statute 21 U.S.C. 356k(h). Thus, the guidance defines “platform technology” as a well-understood and reproducible technology 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.”
- Likewise, a designated platform technology is a platform technology that further: “1) is incorporated in, or used by, a drug approved under Section 505 of the FD&C Act, or a biological product licensed under Section 351 of the PHS Act; (2) preliminary evidence demonstrates that the platform technology has the potential to be incorporated in, or used by, more than one drug without an adverse effect on quality, manufacturing, or safety; and (3) data or information indicates that incorporation or use of the platform technology has a reasonable likelihood to bring significant efficiencies to the drug development or manufacturing process and to the review process.”
- How can sponsors “prove” that these three criteria are met? The first requirement is straightforward: the approach in question must have been used by a product that has already gained FDA approval. As for the second requirement that sponsors must provide “preliminary evidence” that a particular approach can be successfully applied to other products, the guidance offers more detail. In short, this means that the sponsor seeking to repurpose an approach leveraged by an approved product must demonstrate that there are “minimal differences” between the approved product and the new product in terms of their physiochemical composition and manufacturing processes. To demonstrate there are minimal differences, the guidance instructs sponsors to provide “information from completed tests or studies comparing the platform technology used in the approved or licensed drug(s) with the proposed use of the platform technology in the drug(s) under investigation described in the designation request.”
- Information that could be used to form preliminary evidence: Other than stating that sponsors should submit information that shows their product is very similar to another, previously approved product in substance/product composition and manufacturing processes, it doesn’t offer detail on the types (or number) of differences that might be acceptable to the FDA or whether there are certain differences in chemical structure, manufacturing process, biological effect, etc. which would never be acceptable. In any case, it does offer a few examples of what information might qualify as “preliminary evidence.”
- For instance, a sponsor could submit information demonstrating that two drug substances are “structurally similar” because they have similarly sized nucleic acid sequences with comparable backbone chemistry, subunit modifications, and targeting moieties. Likewise, preliminary evidence might include information showing that the formulation of two drug products possess “minimal differences” qualitatively and quantitatively. Finally, information demonstrating that the two products utilize “nearly identical manufacturing processes for drug substance and/or drug product manufacturing, and purification” could also be used – including (as explained in footnote 18) that FDA will “generally” want to ensure that the drug product manufacturing will “occur at the same manufacturing site” for the purposes of establishing preliminary evidence. Otherwise, FDA “may ask for additional quality data, e.g., stability data, to bridge between different manufacturing sites.”
- Next up, sponsors must demonstrate that the use of a platform will convey “significant efficiencies to the drug development or manufacturing process and to the review process for the application.” In lines 157-164, the guidance explains that this means a “prior test, study, or manufacturing process involving the approved or licensed drug described in section 506(K)(b)(1) of the FD&C Act could be leveraged in a subsequent application in such a way as to allow the subsequent application incorporating such information to generally be developed and reviewed in a more streamlined manner.”
- Skipping down to Section V of the guidance, the FDA stresses the importance of these two criteria (i.e., “preliminary evidence” and “significant efficiencies”) in actually securing a designation. It is possible, states the guidance, that a technology meets the statutory definition of a platform technology but is not granted a platform designation by the FDA. “For example, a 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.”
Submitting requests & obtaining the benefits
- The guidance’s recommendations on timing of submission are scattered throughout the document. In short, the first step in the process is that the approach must be utilized by a currently approved product. For the subsequent product, a platform technology designation request can be submitted “concurrent with or at any time after the submission of an IND application.” However, the guidance cautions that sponsors should consider whether they have truly amassed enough product-specific data available for the prior product and subsequent product before submitting a request. It adds that, “Although a sponsor can request designation concurrent with the submission of an IND, FDA recommends that the sponsor submit far enough into their development cycle of the product to permit a determination of suitability for platform technology designation.”
- In most cases, this would “likely be after a safe-to-proceed decision has been made for the IND,” says a footnote (26). Of note, FDA specifies that any designation requests submitted at the same time as a new IND or a subsequent IND amendment will be evaluated separately “from the safety assessment of the new IND or of any subsequent IND amendments (e.g., a proposed new clinical protocol, a Chemistry, Manufacturing, and Controls (CMC) or Pharmacology/Toxicology amendment).”
- However, an important exception: If the IND is placed on a full clinical hold, a simultaneously submitted designation request will be “deemed inadequate for review.”
- Rights of reference: Overall, if a sponsor wishes to submit a platform technology designation request to leverage an approach that they have previously used, the process is much simpler than requesting to leverage a platform technology that has been incorporated in another company’s approved product. The guidance states 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.” While it goes on to state that different sponsors may be able to leverage platform technology data if they “receive a full right of reference to the leveraged data under a business arrangement with the originator of the platform technology,” the guidance indicates that this isn’t a viable option for sponsors developing biological products, as BLA holders are “generally expected to have knowledge of and control over the manufacturing process” for biological products they have licenses for.
- The brass tacks: Requests for platform designations should be submitted electronically to the FDA in accordance with the electronic Common Technical Document (eCTD) format. If the request is being submitted along with a new IND, the administrative documents in Module 1 should clearly specify that the submission contains both an initial IND submission and a request for platform designation. For sponsors submitting platform designation requests at any point after their initial IND has been submitted, the request should be submitted as an IND amendment, also clearly identified in the Module 1 administrative documents. Finally, this section of the eCTD is also where any information on full right of reference agreements should also be submitted. Further instructions on the logistics of platform request submission are provided in lines 307-325. While many of the recommendations are repeated elsewhere in the document, Section IIC provides a neat checklist of the topics that sponsors should consider when preparing designation requests.
- FDA feedback: Within 90 days of receiving a platform designation request, the agency will respond to sponsors. In addition to informing sponsors of the outcome of their proposals, the FDA will also provide an explanation of its decision in each written response to requests. Section IID (lines 279-294) provides instructions for sponsors on how to request feedback from the FDA via a pre-submission meeting before submitting a platform designation request.
- The benefits: For sponsors who are successful in their platform designation requests, the guidance states (lines 171-200) that “one or more of the following” benefits may generally be conveyed to recipients as “deemed appropriate by FDA….” The list adheres closely to the statutory language and is anything but promissory when describing the benefits sponsors can expect. For example, it says that “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.” However, there are some new potential benefits, including those related to stability data and shelf-life data. Notably, FDA says it will also consider “previous inspectional findings by FDA for subsequent marketing applications related to the manufacture of a drug that incorporates or uses the designated platform technology.”
After a designation is secured
- In contrast to the previous section, just two sentences comprise the entirety of Section III. They state simply that the FDA may “revoke the designation” if the FDA finds that the sponsor’s “designated platform technology no longer meets the eligibility factors for the platform technology designation program.” Per the guidance, such a decision will be conveyed to the sponsor in writing.
- Next, Section IV describes the protocol for when sponsors intend to make post-approval changes that “incorporate the designated platform technology.” In terms of when and how proposed changes are conveyed to the FDA by sponsors, it depends on the scope of the change and its potential impact on product identity, strength, quality, purity, or potency. Furthermore, it depends on whether the postapproval change is being made to a product that relies upon a designated platform technology or whether the postapproval change is being made to the designated platform technology, which multiple approved products are reliant on. In cases where the postapproval change applies to an individual product, which uses a designated platform technology, a postapproval change supplement to the application should be submitted, as is outlined in FDA’s other guidances on this topic (e.g., for certain biological products or for new drug products).
- In cases where the proposed changes apply to the platform technology itself, a slightly different process comes into play. In this case, a “single submission of grouped supplements for CMC postapproval changes and a single supplement per proposed change for nonquality-related changes to that platform technology” may be submitted. In general, supplements should include a “rationale to support the conclusion that the updated technology continues to meet the eligibility factors of the platform technology designation program and, as applicable, appropriately cross-reference data and information submitted in other applications.” Furthermore, the guidance states that if changes to a designated platform technology are anticipated, sponsors can preemptively include one or more comparability protocols in an original application or prior approval supplement. Such protocols should “include a risk assessment regarding how the changes to the platform technology would be made for each applicable drug.” Lastly, it says that a “new supplement should be submitted as appropriate for each impacted application.”
What’s next?
- The guidance, though delayed, offers only limited new information. In general, the process laid out in the guidance itself closely reflects the statutory directive. The process advice described should be familiar to sponsors, but does provide some more information than was available in the statutory language about what information the agency will want to see in a designation request – and how it’s going to interpret key terms.
- The list of potentially eligible technologies is particularly useful. Sponsors seeking a platform technology designation request from these types of products might see an easier time receiving a designation – although, as always, it depends on the individual context of the research program.
- The way that the actual designation’s applicability will play out are still to be seen. The guidance does describe the “potential” benefits of a platform technology designation, but how the agency (and sponsors) seeks to leverage these flexibilities still remains to be seen. However, how those will be applied – and what it will look like in practice – will need to be assessed as both the agency and industry gain some experience with the program. In particular, questions remain about what some of the specific benefits of the program will look like – like early interaction with the agency, “receiving timely advice” or “additional engagement” and meetings, or how FDA “might prioritize interactions” or engagements, “depending on resources” for selected sponsors.
- Comments in response to the draft guidance are due by the end of July 2024, leaving stakeholders just 60 days to gather their feedback on a guidance which has taken the FDA nearly 18 months to develop.
To contact the author of this analysis, please email Rachel Coe ( rcoe@agencyiq.com).
To contact the editor of this item, please email Alexander Gaffney ( agaffney@agencyiq.com)