This week, the FDA issued four new contract notices that highlight agency priorities in meeting user fee commitments, ongoing work in oncology dose optimization, and continued commitment to addressing the opioid crisis. AgencyIQ walks through the new projects below.
Quick rundown on how FDA can acquire private sector services
- The process for government entities to acquire or utilize private sector services is intricate, with specific policies and procedures outlined in the Federal Acquisition Regulations (FAR) which govern the entire acquisition process from start to finish.
- FAR regulations require contracting officers to “promote and provide for full and open competition in soliciting offers and awarding Government contracts.” An example of how this rule is used in practice is that any entity within the federal government (such as FDA) that is interested in pursuing a contract valued at more than $25,000 must formally “publicize” the contract opportunity on behalf of the agency via the General Services Administration (GSA) System for Award Management (often referred to as SAM).
- There are several types of contract opportunities that can be posted within SAM which vendors can respond to. Each notice type represents a specific official action and is chosen according to which phase during the acquisition process that the notice is posted (pre-award, award of contract, or post-award).
- In certain circumstances, like when a service is only available from one source, agencies may be exempt from the standard requirement to promote and ensure a competitive bidding process. This is referred to as “sole source” of a service, and might occur in situations where one company has a brand name product that does not have competition in the marketplace or could occur when a vendor retains significant advantage over competition (e.g., if the vendor has worked with a particular agency for years, they might have specific experience and institutional knowledge that is unmatched by other vendors). Generally speaking, sole source procurement of services is discouraged.
- When an agency requests to forego the competitive bidding process, it is still required to post an “Intent to Sole Source” notice on SAM and to consider any additional contracts that are submitted, despite the agency’s intent to utilize a specific vendor. This is one reason an agency may post a contract opportunity as a “Special Notice” on SAM. Though special notices are most frequently used by agencies to notify vendors that they will not be adhering to the competitive bidding process, they are more broadly referred to in the regulations as a means to notify industry of “procurement matters such as business fairs, long-range procurement estimates, prebid or preproposal conferences, meetings, and the availability of draft solicitations or draft specifications for review.”
- This week, FDA posted several new special notice contract opportunities on SAM.
First, an audit of communications and meeting management under the Prescription Drug User Fee Act (PDUFA)
- Quick background: As AgencyIQ has previously discussed, the FDA collects user fees as part of an essential bargain between regulators and industry. Industry wants its products reviewed quickly, efficiently and predictably. Without sufficient resources, the FDA is unable to do so. Therefore, industry pays the FDA “user fees” for nearly all applications for approval, as well as annual fees related to registration and listing. These fees help the FDA hire staff, who help to review applications more quickly. In addition, the FDA agrees to follow certain performance metrics to ensure the timely review of applications. Fees are also used for a host of other activities meant to improve the FDA’s regulatory capacity and capabilities, such as I.T. modernization efforts.
- FDA intends to award a sole source award to Eastern Research Group, Inc. (ERG) to “collect data and to analyze PDUFA meeting management,” according to a new notice. ERG is a current incumbent contract holder, and the firm has previously conducted program analyses for the agency. For example, a review of the functioning of a new biologics review program analyzed industry-FDA interactions and data that was used in PDUFA negotiations.
- According to the notice, the contract includes at least three deliverables: (1) an internal report or presentation to FDA, (2) a public workshop with stakeholders using data collected and published in the Federal Register Notice, and (3) a summary of the public workshop and recommendations to inform potential updates to FDA’s guidances.
- The analysis will likely center on new meeting programs committed to under the PDUFA VII agreement. As AgencyIQ previously discussed, the agreement outlined two new types of regulatory meetings for sponsors to address certain questions with the agency. First, the INTERACT meetings involve enhanced communication and engagement early in the development process. These meetings are used to provide sponsors with early-stage advice on development issues experienced by sponsors of innovative products. Sponsors can also leverage agency engagement through the Type D meeting program, also created under PDUFA VII. As AgencyIQ has previously discussed, these meetings focus on a “narrow set of issues,” such as when the sponsor is seeking specific input with few questions, or a general question about development approaches that will not need extensive input from the agency. [ Read detailed AgencyIQ explainer on the two new meeting types here.]
- While this notice does not provide information on the contract’s timeframe, AgencyIQ expects it to cover the next few years under PDUFA VII. Once the contract is awarded, the agency will likely publicize the Statement of Work (SOW) with more granular details. [ See AgencyIQ’s user fee program performance tracker, with program-by-program analysis, due dates, and links.]
Another sole source contract is headed to the same vendor for a human resources assessment under PDUFA VII
- Also this week, the FDA issued a special notice that it intends to award another sole source contract to ERG to assess “all aspects of [human resources/human capital] operations and transformation to prepare an assessment that expands on the initial baseline, interim, and final assessments of the hiring and retention in HR/HC components ofFDA.” The brief text, with no further links or attachments, provides no further information about the substance of the proposed award.
- As with the other ERG sole source notice, there’s no timeframe attached to this notice. But according to AgencyIQ’s user fee program performance tracker linked above and the FDA’s PDUFA VII user fee commitments, CDER and CBER committed to perform an “assessment of hiring and retention” with experience in HR operations “to conduct a targeted assessment of the hiring and retention of staff for the human drug review program.” This assessment is due to be published for public comment by June 30, 2025, will a public meeting to be held by September 30, 2025 “to discuss the report, its findings, and the Agency’s specific plans to address the report recommendations.”
- Specific deliverables specified in the commitment letter include evaluating “the outcomes of various hiring changes,” building on work done under previous rounds of PDUFA commitments. Metrics to be assessed include looking at hiring and retention performance in general and in specific disciplines in the drug review program, as well as assessing how FDA has used pay authorities at its disposal. The assessment should include recommendations “on further enhancements” for hiring and retention of staff in FDA’s human drug review program.
FDA will also outsource work to bolster its overdose surveillance capacity
- Quick Background: waves of the overdose epidemic. The Centers for Disease Control and Prevention (CDC) explains that the first wave began with increased prescription of opioids in the 1990s. The second wave aligned with an increase in deaths involving heroin, which was followed by a third wave of increased mortality associated with synthetic opioids like illicitly manufactured fentanyl. During the COVID-19 pandemic, the number of opioid-involved deaths climbed sharply, with mortality rates increasing by 38% between 2019 and 2020.
- Now, data trends show that a fourth wave of polysubstance use, driven by stimulants like methamphetamine and cocaine, is again spiking mortality.
- According to a new notice, FDA will award a contract to incumbent American College of Medical Toxicology (ACMT) to “to provide the detailed real-time information on the fourth wave of the overdose crisis and the impact of stimulant co-consumption.”
- FDA has previously worked with ACMT. In 2020, the agency awarded a contract to “establish a COVID-19 Sub-Registry to collect data on the safety of drug products used for the prevention or treatment of COVID-19 infection.” The project leveraged the association’s Toxicology Investigators Consortium (ToxIC), which it describes as a “unique multicenter toxicosurveillance and research network comprised of physicians specifically qualified in the field of medical toxicology.” ToxIC has large and diverse datasets; ACMT reported over 73,000 cases in its patient registry in 2020, coming from 40 participating sites across the United States. In announcing the contract, ACMT explained that while FDA has held a contract for years to access the ToxIC Registry, that contract involved a more specific goal and a concerted effort between the association and CDER’s Office of Surveillance and Epidemiology (OSE) and Office of Translational Sciences (OTS).
- AgencyIQ expects that the new contract, entitled “Near Real-Time Surveillance of Stimulants in the Overdose Crisis – Drug Overdose Toxico-Surveillance (DOTS) Expansion” will similarly provide a focused collaboration within the ToxIC Registry program. While the notice does not contain additional details regarding the specific deliverables and timeline of this effort, AgencyIQ will continue to monitor its progress.
- FDA Commissioner Robert Califf has previously received heat for the agency’s response to the overdose epidemic. In a September 2022 blog post, Califf acknowledged the broad scope of the crisis, saying ,“The opioid crisis has evolved beyond prescription opioids into a broader drug overdose crisis, largely driven by illicit fentanyl and its analogs. Other controlled substances, including benzodiazepines and stimulants (particularly methamphetamine), also are being used in combination with opioids.” The Agency’s handling of this issue was a focal point of Califf’s confirmation hearings, and he has since received continued criticism. For example, a letter from Massachusetts Senator Ed Markey called on FDA to “enhance post-market surveillance of opioids, including by conducting regular, formal reviews of opioid approvals,” among other regulatory activities. [ Read AgencyIQ’s backgrounder on the FDA’s recent responses to the opioid crisis here.].
- In a related development, this week, a new FDA guidance document to support development of medical devices to treat opioid use disorder (OUD) inched closer to release. According to a new notice, a draft guidance document titled: “Clinical Considerations for Studies of Devices Intended to Treat Opioid Use Disorder” was cleared by the White House’s Office of Information and Regulatory Affairs (OIRA) on July 20. The content in the guidance will likely take a high-level approach to sketch out the contours of clinical studies that could address OUD, including potential patient populations or methods. While the exact timeline to publication varies after OIRA clearance, AgencyIQ expects publication to occur this quarter, if not sooner. [ Read the full AgencyIQ analysis here.]
Finally, a bid to use PBPK models to determine the optimal dose for oncology products when used in pregnant women with cancer
- This week also saw a new special notice contract opportunity that indicated FDA is looking for a vendor to “provide analyses in the development of physiologically-based pharmacokinetic (PBPK) models to determine the optimal safe and appropriate dose of oncology drugs for pregnant women with cancer.” This proposal is an exciting example of how new approaches at the forefront of clinical pharmacology can be leveraged to address the problems being discussed in other forums (e.g., oncology).
- Physiologically-based pharmacokinetic (PBPK) models are defined by FDA as drug development tools that mathematically integrate physiological, physicochemical, and drug-dependent preclinical and clinical information to predict an investigational drug’s absorption, distribution, metabolism, excretion (ADME), and pharmacokinetics (PK). A PBPK model starts with the creation of a flow-based compartmental PK model that shows the theoretic course a drug takes through the body along the ADME pathways. Next, mathematical equations are used to quantify changes in drug concentration in tissues and organs as a function of time. These equations use drug-independent inputs (like blood flow, tissue composition, enzyme abundance, membrane transporters in tissue compartments, etc.) and drug-specific values such as tissue-to-plasma concentration ratios and how rapidly the drug is broken down by a given enzyme.
- In theory, valid PBPK models can be used to “predict the drug concentrations achieved—in plasma at particular times—that would result from a specific dose in a patient from a population for which clinical data was unavailable,” according to an FDA Impact Story about PBPK modeling. For example, adapting a “healthy model” to reflect known physiological differences in patients with a rare disease or for those with organ impairment could be especially useful in helping sponsors decide whether, when, and how to conduct a clinical pharmacology study in these situations. FDA’s 2020 draft guidance discusses PBPK analyses for oral drug product development.
- Lately it seems as though FDA, industry, and advocates each harbor strong—though not entirely aligned—opinions on establishing an optimal dose for oncology products, As AgencyIQ learned when we took a deep dive into comments on FDA’s draft dose optimization guidance document. At the same time, oncology products today are not what they used to be, making dose optimization a more complex exercise than it was for chemotherapies. The FDA’s Project Optimus is focused on these issues, which have been explored in a series of meetings, workshops, and FDA advisory committee meetings.
- The population of pregnant people who have cancer are understudied, though numbers of this population are rising with advancing maternal age. Current guidelines recognize risks of malformation and fetal demise with anticancer treatments, especially conventional chemotherapy. Though this population could benefit more than most from a dose optimization strategy, dose-finding studies in human pregnant populations are often infeasible and ethically impermissible. Hence, PBPK approaches could stand to inform regulatory actions and clinical practice for pregnant people with cancer.
- The notice interestingly states that FDA will use the information collected to “determine whether it is necessary to use full and open competition for this requirement.” For this reason, it seems at least possible that FDA actually does have a vendor in mind although FDA indicates it’s planning to conduct a bidding process among certain current contract holders, given the deadline for information to be submitted is just a week away. To contact the authors of this item, please email Amanda Conti ( [email protected]) or Rachel Coe ( [email protected]).To contact the editor of this item, please email Kari Oakes ( [email protected]).
Key Documents and Dates
- Notice: PDUFA VII – Best Practices in Communication Assessment
- Notice: PDUFA/BsUFA VII Hiring and Retention Assessment
- Notice: Near Real-Time Surveillance of Stimulants in the Overdose Crisis – Drug Overdose Toxico-Surveillance (DOTS) Expansion
- Notice: Development of physiologically-based pharmacokinetic (PBPK) models to determine the optimal safe and appropriate dose of oncology drugs for pregnant women with cancer