The COVID-19 pandemic emergency forced federal regulators to take extraordinary measures to ensure that patients were permitted continued access to important medicines.  These government measures included granting temporary exemptions from certain FDA and DEA legal requirements.  When the public health emergency ends on May 11, 2023, so do these exemptions.  By almost all accounts, these exemptions also improved prescribing and dispensing of medication to patients that need them.  The “end” of the pandemic emergency leaves many in the regulated industry wondering how this will affect certain prescribing and dispensing practices that have become ubiquitous since the pandemic’s inception.

Hyman, Phelps & McNamara, P.C.’s panel of legal experts (Karla Palmer, John Claud, Jeff Wasserstein, John Gilbert and Kalie Richardson) invite you to spend your lunch hour (or hour-and-a-half…) with us as we address implications related to the looming end of the pandemic declaration.  We will discuss the state of relevant laws prior to our new “COVID reality” and telemedicine issues during and post-pandemic, both with respect to the prescribing of controlled substances and non-controlled drugs.  Last, but certainly not least, we look forward to introducing our newest colleague, John WM Claud, who recently joined HPM from the Department of Justice’s Consumer Protection Branch.  John will present on considerations and his learned perspective for the future of teleprescribing.

Please see detailed information in the attached flyer, including a link to register for our free webinar.  We hope you join us!

The annual ABA White Collar Crime Institute is a popular venue for prominent Department of Justice officials to make speeches announcing new policies.  This year, Deputy Attorney General Lisa Monaco took the stage, and her speech included many of the well-known past hits from the corporate compliance chart.  But she also mixed some of DOJ’s new tracks into her remarks that had her audience paying attention, even if they weren’t necessarily singing along.

Of course, the traditional corporate enforcement chart-toppers were all there for the DAG.  Prevent corporate wrongdoing before it happens.  Operate legitimate, bona fide, and well-resourced compliance programs.  Cooperate to earn credit when prosecutors make charging decisions.  Inspire a culture of compliance.  Classics, all.  But Ms. Monaco’s remarks on DOJ’s new material was worth listening to, as she hit on three topics that added some new deep cuts to the DOJ corporate enforcement catalogue.

First, Ms. Monaco focused on a DOJ policy change that came out in February:  all the Department’s litigation components will follow consistent voluntary self-disclosure corporate resolution principles.  That means that the Criminal Division, 94 U.S. Attorney’s Offices, and, importantly for readers of this blog, the Civil Division’s Consumer Protection Branch (CPB), will all consistently reward corporations that voluntarily disclose and remediate misconduct.  DOJ will not seek guilty pleas or prosecute companies in such cases, creating what Ms. Monaco said was national transparency and consistency.

Our firm has a great deal of experience in pleading with the Government not to prosecute clients that have discovered serious misconduct by employees (including management) and disclosed it to the Government voluntarily.  The way this usually evolves is that the Board of Directors or a new CEO or a Quality Unit head learns that there has been misconduct – occasionally involving fraud – that he, she, or they previously were not aware of.  They call us and ask us what to do.  We tell them that they need a thorough investigation into the misconduct and if there is other wrongdoing.  We might conduct numerous interviews, look at thousands of documents, and travel to whatever locations are necessary.  We prepare a report that we share with our client and make a recommendation to our client about whether to disclose the information to FDA.

If the facts and the law warrant, and with the client’s approval and participation, we then set up a meeting.  We pledge to cooperate with FDA, and we plead with FDA to recognize that we engaged in a thorough investigation and provided a full disclosure.  As appropriate, we ask that FDA give us credit and not take harsh enforcement action or refer the matter for criminal investigation, and potentially, prosecution.

Our colleague John Fleder has long advocated for a voluntary disclosure program at FDA.  He wrote about the lack of any assurance that FDA would appropriately credit disclosure in a 1999 FDLI article.  Many federal agencies do have policies that provide a safe harbor for voluntary disclosures, but FDA does not.

And, FDA still doesn’t.  But the Deputy AG’s speech was important for regulated industry because FDA doesn’t litigate its own cases.  It relies on the Department of Justice to do so, either in the form of CPB or in individual U.S. Attorney’s Offices around the country.  CPB enforces the FDCA, FTC Act, and Controlled Substances Act, and importantly for companies in this space, CPB’s voluntary disclosure policy not only exempts companies from guilty pleas, but also potentially from the imposition of corporate monitors.

Second, Ms. Monaco announced that DOJ would pursue financial claw backs to tie executive compensation to compliance.  Going forward, corporate resolutions with DOJ will include a requirement for corporations to link compliance to compensation systems.  The Department will reward corporations with reductions in criminal fines, credited to the amount of compensation the company is trying to claw back from culpable executives and employees.  Successful claw backs will be the company’s reward to keep.  The DAG also announced that DOJ will reward good-faith but unsuccessful claw back attempts.

Finally, we learned that DOJ is pouring resources into the offices that factor heavily in the corporate compliance work there.  Offices getting more funding include the National Security Division and the Banking Integrity Unit within the Criminal Division’s Money Laundering and Asset Recovery Section.  And again, relating to food, drug, and device matters—and the potentially related issues of data privacy and cybersecurity that we have recently blogged on in prior posts—CPB is bringing on several new enforcement lawyers in another large-scale expansion for that office.

The current leadership at Justice has been rigorously evolving its strategies to address corporate crime.  DOJ isn’t just playing the same old hits these days, and compliance departments will need to learn to love the new material.

On March 17, 2023, enhancements to FDA’s electronic Medical Device Reporting (eMDR) system will go live. Manufacturers who submit reports via the FDA Electronic Submissions Gateway are being advised to update their systems by this time. Those who use eSubmitter will notice changes in the electronic 3500A template in the first week of March.

Background

FDA first introduced the final rule and guidance on eMDR in 2014, which we blogged about here. Since the final rule took effect on August 14, 2015, medical device manufacturers and importers have been required to submit MDRs in an electronic format. User facilities are not required, but have been encouraged, to submit MDRs electronically. The eMDR requirements pertain to initial and supplemental MDRs and follow-up reports. Additional information responses for an MDR were also encouraged to be submitted electronically.

eMDR submissions can be submitted in one of two ways: Health Level 7 Individual Case Safety Reports (HL7 ICSR) via AS2 (for high volume reporting) or by using FDA’s eSubmitter software (for low volume reporting). The HL7 ICSR option extracts information directly from the reporter’s database to populate the eMDR. The eSubmitter software generates an electronic version of Form 3500A, the form for use by user facilities, importers, distributors and manufacturers for mandatory reporting.

Either way, the information is transmitted to FDA via the ESG. Once the eMDR is submitted through the ESG to FDA, three separate acknowledgement messages are sent to the submitter. These messages are to be maintained as part of the file per 21 C.F.R. § 803.18(b)(1)(iii). Acknowledgment 1 indicates that the submission was received at the ESG. Acknowledgement 2 indicates that the submission reached CDRH. Acknowledgement 3 notifies the submitter that the submission was either successfully loaded into CDRH’s adverse event database or that the submission contained errors, which will be specified in the letter. If errors are identified, the submitter will need to correct the file and re-submit. If there are no issues, the submitter can expect all three acknowledgement letters either on the same day or within 24 hours of the submission.

Updates

The eMDR system will be updated to not accept reports:

• That provide a Patient Age but do not provide the patient age unit in the A2 section of the form;
• That do not identify the Product Code in the D2b section of the form;
• Where the “implant date” (D6a) is after the “explant date” (D6b), if both dates are provided;
• That do not include Adverse Event Problem codes in H6 (for manufacturers) or F10 (for distributors and importers); specifically Medical Device Problem Code and Health-Effect Clinical Code;
• That do not provide a contact email address in G1 (for manufacturers) or F3 (for distributors and importers). (This should serve as a reminder to submitters to carefully review their MDRs ahead of submission.)

In all of the above instances, submitters will receive a rejection message in Acknowledgement 3 describing the error or missing information. Test deployment for the changes listed above were deployed to eMDR on August 19, 2022 and will be deployed to production on March 17, 2023.

The Adverse Event codes accepted in sections F10 and H6 of the 3500A form will be updated to harmonize with maintenance updates from the International Medical Device Regulators Forum (IMDRF). This was deployed to pre-production on August 19, 2022 and implemented in eMDR and eSubmitter the same day.

To provide early notice and predictability about potential eMDR system changes, FDA is adopting a yearly schedule announcing and implementing enhancements to the eMDR system:

1. Announce upcoming enhancements in June,
2. Release the implementation package in August,
3. Deploy enhancements to pre-production (ESG Test) also in August, and
4. Deploy enhancements to production in March of the following year.

Although FDA intends to follow this schedule, emergency fixes may be implemented outside of the schedule. For any major changes, additional time will be granted between the release of the implementation package and production deployment.

To stay up to date with changes or review ones that have been implemented, refer to the regular communications, which can be found here.

As we discussed in our prior post, the electronic Submission Template And Resource (eSTAR) template will take getting used to in terms of form.  It is also going to take some getting used to in terms of process.  As most in the device industry know, preparing a 510(k) is typically a collaborative process—with multiple functions, consultants, and levels of management often involved in its review and creation.

Based on our early experience using the eSTAR template, we discuss some of the challenges in preparing a 510(k) using the eSTAR template as compared to the traditional format.

• Restricted collaboration and inability to track changes. Collaboration and development with iterative reviews and revisions are the biggest challenges we have identified with the eSTAR templates.  The templates do not allow for changes to be tracked by author or the ability to add and reply to comments within the template itself.  These are both features that we use frequently in developing submission content interactively.  The templates allow a version to be saved that allows comments but requires that any changes made in response to the comments be made in the primary version to the file.  If multiple people are reviewing and need to communicate changes it may be challenging to ensure all updates are incorporated.
• Lack of compatibility with cloud-based document sharing. Many teams use cloud-based file sharing systems to work collaboratively on files.  Unfortunately, we have found that the eSTAR template PDF file does not work on these platforms.  It must first be downloaded, revised, and uploaded back to the system.  As above, if multiple people are reviewing simultaneously, and without an easy way to see revisions from each team member, it can be more challenging to ensure all revisions are incorporated.
• Creation of unnecessary documents. For each section that requires an attachment, you must include a file.  There is no option to reference a document that has already been attached elsewhere in the submission.  This may result in the need to create additional documents that you may not necessarily need under the quality system.  One example is a requirement to provide “an attachment that addresses the risks associated with exposure to specific common EM emitters that are not adequately addressed by IEC 60601-1-2.”  This information may be in a system risk analysis that may have been provided as an attachment in the device description or software section versus a standalone document.  Instead of allowing a reference to the location in another attachment where the information is covered, a separate document must be attached.

It is unclear how FDA will handle changes to the template.  For the last 18 years, the 20-section format has been consistent and reliable, although there have been occasional surprises when the refuse to accept (RTA) checklist has been quietly revised.  Sponsors often start working on 510(k)s long before they are filed.  Therefore, we hope that changes to the eSTAR templates are not frequent and that there is ample transition time to use an existing version that a submission was started with when a new version is released.  Overall, we are planning additional time and hope that with a few eSTAR submission under our belts, they will become more easily managed.

For those new to 510(k) submissions or who submit 510(k)s infrequently, having all the necessary content outlined in a single file may be a little less overwhelming compared to the existing process.  Use of the eSTAR templates may decrease the risk that a 510(k)-naïve user submits a 510(k) lacking important information expected by the Agency.  However, not providing the appropriate type of information and level of detail the Agency expects is still possible with eSTAR.  This is especially true for information specific to the device type.  To this end, we doubt there will be fewer requests for additional information for 510(k)s prepared using the eSTAR templates.

FDA has stated that the template aligns with the reviewer templates used within the Agency.  Given the challenges that using the eSTAR template will present to industry, we hope this alignment means we may see some efficiency in FDA review times to balance out the increased time needed for preparation.

A year ago, we blogged about a proposed rule that would replace the Quality System Regulation (QSR) at 21 C.F.R. Part 820 with a newly named Quality Management System Regulation (QMSR) (see here). The proposed rule was published on February 23, 2022 and was first heralded by FDA in 2018 and introduced in the Spring 2018 regulatory agenda. In the proposed rule, FDA stated that any final rule would become effective one year after the date of publication of the final rule in the Federal Register.

It is noteworthy that the one-year anniversary of the proposed rule has come and gone.

Keen observers may have noticed that in the most recent semiannual regulatory agenda, neither the Quality System Regulation nor the Quality Management System Regulation is referenced. This suggests that it is unlikely we will see harmonization of the QSR with ISO 13485 in 2023.

From a historical perspective, FDA issued a final rule in the Federal Register of July 21, 1978, outlining the current good manufacturing practice (CGMP) requirements for medical devices. The regulation became effective on December 18, 1978 and was codified under part 820. In the intervening years between 1978 and 1996, editorial changes were made to update organizational references and revise the list of critical devices included in the preamble.

The Safe Medical Devices Act of 1990 provided FDA with the authority to include design controls in the regulation. FDA also took steps to ensure, to the extent possible, that the CGMP regulation would be consistent with the quality system requirements in applicable international standards. FDA published a proposed rule with revisions to part 820 on November 23, 1993. Nearly three years later, the rule was finalized on October 7, 1996 with the regulation becoming effective June 1, 1997.

This is all to say we recognize the tremendous efforts underway to harmonize the QSR with ISO 13485. We hope to see the topic back on the agenda in the fall and will post an update when the rule is eventually finalized or if anything noteworthy happens before then.

FDA uses its Product Specific Guidance documents (“PSGs”) to provide recommendations as to the bioequivalence testing necessary for approval of a generic drug.  As the Office of Generic Drugs (“OGD”)  has stated, “[t]he clarity and transparency provided by PSGs help streamline generic drug product development, promote timely approval of Abbreviated New Drug Application (ANDA) submissions and increased drug competition, improving patient access to high quality and affordable medicines.”  Indeed, PSGs help facilitate generic competition, and to date, OGD has published more than 2,000 PSGs.

As part of its Generic Drug User Fee Amendments of 2022 (“GDUFA III”) Commitment, FDA agreed to expedited development of PSGs.  Specifically, FDA agreed to issue PSGs for 90 percent of new, non-complex New Chemical Entities within 2 years of reference product approval and 75 percent of complex New Chemical Entities within 3 years of approval.  FDA also agreed, for the first time, to host PSG teleconferences and meetings with applicants to provide feedback on the potential impact of a new or revised PSG on an applicant’s development program.  Pre- and post-submission meetings to discuss alternative approaches than that recommended in PSGs may also be available.

While PSGs are not new—OGD has published them for many years—a new Draft Guidance was released earlier this month covering “Product-Specific Guidance Meetings Between FDA and ANDA Applicants Under GDUFA.”  This new Guidance outlines procedures for requesting and conducting PSG meetings with OGD, including PSG-specific teleconferences, as well as pre- and post-submission PSG meetings.

According to the Guidance, the PSG-specific teleconference—also categorized as pre- or post-submission—is a prerequisite to a pre- or post-submission PSG meeting, and such teleconferences and meetings are available only after the publication of a PSG.  Like the name implies, the pre-submission teleconference or meeting would be held prior to submission of the ANDA while the post-submission teleconference or meeting occurs after submission.  A post-submission PSG teleconference and meeting should occur before responding to a possible bioequivalence deficiency identified during review or in a Complete Response Letter.

The Guidance distinguishes between the PSG teleconference and the PSG meeting.  A PSG teleconference is a forum for applicants to obtain feedback on the impact of a new or revised PSG on an in-progress development program for which in vivo bioequivalence studies have either commenced or completed.  Discussions during these teleconferences are limited to feedback on the potential impact of the PSG recommendations on an existing development program; FDA will not discuss the applicant’s questions regarding an approach other than the approach recommended in the PSG.  Applicants should submit a request for a PSG teleconference within 60 days after publication of the new or revised PSG so that FDA can provide timely feedback to applicants.  FDA may deny a PSG if the applicant’s bioequivalence testing started after the PSG publication.

If OGD indicates in the PSG teleconference that the PSG would impact an applicant’s development program, the Guidance explains that this indicates that the ongoing or completed study alone is unlikely to be sufficient to establish bioequivalence.  Any subsequent changes to the development plan resulting from the recommended PSG can be discussed with FDA in a pre- or post-submission meeting during which the Agency will discuss with the applicant the scientific rationale for an approach other than that recommended in the new or revised PSG.  These pre- or post-submissions meetings (as opposed to teleconferences) are intended to discuss scientific rationale for an alternative to the PSG and address applicant’s questions related to their own proposed bioequivalence approaches.  OGD will deny a pre-submission PSG meeting request if the applicant did not have a pre-submission PSG teleconference or if the applicant has already submitted the ANDA after the pre-submission teleconference.  Similarly, OGD intends to deny a post-submission PSG meeting request if the ANDA applicant did not have a post-submission PSG teleconference or if the ANDA applicant had a pre-submission PSG teleconference and then submitted the ANDA.  OGD may also deny the request if it determines that the questions in the meeting package have been addressed during the ANDA assessment or the ANDA applicant has already responded to the possible deficiencies to be discussed.

Specific timing goals, as well as procedures for requests, apply to each type of PSG meeting.  Meeting package content, timing of submission, and directions for submission are also covered by this Guidance.

And, of course, the Controlled Correspondence process remains an option as an alternative to a pre- or post-submission PSG meeting.

As of the morning of March 1, the hotly anticipated Joint Meeting of the Nonprescription Drugs Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee originally scheduled for March 20 has been cancelled.  The March 20 Joint Meeting concerned the NDA for naloxone hydrochloride nasal spray for nonprescription use as an opioid reversal agent in the emergency treatment of opioid overdose which was submitted by Harm Reduction Therapeutics under the trade name RiVive.  RiVive would be a direct-to-OTC approval and would represent a potential first in class product in a new therapeutic category for nonprescription drugs.  The issues for discussion at the March 20 Joint Meeting were intended to cover the adequacy of the data supporting the nonprescription application for the product.  The reason for the cancellation—scheduled to be published in the Federal Register on March 2—is that “the meeting is no longer needed.”  No further information concerning the cancellation has been made available at this time.

We previously blogged on the February 15, 2023 Joint Meeting of the same advisory committees concerning the rx-to-OTC switch application for Narcan Nasal Spray (NNS).  All 19 members of the joint Advisory Committee agreed that the benefit-risk profile of NNS is “supportive of its use as a nonprescription opioid overdose reversal agent.”  FDA has not yet taken action on the NNS application, but the Prescription Drug User Fee Act (PDUFA) goal date by which a decision is expected is March 29, 2023.

In January 2023, FDA published a paper summarizing its lessons learned from two pilot Quality Management Maturity (QMM) Pilot Programs, such as best practices for conducting QMM assessments and developing the QMM scoring system.  The lessons learned were also discussed during a November 2022 workshop hosted by the FDA.  The purpose of these two pilot programs was initially to inform development of a FDA rating system to characterize the QMM of a facility.  FDA published two Federal Register Notices in October 2020 to recruit domestic drug product manufacturers of finished dosage forms and foreign manufacturers of active pharmaceutical ingredients to participate in the QMM Pilot Programs.

Before discussing the 2023 paper, it’s important to know that the QMM Program is separate from the Quality Metrics Program, which we previously blogged about here, here, and here.  QMM is an umbrella program that includes quality metrics as well as quality culture, risk management, continual improvement, etc.  FDA describes the QMM as “above-the-bar behaviors” that exceed good manufacturing practices (GMPs).  The QMM rating is based on an evaluation of a facility’s quality practices and it is meant to be a leading indicator for detecting problems before they occur, such as a drug shortage.  By way of background, FDA first proposed using a QMM rating in its 2019 Report on Drug Shortages and Potential Solutions.  In this report, it’s stated that 62% of drug shortages reported between 2012 and 2017 were due to quality issues which is attributed in part to a lack of recognition or reward for manufacturers with mature quality management systems that focus on continuous improvement and early detection of supply chain issues.  The report recommends using a QMM rating that is shared throughout the market (purchasers, consumers, competing manufacturers) to provide manufacturers committed to QMM with a competitive advantage.  FDA intends to provide regulatory incentives to manufacturers with robust QMM systems, such as reduced inspection frequency and increased regulatory flexibility in making post-approval changes.  FDA proposed using QMM ratings as part of its decision in selecting sites for surveillance and preapproval inspections.

On November 2, 2022, the FDA’s Pharmaceutical Science and Clinical Pharmacology Advisory Committee held a meeting on CDER’s QMM Program.  In addition to providing some background on QMM, the FDA presented lessons learned from the QMM Program Pilots.  During the workshop, FDA stated that the QMM Pilot Programs will be used to develop a suitable assessment tool to identify indicators of mature quality systems to build a framework to evaluate QMM best practices and identify areas for continual improvement.  Development of this framework to measure a facility’s QMM was included in the July 2021 White House’s 100 Day Report.

The QMM Pilot Programs were conducted using two contractors who developed the QMM assessment protocol questions and the scoring system.  The contractors also conducted the QMM assessment of seven domestic manufacturers of finished dosage form and eight foreign manufacturers of active pharmaceutical ingredient.  FDA staff served as pilot program observers, but also met with the contractors to provide feedback.  The paper discusses lessons learned about the QMM assessment process, scoring approach, assessor behaviors, and perceptions of the assessment questions, reports, and ratings.  A brief discussion on the scoring approach is provided below.

FDA’s 2022 presentation and the information in the FDA’s 2023 paper on the QMM Pilot Programs are similar, but the paper provides more detail on what general aspects were assessed (referred to as practice areas) and the topics within those practice areas.  For example, domestic establishments that manufacture finished dosage forms were evaluated for the following practice areas: 1) leadership and governance, 2) continual improvement, 3) stakeholder engagement and satisfaction, 4) knowledge management, 5) workforce engagement, and 6) operations.  Topics within the practice areas were assigned scores between 1 and 5 with one representing the lowest quality maturity level and five the highest quality maturity level.  FDA provided teasers in Figure 2, showing that topics under leadership and governance may include management commitment, management reviews, oversight, and monitoring, business excellence and societal contribution, and topics under continual improvement may include customer/patient focus and stakeholder feedback and engagement.  The paper did not provide any detail into how the practice areas and topics were developed, but FDA referenced a number of organizations involved in researching and developing measures of QMM, including the University of St. Gallen and the Parenteral Drug Association (PDA).  A recent 2022 study funded by the FDA was intended to study how QMM characterizes quality and may include potential practice areas and topics for future QMM rating development.  Figure 2 of the 2023 paper showed facility and assessor scores, but it did not describe how assessors and the facilities determined the scores.  There also was not a lot of discussion on how often the scores between the assessors and the facilities aligned or not and what this meant, if anything.  FDA recognized in the paper that multiple assessors may be needed per assessment to minimize bias and to maximize inter-rater reliability.

We will continue to monitor the QMM program’s development and will post further information as it becomes available.

Since 2005, 510(k) submissions have been formatted according to FDA guidance Format for Traditional and Abbreviated 510(k)s.  The guidance describes twenty sections to be included in a Traditional or Abbreviated 510(k).  With 18 years’ experience, we have developed a pretty good system for preparing 510(k) submissions in this format.  The general structure of our submissions, and of many others that we have seen, is to have a document for each of the twenty sections and then to refer to other files, such as labeling and test reports, as attachments.  We have made improvements to the content of each of these sections over the years and have included additional information to address other guidance documents and the refuse to accept (RTA) checklist, but the general structure has been constant.  This method of submission development allows for efficient development of each section and collaboration across numerous subject matter experts and internal reviewers.

FDA announced on October 3, 2022 that the voluntary electronic Submission Template And Resource (eSTAR) templates would be required beginning October 1, 2023, as we blogged about here.  The eSTAR templates are interactive PDF forms used to develop and submit 510(k)s (Traditional, Special, or Abbreviated) or De Novo applications, or to submit additional information to these submission types.  There are two forms:  one for non-IVD devices and one for IVD devices.  The same forms are used for both 510(k)s and De Novo submissions.  It appears that use of eSTAR for PMAs may be in the future as it is seen on the templates in the selection for application purpose but is not currently able to be selected.

In order to start learning the format, and also because some submissions can take more than a year for everything to come together and we do not want to switch formats should this occur, we have decided to start some of our newest submissions using the eSTAR non-IVD and IVD templates.  While it may have to do with old dogs learning new tricks, our initial experience suggests that there is a bit of a learning curve and that it might be easier to teach Fido to roll over than it is to figure out a good process for developing 510(k)s in the new format, especially when collaborating with multiple subject matter experts and reviewers, and using cloud-based file sharing.

This post shares some our early learning on how the template works (the good and the bad).  We hope it may be of help to those embarking on an eSTAR submission for the first time.  In a second post, we will cover some of the process challenges that industry may face when using eSTAR.

By way of background, the eSTAR template is a structured form that takes a user section-by-section and question-by-question through the content of the 510(k).  The questions are generally targeted on determining what information needs to be included in the 510(k).  For example, in the Device Description section of the eSTAR template you are asked questions related to, among other things, tissue contact, software/firmware, sterility, device environment, and electrical power.  Based on responses, additional sections, questions, data fields, and places to link files, called attachments, are added.  For example, answering “yes” to the question related to use of software/firmware opens new fields for selecting related technology, including use of cloud communication, network connection, wireless communication, USB/serial ports, and software upgrades.  The selections made here impact the content that will be required later in the section of the templates related to software.

In some sections, there is a field within the template that can be used to enter the requested information or to justify why the information is not needed, or why an alternative approach was used.  In other sections of the template, attachments will be needed to include this type of information.  The text boxes also cannot accommodate tables or figures, which are often helpful particularly in comparing to a predicate device and/or explaining technological features of a device.

While this sounds like a helpful, step-wise process, it is not as easy as it may sound.

Learnings on how eSTAR works

• Starting Too Early. We all know sponsors are eager to get to clearance and sometimes even start working on their 510(k) submissions while still in development/before the device is finalized.  This could be done with the old format because the sections were fixed at the outset and could be iterated on.  In the eSTAR template, because answers to early questions cause various sections to appear in the template or not (e.g., if a user answers no to a device being sterile, the sterility sections does not present for population), a user may not know answers to all of the questions when they want to start preparing the information and/or they may miss a section depending on how they answer.
• Know Your Guidances. Several sections of the eSTAR templates have questions that walk through related guidance documents.  For example, the template asks for the number of reprocessing instructions, sterile methods, tissue contact materials, and electronic interfaces and then requests information related to the reprocessing instructions and validation, sterilization validation, biocompatibility, and interoperability in line with relevant guidance documents.  It is important to be familiar with the relevant guidance documents to answer the questions in an appropriate manner.  There are additionally places to provide attachments for test reports and other supporting documents.
• Performance Testing Summaries No Longer Needed? Maybe.  The required content related to performance testing seems to be a bit light in comparison to other sections.  The RTA checklist for eCopy 510(k) submissions requires a summary of bench performance testing formatted per FDA guidance Recommended Content and Format of Non-Clinical Bench Performance Testing Information in Premarket Submissions.  In the eSTAR template, the only requirements are a complete test reports for the testing.  This omission is quite surprising given that we have recently seen some RTA deficiencies related to lack of this summary.
• Performance Testing Comparator versus Predicate. Also, in the performance testing section of  the eSTAR template, the sponsor must identify the 510(k) number for a device “that is the best comparator for the testing.”  We find it interesting that the template calls for a predicate device that may not be the same as the predicate device used to support substantial equivalence.
• Missing Human Factors. We also note that there is no specific section of the eSTAR templates for human factors documentation to be included. We find this omission somewhat ironic seeing that this template was clearly not prepared using a human factors approach.  We plan to provide the performance test summary and human factors documentation as attachments to the bench performance testing section of the templates.
• New Labeling Requirements. As we navigate the questions throughout the template, we find that there seem to be some embedded labeling requirements that we have not previously seen.  For example, in the section for EMC, Wireless, Electrical, Mechanical and Thermal Safety there is a requirement to provide testing to support use in an aircraft or a reference to a specific attachment and page where a labeling mitigation that cautions against the use of the device in an aircraft is located.  So even if it is completely obvious that a device would not ever be used in an aircraft, sponsors will need to make sure labeling covers this issue.  Submitters should be sure to review all questions of the template carefully early in development to ensure specific labeling information is incorporated (although not too early in development – see our first point above).
• Option to Automate the 510(k) Summary. There is an option to provide a 510(k) summary as an attachment or you can enter summary information in fields throughout the template that will be used to auto generate a 510(k) summary.  We will be opting for the attachment as we often use tables or other formatting in 510(k) summaries that are not possible in the eSTAR template fields.
• Unnecessary Sections Cannot Be Omitted. For submissions of a modification to an existing device, the template requires information for all sections, even if the content of the section is not affected by the change.  In eCopy submissions, a single paragraph could often be used to make statements regarding the nature of the change and explain why new information or testing was not required compared to the previous clearance.  In eSTAR, these statements require repetition in multiple fields and attachments – making it anything but least burdensome.  For example, for a patient contacting device, the number of tissue contacting materials are identified in the template and then, for each material, the contact type and duration are filled in.  The template uses this information to generate tabs for each biocompatibility endpoint that should be evaluated per the relevant guidance.  For a modification to a patient contacting device that does not affect materials or biocompatibility, each tab for each material will require the justification for why that test was not repeated.   The situation is similar for submissions where software is not changing.  The eSTAR template will require a separate attachment for each document type (e.g., SDS, architecture document, software verification and validation) even if the same justification and reference to the prior clearance can be used across all required documents.

But, it is not all doom and gloom when it comes to eSTAR—a few things will remain unchanged (thank goodness!). First, in the eSTAR template, the sections for the Device Description, Substantial Equivalence, and Executive Summary require attachments.  This means the attachments can be formatted and organized in whatever way the sponsor prefers.  Based on our work to date, we have needed to make only a few updates to the format we used for eCopy submissions.  Given that these are some of the most critical sections in the 510(k), it is a great relief to know their structure and organization can largely remain the same.

Second, there is an option to continue to submit responses to additional information (AI) requests in an eCopy format. The eSTAR templates can also be used to respond to requests for additional information.  When entering the template, the user can select “additional information” as the submission type.  When doing so, a pop-up window provides two options.  The options are (1) to provide responses and attachments as an eCopy without an updated eSTAR template, or (2) to provide an updated eSTAR template (using the same version used for the original submission).  In this case, a section of the eSTAR template will be completed by copying the deficiency into one field and providing the response in another field.  New attachments are then included in the relevant section of the eSTAR template itself.  Depending on the nature of the deficiency, the fields in the template may not be sufficient for providing lengthy explanations that require tables, figures, or formatting to keep the response clear and organized so we are glad the eCopy option will still be available.  As anyone who has ever worked on a lengthy and/or complicated AI response knows, these responses do not always fit neatly in a text box.

Transitioning to the eSTAR template will taking some getting used to.  In both the form, as discussed above, and in process—which we will cover in Part 2 of our post.

The Drug Enforcement Administration’s (“DEA’s”) February 13th determination that THC acetate ester (“THCO”) is a schedule I controlled substance under the federal Controlled Substances Act (“CSA”) has received a good amount of attention in the cannabis press.  That determination, however, was neither a stretch nor a surprise to Rod Kight, the North Carolina attorney who posed the question to DEA, and to those who have recently analyzed whether certain cannabinoids are controlled, and if so, how.

THC acetate esters are different than delta-9-THC, the psychoactive compound found naturally in the cannabis plant.  Terrence L. Boos, Ph.D., Chief of the DEA Diversion Control Division’s Drug and Chemical Evaluation Section, responding to Kight, observed that the only THC acetate esters his agency is aware of are delta-9-THCO (“delta-9-THC acetate ester”) and delta-8-THCO (“delta-8-THC acetate ester”).  Letter from Terrence L. Boos, DEA, to Rod Kight (Feb. 13, 2023).  Dr. Boos noted that under 21 C.F.R. § 1308.11(d)(31) tetrahydrocannabinols (“THC”), controlled as schedule I substances, are “naturally contained” in the cannabis plant, but include “synthetic equivalents of the substances contained in the cannabis plant and/or synthetic substances, derivatives, and their isomers with similar chemical structure and pharmacological activity” to substances in the plant.

Dr. Boos explained that delta-9-THCO and delta-8-THCO have similar chemical structures and pharmacological activities as compounds in the cannabis plant so they fall within the definition of THC.  But, he noted, because neither delta-9-THCO nor delta-8-THCO occur naturally in the cannabis plant, they can only be obtained synthetically.  And because they do not occur naturally within the cannabis plant, they are not hemp and not excluded from control by the Agricultural Improvement Act of 2018 (“the Farm Bill”).  Dr. Boos’ determination is consistent with DEA’s August 21, 2020, interim final rule implementing the Farm Bill, noting that statute limited non-controlled THC to compounds within the statutory definition of “hemp,” that is only materials derived from the cannabis plant and did not impact the schedule I control of synthetically-derived THC.  Implementation of the Agriculture Improvement Act of 2018, 85 Fed. Reg. 51639, 51641 (Aug. 21, 2020).  (He also noted that because delta-9-THCO and delta-8-THCO are controlled substances, they do not meet the CSA’s definition of a “controlled substance analogue.”)

DEA’s determination that delta-9-THCO and delta-8-THCO are schedule I controlled substances reaffirms that any synthetic compound that does not occur naturally within the cannabis plant but which has similar chemical structure and pharmacological activities as THC, is a schedule I controlled substance.

The FDA Alumni Association (FDAAA) named Hyman, Phelps & McNamara, P.C.’s Director Deb Livornese as its 2022 Volunteer of the Year for her remarkable leadership steering its Activities Committee through COVID and many new challenges.

The FDAAA, whose members are FDA alumni and current employees, helps alumni stay in touch with the issues of the day facing FDA and supports the Agency’s public health mission.  The award was given at the association’s well-attended Winter Celebration on February 21, 2023.

“Having top-notch lawyers like Deb who have experience at the Agency is part of what contributes to our success as a firm.  We’re thrilled for Deb and pleased that her excellent work has been recognized,” said JP Ellison, HPM’s Managing Director.

The 2008 Ryan Haight Online Pharmacy Consumer Protection Act placed strict limits on online prescribing or the use of telemedicine encounters to prescribe controlled substances. The Ryan Haight Act was enacted to address the legal “grey area” in which prescribers and pharmacies operated via the creation of two new statutory requirements: 1) the at least one “in-person” medical evaluation requirement for prescribing practitioners, 21 U.S.C. § 829(e); and 2) the modified registration requirement for online pharmacies. 21 U.S.C. § 823(f).  The Act also established new definitions for “Internet,” “online pharmacy,” “practice of telemedicine,” among others. Notably, the Ryan Haight Act (and the later SUPPORT Act of 2018) also required DEA to promulgate regulations related to a “special registration” to engage in the practice of telemedicine, which now 15 years since the 2008 Act’s passage, DEA announced on February 24th – likely as a result of the relaxation of telemedicine requirements during the COVID-19 public health emergency.  21 U.S.C. § 802(54)(D)(i). That emergency declaration is set to expire on May 11, 2023. While no “special registration” will yet be required to engage in telemedicine prescribing of controlled substances, DEA is proposing parameters to guide the practice of telemedicine encounters in a post-COVID world.

The Ryan Haight Act did not limit the ability to prescribe controlled substance medications by telemedicine so long as the patient and prescriber had a least one in-person visit.  DEA’s proposed rule when finalized would authorize telemedicine pursuant to the Controlled Substances Act, 21 U.S.C. § 802(54)(G), where: 1) the prescribing practitioner has not conducted an in-person medical evaluation with the patient; 2) the prescription was issued pursuant to a telemedicine encounter; and, 3) the telemedicine encounter results in a prescription for a controlled substance medication. Section 502(54)(G), unlike the other six “permissible” telemedicine encounters in the Ryan Haight Act, permits DEA to pass regulations to expand the use of telemedicine.  See 21 U.S.C. § 503(54)(G) (specifically, telemedicine “being conducted under any other circumstances that the Attorney General and the Secretary have jointly, by regulation, determined to be consistent with effective controls against diversion and otherwise consistent with the public health and safety.”) The rule would require that the prescriptions be issued consistent with both state and federal law, and the practitioner to maintain an active DEA registration in the state in which the practitioner is located.

General Telemedicine Proposed Rule

One of the proposed rules, titled “Telemedicine prescribing of controlled substances when the practitioner and the patient have not had a prior in-person medical evaluation,” linked here, addresses a practitioner’s use of a defined “telemedicine encounter” to prescribe schedule III-V non-narcotic controlled substances and related parameters surrounding such prescribing when the patient and prescriber have not had a prior in-person evaluation.

The rule would permit a practitioner using a telemedicine encounter to prescribe controlled substances without an in-person visit under various situations involving both an audio-visual telehealth evaluation, or an in-person evaluation performed by a “referring” provider.  Notably, for services furnished for purposes of diagnosis, evaluation, or treatment of a mental health disorder to a patient generally in their home, interactive telecommunications may include two-way, real-time audio­only communication technology, if the “distant site” physician or practitioner is technically capable to use an interactive telecommunications system, but the patient is not capable of, or does not consent to, the use of video technology.  These audio-only encounters would seem to be an exception to DEA’s stated preference for use of audio-video telemedicine encounters.  The rule would also require enhanced recordkeeping requirements for both the referring practitioner (i.e., a prescriber that conducts an in-person visit) and prescribing practitioner (i.e., a prescriber that engages in telemedicine with the patient), including a review of PDMP data for the past year.

Importantly, if relying on a telemedicine visit, the prescription must be for an initial 30-day period, and only for schedule III-V non-narcotic controlled substances. If the patient seeks greater than the initial 30-day supply, then the telemedicine prescriber or referring prescriber must perform an in-person evaluation prior to prescribing additional controlled medications beyond the 30-day period. The visit may, however, include a patient’s in-person visit with another practitioner while on an interactive video link with the prescribing practitioner.

If an in-person evaluation is performed by either a referring provider or the prescribing provider, the patient may also receive schedule II controlled substances, consistent with Ryan Haight requirements already in place.

Lastly, the proposal permits continued prescribing of controlled substances (schedules II-V) for a period of 180 days following the end of the COVID-19 emergency declaration (i.e., 180 days past May 11, 2023) for those telemedicine relationships established during the COVID-19 emergency.

DEA is Seeking Comments, But on a Short Fuse

The proposal lastly notes that DEA is seeking public comments on various topics, but on a short, 30-day timeline given the looming end of the pandemic emergency.  Comment topics suggested by DEA include the following:

• Whether the rule should limit the issuance of prescriptions for controlled medications to FDA-approved indications contained in the labeling for those medications.
• Proposed practitioner recordkeeping obligations.
• Comments, including data from research and clinical practice, that provides evidence that an alternate maximum day supply (other than the proposed 30-day supply).
• Additional safeguards or flexibilities that should be considered with respect to the rule.
• Whether the proposed rule concerning the induction of buprenorphine via telemedicine (see below) should be combined with the general telemedicine rulemaking.

Telemedicine Prescribing of Buprenorphine for the Treatment of Opioid Use Disorder

DEA is also proposing regulations, linked here titled, “Expansion of induction of buprenorphine via a telemedicine encounter,” which would expand the circumstances under which practitioners are authorized to prescribe any schedule III, IV, or V narcotic controlled substance — approved by FDA specifically for use in the maintenance or detoxification treatment of OUD — via a telemedicine encounter.  The encounter may include an audio-only telemedicine encounter that meets the standards for the same set forth in CMS’s telehealth services regulations at 42 C.F.R. § 410.78(a)(3), provided certain requirements, including requirements under state laws and conditions are met. \

Specifically, DEA notes that in those states where state law prohibits the prescription of a controlled substance based solely on an audio-only evaluation, the proposed regulation would not authorize the audio-only prescription of buprenorphine for opioid-use disorder (OUD). Thus, the  authorization of audio-only OUD telemedicine prescribing, and audio-video prescribing, would only apply in those states where such prescriptions are consistent with state law. The same is true with the general telemedicine proposed rule, above.

The only schedule III-V narcotic drug that is currently approved by the FDA for OUD treatment is buprenorphine. DEA notes that expanding a registered practitioner’s authority to prescribe buprenorphine for the treatment for OUD via telemedicine, including an audio-only telemedicine encounter, would expand access to needed medical treatment. Relatedly, DEA states:

Recent studies have revealed that, in some populations, upward of 94 percent of the unhoused community had a cell phone, while a limited amount owned or had access to computers, tablets, or internet access. Not only would this rulemaking make it easier for patients to obtain treatment, many practitioners have shown a willingness to treat patients using an audio-only telecommunications system.

The rule would require the practitioner to check and maintain PDMP data for patients prior to issuing the prescription, which DEA asserts will assist the practitioner in making clinical decisions.

The authority to prescribe buprenorphine by telemedicine is not unlimited, however.  Not only must prescribing be consistent with state laws addressing use of telemedicine, but the patient must also receive a medical evaluation meeting certain requirements within 30 days of being prescribed buprenorphine via telemedicine for the induction of OUD treatment in order to obtain an additional supply of buprenorphine.  Thus, the regulations would require that, within 30 days, the patient must either be examined in person by the prescribing practitioner or practice, or the prescribing practitioner would have to examine the patient remotely while the patient is in the physical presence of another DEA­ registered practitioner that is participating in an audio-video telemedicine encounter with the prescribing practitioner.

Alternatively, the requirement of a medical evaluation is satisfied when the prescribing practitioner receives a qualifying telemedicine referral for medication assisted treatment for OUD from a DEA-registered practitioner prior to issuing a prescription for controlled substances.  Under this scenario, DEA notes the patient has already received the in-person medical evaluation from the referring practitioner, and thus the prescribing practitioner is authorized to prescribe beyond the 30-day limit.

***

For both proposed rules, the bottom line is that, while telemedicine is here to stay, circumstances permitting it are indeed not limitless. Remaining at the heart of any telemedicine encounter and controlled substances prescription is the need for an in-person medical examination – at some relatively early point (i.e. within 30 days) in the doctor-patient relationship.

And, as one who loves easy-to-follow charts… DEA has published one here, setting forth the various general parameters for prescribing via both telemedicine and in-person visits – and covering both the general and buprenorphine telemedicine proposed rules. Helpful practitioner prescribing guidance is set forth in a simplified document here.  We will release exciting details of our upcoming webinar addressing telemedicine soon.  Stay tuned.

One misnomer that has been repeated over the years has been the reference to the “Drug Enforcement Administration” (“DEA”) as the “Drug Enforcement Agency.”  This error has appeared not just in articles and other news publications but in some court documents as well.  The DEA has even made the same mistake.  Default Provisions for Hearing Proceedings Relating to the Revocation, Suspension, or Denial of a Registration; Correction, 87 Fed. Reg. 73246 (Nov. 29, 2022).  Interestingly, this same issue does not appear to have occurred with the Food and Drug Administration, in that, I am not aware of erroneous public references to the “Food and Drug Agency.”

This faux pas may take on new meaning given that recently the Department of Justice (“DOJ”) and DEA have argued that DEA is not an “agency” after all.  In a case involving a challenge to a Freedom of Information Request (“FOIA”) submitted to DEA, the DOJ and DEA appear to now argue that DEA is a “component” of the DOJ and not an agency.  Aims Institute, PLLC, v. Merrick Garland, et. al, Case No. 4:2022-cv-02396 S.D. Tex. (2023).  In an erratum filed to the deposition of an official previously self-identified as the Chief FOIA Officer, the government stated that the individual was in fact, not the Chief FOIA Officer for DEA but Chief of the FOIA/PA Unit at DEA.  The errata further stated that the Chief FOIA Officer was Vanita Gupta, Associate Attorney General of DOJ.  Also, the errata stated that DEA is a “component” of DOJ not an agency.

I refer you to the pleadings in the case and the recent motion filed by the Plaintiff that discusses the merits of the argument as to why DEA is an “agency” and should be held to statutory and regulatory requirements of any administrative agency.  The arguments in this case also highlight a longstanding frustration with obtaining FOIA information from the DEA.  In many cases, it appears DEA does not have the resources or infrastructure to maintain and produce the information to respond to FOIA requests as do other administrative agencies such as FDA.  DEA has always been somewhat unique in that arguably it is primarily a law enforcement agency that has been “burdened” with serving as an administrative agency tasked with regulating manufacturers, distributors, pharmacies and practitioners.

This case may have deeper ramifications on many of DEA’s administrative functions if there is a finding that DEA is not an agency.

More than a decade ago, FDA began systematically to incorporate review of human factors (HF) design validation within 510(k) reviews.  In 2016, the agency issued its definitive HF guidance to guide manufacturers through human factors engineering processes during the development of new medical devices, focusing specifically on the user interface.   All this time, FDA has applied the requirement for HF data to a subset of device types that pose the highest usability‑relate risks, e.g., software controlled devices, some hospital devices, and home use devices.  Accordingly, only a subset of 510(k) submissions have historically included HF validation data.

Now FDA has issued a draft guidance, Content of Human Factors Information in Medical Device Marketing Submissions (Dec. 9, 2022).  This guidance is intended as a complement to the earlier one, focusing on the type of HF data manufacturers should supply in a marketing submission.

In one way, this is good news.  The generation of HF data is a detailed and fairly burdensome process, although certainly short of a full-blown clinical study.  Furthermore, FDA’s HF reviews tend to generate a good percentage of the burdensome additional information (AI) requests in 510(k) reviews.  Many of these AI requests arise because of manufacturer unfamiliarity with the peculiarities in vocabulary and requirements current among FDA’s HF review staff.  And HF‑related AI requests are especially nerve‑racking to manage, because of the ever‑present threat that the study must be repeated to adequately respond.  Industry would certainly welcome guidance intended to smooth the HF aspects of 510(k) reviews.

But there is a very big fly in this ointment.  At least as currently drafted, it appears that the draft HF guidance dramatically expands the number of 510(k) submissions that require HF data.  The threshold is set extremely low:  if there is one “critical task” identified for a new or modified device, HF data must be addressed in some fashion.  (A “critical task” is a “user task which, if performed incorrectly or not performed at all, would or could cause serious harm to the patient or user, where harm is defined to include compromised medical care.”)

To put it another way, according to the draft guidance, the only valid justification for not including human factors data for a new device is that there are no critical tasks.  In the past, FDA made relatively specific determinations as to the HF data requirements (or lack thereof) for various types of device.  This approach is one-size-fits-all.  It will dramatically increases the burden and uncertainty associated with every submission across many device types.

If a single critical task is identified, then human factors validation must be included, regardless of whether such testing was required for the identified predicate.

If the submission is for a modified device which involves a new critical task or which impacts an existing critical task, then a human factors engineering report is required even if usability data were not required for clearance of the original unmodified device/predicate.

The only exception for a modified device is when there were no changes to: the user interface; intended device users; intended device uses; intended use environment(s); training or labeling.  Even in those cases, a high-level summary of the HF evaluation must be included.  FDA could challenge a company’s rationale for concluding that a change did not impact “human factors considerations” and thereby request HF data.  Once again, the uncertainty associated with the submission process will increase.

The draft guidance is at odds with the fundamental purpose of the 510(k) program, to enable an efficient risk-based process for FDA review and clearance of low to moderate risk devices.  A fundamental tenet of the program is that the same testing required for the predicate is generally required for the subject device.  Typically, only changes in technological characteristics from the predicate require use of test methods not required for the predicate.

Consider this scenario:

• A manufacturer files a 510(k) for a Class II device, a surgical mask.
• The subject device is identical to the predicate in all respects.
• Both devices have a single critical task (they must be correctly fitted by the user).
• FDA did not require HF data as a basis for clearance of the predicate.
• The device-specific guidance for surgical masks does not require HF data Surgical Masks – Premarket Notification [510(k)] Submissions | FDA.
• Per this new HF draft guidance FDA would require the highest level, tier 3 HF usability data for 510(k) clearance of the new surgical mask.

As the example shows, this draft guidance departs from the long-standing approach and introduces a new requirement for HF testing, regardless of whether such testing was required for the predicate and regardless of whether alternative methods of addressing differences in technological characteristics are available and less burdensome.  The new policy needs to be justified on a cost/benefit basis, which has not been done, at least as far as can be discerned from the draft guidance.  For example, the agency has not offered how many 510(k) submissions currently require HF data, the adverse effects of not applying an HF requirement more widely, and how many submissions would now present HF validation data after the change goes into effect.

At least to our knowledge, it appears that currently a relatively focused subset of all 510(k)s currently require HF validation.  If so, implementation of the draft guidance will likely cause in dramatic increase in burden on applicants and FDA.  For example, there could be a significant increase in Q‑Subs in order to work out the HF validation protocol or ensure that the agency agrees that HF data is not required.  This issue will increase uncertainty in the 510(k) modification decision making process. For example, if a critical task is introduced or impacted does that trigger the need for a new 510(k)?

The draft guidance can be fixed by simply deferring to existing requirements as to when HF data are required (e.g., as a de novo special control or in a guidance document for a specific device type).  To justify an expansion of the 510(k) burden of this magnitude, FDA needs to provide a clear and detailed accounting of what the problem is, the cost of this change, and why it will improve safety without hindering the development of better devices.

FDA says the primary purpose of this draft guidance is to smooth 510(k) reviews by providing more granular information about how to address the requirement.  It seems like mission creep for FDA to go beyond this primary purpose to impose a dramatic expansion of the requirement.

In short, this draft guidance imposes a major policy change with far-reaching implications.  Simply saying that the approach is “risk-based” is not adequate justification.  The costs and uncertainty of this expansion to HF requirements are significant.  The countervailing need for the change, however, is not well‑documented.  FDA should be careful not to upset the balance inherent in the current 510(k) system, which is used to bring the majority of medical device to market.

Comments on the draft guidance are due on or about March 8, 2023.

Last October, President Joe Biden directed the Secretary of Health and Human Services (“HHS”) and the Attorney General to begin the administrative process of reviewing current marijuana scheduling under federal law.  Then, Congress passed and the President signed the Medical Marijuana and Cannabidiol Research Expansion Act into law in December.  Last month, the Food and Drug Administration (“FDA”) announced in a release that it would not conduct rulemaking that would allow cannabidiol (“CBD”) to be marketed in dietary supplements or conventional foods because “a new regulatory pathway for CBD is needed that balances individuals’ desire for access to CBD products with the regulatory oversight needed to manage risks.”  FDA Statement, FDA Concludes that Existing Regulatory Frameworks for Foods and Supplements are Not Appropriate for Cannabidiol, Will Work with Congress on a New Way Forward.

FDA Principal Deputy Commissioner Janet Woodcock, M.D. issued the release on January 26th stating that she had chaired an FDA “high-level internal working group to explore potential regulatory pathways for CBD products.”  Dr. Woodcock announced that a new regulatory pathway is needed, noting that FDA is prepared to work with Congress on the matter.  She also announced denial of three citizen petitions asking FDA to conduct rulemaking to allow CBD products marketed as dietary supplements.

The release explained that studies have suggested that CBD can potentially harm the liver and male reproductive system and can interact with certain medications.  Exposure to vulnerable populations including children and pregnant women is also a safety concern.

A new regulatory pathway, the statement opines, would provide safeguards and oversight, managing and minimizing risks related to CBD products.  But what would an adequate regulatory pathway require?  What safeguards would it employ?  The statement explains that risk management tools could include clear labeling, prevention of contaminants, CBD content limits, and age restrictions to mitigate the risk of ingestion by children.  A new pathway could also provide access and oversight for animal CBD-containing products.

FDA’s current food and dietary supplement authorities provide limited tools for managing the risks associated with CBD products.  Under current law, the statement warns, any substance, including CBD, must meet specific safety standards to be lawfully marketed as a dietary supplement or food additive.

The working group reviewed studies related to CBD-based Epidiolex, published scientific literature, information submitted to a public docket, and studies conducted and commissioned by FDA.  The working group determined it is not apparent how CBD in dietary supplements and foods could meet safety standards because FDA has “not found adequate evidence to determine how much CBD can be consumed, and for how long, before causing harm.”

The release further noted that CBD also poses risks to animals and humans who could unknowingly be exposed to CBD by consuming meat, milk, and eggs from animals that ingest CBD.  For that reason, FDA also does not intend to pursue rulemaking that would allow CBD in animal food because it is not apparent how CBD products could meet the safety standards for animal food.  As with CBD in dietary supplements and human food, a new regulatory pathway could provide access and oversight for CBD-containing animal products.

The release warned that FDA would continue to take enforcement action, in coordination with state regulators, to protect the public against CBD and other cannabis-derived products.  FDA promised to remain diligent in monitoring the marketplace, identifying products that pose risks and acting within its authorities.  The statement observed that FDA looks forward to working with Congress to develop a cross-agency strategy to regulate CBD-containing products to protect public health and safety.

Meanwhile, dietary supplements and foods containing CBD continue to be marketed and consumed.  Key among questions raised by the release are:

1. What will the new regulatory pathway look like?
2. How will FDA work with Congress on CBD in dietary supplements and foods?
3. Will Congressional Democrats and Republicans work together on these issues or will such efforts be hindered by partisan deadlock?
4. How long will it take to agree upon and establish an acceptable regulatory pathway?

Inquiring minds are waiting.