With the Quality Management System Regulation (QMSR) compliance date of February 2, 2026, FDA has been convening a series of town hall discussions to help industry with compliance.  In our previous post we discussed FDA’s final town hall prior to the compliance date and the Agency’s emphasis on risk, design, and culture of quality.  On April 1, FDA held another town hall that reviewed the updated Inspection of Medical Device Manufacturers Compliance Program Manual (CP-7382.850) (the CP), which we blogged about previously.

In the opening remarks, FDA summarized the two inspection models and noted that unlike prior inspections under the Quality System Inspection Technique (QSIT) that each inspection will include evaluation of each area of a company’s Quality Management System (QMS).  After the summary, FDA turned to a panel of experts who responded to frequently asked questions related to FDA inspection under QMSR and the new CP.

There were several points made by the panel that are worth highlighting.

Risk-based approach

FDA noted that while they previously requested risk management (RM) documentation during QSIT inspections, under QMSR inspections they will emphasize RM documents and risk controls throughout the QMS. During inspections, FDA will review RM files and reports for products, risk analysis (hazard/harm), documentation showing how risk controls are implemented, and documentation to show risk controls are effective.

When asked about methodology to assess risk in different areas of the QMS, FDA noted that different processes carry different levels of risk and that manufacturers can use different RM approaches as long as the approach used is appropriate for risks involved and risk-based decisions are documented in the QMS.  FDA stated that the risk-based approach for administrative processes, such as document control or training,  is different from the formal risk process used to evaluate product risk under clause 7.1 of ISO 13485.  FDA noted that manufacturers will not need separate risk assessments for administrative processes.  Instead, when making decisions, manufacturers should reference risk documents related to the product.  As an example, FDA noted that risk documentation related to the manufacturing process may be used to determine training frequency.  FDA did not, however, explain what happens when an entity is not the owner of the product risk documentation.  For example, when the establishment is the contract manufacturer and does not own the design or it is merely the initial importer.  As with other town halls, FDA did not take questions from the audience during this one either.

Inspection Technique

FDA noted that the inspection process will be largely the same under the CP as it was under QSIT, though there are some notable differences.  What isn’t changing is that investigators will still provide a Form 482, tour the facility, ask to see how products and processes work, ask about roles and responsibilities, review quality data and documents, observe and watch processes in action, and issue a Form 483 for any inspectional observations, which can be annotated or responded to in writing after the inspection.  Specific documents and evidence reviewed will continue to depend on the risk of the device and priorities for the inspection, and the threshold for compliance action has not changed.

One difference in inspections under the CP is that a statistical sample, as used in QSIT inspections, is not required.  Investigators will conduct record review as they deem appropriate, with the number and type of records being selected based on product risk, and the investigators’ experience and professional knowledge.

As noted above, unlike QSIT inspections, each Model 1 or Model 2 inspection under the CP will evaluate all applicable QMS areas and Other Applicable FDA Requirements, with Model 1 inspections evaluating at least one element in each area and Model 2 inspections evaluating all elements.  FDA noted that in Model 1 inspections, the number of elements reviewed is the minimum and is flexible, allowing inspectors to expand as needed in accordance with a risk-based approach.  FDA noted that investigators will typically cover more than one element to ensure risks are controlled.

QMSR inspections will now include review of management review, internal audits, and supplier audits, which were out of scope in previous inspections under the Quality System Regulation.  When asked how far back inspectors will look at records for management review and audits, and what guidance inspectors are given for review of these new record types, FDA noted that for baseline inspections and pre-approval inspections, these records will be specifically requested.  In other inspections, FDA expects to use their findings to determine when to review these records.  For example, if the inspection identifies issues in design, the inspector may look at how internal audits have evaluated design.

FDA additionally commented that inspections will not follow the Medical Device Single Audit Program (MDSAP) approach and that there are no additional guidance documents planned to support the CP.

Culture of Quality

In prior town hall discussions, FDA emphasized the need for a culture of quality.  When asked how to demonstrate a culture of quality, FDA stated there are no special steps to document quality culture – it is reflected in decisions made and actions taken throughout the QMS.  FDA investigators will look at how manufacturers operate and make risk-based decisions.

FDA also noted that the manufacturers should ensure the internal audit program is evaluating how risk management is integrated throughout product development, how a risk-based approach is used throughout the QMS, and how risk controls are implemented in each impacted process.

FDA’s most recent QMSR town hall discussion provided valuable insight into how inspections will be conducted and where investigators will focus their attention. While many elements of QMSR inspections will feel familiar, the shift toward evaluating the entire QMS, the increased emphasis on risk management integration, and the broader discretion afforded to investigators represent meaningful changes that manufacturers should not underestimate.

The Byrds was one of my favorite bands growing up.  I find much of their music fresh and timely today due in no small part to Roger McGuinn’s trademark jingle-jangle on the Rickenbacker twelve-string guitar.  The Byrds’ version of Pete Seeger’s “Turn! Turn! Turn!” reached Number One on the Billboard charts in December 1965.  Seeger took the lyrics, ascribed to King Solomon in the 10^th Century B.C., mainly from the King James Bible, thereby giving the Byrds recording of the song the distinction of being the Number One Billboard hit with the oldest lyrics.

For those unfamiliar, the powerful song’s theme is that there is a season and a time for everything: a time to be born, a time to die; a time for war, a time for peace.

However, an updated version of the lyrics might include the timely line:
“A time to cast away meds, and a time to gather meds together.”

Which segues us lyrically to the Drug Enforcement Administration’s (“DEA’s”) 30^th National Prescription Drug Take Back Day.  Unwanted and expired controlled prescription medication languishing in medicine cabinets are prime candidates for theft, misuse and abuse.  DEA and its law enforcement partners will once again host about 4,200 local drop-off locations nationwide for safe disposal of unneeded medication on Saturday, April 25th, from 10:00 a.m. to 2:00 p.m. local time.

DEA holds the ever-popular drug take back event each spring and autumn.  Last October’s Take Back Day collected over 571,000 pounds, or 286 tons, of unneeded medication at 4,263 collection sites nationwide.  DEA has collected over 20.3 million pounds, or 10,196 tons, of unneeded medication since 2010.  Additional information about National Prescription Drug Take Back Day, including disposal locations, can be found here.  DEA’s Diversion Control website also lists permanent year-round drug disposal locations and provides other disposal information.

So, in the spirit of an updated “Turn! Turn! Turn!,” we’ve gathered meds together, but now its time to cast them away.

Last week, FDA released its Justification of Estimates for Appropriations Committees for the Agency’s Fiscal Year 2027 (“FY2027”) budget request.  Prior budget requests included a separate document titled “FDA Legislative Proposals” (see, e.g., here, here, here, and here; and our prior post here).  The FY2027 budget request incorporates them into the broader Justification of Estimates for Appropriations Committees document (Pages 16-27).  But that’s not the only difference this year compared to prior years.  For FY2027, FDA’s budget request includes a whopping 27(!!) legislative proposals.  Here’s the run-down:

1. Holding Firms Accountable Using Misleading Advertising to Drive Profits at the Expense of Consumers
2. Strengthening Oversight of Critical and Other Foods to Better Protect Infants and Children
3. Allow Companies Manufacturing Generic Medications Domestically to File Paragraph IV Certifications Earlier, Giving Exclusivity Rights to US Manufacturers
4. Ensure FDA Access to Industry Data to Strengthen Food Chemical Safety
5. Allow Disclosure of Certain Information in Complete Response Letters
6. Require Destruction of Imported Products that Pose a Significant Public Health Risk
7. Create Efficiencies for Review and Approval of Biosimilar Applications and Deem that Approved Biosimilars are Interchangeable
8. Increase Agency Flexibility Regarding the Convening of Advisory Committees and the Composition of Such Committees
9. Strengthen Enforcement Against Importation of Unauthorized Electronic Nicotine Delivery Systems (ENDS) and Other Illegal Tobacco Products
10. Mutual Recognition Authority for Bioresearch Monitoring Inspection
11. Collect Foreign Food Facility Registration Fees
12. Create an Additional Abbreviated Licensure Pathway for Biological Products
13. Explicitly Address Generic Drug-Device Combination Products
14. Clarify When Patent Information Must Be Submitted for a 30-Month Stay to Be Available
15. Creating Parity Between Nicotine and Nicotine Analog in Statute
16. Require Retention of Data and Records Supporting Marketed Medical Products and Marketed Medical Product Applications and to Address Fraudulent Data
17. Authorize the Disclosure and Use of Certain Information Related to Impurities in Drugs That Pose a Risk to Human and Animal Health
18. Postapproval Quality Updates
19. Modernizing the Requirements in BPCA and PREA for Agency Review of Pediatric Postmarket Safety Reporting
20. Share Food Safety Information with State, Local, Tribal, and Territorial Authorities
21. Disrupt the Flow of Problematic Imported Medical Devices
22. Clarify FDA’s Enforcement Authority Regarding Manufacturing Changes to Approved Drugs and Biological Products
23. Align the FD&C Act with Longstanding Timelines and Procedures Governing Application Reviews and Streamline Appeals When an application is Not Approvable
24. Provide Medical Assistance and Evacuation Insurance for Food and Drug Administration (FDA) Employees
25. Create a new Clinical Trial Notification Pathway to Serve as an Alternative to the Burdensome Existing Investigational New Drug Pathway to accelerate drug development timeline to Make America Healthy Again
26. Give FDA significant enforcement authorities, including civil monetary penalties and the authority to pull products off of market if active pharmaceutical ingredient source data is not reported.
27. Permanently authorize the rare pediatric disease priority review voucher program and related user fees.

Some of these proposals are of greater interest to this blogger than others, given my focus on the Hatch-Waxman Amendments and the Biologics Price Competition and Innovation Act (“BPCIA”).  To that end, lets take a closer look at certain FY2027 Legislative Proposals (the full legislative proposals are in italicized typeface below):

Allow Companies Manufacturing Generic Medications Domestically to File Paragraph IV Certifications Earlier, Giving Exclusivity Rights to US Manufacturers

This proposal would amend current law to allow domestic generic drug manufacturers to submit Abbreviated New Drug Applications earlier than foreign manufacturers in certain circumstances, which may help repatriate the U.S. pharmaceutical supply chain by making domestic generic drug manufacturers more likely to be eligible for 180-day exclusivity. The proposal would amend section 505(j)(5)(F)(ii) of the Federal Food, Drug, and Cosmetic Act (the Act) to allow generic companies based in the U.S. that currently manufacture a generic drug in the U.S. or are making investments in new domestic manufacturing facilities to substantially increase manufacturing capacity of a generic drug in the U.S., to file their application and paragraph IV certification(s) on the timeline currently codified in section 505(j)(5)(F)(ii) of the Act, and delay by one month when other companies can file their application and paragraph IV certification(s).

Ohhhh. . . .  This is a nice idea, and somewhat similar to one idea that this blogger has promoted for years as a “Made in the USA” or “First Applicant Prime” generic drug incentive (though usually in the form of additional or separate exclusivity, which Congress should consider given how watered-down 180-day exclusivity has become).  Under this proposal, generic drug manufacturers who meet certain “America First” prerequisites would be the only ANDA applicants that can qualify for 180-day Paragraph IV exclusivity for some drug products by virtue of being allowed to submit on the so-called NCE-1 date, while other, “non-America First” ANDA applicants would need to wait a month (a new “NCE-1+1 month” scheme).

Create Efficiencies for Review and Approval of Biosimilar Applications and Deem that Approved Biosimilars are Interchangeable

This proposal would streamline the review and approval of biosimilars by amending section 351 of the Public Health Service (PHS) Act to no longer include a separate statutory standard for a determination of interchangeability and deem all approved biosimilars to be interchangeable with their respective reference products. A determination of interchangeability pertains to pharmacy substitution of an interchangeable biosimilar for its reference product without the intervention of the prescribing health care provider. The statutory distinction between biosimilar products and interchangeable biosimilar products has led to confusion and misunderstanding, including among patients and healthcare providers, about the safety and effectiveness of biosimilars and about whether interchangeable biosimilars are safer or more effective than other biosimilars. Both biosimilars and interchangeable biosimilars are just as safe and effective as their respective reference products and can be used in place of their respective reference products. This proposal would make the U.S. biosimilar program more consistent with current scientific understanding, as well as with the approach adopted by other major regulatory jurisdictions such as the European Union that permit interchangeability of biosimilars with their respective reference products upon approval, thus making the US biosimilar market more competitive with our European counterparts and lower costs for consumers. 

This proposal would also create a presumption that a comparative clinical study that includes the assessment of efficacy is unnecessary to support a demonstration of biosimilarity upon a prospective applicant’s written request, unless FDA provides a justification within an agreed-upon time period as to why such study is necessary or why additional scientific information is needed for the determination. This would further streamline biosimilar development programs, where scientifically appropriate, and provide additional clarity to prospective applicants about the type(s) of assessments that are necessary to support a determination of biosimilarity for specific biological products. 

This proposal would also amend the PHS Act to remove the requirement in section 351(k)(5)(B) that biosimilar applications specifically be reviewed by the review division responsible for the review and approval of the reference product application. This change will increase the efficiency of the review of biosimilar applications by allowing the FDA to concentrate all biosimilar reviews in a single review division that specializes in biosimilar review and licensure.

This legislative proposal would codify FDA’s evolved position on biosimilars—and interchangeable biosimilars in particular—since the March 23, 2010 enactment of the BPCIA.  We’ve seen the most dramatic change within the past year as FDA accelerates incremental policy changes that reduce testing requirements and effectively erases the distinction between “highly similar” and “interchangeable” biosimilar biological products.

In 2010, there was no then-currently scientific, regulatory, or medical consensus regarding the data needed to show that a proposed biosimilar can be expected to produce “the same clinical result as the reference product in any given patient”—the statutory standard for biological product interchangeability.  42 U.S.C. § 262(k)(4)(A).  As a result, FDA initially recommended dedicated switching studies to support interchangeability.  In addition, comparative efficacy studies were the norm to demonstrate biosimilarity for both “highly similar” and “interchangeable” biosimilars.

But given both the precision of current analytical methods and accumulating experience showing that the risk from reference product and interchangeable product switching is insignificant, FDA’s thinking has evolved.  Today, clinical switching studies are generally no longer needed to demonstrate interchangeability; nor are comparative efficacy studies the norm for demonstrating biosimilarity, but rather a comparative analytical assessment of certain attributes.  Thus, FDA’s  requirements for demonstrating biosimilarity and interchangeability are, for practical purposes, the same for both statutory categories of biosimilars (at least for therapeutic protein products), and the line between “highly similar” and “interchangeable” biosimilar biological products is blurred nearly beyond recognition outside of the outdated statutory bifurcation.

A version of this legislative proposal is already pending in Congress: The Biosimilar Red Tape Elimination Act (S. 1954 & H.R. 5526).

Create an Additional Abbreviated Licensure Pathway for Biological Products

This proposal would amend section 351(a) of the Public Health Service Act (PHS Act) to create an abbreviated licensure pathway for biological products that are intended to differ from an FDA-approved biological product, but for which scientifically justified reliance on FDA’s previous determination of safety, purity, and potency for a biological product and/or on published literature would enable a more streamlined and efficient development program. The proposed abbreviated licensure pathway would be conceptually similar to the pathway for follow-on drug products in section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, which expressly allows an applicant to rely for approval on investigations that were not conducted by or for the applicant (and for which the applicant has not obtained a right of reference or use). Such an abbreviated licensure pathway would enhance biological product competition and innovation and enable more streamlined and efficient development programs while maintaining robust safety, purity, and potency standards.

This legislative proposal is another one of those “Ohhhh. . . .  This is a nice idea.”  It would, as stated above, create an “abbreviated licensure pathway. . . conceptually similar to the pathway for follow-on drug products in section 505(b)(2) of the [FDC Act], which expressly allows an applicant to rely for approval on investigations that were not conducted by or for the applicant (and for which the applicant has not obtained a right of reference or use),” and allow for “enhance[d] biological product competition and innovation.”  It is also an idea we’ve seen bandied about for a few years, as we noted in a May 2022 post.

Explicitly Address Generic Drug-Device Combination Products

This proposal would amend section 505(j) of the FD&C Act to explicitly address the submission and review of drug-device combination products submitted in abbreviated new drug applications (ANDAs), as well as drug products submitted in an ANDA that are used with a device. Currently, section 505(j) of the FD&C Act does not explicitly address ANDAs for drug-device combination products and generic drugs used with a device, and also states that FDA cannot require ANDAs to contain information beyond that set forth in this section. The lack of clarity in certain statutory provisions in this section – which was established nearly 40 years ago at a time when most products were simpler – may, in certain circumstances, make it difficult for companies to develop generic versions of these products and for FDA to efficiently approve ANDAs for these products. As a result, these products, which are often complex products such as autoinjectors and inhalers, can see delayed generic market entry. FDA seeks amendments to clarify, among other things, that FDA can request and review data for such applications, that certain differences between the device constituent parts of the reference listed drug (RLD) and the proposed generic are permissible, and that differences in labeling between the RLD and the proposed generic as a result of permissible differences in the device are also permissible. This proposal would help promote generic competition and reduce the time, uncertainty, and cost of drug development for combination products.

This legislative proposal is a repeat from prior years.  More than 40 years ago, the Hatch-Waxman Amendments created the conventional ANDA pathway to approval for generic drugs.  At that time in the early 1980s, most products were in simpler dosage forms (e.g., tablet and capsule).  Today, products are increasingly in much more complex and sophisticated forms, including drug-device combination products like auto-injectors and next-generation inhalers.

Drug-device combination products are difficult for generic drug manufacturers to develop and for FDA to efficiently approve ANDAs within the current statutory framework for generic drugs because the statute does not explicitly reference the data and information that FDA may consider in assessing these products.  Without explicit authority addressing drug-device combination products, it has been challenging for industry to know which types of data and information applicants can use to develop a generic version of a brand-name drug that utilizes these new technologies, and FDA historically has required significant more time to review and act on ANDAs for these products compared to drug products in conventional forms.  This has resulted in delayed patient access to more affordable versions of these important products.

Accordingly, this legislative proposal would amend the Hatch-Waxman Amendments to accommodate recent—and to anticipate future—advances in therapeutic product evolution and emerging technologies.  In particular, FDA would get explicit authority to assess data and information for generic drug-device combination products, including those combination products that feature a device with differences from the brand-name product.

Clarify When Patent Information Must Be Submitted for a 30-Month Stay to Be Available

This proposal would amend provisions in the Federal Food, Drug, and Cosmetic Act (FD&C Act) to clarify that a 30-month stay of approval of an abbreviated new drug application (ANDA), 505(b)(2) new drug application (NDA), or abbreviated new animal drug application (ANADA) is available only in connection with patents that are submitted by the holder of the brand drug application under section 505(c)(2) or 512(c)(3) of the FD&C Act before the ANDA, 505(b)(2) application, or ANADA is submitted. If a patent is submitted for listing in the Orange Book by the NDA holder before an ANDA or 505(b)(2) application is submitted and, in response to notice of a paragraph IV certification, the NDA holder or patent owner initiates a patent infringement action against the ANDA or 505(b)(2) applicant within 45 days of receiving the required notice, approval of the ANDA or 505(b)(2) application generally will be stayed for 30 months from the later of the date of receipt of the notice by any owner of the patent or the NDA holder or such shorter or longer time as the court might order. However, if a patent is submitted for listing in the Orange Book after an ANDA or 505(b)(2) application is submitted but before it is approved, the applicant for the pending ANDA or 505(b)(2) application generally must amend its application and provide an appropriate patent certification or statement to the newly listed patent, but no 30month stay will be available in this circumstance. 

Current law is ambiguous with respect to whether patent information submitted as part of the NDA or New Animal Drug Application (NADA) before approval of the brand drug product can give rise to a 30-month stay of approval for an ANDA, 505(b)(2) application, or ANADA submitted after approval of the brand drug product and that relies upon the brand drug product if the ANDA, 505(b)(2) application, or ANADA is submitted before the NDA or NADA holder for the brand drug product has submitted patent information after approval for listing in the Orange Book (for NDAs) or Green Book (for NADAs). This proposal would address that ambiguity.

This legislative proposal appears to be intended to address an issue that was raised in litigation against FDA in early 2024 concerning a 505(b)(2) NDA new strength supplement for Epinephrine Injection, 30 mg/30 mL (1 mg/mL), and that could be raised again in other Hatch-Waxman litigation.  In that case, which the D.C. District Court ruled on on May 2024, FDA issued a Letter Decision explaining the following in footnote 5:

The Agency has identified examples in which FDA has recognized a 30-month stay for new strength supplements for abbreviated new drug applications (ANDAs) based on an infringement action brought for patents listed after the date the original ANDA was submitted. To the Agency’s knowledge, the 30-month stays for these new strength supplements for ANDAs have either expired or have otherwise been terminated by a court and thus are moot. In these examples, the Agency appears to have recognized a 30-month stay because a new strength supplement is referencing a new listed drug with separately listed patent(s) in the Orange Book. However, the Agency looked more closely at these issues in the context of NDA 205029/S-013 and reevaluated the statutory language at section 505(j)(5)(B)(iii) of the FD&C Act. Section 505(j)(5)(B)(iii) of the FD&C Act does not exclude new strength supplements from the provision that limits the availability of a 30-month stay to patents for which the NDA holder submitted information to FDA “before the date on which the application (excluding an amendment or supplement to the application) . . . was submitted” and largely mirrors the language at section 505(c)(3)(C) of the FD&C Act. As a result of this reevaluation, FDA intends to change its practice with respect to new strength supplements for ANDAs and bring it into conformity with the statutory text. Going forward, the result will be that a 30-month stay will not be available for new strength supplements for ANDAs for patents submitted after the original ANDA was submitted (even where those patents were submitted before the submission of the new strength supplement). Because it is not directly implicated by this decision, FDA has not yet completed its assessment of new strength amendments that may be implicated by this issue. If FDA identifies any example in which FDA erroneously determined that there is an active 30-month stay either in the context of a new strength supplement or new strength amendment, it will review its decision to ensure that it conforms with the statutory text.

. . . . And we will add in one honorable mention . . . .

Align the FD&C Act with Longstanding Timelines and Procedures Governing Application Reviews and Streamline Appeals When an application is Not Approvable

FDA proposes to amend the FD&C Act to codify longstanding timelines and procedures that are central to FDA’s review of new drug applications (NDAs) and abbreviated new drug applications (ANDAs). Specifically, FDA proposes to amend subsections 505(c) and (j) of the FD&C Act (21 U.S.C. 355(c) and (j)) to remove the 180-day timeframe to either approve the application or give the applicant notice of an opportunity for a hearing (NOOH) on whether the application is approvable. FDA proposes to reference the goals identified in commitment letters under the Prescription Drug User Fee Act (PDUFA) and Generic Drug User Fee Amendments (GDUFA). FDA also proposes to amend section 505(c) and (j) of the FD&C Act to expressly include (1) the filing and receipt determinations described in FDA’s regulations and (2) FDA’s longstanding complete response letter (CRL) procedures. FDA further proposes to enhance efficiency by replacing the hearing-related processes described in section 505(c) and (j) of the FD&C Act with an appeal process modeled after the expedited withdrawal procedures for accelerated approval described in section 506(c)(3)(B) of the FD&C Act. 

Let’s call this legislative proposal the “Anti-Vanda Proposal,” as it appears to be an effort to legislatively address some of the litigations filed by Vanda Pharmaceuticals, Inc.  As we previously posted, Vanda has been anything-but-shy about suing FDA about anything and everything.  This includes Vanda’s February 2024 Complaint effectively challenging FDA’s PDUFA performance goals given the 180-day statutory review clock for marketing applications.

On April 22 and 23, 2026, the Association of Medical Diagnostic Manufacturers will hold its Annual Meeting at the Canopy by Hilton in Bethesda, MD.  The day and a half meeting, which is preceded by the group’s annual IVD 510(k) conference will be kicked off by Dr. Courtney Lias who will give the opening address providing the agency’s in vitro diagnostic regulatory update and overview.  Heads of the other OHT7 offices will also participate in a Q&A session.  Other highlights include a mock deposition, which will be conducted by HPMers Allyson Mullen and Jeff Gibbs with former FDA Special Agent in Charge, George Scavdis.  The case study will be sure to entertain the audience and underscore the key role FDA regulatory compliance – and internal documentation – can play in civil litigation.

The full agenda can be found on AMDM’s website (here).  FDA Law Blog readers can receive a 10% discount off the conference registration price.  To receive the discount, enter the code HPMBLOG at registration.  To register, visit the AMDM website.

As many of our blog readers already know, direct-to-consumer (“DTC”) prescription drug promotion has been a regulatory flashpoint for years, and especially recently with FDA’s DTC crackdown (see our previous posts here, here, and here), but a new bipartisan push suggests the conversation may be shifting from post-publication enforcement to pre-publication review for television ads.

This Most Recent Congressional Push

On March 31, 2026, Senators Dick Durbin (D-IL) and Roger Marshall (R-KS) urged FDA by letter to require pre-submission of certain DTC drug ads before they air.  The Senators’ request builds on prior legislative efforts and reflects growing bipartisan concern that existing enforcement may not be effective in curtailing the “sheer volume of deceptive [drug] advertisements.”  See our previous coverage of Senator Durbin voicing concerns over FDA’s operational capacity to review DTC prescription drug advertising during the various workforce reductions.

FDA has issued well over a hundred Warning and Untitled Letters since September 2025 for false or misleading prescription drug promotion across television, the internet, and social media.  Yet Durbin and Marshall posit the airwaves—and social media feeds—remain saturated with problematic messaging.

Their concern is straightforward:  Some companies may view post-hoc enforcement as simply the cost of doing business.

Why Doesn’t FDA Exercise its Review Authority?

Here’s the key “nuance”:  FDA, per 21 U.S.C. § 353c, already has authority to review prescription drug television advertising before it appears on the public’s TV screens. Although FDA never issued proposed rulemaking implementing § 353c, FDA did publish a Draft Guidance for Industry, “Direct-to-Consumer Television Advertisements – FDAAA DTC Television Ad Pre-Dissemination Review Program” (Draft Guidance) back in 2012, setting forth FDA’s intention to require sponsors to submit certain TV ads for pre-review.  The Draft Guidance, which was never finalized, has been removed from FDA’s website, although there was no FDA notification that it was being withdrawn.  Draft guidances, as well as final guidances, do not establish legally enforceable responsibilities.

Although FDA’s Draft Guidance was never finalized and even in the absence of a proposed rule, many within industry have voluntarily submitted TV ad storyboards or rough videos for FDA review and comment.  It is important to note that the animating statute, 21 U.S.C. § 353c(c), explicitly denies FDA the authority to require industry to implement changes to their television ads, excepting certain specific disclosures (e.g., serious risk).  However, given the significant risk of an enforcement action, companies generally modify their content to address FDA concerns.

Durbin and Marshall highlight that the current environment warrants greater and more aggressive use of FDA’s pre-review authority, particularly for high-risk products and drugs with the greatest population health impact.  This would not be a small shift—it would represent a significant move toward front-end regulatory oversight.

What This Could Mean for Industry?

If FDA leadership decides to embrace pre-review authority, the ripple effects could be significant:  1) increased promotional timelines (i.e., delays in pre-review clearance due to FDA’s operational capacity—see our previous blog post cited above); 2) an increased strain on internal resources for industry (e.g., FDA requesting to review the finalized television ad rather than the storyboard and then requesting changes to the television ad); 3) early and often engagement with FDA; and 4) a regulatory/industry shift in philosophy emphasizing identifying and remediating misleading promotion before it reaches the airwaves.

However, pre-review does not always ensure detection and prevention of dissemination of misleading ads.  For example, in 2024, FDA issued an Untitled Letter to AbbVie, Inc. over its DTC promotion of its migraine medication Ubrelvy.  FDA issued the Untitled Letter because of a DTC television ad featuring Serena Williams, alleging the television ad made false or misleading efficacy claims; specifically, FDA alleged the ad implied the drug could quickly eliminate migraine pain after a single dose, even though clinical data show only about 19-22% of patients achieved freedom from pain within two hours, meaning most did not experience that outcome.  In footnote 6, FDA acknowledges review of a storyboard that suggests several hours pass between dosing and effect, but notes the time lapse is lost in the finished television ad.  See our previous post on the Untitled Letter here.

If the pre-review process were more widely and rigorously applied to finished television ads, the costs of changing a television ad to obviate FDA’s concerns could prove to be another effective tactic that would effectively reduce the universe of misleading DTC ads.  In addition, whether intentionally or unintentionally, this also may reduce the sheer number of television ads due to the costs and time involved in bringing an ad to fruition under the more rigorously applied pre-review process.  As mentioned above, it’s important to note that FDA review of a final television ad before airing as opposed to a storyboard before filming of the television ad are two very different substantive reviews.

So What are the Takeaways?

The United States remains one of two countries that permits widespread DTC prescription drug advertising.  That reality has long shaped the pharmaceutical marketing landscape as well as the compliance challenges that come with it.  The current bipartisan push and recent FDA enforcement actions and statements suggest a growing congressional and regulatory appetite to rethink how that system is executed.

Whether FDA embraces pre-review authority fully, selectively, or not at all remains to be seen; however, this latest push crystallizes one potential key shift in FDA behavior—if the Senators’ call to action gains traction and support, the question will no longer be “Should FDA act?” but rather “How early should FDA act?”  And in an environment where HHS and FDA leaders have focused (improperly, we might add) on the “adequate provision loophole” as a means to curtail prescription drug television ads, FDA could more effectively reduce the number of ads by simply embracing its already granted statutory authority to require FDA pre-review.

We will continue to monitor and report on developments in the DTC drug advertising space.

FDA recently issued a Federal Register notice (Docket No. FDA-2026-N-2476) announcing a request for information and comments titled Advancing the Use of Digital Health Technologies  in Clinical Investigations for Drugs and Biological Products.  A digital health technology (DHT) is a system that uses computing platforms, connectivity, software, and/or sensors, for health care and related uses.  There were several goals for enhancing use of DHTs to support drug development and review as part of PDUFA VII.  In the first year of PDUFA VII (FDA FY 2023) we saw significant progress on these DHT goals, as we blogged about here.  In late 2023, FDA finalized its guidance on use of DHTs for remote data acquisition in clinical investigations, which we blogged about here and in June 2024, FDA held its second of five public meetings or workshops.  Recently, however, discussion of DHTs at the Agency has been relatively quiet.

In the notice, FDA acknowledges that there have been significant advances in sensor technology and states that they will use the information gathered in the request for information for development of guidance documents and to support other activities related to use of DHTs in clinical investigations of drugs and biological products.

Specifically, FDA seeks responses to the following questions.

1. What regulatory challenges do DHT manufacturers, sponsors or other interested parties face regarding the use of DHTs in clinical investigations of drugs and biological products?
2. What opportunities are there for CDER and CBER to support and facilitate the adoption of DHTs in clinical investigations of drugs and biological products?
3. What areas of guidance would support the use of DHTs in clinical investigations?
4. What specific DHT related topics, such as digitally derived endpoints in certain disease areas, would benefit from discussion in a public workshop?

For sponsors considering, or already implementing, DHTs in clinical investigations, this is a timely opportunity to highlight real‑world challenges and help shape the next phase of FDA policy.  Ultimately, the extent to which DHTs are more fully integrated into drug and biologics development will depend not only on technological advances, but also on regulatory clarity.  Stakeholder engagement in response to this notice—and in any future workshops—will be critical to ensuring that FDA’s framework supports innovation while maintaining data integrity and patient protection.

Interested parties should submit comments by June 1, 2026 following instructions provided in the Federal Register notice.

Hyman, Phelps & McNamara, P.C., one of the nation’s largest boutique food and drug regulatory law firms, seeks to add a junior to mid-level associate with two to five years of experience to its healthcare compliance team.

This associate should have experience providing advice to life sciences clients (pharmaceutical, biotech, and device companies) on some or all of the following matters:

• Federal healthcare program antikickback statute and state equivalents
• False Claims Act
• PhRMA and/or AdvaMed Code compliance
• Government price reporting and discount programs

Strong verbal and writing skills are required.  The ideal candidate will have prior law firm or in-house experience.

Candidates must be members of the DC Bar or eligible to waive in.  Compensation is competitive and commensurate with experience.  HPM is an equal opportunity employer.

Please send your curriculum vitae, transcript, and a writing sample to recruiting@hpm.com

The Drug Enforcement Administration (“DEA”) and the United States Attorney’s Office for the Eastern District of California just announced that Sutter Medical Center and Sutter Fairfield Surgery agreed to pay $3.2 million to resolve allegations that they failed to effectively guard against theft and diversion of controlled substances.  The press releases note that the settlement relates to at least 628 recordkeeping and security violations of the Controlled Substances Act (“CSA”), including failure to notify DEA of the theft or loss of controlled substances.  The press releases note that DEA began investigating following the death of a pediatric anesthesiologist.

The Sutter Medical Center and Sutter Fairfield Surgery Center settlement is the latest high-profile example of a healthcare system paying millions to resolve allegations of CSA violations.  Recent diversion of significant controlled substance quantities by pharmacists, physicians, nurses, and other healthcare professionals highlight the vulnerability of hospitals and healthcare systems.  Failure to provide effective controls and procedures to guard against theft and diversion of controlled substances pose risks to a hospital’s patients for undertreatment and, worse, employees for misuse, abuse, overdose, and death.  Employee diversion from hospitals has also resulted in large civil monetary settlements, costly compliance remediation programs, and unwanted local and national publicity.

Hyman, Phelps & McNamara, P.C. Director Larry Houck is speaking on “Hospital Controlled Substance Diversion Case Studies: Cautionary Tales,” focusing on this timely topic, at the International Association for Healthcare Security and Safety’s (“IAHSS’”) Annual Conference and Exhibition in New Orleans on April 13th-15th, 2026.

Mr. Houck will address:

• How employees in other high-profile cases were able to divert significant controlled substance quantities;
• Red flags that hospitals missed;
• Safeguards for minimizing internal diversion risks; and

• Best practices for maximizing diversion detection.

Click here for information about the IAHSS 58th Annual Conference and Exhibition.

Hyman, Phelps & McNamara, P.C. (HP&M) seeks to add a 3rd to 6th year associate to our busy drug development team.

Our team of lawyers and regulatory experts assists clients with a wide variety of FDA regulatory issues arising in the pre-market arena for clients developing drugs and biologics.  Types of matters include:

• Informing development and providing guidance on associated regulatory strategy from early-stage (Pre-IND) activities through obtaining marketing authorization;
• Writing and advising on materials for submission to FDA during the course of product development including meeting briefing books, requests for expedited programs, INDs/NDAs/BLAs, and responses to inquiries from the Agency;
• Assisting clients with regulatory issues arising during the planning and conduct of clinical trials, including clinical trial design and IRB-related matters;
• Meeting with FDA on behalf of clients as part of FDA-sponsor meetings at stages of development and in other interactions with the Agency;
• Conducting due diligence related to transactions and securities offerings for companies with drug and biologic products; and
• Representing clients in FDA’s formal dispute resolution process, including related to clinical holds and complete response actions.

Strong verbal and writing skills are required; candidates with a scientific degree or background are preferred.

The ideal candidate will have experience working at FDA, in regulated industry, or prior big firm experience, including working with clients on pre-market drug or biologic FDA regulatory issues.

Candidates must be members of the DC Bar or eligible to waive in.

The boutique, collaborative nature of our firm provides associate attorneys unique opportunities to work directly with clients and to contribute in substantive ways to sophisticated, high-end matters.

Compensation is competitive and commensurate with experience.  HP&M is an equal opportunity employer.

Please send your curriculum vitae, transcript, and a writing sample to recruiting@hpm.com

The Drug Enforcement Administration’s (“DEA’s”) final rule issued September 30, 2019, implemented the single sheet format for DEA Forms 222 (“DEA-222s”) and allowed a two-year transition from the triplicate form to the single sheet.  New Single-Sheet Format for U.S. Official Order Form for Schedule I and II Controlled Substances (DEA Form 222), 84 Fed. Reg. 51,368 (Sept. 30, 2019).  However, the final rule failed to amend several regulatory provisions that has created ambiguities.  DEA has issued a final rule/technical amendment correcting those provisions that the 2019 final rule did not amend.  Ordering Schedule I and II Controlled Substances Using DEA Form 222; Technical Amendments, 91 Fed. Reg. 13,498 (Mar. 20, 2026).  The final rule/technical amendment clarifies who can execute or revoke a Power of Attorney authorizing who may sign DEA-222s ordering schedule I and II substances, and relatedly who can sign the DEA-222s themselves.  The final rule/technical amendment also removes the now obsolete provision transitioning from triplicate DEA-222s to single sheet DEA-222s.

Registrants “may authorize one or more individuals . . . to issue orders for Schedule I and II controlled substances on the registrant’s behalf by executing a power of attorney for each such individual.”  21 C.F.R. § 1305.05(a).  The 2019 final rule amended 21 C.F.R. § 1305.05(d)(1) to require that a Power of Attorney be executed by “[t]he registrant, if an individual; a partner of the registrant, if a partnership; or an officer of the registrant, if a corporation, corporate division, association, trust or other entity.”  Previously, a person who signed the most recent application for a DEA registration could execute or revoke a Power of Attorney.

DEA noted after receiving numerous comments regarding the Power of Attorney that due to “the significance of Form 222 signature authority, and the potential for diversion when that authority is abused, the DEA deems it appropriate to require an officer, a partner, or the registrant him- or herself to sign POAs under 21 C.F.R. § 1305.05.”  84 Fed. Reg. at 51,368.  In implementing the 2019 final rule DEA failed to modify two related provisions of 21 C.F.R. § 1305.05: 21 C.F.R. § 1305.05(c) providing format and language for a DEA-222 Power of Attorney and the notice of revocation, and 21 C.F.R. § 1305.05(e) explaining who must revoke a Power of Attorney.  The final rule/technical amendment replaces the language in those provisions to mirror the language of 21 C.F.R. § 1305.05(d)(1) specifically identifying who may execute a Power of Attorney to order schedule I and II controlled substances.  A person who signed the most recent application for registration is not authorized to execute or revoke a Power of Attorney to sign DEA-222s.

The final rule/technical amendment similarly amends 21 C.F.R. § 1305.12(d) requiring that a DEA-222 must also be signed by the registrant, if an individual; a partner of the registrant, if a partnership; or an officer of the registrant, if a corporation, corporate division, association, trust or other entity or a person granted Power of Attorney.  Prior language referred to 21 C.F.R. § 1305.05 that also included a provision allowing a person who signed the last application for registration to sign a DEA-222.

Lastly, DEA promulgated the 2019 final rule when registrants were still using triplicate DEA-222s.  DEA provided registrants with a two-year transition period allowing them to continue using triplicate DEA-222s before switching to single sheet DEA-222s.  DEA stopped accepting triplicate DEA-222s on October 30, 2021.  The final rule/technical amendment removed 21 C.F.R. § 1305.20 because it is obsolete.

The final rule/technical amendment is effective immediately.

It gets repeated as an article of faith: The generally recognized as safe (GRAS) exception to the definition of “food additive” in section 201(s) of the FD&C Act was intended to encompass only common food ingredients such as vinegar and salt.

Not so fast. Just a few months after passage of the 1958 Food Additives Amendment, FDA published a proposed rule [that included the following text:

121.100 Substances that are generally recognized as safe. It is impractical to list all substances that are generally recognized as safe for their intended use. However, by way of illustration, the Commissioner regards such common food ingredients as salt, pepper, sugar, vinegar, baking powder, and monosodium glutamate as safe for their intended use. In addition, the following lists include some substances that, when used for the purposes indicated, in accordance with good food manufacturing practice, are regarded by the Commissioner as generally recognized as safe for such uses.

The proposed rule went on to list over 200(!) substances categorized by uses that included buffers, neutralizing agents, preservatives, sequestrants, antimycotics, antioxidants, sweeteners, nutrients, stabilizers, and emulsifying agents. The nature of those substances and the range of their uses may come as a surprise to those who’ve only been exposed to the party line.

It seems doubtful that Congress would have been completely unaware of the uses of such substances in food at the time the ’58 amendment was being debated. Further – and as was noted by our friend Stuart Pape at FDLI’s recent Food and Dietary Supplement Safety and Regulation Conference – it makes little sense that Congress would have provided the option of demonstrating GRAS status through scientific procedures if the GRAS exception was intended to encompass only common food ingredients. In that instance, the option of demonstrating GRAS based on common use in food prior to ’58 would have sufficed.

By all means, let’s have a robust debate over the future of GRAS. Let’s see if we can do it without resorting to distortions of the historical record.

As regulatory frameworks for orphan medicinal products continue to evolve on both sides of the Atlantic, understanding the practical and strategic implications is increasingly important. On M April 14th, 10:00 to 11:00 ET, Pinsent Masons and Hyman, Phelps & McNamara, P.C. are pleased to host a joint webinar.  Catherine Drew, Partner, Pinsent Masons and Sara W. Koblitz, Director, Hyman, Phelps & McNamara will share insights into current trends and emerging issues in orphan medicines regulation and compliance.  (Please note that this webinar has been rescheduled from the original date of 17 March 2026.)

During the session, our speakers will provide practical insights into the orphan medicines regulatory landscape, including:

• A comparison of criteria for designation as an orphan medicinal product in the US & Europe;
• The benefits of orphan designation; a consideration of exclusivity rewards for such products and comparison to exclusivity rights granted to NCEs or NBEs;
• An overview of upcoming changes to the orphan regime as part of reform of EU pharmaceutical legislation.

This session is designed for regulatory affairs professionals, in-house counsel, compliance teams, and others with an interest in medicines regulation.

We hope you can join us for what promises to be an informative and engaging discussion.

Registration Link: 2026-04-14 – Webinar – Navigating Orphan Medicines Regulation: Strategic Insights from the US and Europe | Hyman Phelps registration

Hyman, Phelps & McNamara, P.C., one of the nation’s largest boutique food and drug regulatory law firms, seeks to add a junior to mid-level associate with three to five years of experience to its healthcare compliance team.

This associate should have experience providing advice to life sciences clients (pharmaceutical, biotech, and device companies) on some or all of the following matters:

• Federal healthcare program antikickback statute and state equivalents
• False Claims Act
• PhRMA and/or AdvaMed Code compliance
• Development and implementation of compliance programs
• HIPAA Privacy Standards
• State marketing and compliance code requirements
• State price transparency reporting requirements
• Government price reporting and discount programs

Strong verbal and writing skills are required.  The ideal candidate will have prior law firm or in-house experience.

Candidates must be members of the DC Bar or eligible to waive in.  Compensation is competitive and commensurate with experience.  HPM is an equal opportunity employer.

Please send your curriculum vitae, transcript, and a writing sample to recruiting@hpm.com.

The FDA continues to refine its approach to biosimilar development. On March 9, 2026, the Agency announced the release of the revised draft guidance titled “New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4).”

The guidance updates FDA recommendations for biosimilar – and interchangeable – product development and is part of the Agency’s broader effort to streamline development programs while maintaining the scientific standards required to demonstrate biosimilarity.

The latest draft revises three questions and answers—Q&A I.8, I.10, and I.19—from the Agency’s earlier guidance “Questions and Answers on Biosimilar Development and the BPCI Act” issued in September 2021. These Q&As have been withdrawn from the final guidance while FDA seeks public comment on the revised versions.

The most significant changes appear in Q&A I.8, which now addresses the use of clinical data generated from a comparator product approved outside the U.S. (non-U.S. licensed comparator product). The revised Q&A is organized into two parts.

Part (a) explains how clinical studies—including pharmacokinetic (PK) studies—comparing a proposed biosimilar with a non-U.S.-licensed comparator product may, in certain circumstances, help address statutory requirements and support a demonstration of biosimilarity to a U.S.-licensed reference product. It also outlines when clinical data generated using a non-U.S. licensed comparator product may be acceptable.

Overall, this signals the Agency’s flexibility for scientifically justified scenarios in which prospective biosimilar applicants may be able to rely on clinical data generated using a comparator product approved outside the United States without conducting an additional three-way PK study involving the proposed biosimilar, the U.S.-licensed reference product, and the non-U.S. licensed comparator product.

The revised recommendations also remove an earlier expectation that at least one clinical PK study directly compare the proposed biosimilar with the U.S.-licensed reference product. Instead, a PK study using a non-U.S. comparator product may be acceptable if scientifically justified.

Part (b) focuses on the comparative analytical data needed between the non-U.S.-licensed comparator product and the U.S.-licensed reference product. These analytical comparisons can help justify the scientific relevance of clinical data generated using the non-U.S. licensed comparator product.

FDA is specifically requesting comment on the value of these analytical comparisons as part of the scientific justification supporting the relevance of clinical data derived from studies using non-U.S. licensed comparator products.

These changes reflect the Agency’s evolving scientific thinking after more than a decade of experience reviewing biosimilar applications. As part of this shift, FDA also announced it is withdrawing the guidance “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product,” issued in 2015, because it no longer reflects the Agency’s current thinking.

For biosimilar applicants, the draft guidance offers another indication that FDA is continuing to refine the biosimilar development framework—particularly around the role of clinical studies and the use of non-U.S. licensed comparator products. According to FDA, streamlining comparative efficacy studies could save biosimilar manufacturers up to $150 million in development costs and approximately 2 to 4 years of time. Similarly, reducing unnecessary PK testing could lower study costs by as much as 50%, unlocking competition and facilitating market entry of more biosimilar manufacturers.

Stakeholders have an opportunity to weigh in. FDA is accepting comments on the draft guidance through May 11, 2026, before the Agency begins work on a final version.

In response to what FDA calls “inadequate responses to FDA 483 observations due to a lack or omission of relevant data, excessive amounts of data, and/or failure to address the root cause of observations,” the Agency published a new Draft Guidance on Responding to FDA Form 483 Observations at the Conclusion of a Drug CGMP Inspection.  The Draft Guidance is applicable to inspections of all foreign and domestic human and animal drug manufacturers, including 503B outsourcing facilities and manufacturers of combination products where CDER or CBER is the lead center.  FDA explains that the Draft Guidance explicitly does not apply to medical devices because the expectation that manufacturers thoroughly investigate unexplained discrepancies is a requirement specific to the drug CGMP regulations (21 CFR 211.192).  However, medical device manufacturers also have a corresponding expectation that they conduct root cause investigations of nonconformities, and as FDA notes in footnote 3, CDRH has a similar expectation described in the Nonbinding Feedback After Certain FDA Inspections of Device Establishments Guidance (April 2020), which we covered previously.

While much of the Draft Guidance documents what are generally industry best practices—particularly those described in ICH Q9 Quality Risk Management and ICH Q10 Pharmaceutical Quality System—there are a few surprises and areas of continuing uncertainty.  Comments on the Draft Guidance can be submitted to Docket FDA-2025-D-1504 through May 8, 2026.

Response Timing

As a reminder, an FDA 483 is issued to a manufacturer during the closeout meeting at the conclusion of an inspection if FDA identifies objectionable conditions or practices that in the investigator’s judgment may constitute violations of the Food, Drug, and Cosmetic Act.  The manufacturer then has 15 business days (excluding weekends and federal holidays) after receiving the FDA 483 to submit a substantive response.  For the purposes of calculating the 15 days, the day the FDA 483 is issued is “day 0.”

The Draft Guidance reiterates FDA’s longstanding position that it will conduct a detailed review of an FDA 483 response submitted within 15 business days before determining whether to take any further action (e.g., issuance of a Warning Letter).  While responding to an FDA 483 is not strictly a legal requirement, we always advise that manufacturers submit a substantive response within the 15-business day timeframe for this reason.  Despite the language in footnote 3, we would not consider this to be a mere “recommendation” as the failure to (or decision not to) respond leaves a manufacturer’s fate wholly in the hands of the Agency.  Similarly, given the importance of the initial FDA 483 response, we recommend that manufacturers take the full 15 business days to prepare a substantive response: there’s no extra credit for responding early.  If all observations have not been completely remediated by the time the initial response is due, which is often the case, manufacturers should provide a list of remediation commitments, timeline for completion of the outstanding commitments, description of interim controls, and the anticipated schedule of response updates.

Format and Content

The Draft Guidance attempts to create a somewhat standardized format for certain portions of the response.  The most significant portion is the Executive Summary table, in which FDA wants to see a detailed description of each observation (or group of related observations) and the status of associated remediation activities.  FDA has provided an example of the Executive Summary table in the Draft Guidance, and we note that this template looks very similar to the Table of Key Elements of a Meeting Package provided in the Post-Warning Letter Meetings Under GDUFA Guidance for Industry.  While many manufacturers already use a similar table format for sections of the response, FDA recommends that the Executive Summary also include the following information for each observation:

1. Patient- and product-focused risk assessment: including an assessment of inventory and distributed drugs still within expiry and any possible effects on safety, identity, strength, quality, and purity of potentially affected drugs.
2. Detailed investigation report: identified root cause(s) of the observation and related systemic issues, list of associated drugs and lot numbers, CAPA plan, summary of completed actions, and planned effectiveness evaluation.
3. Attachments: all should be signed “indicating support for the contents contained therein.” More on the signature recommendation below.

What FDA describes as an “Executive Summary” strikes us as the content for a substantive response in its entirety, but the Draft Guidance states that the “discussion of each FDA 483 observation” is a separate element of the response.  The Draft Guidance also makes clear that investigations initiated in response to the FDA 483 observations need to be comprehensive and not limited to the specific examples cited in the FDA 483.  While it is expected that investigations and CAPAs be extended to other batches, facilities, equipment, personnel, etc., the Draft Guidance specifies that an investigation plan also needs to include a justification for any part of an establishment’s operations that is excluded from the investigation.

Key Takeaways and Outstanding Questions

Overall, while the Draft Guidance provides a recommended format that will presumably make a company’s response easier for FDA to review, the level of detail the Agency expects would be difficult for most manufacturers to prepare by the 15 business day deadline for an initial response.  Beyond the general expectations on format and content, the Draft Guidance has also left us with questions on several specific topics.

1. Discussion items: during an inspection close-out meeting some FDA investigators will discuss what they perceived to be CGMP deficiencies that don’t rise to the level of significance of an FDA 483 observation. These items are noted in the Establishment Inspection Report, but not written on the FDA 483.  In our experience, some firms choose to include a written response to verbal discussion points in their FDA 483 response, others do not.  While the Draft Guidance acknowledges that “Establishments may also provide additional information in their FDA 483 response (e.g., responding to verbal discussion items),” FDA has not provided a clear recommendation on whether manufacturers should reply to discussion points and implications if they do not.
2. Language: if the response includes documents in a foreign language, FDA “does not intend to include these documents in the Agency’s review of the response” unless an English translation is also provided. Additionally, any English translations must be “verified as complete and accurate, with the name address, and brief statement of the translator’s qualifications” [one of the bloggers is a translator by education and she finds this requirement quite interesting].  It is our understanding that, for example, if one of the corrective actions taken in response to an FDA 483 observation were to add a single provision to an existing work instruction, the manufacturer will need to translate the document in its entirety—even if the operating language at the facility is not English and CGMP documentation would not otherwise be maintained in English.
3. Attachments: FDA 483 responses can easily contain dozens, and sometimes hundreds, of attachments. Most, if not all, of these attachments would be CGMP documents (e.g., training records, laboratory reports, SOPs), so it’s unclear why FDA thinks it is necessary for firms to separately sign each attachment.  And it is even less clear why FDA wants its own FDA 483 included as an attachment and sent back to the Agency with the response.
4. Identity of the response preparer: the Draft Guidance says this is required if the response is “not prepared by the establishment.” However, it is ambiguous whether this refers solely to the preparation of the response in its entirety by a third party.  For example, if outside counsel or a CGMP consultant drafts portions of the FDA 483 response, or reviews and revises the response in its entirety, would they be considered the “preparer” of the response?  For larger organizations with multiple sites, corporate Quality personnel may often assist with the preparation of an FDA 483 response for an individual facility, so would they need to be separately identified as a “preparer”?

While the Draft Guidance may not provide absolute certainty around how to respond to an FDA 483, it does stress the importance of submitting a robust response.  HPM attorneys regularly assist drug (and device) manufacturers around the globe with initial FDA 483 responses and response updates, and we can help your company effectively and comprehensively answer FDA’s identified concerns, with the goal of avoiding any further regulatory action.