Two draft guidances issued together late last month seek to increase both clinical trial efficiency and the amount of information that is available about a drug’s safety and benefits.  The two draft guidances address, respectively, adaptive designs and master protocols.  This blog post discusses FDA’s recommendations for adaptive designs; master protocols will be addressed in a subsequent blog post.

An adaptive design is a “clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on the accumulating data from subjects in the trial.”  The ability to make changes to a study in progress allows investigators to take into account new information that was not known when the study began.  According to FDA, adaptive designs can both provide a greater chance to detect a true drug effect and reduce the number of patients exposed to ineffective investigational treatments (since effectiveness will be more easily detected earlier in the trial).  Because adaptive designs allow for greater flexibility, they also may be more acceptable to those conducting and those participating in clinical trials. For sponsors in particular, adaptive designs can potentially both save time and reduce costs.  Adaptive design can also have ethical advantages by facilitating early termination of trials once it becomes clear that a trial is unlikely to demonstrate effectiveness, thereby minimizing risk to participants.

At the same time, the draft guidance recognizes that adaptive designs increase the risk of “Type I” (false positive) errors, i.e., concluding that a drug has a beneficial effect when it does not.  To mitigate this risk, the draft guidance recommends sponsors employ methods to determine appropriate statistical thresholds for interim and final analysis to ensure that the overall Type I error is controlled at 2.5 percent.  Similarly, the draft guidance acknowledges the risk of bias that can result from early unblinding of a study, and recommends limitations on who may access such data to mitigate this risk.

A key element of adaptive design is pre-specification (i.e., planning in advance), including pre-specification of the number and timing of interim analyses, what statistical methods will be used to interpret the interim data, and how the study design will be changed depending on the results of such analyses.  Failure to pre-specify can result in the introduction of bias and thereby put the quality and integrity of study data at risk. Therefore, FDA strongly recommends that prespecified protocols are included in the clinical study design to ensure that access to comparative interim results are limited to individuals with relevant expertise who are independent from personnel involved in conducting or managing the trial.

Because adaptive designs introduce certain added complexities, FDA recommends that sponsors provide additional information when submitting a protocol for FDA review, including a detailed description of the monitoring and adaptation plan, information on who will be responsible for implementing the adaptive design, pre-specification of the statistical methods to be used, and a comprehensive written data access plan to maintain data integrity and quality.

The new adaptive designs draft guidance supersedes an earlier draft guidance issued in 2010.  At that time, adaptive designs were in their infancy, and proponents of adaptive designs viewed FDA’s initial guidance as a first step in considering how best to integrate them into clinical trials to support FDA regulated products and recommended that FDA guidance evolve in response to greater experience with the use of different adaptive study designs.  The new draft guidance reflects such evolution in FDA’s thinking; for example, in acknowledging the potential adverse impact arising from Type I error and in eliminating confusing categorization of “well understood” and “not well understood” adaptive design methods in favor of a more focused assessment of factors, such as unblinding, that can increase risk of bias.

FDA encourages sponsors to consider and discuss prospective design options with FDA.  Clinical trial sponsors and other stakeholders may want to consider the potential impact of the new guidance on their approach to clinical trials, and to submit comments to the FDA.  The deadline for submitting comments is November 30, 2018.

On September 20, 2018, the U.S. Food and Drug Administration (“FDA”) released draft guidance “Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank” (“Guidance”). The purpose of this Guidance is to explain FDA’s protocol in (1) determining how the centers will identify whether responsible parties failed to comply with submission and certification requirements to the ClinicalTrials.gov or submitted false or misleading documents to the data banks and (2) deciding when, why, and what civil monetary penalties will be assessed against the responsible parties or submitters. The new guidance seeks to address requirements of responsible parties involved in the performance of clinical research and submission of applications for marketing authorizations to register their trial, submit clinical results information and make certain certifications regarding their compliance with these requirements.  In order to mitigate their risk of civil money penalties in accordance with this guidance,  sponsors and researchers should (1) have policies and procedures that ensure correct clinical trial information is submitted to the ClinicalTrials.gov data bank, (2) have policies and procedures that ensure routine monitoring for missing or inaccurate clinical trial information in the data bank, (3) make timely submissions of the required information, and (4) remain responsive to any inquiries by FDA concerning clinical trial data and/or certifications to FDA.

Background

Under section 801 of the Food and Drug Administration Amendments Act of 2008 (the “FDAAA”), which amended section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)(5)(B)), responsible parties engaged in certain clinical research activities are required to submit registration and results information to the ClinicalTrials.gov data bank. Additionally, submitters of certain applications and other items to FDA regarding drug, biological, and medical device products are required to certify to FDA that all requirements of section 402(j) have been met. Similarly, the FDAAA amended section 301(jj) of the Food Drug and Cosmetics Act (the “FD&C Act”) to prohibit: (1) the failure of submitting or knowingly submitting a false certification to FDA, (2) the failure to submit required clinical trial information, and (3) submitting false or misleading clinical trial information to the ClinicalTrials.gov data bank. Further, the FDAAA amended section 303(f)(3) of the FD&C Act, authorizing FDA to assess civil monetary penalties against the person committing the prohibited acts.

Identifying Noncompliant Responsible Parties and Submitters

In this Guidance, FDA states its intention to utilize evidence collected during FDA’s Bioresearch Monitoring Program (“BIMO”) inspections to assess compliance with registration and results reporting requirements as described in Form FDA 2438 – Chapter 48 – Bioresearch Monitoring (Apr. 19, 2017). FDA also intends to identify violations as a result of complaints received by the Agency, which may entail reviewing public and non-public information, including, but not limited to information submitted to the ClinicalTrials.gov data bank and to FDA.

It is in the best interest of sponsors, researchers, and other parties subject to an obligation to submit clinical trial registration, information, results, and/or certifications to FDA to have policies and procedures in place to ensure correct information is submitted to ClinicalTrials.gov data bank. Policies and procedures should also include periodic review of the data bank to monitor for any missing or inaccurate clinical trial information. Developing and implementing these policies and procedures will mitigate the risk of enforcement for noncompliance with registration and clinical trial results reporting requirements, as outlined in the Guidance.

Determining When to Seek Civil Monetary Penalties

Under Guidance, FDA intends to provide the responsible parties with an opportunity to remedy any prohibited acts under section 301(jj) of the FD&C Act and corresponding regulations (42 CFR Part 11) before initiating an action to recover penalties. Pursuant to the procedures detailed in the Guidance, when FDA determines that when submissions are not timely filed or inaccurate, FDA will generally send the responsible party or submitter a Preliminary Notice of Noncompliance Letter describing the potential violation. The responsible party or submitter will have thirty (30) calendar days to remedy the violation. Should FDA conduct further review and find further or continued noncompliance with the applicable clinical trial requirements, the agency will then issue a Notice of Noncompliance, giving the responsible party or submitter another thirty (30) days to remedy noncompliance after receipt of the notice.

It is in the best interest of sponsors and researchers to promptly respond to any FDA inquiries and notices concerning registration, clinical trial information or certification issues related to the ClinicalTrials.org data bank. Failure to comply within the thirty (30) days of receipt of Notice of Noncompliance will result in FDA escalating regulatory action, including civil monetary penalties, of up to $10,000 for all violations adjudicated in a single proceeding.  Additional penalties of up to $10,000 each day may be included if the violation continues and if said violation is not corrected within thirty (30) days following notification. FDA may also pursue injunction and/or criminal prosecution.

In determining monetary penalties, the FDA will evaluate the circumstances, nature, extent, and gravity of the violation(s) with respect to the individual.  Other factors will include the violator’s ability to continue conducting business, any prior history of such violations, and the degree of culpability in the matter.

Responding To Civil Monetary Penalties by FDA

If FDA seeks civil monetary penalties, according to 21 CFR Part 17, the responsible party or submitter has the opportunity to either: (1) pay the penalty prescribed in the complaint or (2) file an Answer, contesting the allegations either in part or in whole, within thirty (30) days of date of service.

Should the responsible party or submitter contest the allegations by submitting an Answer, generally settlement discussions with FDA are entered into, providing the responsible party or submitter to present mitigating evidence to FDA for purposes of reducing the penalty amount. If a settlement is not reached before a decision on appeal, a presiding officer will make an initial decision, followed by the usual administrative appeal process (e.g., Department of Health and Human Services Departmental Appeal Board and then the U.S. Court of Appeals for the District of Columbia or any other circuit in which the responsible party or submitter resides or conducts business), should either party appeal the initial decision.

 

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A recent BMJ article, “Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource,” reported that for approximately half of the clinical trials, the responsible person did not report results on the EU register while a 2015 New England Journal of Medicine article, “Compliance with Results Reporting at ClinicalTrials.gov,” reported that approximately 20% of industry trials did not report results when required to do so, and 50% of NIH-sponsored research went unreported. While the registration, reporting, certification requirements, and the penalties for noncompliance are not new, FDA’s release of this Guidance should be taken as a signal to sponsors and researchers of its plan to enforce those requirements more rigorously. Therefore, sponsors and researchers should take this opportunity to evaluate the sufficiency of their policies and procedures for compliance with registration and reporting requirements and audit their submissions to ensure they are up-to-date.  Comments are due by November 20, 2018.

Eighty years ago today, President Roosevelt signed the Federal Food, Drug, and Cosmetic Act (“FD&C Act”).  In recognition of this anniversary, EBG reviews how the FD&C Act came to be, how it has evolved, and how the Food and Drug Administration (“FDA”) is enforcing its authority under the FD&C Act to address the demands of rapidly evolving technology.

I’m Just a Bill

The creation of the FD&C Act stems from a sober event in American History.  In 1937, a Tennessee drug company marketed elixir sulfanilamide for use in children as a new sulfa drug.  The diethylene glycol (“DEG”) used as a solvent for the elxir is poisonous to humans.  The untested drug killed over 100 people, including children.  The public’s response to the disaster prompted and ensured the passage of the FD&C Act in 1938, which included the creation of the process known as pre-market approval, requiring that new drugs be proven safe before going on the market.

Growing Pains and Milestones

Since 1938, FDA’s jurisdiction has expanded as various public health emergencies and other challenges faced by the health care system have caught national attention.  Among the many legislative acts passed over the years, the following are of particular relevance to current developments:

(1) Food Additives Amendment of 1958, addressing safety concerns over new food additives and implementing generally recognized as safe (“GRAS”) requirements;

(2) Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman” Act), establishing the modern generic drug approval system;

(3)  Nutrition Labeling and Education Act of 1990, granting FDA authority to require nutrition labels on most foods, and compelling FDA-compliant nutrient and health claims;

(4) Safe Medical Device Amendments of 1990, giving FDA post-market device surveillance authority and device tracking capability at the user level;

(5) Dietary Supplement Health and Education Act of 1994, defining “dietary supplement” and establishing a regulatory framework for such products;

(6) Food and Drug Administration Modernization Act of 1997, making changes to several FDA regulatory schemes, including biologics, devices, pharmacy compounding, food safety and labeling, and standards for medical products;

(7) Food and Drug Administration Amendments Act of 2007, authorizing FDA to require a Risk Evaluation and Mitigation Strategy (“REMS”) to ensure that drug benefits outweigh risks;

(8) Family Smoking Prevention and Tobacco Control Act of 2009, expanding FDA authority over manufacturing, distribution, and marketing of tobacco products;

(9) Drug Quality and Security Act of 2013, expanding FDA’s authority to regulate the manufacturing of compounded drugs as a reaction to a meningitis outbreak caused by contaminated compounded drug products; and

(10) 21st Century Cures Act of 2016, creating the Breakthrough Devices Program, the Regenerative Medicine Advanced Therapy Designation, and exempting certain software products from the definition of “medical device.”

An Old Dog Learning New Tricks

Over the last few years, FDA has felt the impact of and the need to respond to several societal developments.  The country is calling for the government to address drug prices and to gain better control over access to drugs containing controlled substances, such as opioids.  The surge in development of new technology has forced FDA to adapt its historically rigid device regulatory structure to accommodate innovations such as regenerative medicine therapies.  A renewed public focus on the nutritional value of food requires updates to nutritional labeling and food safety regulations, and the new “vaping” trend raises questions surrounding the sale and promotion of new tobacco products.  Across all of these developments, there is a trend toward more focused regulatory pathways that take into account the particular needs and challenges of specific product categories.  Many of these changes are either required or authorized by legislation, such as the 21st Century Cures Act; and statements by the agency, as well as numerous new draft and final guidance documents, give indications as to where FDA is headed in the next few years.

A. Drugs

Increasing Market Competition and Access: FDA is focused on increasing market competition for and patient access to prescription drugs. In furtherance of its Drug Competition Action Plan, the agency published a draft guidance to address the exploitation of REMS and prevent problematic pay-for-delay schemes. In the same vein, FDA implemented a Biosimilar Innovation Plan to facilitate development and approval of biosimilars, hoping to increasing patient access to costly biologics. Last week, FDA also withdrew its draft guidance on biosimilar analytical studies, announcing intent to issue a revised draft guidance in the future.

Drug Development Efficiency: Recent FDA publications also suggest that the agency is prioritizing a more streamlined drug development process. In February 2018, FDA released five guidance documents emphasizing a faster, patient-focused approach for drug development for neurological conditions. In March 2018, FDA updated its benefit-risk framework to further incorporate patient experience into the agency’s regulatory decision-making process. FDA published the first of four of its patient-focused drug development guidances on June 13, 2018.

In response to the opioid crisis, FDA is focusing heavily on changes to the drug compounding and controlled substance space. In March 2018, FDA published a draft guidance on evaluation of bulk drug substances nominated for inclusion in the 503(B) bulks list, requiring a showing of clinical need. FDA also plans to issue notice of proposed regulations for outsourcing facilities later in 2018.  FDA held a Patient-Focused Drug Development Meeting for Opioid Use Disorder in April 2018 and published an associated draft guidance on buprenorphine drug development and clinical trial design issues. We expect to see more FDA movement on drug development as the year progresses, particularly with respect to opioid use disorder treatment therapies.

B. Devices

Streamlining the Device Pathway: FDA continues to implement changes to the regulatory pathway for manufacturers to bring their devices to market.  Per a draft guidance released in April 2018, the agency is expanding the abbreviated 510(k) pathway by creating a voluntary option for manufacturers when there is no acceptable predicate for a new device, but there is another device with the same intended use.  Manufacturers will be able to use the similar device as a “predicate” and demonstrate how their product conforms to newly-developed device-specific objective performance criteria.  While these performance criteria are still under development, they will eventually pave the way for more manufacturers to bring their products to market faster.

Precision Medicine: The national focus on precision medicine has encouraged many manufacturers to develop new products that incorporate genomics-based technology.  FDA is encouraging development of next generation sequencing (“NGS”)-based tests, which analyze larger sequences of the human genome, if not the whole genome, for a variety of different genetic variants.  FDA released two final guidance documents in April 2018, making recommendations on (1) the design and development of a NGS-based test for germline diseases and (2) use of public human genetic variant databases to support clinical validity of NGS-based tests and routes for establishing and justifying algorithms for variant annotation and filtering.

FDA is also evaluating its approach to the regulation of gene therapy products. Commissioner Gottlieb stated that the agency is at “an inflection point” with gene therapy thanks to increased reliability of vectors.  The focus has shifted from the efficacy of gene therapy to its durability, i.e. the long term effects of the treatment.  Recently, Commissioner Gottlieb announced FDA’s intent to start developing gene therapy guidance for products intended to treat hemophilia.

Regenerative Medicine: In efforts to implement its comprehensive policy framework for regenerative medicine and respond to certain provisions of the 21st Century Cures Act, FDA intends to create an expedited regulatory pathway for novel regenerative medicine therapies.  FDA is also actively enforcing against stem cell clinics promoting certain regenerative medicine therapies without approval and in violation of current good manufacturing practices.

Software and Artificial Intelligence (“AI”): In acknowledgment of the current “digital age,” FDA published a Digital Health Innovation Action Plan.  In April 2018, FDA released two policy documents – (1) a working model for the Digital Health Software Pre-Certification (Pre-Cert) Program Pilot and (2) guidance on regulation of digital health products with both FDA-regulated and unregulated functions.  Also in 2018, FDA authorized the marketing of AI-based clinical decision software (“CDS”) that functions to alert specialists when computed tomography (“CT”) indicates a potential stroke, as well as an AI algorithm for detection of wrist fractures.

C. Food

Food Safety: Since the Food Safety Modernization Act (“FSMA”) was passed, sixteen rules and dozens of guidances have been released (many of which have been in the last two years), bringing the law close to full implementation. These rules and guidances address the mandatory preventive controls for food manufacturing facilities; mandatory product safety standards; FDA’s new mandatory food recall authority; and the initial required inspection of over 600 foreign facilities and the subsequent requirement to “double those inspections every year for the next five years.” In light of the recent high profile foodborne illness outbreaks at chain restaurants and attributed to romaine lettuce, the agency is hoping the full implementation of the FSMA rules, in tandem with keeping food safety as a high priority for the agency, will minimize the risk of future outbreaks.

Nutrition: In 2018, the agency launched the FDA Nutrition Innovation Strategy, which, in addition to implementing new Nutrition Facts Label and Menu Labeling requirements, demonstrates that the agency is looking for more ways to modernize food labels and standards of food product identity to help consumers make healthier decisions. FDA also plans to release short-term voluntary sodium targets for food products in 2019.

Food Labeling: FDA issued a guidance in 2016 on the use of the term “healthy” in food labeling, and continues today to seek stakeholder input on how to redefine the term in such a way as will keep up with scientific advancements and help consumers understand what is in their food products.  FDA is also reviewing stakeholder input on how to define “natural,” and indicated in March 2018 that the agency will “have more to say on the issue soon.”

Dietary Supplements: The dietary supplement industry is a growing industry, and consumers are more interested in alternative products to promote wellness lifestyles. The industry is considered by some to still be the “wild wild west” in terms of enforcement, but FDA seems to be putting its foot down on companies making unsubstantiated claims about dietary supplement products or making claims that would otherwise classify the product as a drug.

D. Tobacco Products

Using its authority to regulate all tobacco products, FDA is addressing the rise in the use of vapes, vaporizers, pens and electronic cigarettes by children.  In April 2018, Commissioner Gottlieb announced the intent to issue new enforcement actions against bad actors, as well as to implement a Youth Tobacco Prevention Plan, seeking to reduce the amount of children exposed to e-cigarettes and vapes and those manufactures who target children with enticing flavors.   In May 2018, Commissioner Gottlieb stated “If you target kids, then we’re going to target you.”  FDA is also in the process of developing guidance for the development and regulation of e-cigarettes generally, suggesting that e-cigarettes could fall into the over-the-counter pathway due to their potential role in smoking cessation, and is reviewing the toxicology of the products.

Andrew Do, a Summer Associate (not admitted to the practice of law) in the firm’s Washington, D.C. office, contributed  to the preparation of this post.

Two cases decided over the last three months have added California[1] and Massachusetts[2] to the list of minority states that hold brand name manufacturers of drugs (“Brand Manufacturers”) liable under state “failure to warn” laws when sued by patients that exclusively used a generic version of the Brand Manufacturer’s drug.  These cases follow the US Supreme Court decision in PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011) (“PLIVA”), which held that generic drug manufacturers cannot be held liable for failure to update the safety label of a drug or biologic in violation of state “failure to warn” tort law since regulations from the U.S. Food and Drug Administration (“FDA”) prohibit generic manufacturers from unilaterally updating a generic drug’s label.  Following PLIVA, the FDA proposed a rule entitled, “Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products” (“Proposed Rule”) meant to allow generic drug or biologic manufacturers (“Generic Manufacturers”), under certain circumstances, to update safety labels without the requirement that the label match the label of the Brand Manufacturer.  The Proposed Rule also would have required Generic Manufacturers in certain circumstances to collect post-market safety information.  However, after twice delaying publication of a final rule, the FDA withdrew its Proposed Rule last year.   Now that the Proposed Rule has been withdrawn, manufacturers holding New Drug Applications or Biological License Applications (collectively herein, “NDAs”) for the drugs or biologics they manufacture are faced with increased uncertainty with regard to the application of state “failure-to-warn” duties and liabilities, especially in light of the recent decisions by the California  and Massachusetts supreme courts.

The Evolution (or lack thereof) of Failure to Warn Cases

PLIVA held that Generic Manufacturers have only “an ongoing federal duty of ‘sameness’” meaning that a Generic Manufacturer is required only to keep its warning label identical to the Brand Manufacturer’s.  However, PLIVA left the determination of whether Brand Manufacturers would be liable under the same laws up to each state to decide.  Most state courts have not imposed a duty to warn onto Brand Manufacturers when the injury stems from the exclusive use of a generic drug.   However, two recent cases in California and Massachusetts have expanded the number of minority-view states.

While following PLIVA, the California Supreme Court’s decision in T.H. v. Novartis Pharmaceuticals Corp., 4 Ca. 5th 145 (Cal. Dec. 21, 2017) (“Novartis”) in many ways is an extension of Conte v. Wyeth, Inc., 168 Cal.App.4th 89, 94 (2008) (“Conte”), a decision that pre-dates PLIVA.  Conte was the first case to hold that Brand Manufacturers owe a duty of care to patients whose “doctors foreseeably rely on the name-brand manufacturer’s product information when prescribing a medication, even if the prescription is filled with a generic version of the prescribed drug.”  Novartis held that “a brand-name drug manufacturer owes a duty of reasonable care in ensuring that the label includes appropriate warnings, regardless of whether the end user has been dispensed the brand-name drug or its generic bioequivalent.”  The majority’s decision applied factors that focused on foreseeability and public policy justifications for (or against) carving out exceptions to the general duty to warn.  Ultimately, noting that California places greater emphasis on foreseeability than other states when determining whether to obligate a party as having a duty, the Court held that Brand Manufacturers have a duty and “can be liable for the effects of its deficient warning label, despite transferring the NDA to a successor, if the harm is reasonably foreseeable and is proximately caused by the label.”   The Court stated that the federal requirement to revise “a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug” without needing causal proof under 21 C.F.R. § 201.80(e) created a “continuing duty to warn of potential risks.”  The decision was not without controversy mostly because the Court held that the Brand Manufacturer was still duty-bound despite divesting itself from ownership and control of the NDA.

The dissent in Novartis noted that “predecessor liability for failure to warn has never before been recognized by any court, in any jurisdiction” and that two prior decisions, In re Darvocet, Darovan and Propoxyphene Products Liability Litigation, 2012 WL 767595 (E.D.Ky. Mar. 7, 2012) and Lyman v. Pfizer, No. 2:09-cv-262 (D.Vt. July 20, 2012), each rejected predecessor liability as the original manufacturer’s “failure to warn” would be too remote to establish proximate cause of the injury.  In terms of transferring the duty through divestment, the dissent noted that “[t]here is no logical stopping point” for this broad and continuing duty for Brand Manufacturers.   The majority’s opinion offers no guideposts as to when divestment is sufficient to cease liability or at what time interval the predecessor is relieved of this duty.

The Massachusetts Supreme Court struggled with when to impose the duty to warn on a Brand Manufacturer in its recent opinion in Rafferty v. Merck & Co, Inc., 479 Mass. 141 (Mar. 16, 2018) (“Merck”).  While following PLIVA’s strict guidance that Generic Manufacturers cannot be held accountable under failure to warn laws where the Generic Manufacturer has adhered to the “duty of sameness,” the Court found that “public policy is not served if generic drug consumers have no remedy for the failure of a [Brand Manufacturer] to warn in cases where such failure exceeds ordinary negligence.”  However, rather than impose a duty under the plaintiff-friendly negligence standard, the Court held that a Brand Manufacturer’s duty is “the duty not to intentionally or recklessly cause harm to others.”  The court reasoned “that allowing a generic drug consumer to bring a general negligence claim for failure to warn against a brand-name manufacturer poses too great a risk of chilling drug innovation, contrary to the public policy goals embodied in the Hatch-Waxman amendments.”  After establishing this new standard, the Court permitted the plaintiff to amend his complaint to add “a common-law recklessness claim” if the plaintiff could allege that the Brand Manufacturer “intentionally failed to update the label on its drug, knowing or having reason to know of an unreasonable risk of death or grave bodily injury associated with its use.”

Perhaps in response to Novartis, the Court described its holding as applying to a Brand Manufacturer “that controls the contents of the label on a generic drug,” though no additional guidance was provided on the issue of predecessor liability.  By choosing a recklessness standard, Massachusetts becomes the first “middle ground” state on the issue: while becoming a minority state in terms of finding a duty to warn for Brand Manufacturers under the circumstances, it is also “the only court to limit the scope of liability arising under this duty to reckless disregard of the risk of death or grave bodily injury.”

The Federal Regulatory Landscape

FDA regulations require a Brand Manufacturer to obtain FDA approval of all labeling and to update the label of its drug “as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.”  The FDA allows the company that holds an NDA to submit a “Changes Being Effected” supplement or “CBE-0” which allows Brand Manufacturers to unilaterally update their labels immediately upon receipt by the FDA of the supplement, under certain circumstances, including strengthening a safety label or adding additional warnings.

However, as the PLIVA decision made clear, this requirement falls squarely on the shoulders of the NDA holder and does not pass onto Generic Manufacturers.  Instead, Generic Manufacturers, under PLIVA, must maintain a duty of “sameness”.  As a result, a Generic Manufacturer may not unilaterally update the drug’s label if the update will cause the label to be different from the brand name drug’s label.  The FDA originally enacted this requirement as part of the Hatch-Waxman Act  to assure prescribers that the generic drug is bioequivalent to the brand name drug, thereby encouraging the use of generic drugs.  However, the Proposed Rule indicates that the FDA was considering changing its position on the issue.

Under the Proposed Rule, a Generic Manufacturer would have had the ability to unilaterally change its drug’s label under CBE-0.  Additionally, a Generic Manufacturer would have been able to send a “Dear Health Care Provider” letter describing the reasons for the change in an effort to disseminate urgent information regarding the drug’s safety, dosage, administration, or efficacy information.  Unfortunately, after extending a public comment period and hosting a Public Hearing to discuss the Proposed Rule, the FDA  withdrew the rule on September 29, 2017.  This decision leaves states in the precarious position of trying to balance the rights of Brand Manufacturers and clients of Generic Manufacturers, as well as traditional theories of tort liability, as the Merck decision clearly demonstrates.   The dissent in the Novartis decision specifically discussed the Proposed Rule and how a final rule on the issue would likely have altered the Court’s analysis and changed its decision.

Conclusion

In the wake of these cases, only one thing is clear: state courts continue to struggle with how to apply the federal preemption of liability for Generic Manufacturers from state failure to warn liability under PLIVA.  Even where states have adopted liability for Brand Manufacturers, additional questions persist.  The Novartis decision creates no clear line of when a Brand Manufacturer’s liability evaporates through the passage of time or divestment from an NDA.  The Merck decision sets out a new standard without applying it.  This leaves Brand Manufacturers with few answers when determining whether to expand their monitoring activities and determining how aggressive to be in filing for a CBE-0 for products the Brand Manufacturer may no longer manufacture or own.

[1] T.H. v. Novartis Pharmaceuticals Corp.  4 Cal. 5th 145 (Dec. 21, 2017)

[2] Rafferty v. Merck & Co, 479 Mass. 141 (Mar. 16, 2018)

New rules issued on November 7, 2017 by FDA will make it easier for companies to offer certain types of genetic tests directly-to-consumers (DTC), without a health-care provider intermediary.

The first rule exempts “autosomal recessive carrier screening gene mutation detection systems” that are offered DTC from FDA premarket review.  FDA first proposed this exemption in 2015, on the same date as the agency issued a final order classifying these types of tests as Class II medical devices, in response to a request from 23andMe.  The 2015 final rule specified the conditions under which all companies could offer autosomal recessive carrier tests directly to the public.  By finalizing the exemption, FDA is permitting companies to offer these tests DTC without the need for prior FDA review.  These companies will still be subject to general requirements applicable to all medical device manufacturers, as well as to the “special controls” specified by FDA for these types of tests in the final rule.

Similarly, the second rule finalizes a new medical device classification for  DTC “genetic health risk assessment” (GHR)  (i.e., predictive) tests.  The classification specifies the conditions under which these tests may be marketed, and includes the requirement for a 510(k) premarket notification to FDA. However, in a Federal Register Notice, also issued yesterday, FDA proposes to exempt GHR tests from the 510(k) premarket submission requirement after a company has successfully obtained FDA clearance of its first GHR assay, and provided that the company continues to follow the specified special controls for this class of tests.  Comments to this proposed exemption are being accepted by FDA until January 8. 

Please reach out to Gail Javitt or the Food and Drug Law practice team members for additional information.

The passage of the 21st Century Cures Act (“Cures Act”) and revisions to the Common Rule (45 CFR Part 46) (“Common Rule”) in the last year mandated significant changes to informed consent laws.  As a result of these changes, sponsors of research (“Sponsors”), institutions conducting research (“Institutions”), and the institutional review boards (“IRBs”) approving research will need to review policies and practices involving informed consent.  As explained below, a recently published FDA guidance document makes a first step toward implementing some of these changes by permitting waiver of certain consent requirements for low risk research involving human subjects. Additionally, a recent ruling by the Pennsylvania Supreme Court discussed below reminds investigators, Institutions, and Sponsors performing clinical research in Pennsylvania that state informed consent laws and common law must also be considered before conducting clinical research involving human subjects.  The following brief discussion provides some insight into how Sponsors, Institutions, and IRBs should take into account varying sources of law when determining when to require consent for research involving human subjects.

FDA Guidance on Waivers of Consent

On July 13, the United States Food and Drug Administration (“FDA”) issued a guidance document titled “IRB Waiver on Alteration of Informed Consent for Clinical Investigations Involving No More Than Minimal Risk to Human Subjects” (“Consent Guidance”).  The Consent Guidance states that “FDA does not intend to object to a sponsor initiating, or an investigator conducting, a minimal risk clinical investigation for which an IRB waives or alters the informed consent requirements” to the extent that the IRB documents that: the research “involves no more than minimal risk;” the waiver “will not adversely affect the rights and welfare of the subjects;” the research “could not practicably be carried out without the waiver;” and “subjects will be provided with additional pertinent information after participation,” if appropriate.  The Consent Guidance is an initial step toward implementing Section 3024 of the Cures Act, which amended the Food, Drugs, and Cosmetic Act to provide FDA with the authority to exempt certain research of drugs or medical devices from informed consent requirements if the research poses “no more than minimal risk” to human subjects and includes “appropriate safeguards to protect the rights, safety, and welfare” for participating subjects.  However, current FDA regulations do not provide IRBs with the power to waive consent except in certain circumstances involving an emergency or a life-threatening situation.  While FDA’s guidance documents contain disclaimers that the documents, themselves, lack any authority and cannot be relied upon, Sponsors, Institutions, and IRBs should be confident moving forward under the Consent Guidance as it stems directly from authority granted to FDA under the Cures Act and is consistent with the approach taken by the revised Common Rule.  The FDA is expected to provide updates to its own human research subject protection regulations in 21 CFR Parts 50 and 56, which based on the Consent Guidance will include “minimal research” provisions similar to the Consent Guidance and the revised Common Rule.  These rules will also address new provisions regarding identifiable biospecimens, which are not addressed under the Consent Guidance.  Once these new rules are established, FDA has stated that it will withdraw the Consent Guidance.

Recent Case Law

While Federal laws and regulations shape many aspects of informed consent, state laws may impose additional nuances that providers must understand. For example, a recent decision by the Pennsylvania Supreme Court will impact the manner in which informed consent must be obtained by physicians practicing in the state of Pennsylvania.  In Shinal v. Toms, M.D., 162 A.3d 429 (2017), Court held that physicians may no longer rely upon information provided by non-physicians to satisfy physician obligations under the MCARE Act, 40 Pa.  Stat. § 1303, et seq, which imposes a duty on physicians to obtain informed consent before performing certain procedures.  The specific law at issue was Section 504 of the MCARE Act, which creates a duty for a physician “to a patient to obtain the informed consent of the patient” before performing surgery, administering radiation or chemotherapy, administering a blood transfusion, inserting a surgical device, or “administering an experimental medication, using an experimental device or using an approved medication or device in an experimental manner.”  In Shinal v. Toms, M.D., 162 A.3d 429 (2017), the plaintiff asserted that Section 504 required Dr. Toms, the plaintiff’s surgeon, to provide all information and receive a patient’s informed consent personally in order to fulfill the physician’s duty for obtaining informed consent under the statute.  After an initial discussion with Dr. Toms regarding certain surgical options, the plaintiff later called to ask additional questions regarding different surgical procedures and was directed to a nurse to have her questions answered.  The plaintiff argued that her consent for the surgery was not sufficiently informed because the information provided to her about her surgical options should have been provided by Dr. Toms.  The Court agreed, and its 4-3 decision held that physicians in Pennsylvania must directly “disclose the information required to obtain informed consent.”

While Shinal involved consent for a surgical procedure, Section 504 of the MCARE Act also requires physicians to obtain informed consent  before administering an experimental drug or device.  This ruling will undoubtedly require many Institutions in Pennsylvania to change how informed consent is obtained from potential subjects in clinical trials, as it is common practice within the industry for physician investigators to delegate the informed consent process, or at least certain portions of the consent discussion with potential research subjects, to members of the Institution’s study staff.  Sponsors will likewise want to investigate the consent processes of Institutions conducting research on their behalf in Pennsylvania and review informed consent templates used by these Institutions to ensure they reflect the holding in Shinal.

The position expressed by the Shinal Court that only information provided by a licensed physician may be considered in determining whether the physician fulfilled his or her duty to provide informed consent appears to be unique among the states.  Nevertheless, it demonstrates to Sponsors, Institutions, and IRBs the importance of looking beyond FDA regulations and the Common Rule when developing and maintaining standard operating procedures and templates for obtaining informed consent.  Even if certain research may meet “minimal risk” rules at a federal level, Institutions must still abide by applicable state laws with regard to the requisite consent required before treating patients within the study.

At the end of July, FDA released a tangible plan for promoting innovation in the development of digital health products. In this Digital Health Innovation Action Plan, FDA acknowledges that digital health technologies are critically important in advancing health care, and that traditional FDA pathways to market are not well suited for all of these technologies. Over the last few years, FDA has taken a deregulatory approach with respect to low risk digital health products and has issued guidance regarding its enforcement discretion approach to wellness products, medical device data systems, medical imaging communication and storage devices and certain mobile apps. However, there still has been uncertainty with respect to whether, and how, other digital health technologies will be regulated. This new plan paves the way for additional regulatory clarity and streamlined pathways to market for digital health developers.

Some of the key aspects of the plan include:

  • Issuing 21st Century Cures Act implementation guidance. The Cures Act, which was passed in December of last year, includes provisions clarifying FDA’s regulation of software. Specifically, these provisions explicitly exclude certain software from FDA’s definition of a “medical device,” including electronic health records and software that encourages healthy living, displays, transmits, stores or performs limited conversion of medical device data and supports administrative activities. As a result, these products are not subject to FDA’s oversight. The planned draft guidance, which the Agency hopes to release by the end of the year, will reconcile these new Cures provisions with existing FDA guidance. Cleaning up and clarifying policies in this space will help solidify FDA’s interpretations and reduce regulatory uncertainty.
    FDA also commits to providing guidance regarding products that include regulated and unregulated functionality. The Cures Act makes clear that the fact that an unregulated application co-exists with a regulated application within a solution does not submit the unregulated functionality to FDA oversight. FDA still may consider how the unregulated software impacts the safety and effectiveness of the regulated software, but the unregulated software nevertheless remains unregulated.
  • Running a pilot program focused on “pre-certification” of digital health developers. In September, FDA will launch a pilot pre-certification program applicable to manufacturers of stand alone medical device software. The purpose of the program is to develop objective criteria that, if met, would demonstrate an entity’s ability to reliably develop high quality, safe and effective software. The intent is for FDA to use these criteria to develop a framework to pre-certify software developers that satisfy the requirements. In turn, pre-certified developers would be subject to a streamlined premarket review for new lower-risk products (e.g., less premarket submission information would be required and/or review times would be faster). FDA indicated that, in some instances, pre-certified companies would be able to market certain lower risk products, that presumably would be subject to 510(k) clearance today, without any premarket review at all. However, to account for reducing the front end requirements, FDA envisions that developers will collect real-world data once their products hit the market to assure they are safe and effective.
  • Issuing CDS software guidance. By the first quarter of 2018, FDA plans to issue draft guidance detailing which CDS is not subject to FDA regulation. The Cures Act carves out transparent, professional use CDS from the definition of a medical device. This carved-out CDS is software that is not intended to be relied upon as the primary basis for a clinical decision, but rather allows the healthcare professional to independently review and assess the underlying rationale for the software recommendation in connection with making a clinical decision. While guidance on how FDA interprets the relevant Cures language on this issue will be helpful, it is equally, if not more important, for the Agency to provide guidance on CDS that falls outside of the Cures Act exemption (e.g., consumer clinical decision support, machine learning and non-transparent CDS).
  • Finalizing 510(k) Guidance on Software Changes. FDA’s Digital Health Innovation Action Plan also includes finalizing the draft guidance on “Deciding When to Submit a 510(k) for a Software Change to an Existing Device.” This guidance is the software counterpart to FDA’s draft guidance on “Deciding When to Submit a 510(k) for a Change to an Existing Device,” which has had a controversial past. FDA first attempted to revise its guidance on when a 510(k) is required due to a change made to a device in 2011. FDA was required by Congress to withdraw its 2011 draft guidance due to the potentially significant impact the draft guidance would have on industry. In August 2016, FDA published this pair of draft guidance documents. Given the disagreement and debate that has surrounded this topic, a definitive FDA approach will provide manufacturers greater certainty regarding any submission requirements for the range of software changes made to traditional medical devices, as well as to stand alone software devices.
  • Adopting the IMDRF’s Approach to Clinically Evaluating SaMD Once Finalized. FDA also intends to adopt the final version of the Software as a Medical Device (SaMD): Clinical Evaluation guidance as published by International Medical Device Regulators Forum (IMDRF). FDA released draft guidance that incorporated this IMDRF document in 2016. While it is unclear how procedurally FDA will adopt a final version of the IMDRF policy without public review and comment, the IMDRF framework will nevertheless provide insight into FDA’s thinking on clinical evaluation requirements for medical device software given the Agency’s leadership in the IMDRF work group that drafted the document and this pre-emptive endorsement. It also serves as a reminder that despite FDA efforts to minimize regulatory burdens for low risk digital health products, moderate and high risk medical device software remains subject to FDA’s premarket review. The 21st Century Cures and CDS guidance, both of which are expected after IMDRF’s SaMD’s Clinical Evaluation document is finalized, will be instrumental in clarifying which digital health products are subject to such requirements.

Although FDA has been expected to release many of these policies for years, the Digital Health Innovation Action Plan is aggressive, promising five draft or final guidance documents in just over six months, while at the same time conducting the pre-certification pilot program.  Whether this is a reflection of the new administration, a new Commissioner or a new (or renewed) focus on digital health innovation, it is a welcome development and one that will be watched closely by software companies, traditional medical device manufacturers and patients alike.

On May 9, 2017, Scott Gottlieb, M.D. was confirmed by the Senate as the new Commissioner of the Food and Drug Administration (“FDA”).  As Commissioner, he will be immediately responsible for shaping FDA policy on a number of current issues, including addressing and implementing several mandates stemming from the 21st Century Cures Act, (“Cures Act”), which was signed into law on December 13, 2016 with tremendous bipartisan support. The Cures Act contains over 200 sections that create new obligations for FDA; however, most pressing for Commissioner Gottlieb are three requirements that must be fulfilled within 180 days of the Cures Act’s passage (June 11th, 2017).

These requirements are:

  • Submission of a work plan to the Committee on Health, Education, Labor, and Pensions and the Committee on Appropriations of the Senate and the Committee on Energy and Commerce and the Committee on Appropriations of the House of Representatives for any projects, which will use funding from the FDA Innovation Account created under Section 1002 of the Cures Act;
  • Development of “a plan to issue draft and final versions of one or more guidance documents, over a period of 5 years, regarding the collection of patient experience data, and the use of such data and related information in drug development” pursuant to Section 3002 of the Cures Act, which is codified at 21 U.S.C. 360bbb-8c; and
  •  Publication of “a list of reusable device types” pursuant to Section 3059 of the Cures Act, which is codified at 21 U.S.C. 360.

Commissioner Gottlieb has a long professional history in the pharmaceutical industry working in both the public and private sectors. His firsthand experience as a former Deputy Commissioner at the FDA provides him with unique insights into the internal workings of the administration. As a former consultant advising on FDA policies to the pharmaceutical industry, Commissioner Gottlieb is also familiar with recent issues and trends affecting the industry, many of which are addressed within the Cures Act.  Despite having only one month to organize and address the mandates of the three above-referenced sections of the Cures Act, we believe Commissioner Gottlieb will likely meet these deadlines based on his prior knowledge and experience.

We will continue to monitor and provide insight on Commissioner Gottlieb’s activity as FDA Commissioner, and the implementation of key Cures Act provisions as they develop. For insight into how Commissioner Gottlieb has historically viewed key issues impacting the FDA, and mandates under the Cures Act, please view our previously published client alert.

On January 19, 2017, the United States Food and Drug Administration (“FDA”) unveiled a new drug designation process for regenerative advanced therapies, an important first step toward implementation of the regenerative medicine provisions of the 21st Century Cures Act.  Products for which a designation as a regenerative advanced therapy (“RAT”) is obtained are eligible for accelerated approval under the 21st Century Cures Act, which was signed into law by former President Obama on December 13, 2016 with sweeping bipartisan support.

The accelerated approval provisions for RATs under the 21st Century Cures Act are intended to facilitate expedited review and approval of stem cell therapies and other cellular and tissue products for use in serious or life threatening diseases, which are currently subject to regulation as unapproved drugs. Under the 21st Century Cures Act, regenerative medicine therapies eligible for a RAT designation may include any “cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those products regulated solely under Section 361 of the Public Health Service Act (“PHS”), and part 1271 of Title 21, Code of Federal regulations.”[1]

Under the 21st Century Cures Act, the sponsor of a product must show the following to be eligible for a RAT designation:

  • The drug is a regenerative medicine therapy;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition;[2] and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.

Pursuant to the FDA website on the Regenerative Advanced Therapy Designation, a sponsor requesting a RAT designation for its product must make such a request either concurrently with submission of an Investigational New Drug application (“IND”), or as an amendment to an existing IND. Consistent with requests for fast track and breakthrough therapy designations, the FDA only requires that a sponsor describe the preliminary clinical evidence that supports a RAT designation, and does not require the sponsor to submit primary data.  Information that will be considered includes: a description of any available therapies for the disease or condition already in existence, the study design, the population studied, the endpoints used, and a description of the study results and statistical analyses.

The RAT designation process will be overseen by the newly created Office of Tissues and Advanced Therapies (OTAT). The OTAT will manage the application process for RAT designation, and will notify the sponsor within 60 days of receiving an application as to whether the RAT designation is granted. If a sponsor does not receive a RAT designation for its product the OTAT will provide an explanation in writing of its rationale for the denial.

A sponsor that obtains a RAT designation for its product is entitled to meet with the FDA early in its development program to discuss the potential use of surrogate or intermediate endpoints that may be used to support accelerated approval of the product. RATs may be eligible for accelerated approval based upon surrogate or intermediate endpoints reasonably likely to predict a long-term clinical benefit, and based on data obtained from a “meaningful number of sites” with subsequent expansion to additional sites, along with the collection of additional data in the post-market phase.

The implementation of the RAT designation process will enable manufacturers to begin to take advantage of the less burdensome review process enabled by the 21st Century Cures Act.  While some patient advocates have expressed concern that the availability of an accelerated approval pathway for regenerative medicine products may impede the development of robust evidence establishing their safety and effectiveness, and may ultimately result in patient harm, 21st Century Cures’ accelerated approval provisions are likely to be a harbinger of a new wave of regenerative medicine therapies that provide additional options for patients facing serious or life threatening conditions.

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[1] 21st Century Cures Act Sec., Sec. 3033(8).  Human Cells, tissues, and cellular and tissue-based products (HCT/Ps) are regulated solely under section 361 of the PHS Act and the regulations of 21 C.F.R. Part 1271 if all of the following criteria are met: the HCT/P is minimally manipulated, intended for homologous use (as reflected in labeling and advertising), is not manufactured by combining cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving or storage agent, and does not have a systemic effect nor is dependent upon the metabolic activity of living cells for its primary function. Therefore, if a product meets all of the aforementioned criteria, the HCT/P will still be regulated under 21 C.F.R. Part 1271 and will not be subject to regulation as a drug product.

[2] The FDA will use its standard definitions found in its Expedited Program Guidance as a guide to determining whether a product meets the required criteria, such as whether a condition is “serious or life-threatening” or whether a drug is “intended to treat a serious disease or condition.”

Congress is currently considering two bills that would dramatically alter the ways in which all federal agencies develop and publish rules. If enacted, both would create significant new obligations for agencies such as CMS and the FDA, expand the scope of judicial review of rules, and would increase the potential for political influence over the rulemaking process. Both bills passed the House on party-line votes, and are under consideration by the Senate.

The first bill, H.R. 5, would overhaul multiple phases of the federal rulemaking process. These proposed changes would make the rulemaking process significantly longer and more complex for agencies, and includes provisions that could prevent some rules from ever taking effect. The key provisions of the bill are summarized below:

  • Prior to publishing any rule (1) with an expected annual impact of $100 million or more, (2) that may reduce employment, or (3) that involves a novel legal or policy issue, an agency would have to publish an advance notice that it intends to publish a proposed notice of rulemaking, and must solicit comments on the notice. A proposed rule could only be published after this new additional process is complete.
  • Whenever an agency publishes a proposed rule for public comment in any of the categories described above, it would have to explain the basis for the rule, the data it relied on, and would have to explain the alternatives to the rule and justify why they were not adopted. In addition to the current public comment period, once a proposed rule was published an interested party could then request a hearing to contest the quality of the information relied on by the agency. Any resolution of this new step would slow down the rulemaking process further.
  • In all cases where a rule is expected to have an annual impact of at least $1 billion annually, the agency would now be required to conduct a public hearing limited to fact issues. This would add to the time and cost of publishing a new or revised rule.
  • When a final rule is published, the agency would be required to explain in the preamble to that rule why the rule will have the lowest possible cost unless it involves public health, safety, or welfare.
  • All agencies would be required to publish all documents considered by an agency prior to publishing the rule.  This would eliminate the deliberative process privilege that has been in place for decades, which is intended to promote the exchange of views within an agency, and may have a chilling effect on agency deliberation. In many cases, a final rule could not take effect until all of the information relied on by the agency had been made available electronically for at least six months unless the agency or the President claims an exception.
  • Recipients of federal funds would be prohibited from advocating for or against the rule, or appealing to the public to either support or oppose the rule.
  • Guidance documents issued by agencies, including manuals, circulars, and other subregulatory publications would no longer have any legal effect and could not be relied on by the agency for any actions. The bill does not explain how many important parts of federal programs, such as the administration of grants or cost accounting for hospitals in the Medicare program would be handled. These and other programs rely heavily on the detailed information found only in agency manuals and guidance. Without these guidelines, health care providers, suppliers, manufacturers, and researchers among others would find it increasingly difficult to comply with federal laws.

The bill would also make drastic changes in the scope of any judicial review of published agency rules. The bill would overturn the Supreme Court’s landmark Chevron decision, which established the principle that when an agency is charged with administering a statute and interprets ambiguous statutory language in a regulation, courts will defer to the agency’s permissible interpretation of the law. In its place, the bill would authorize courts to review all questions of law involving a regulation without giving weight to the agency’s experience or expertise. Courts would be empowered to impose their own constructions of the law on an agency, upending decades of precedents. This has the potential to increase federal courts’ dockets and place those courts in the position of reviewing technical information without all of the resources available to conduct a review. In addition, by allowing courts to decide cases without relying on the agency’s rationale, this increases the potential for inconsistent decisions and confusion among regulated entities such as health care providers, suppliers, and manufacturers seeking to comply with federal laws.

The second bill, H.R. 26, focuses more on expanding Congress’s control over the rulemaking process once an agency has completed the public notice and comment procedure under current law. It also expands the legislative veto over rules, which currently is authorized only when Congress disapproves of a rule and requires the President’s concurrence.

Under the bill, agencies would be required to report all new rules to Congress, and must identify all “major rules” as determined by the Office of Management and Budget that (1) will have an annual impact of $100M or more, (2) increases costs or prices, or (3) will have a significant impact on competition, employment, investment, or foreign trade. The report to Congress must also contain an analysis of the projected number or jobs that would be gained or lost as result of the rule. All major rules with the exception of those necessary for an emergency, enforcement of criminal laws, or to implement a trade agreement would not go into effect unless both houses of Congress approve the rule by a joint resolution within 70 legislative days after the agency submits its report. There is only one chance to obtain approval of a major rule during a session of Congress; if the joint resolution is not approved, or if no action is taken, the bill would bar Congress from considering a second resolution on the same rule during the same two-year session of Congress. This would allow Congress to override an agency and force the agency to begin the rulemaking anew, if at all. Congress would retain the authority to disapprove all other rules by a joint resolution. The bill also allows for judicial review of Congress’s actions only to review whether or not it followed the procedure in the statute; the merits of any action would be unreviewable.

In addition to expanding control over prospective rules, the bill would also add a sunset provision for existing rules. All agencies would be required to review current rules at least once every ten years and report to Congress; if Congress then failed to enact a joint resolution to retain the rules, they would be nullified.

Although the bills passed the House, it will be much harder for the Senate to pass them as well. Under Senate rules, 60 votes are required to end debate and bring the bills to a vote. Since the Republicans only hold 52 seats, they would need additional votes from Democrats in order for the bills to pass.