Category Archives: Policy

Our Comments on the FDA Draft Guidance for Industry Concerning Dietary Guidance Statements in Food Labeling

September 25, 2023


We appreciate the opportunity to comment on the Food and Drug Administration (FDA) draft guidance for industry concerning questions and answers about Dietary Guidance Statements in food labeling.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

We support the use of Dietary Guidance Statements to improve dietary patterns, reduce the burden of nutrition-related chronic diseases, and advance health equity. Dietary Guidance Statements provide important nutrition information to consumers, and are especially important to consumers with poor nutritional habits. They also encourage industry to reformulate products to improve nutritional standards.

We recommend the following to improve this guidance:

  • Revise the recommendation that manufacturers may use Dietary Guidance Statements on products that exceed recommended limits on saturated fat, sodium, or added sugar.

Manufacturers should not be allowed to use Dietary Guidance Statements on products that exceed recommended limits on saturated fat, sodium, or added sugar, even with an added disclosure statement explaining the nutrient levels the product may exceed. This would be confusing and potentially misleading to many consumers. If the FDA insists on this confusing strategy, the agency should clearly describe which recommended nutrient level is exceeded, and should be designed to grab the attention of consumers, similar to that of a black box warning on medical products.

  • Provide an explicit definition that includes examples of a “consensus report.”

In this draft guidance, FDA defines a “consensus report” as: “A report that represents the consensus produced by a group of qualified experts whose bias and conflicts of interest have been minimized and that are convened to study a specific issue. The consensus report conveys agreed-upon recommendations that reflect widely accepted, objective views of current scientific evidence.” This definition does not specify what FDA considers a “minimized” conflict of interest. This definition needs to be explicit to ensure that inappropriate sources are not included and that Dietary Guidance Statements do not conflict with recommendations in the Dietary Guidelines for Americans released every five years by HHS.[1]

We recommend that FDA provide a list of which published reports from U.S. Federal government agencies, U.S. scientific bodies, or U.S. health organizations outside the Federal government are appropriate to serve as the basis for Dietary Guidance Statements. The list should be updated at least every five years, and be in agreement with the release of updated Dietary Guidelines for Americans.

  • Amend the use of Dietary Guidance Statements related to juice and reduce misleading claims about fruit drinks.

The FDA guidance recommended that products should contain at least ½ cup equivalent of fruit per Reference Amount Customarily Consumed (RACC), which can also be ½ cup of fruit juice per RACC. However, a Dietary Guidance Statement on a product that contains fruit only in the form of juice would be misleading to consumers, because the Dietary Guidelines for Americans place an emphasis on the importance of whole fruits. FDA should amend the guidance to clarify that Dietary Guidance Statements involving fruit should emphasize the benefits of whole fruit over fruit juice, as well as the benefits of fruit juice compared to fruit drinks.

  • Amend the use of Guidance Statements regarding whole grains.

Consumers are often misled by claims of products that “contain whole grains” despite whole grains constituting a small amount or small proportion of the total grains. The Dietary Guidelines for Americans recommend a diet including “grains, at least half of which are whole grain.” As an example guidance statement, the FDA provides a label saying, “Make half your grains whole grain.” This should be amended to recommend that “at least half” your grains should be whole grain. Additionally, for products that contain high amounts of grain, the FDA should recommend at least 50% of the total grains be whole grains.

  • FDA should provide guidelines for Dietary Guidance Statements on alcohol.

Evidence regarding the harmful effects of alcohol, including moderate amounts of alcohol, is well documented and we therefore urge that the Dietary Guidance Statement should include that information.  That would require amending the definition of Dietary Guidance Statements to include those that “represent or suggest that a food or food group may or may not contribute to or help maintain a nutritious dietary pattern. ” Dietary Guidance Statements regarding alcohol should emphasize the recommended limits as well as established evidence about the impact of alcohol consumption on health.

[1] https://www.dietaryguidelines.gov/about-dietary-guidelines/purpose-dietary-guidelines

Our Comments On FDA’s Requirements for Tobacco Product Manufacturing Practices

October 6th, 2023


We appreciate the opportunity to comment on the FDA’s proposed guidance regarding tobacco product manufacturing practice requirements: “Requirements for Tobacco Product Manufacturing Practice.”

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

Overall, we support FDA’s proposed rule for regulating tobacco manufacturing practices. Prior evidence suggests that the absence of agency established tobacco regulations may expose consumers to unnecessary hazards, addictive products, and risks associated with tobacco products.1 While this proposal will not make tobacco products safe, it will help to limit health risks that are not normally associated with the use of tobacco products. Tobacco consumers will still remain at higher risk for cancer, stroke, heart and vascular disease, and chronic obstructive lung disease compared to non-tobacco users. Thus, NCHR urges the FDA to make it clear that this rule will not make tobacco products safe or protect consumer health, but rather is intended to reduce the risks.  We also strongly urge the FDA to put more emphasis on implementing explicit policies that protect the public health as much as possible, rather than emphasizing the agency’s willingness to be flexible in how companies implement this rule.

We agree with the FDA’s proposed requirement that each manufacturer maintain a master manufacturing record (MMR) so that the FDA is able to hold manufacturers accountable and is able to track whether the tobacco products conform to packaging and labeling specifications. Further, as part of the MMR, it is imperative to require tobacco manufacturers to make products that consistently and accurately reflect the nicotine concentration printed on the label. This is essential for e-liquids and e-cigarettes, as they have been shown to range from having anywhere from 35% less nicotine to 52% more nicotine than is printed on the label.2 Moreover, younger e-cigarette users frequently misinterpret the concentration and strength of nicotine in e-cigarettes and many are uncertain about whether some e-cigarettes even contain nicotine.3 When the amount of nicotine consumed is unclear, it has the potential to increase the chances of consumers becoming addicted. Therefore, in addition to requiring manufacturers to accurately and clearly specify the nicotine concentration contained in the product, we also recommend that the FDA require clear, user-friendly labeling to help consumers better understand and calculate their nicotine consumption.

We also strongly agree with the FDA’s proposed regulations to restrict flavor additives, reduce hazardous contamination, and impose maximum nicotine levels in order to mitigate unnecessary health risks. These standards are essential for everyone, but may be especially likely to decrease tobacco initiation among younger consumers, as well as reduce the duration of use and risk of tobacco addiction. E-cigarettes have been shown to contain hazardous contaminated substances such as volatile organic compounds, metals, glass, and plastics and so we support FDA’s proposal for a Quality Management System (QMS), to help reduce contamination, hasten recalls, and prompt regulatory action for contaminated or misbranded tobacco products.

While we agree with the FDA’s proposed approaches for measuring and imposing tobacco standards, we find the enforcement mechanisms and corrective actions against manufacturers who violate these proposed regulations to be inadequate. The incentive for compliance is low, the FDA’s responses to noncompliance have not been sufficiently rigorous, and prior corrective actions have not been commensurate with the gravity that violations pose to the public. For example, the civil monetary penalties that have been previously issued for past e-cigarette violations are relatively rare and not sufficient to improve compliance. As of August of this year, the FDA had sought injunctions against only six companies and filed monetary penalty complaints against only 21 companies for illegally selling e-cigarettes, which pales in comparison to the scope of the problem.4 Thousands of unauthorized and illegal e-cigarettes remain on the market, posing a major threat to public health. NCHR recommends that the FDA enforce more violations and implement more stringent and aggressive enforcement strategies for each violation. For example, when there are multiple violations, rather than charging manufacturers with a single violation in one proceeding, which results in a maximum fine of $19,192, we urge that the manufacturer be charged for each violation, since the FDA has the authority to charge a manufacturer with multiple violations up to $1.2 million in a single proceeding.5 Incentives for compliance would be much greater if the statutory maximum is issued for each violation of the Family Smoking Prevention and Tobacco Control Act. Charging manufacturers with a single violation is not having the desired impact; stiff monetary penalties are needed to increase compliance among manufacturers that repeatedly market flavored e-cigarette products, produce tobacco products with hazardous foreign material, or are non-adherent to regulatory and label requirements.

We are very concerned that in each of the injunctions filed by the FDA, there was a delay of over a year between the time the FDA sent a warning letter to the companies in violation and the commencement of injunction proceeding. Throughout this period, these companies continued to profit from the sale and distribution of illegal products, including menthol flavored cigarettes and all types of flavored e-liquids that are especially attractive to children and teenagers. This substantial delay between the FDA’s identification of violations and initiation of injunction proceedings has clear adverse effects on public health, making it especially likely that children and adolescents will try these products and become addicted to them. We strongly recommend that the FDA streamline the process, more quickly imposing corrective actions in order to reduce harm to individuals and to public health.

In conclusion, we appreciate the opportunity to comment on the proposed rule to regulate tobacco manufacturing practices. We strongly recommend requiring manufacturers to accurately reflect the nicotine concentration contained in the product on the label using clear, plain language in large font. Further, we support the proposed regulations to restrict flavor additives as required by law, reduce hazardous contamination, and impose maximum nicotine levels. Even more important, the FDA should exercise its full authority when imposing monetary penalties for violations to improve incentives for manufacturer compliance. Although tobacco products are inherently unsafe, these proposed regulations, if properly enforced, will be more effective at reducing health risks related to tobacco consumption. 

References:

  1. Lange, T et al. “Regulating Tobacco Product Advertising and Promotions in the Retail Environment: A Roadmap for States and Localities.” Journal of Law and Medical Ethics. 2015.
  2. Raymond et al. “The Nicotine Content of a Sample of E-cigarette Liquid Manufactured in the United States.” Journal of Addiction Medicine. 2018.
  3. Morean et al. “Adolescents’ awareness of the nicotine strength and e-cigarette status of JUUL e-cigarettes. Drug and Alcohol Dependency. 2019.
  4. FDA, Advisory and Enforcement Actions Against Industry for Unauthorized Tobacco Products. August 10, 2023.
  5. Zuckerman Spaeder. “Effective Use of Civil Monetary Penalties to Control Illegal Marketing of E-Cigarette Products. 2023. Link: Federal Register :: Requirements for Tobacco Product Manufacturing Practice

We Comment to FDA on the Draft Guidance Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act

September 12, 2023


Docket No. FDA-2023-D-0559

We appreciate the opportunity to comment on the Food and Drug Administration (FDA) proposed guidance: Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act Guidance for Industry.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

Noncompliance with required post-market studies (PMRs) is a serious problem that undermines FDA’s authority and the public trust in FDA decision-making. We support FDA’s efforts to ensure clarity and transparency regarding situations when noncompliance with postmarket requirements is acceptable.  These situations should be rare; the more exceptions that are made, the more noncompliance becomes harmful to patients and unfair to companies that comply.

The PMRs that are the focus of this draft guidance are typically required following adverse events that have been reported to the FDA resulting in a serious enough event to warrant further examination into the safety and effectiveness of the drug. Any delay in this process places patients at undue risk and it is FDA’s responsibility to ensure that applicants avoid delays.

We understand this guidance document is specifically referencing non-compliance of PMRs which are not required as a condition of accelerated approval. However, we strongly recommend issuing similar guidance for applicants using this pathway.

We agree that applicants should continue to report regular updates to the FDA throughout the completion of the PMRs. The timelines and milestones established are agreed to by both the applicant and the FDA and should be adhered to. We appreciate the detail provided by FDA in the draft guidance stressing the importance of maintaining regular updates and providing multiple opportunities for applicants to inform the agency of missed milestones. These details, along with specific examples of what would or would not be considered good cause for non-compliance, should minimize overall non-compliance with the regulations. Documentation of delays is not sufficient to justify noncompliance, especially if the delays were foreseeable and avoidable and could suggest inadequate efforts to complete the study as was agreed to.

We support the process described in the guidance for applicants to correct circumstances that led to non-compliance with the agreed upon PMRs; however, we urge that the description of the actions taken by the applicant to address these issues be more explicit and less subjective. The guidance document states that the “FDA considers an applicant to have undertaken appropriate action if the applicant promptly develops and implements a reasonable plan to correct the underlying circumstance(s) leading to the PMR noncompliance” (emphasis added). The guidance document describes the term “promptly” as something the FDA will determine on a case-by-case basis. This is too vague; the FDA should clearly define the agency’s standards by providing examples of what could be considered inappropriate delays that will warrant escalation of actions taken by the agency. We also strongly urge that the FDA take into consideration if a company has a track record of delays in satisfying PMRs, regardless of whether the company’s justifications for those delays seem reasonable. The FDA should scrutinize the reasons given to determine if a company’s track record of delays show a pattern of making commitments to the FDA that the company has shown it is unlikely to meet. This would indicate that what might individually seem like justifiable delays may instead be based on a pattern of foreseeable and preventable delays.

As noted above PMRs which are required as a condition of accelerated approval warrant similar guidance. There have been unacceptable delays in postmarket trials for drugs granted accelerated approval status. More than 280 drug applications have been awarded accelerated approval since the program began; at least 100 of those applications still have incomplete confirmatory trials.1 Approximately 35 percent have at least one trial past its original planned completion date.1 A recently published journal article pointed out that Exondys 51, for Duchenne Muscular Dystrophy, was granted accelerated approval in 2016 with the PMR results required in 2020. Instead, that post-market study was not started until 2020 and FDA granted an extension until 2024, while also granting accelerated approval to 3 other drugs made by the same company, none of which have yet submitted their post-market studies.2 As a result of these delays, patients, insurance companies, and the Medicaid program have paid billions of dollars for treatments that have never been proven to work. This is unfair to patients and their families and threatens the financial integrity of Medicaid programs in States that have been subject to these expenses. We strongly urge that the FDA issue guidance about compliance with PMR for drugs granted accelerated approval before the end of 2023.


1.U.S. Department of Health and Human Services: Office of Inspector General. (2022). Delays in Confirmatory Trials for Drug Applications Granted FDA’s Accelerated Approval Raise Concerns. https://oig.hhs.gov/oei/reports/OEI-01-21-00401.asp#:~:text=WHAT%20WE%20FOUND,104%20have%20incomplete%20confirmatory%20trials.

2. Liam Bendicksen, Diana M. Zuckerman, Jerry Avorn, et al. (2023). The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence. Ann Intern Med. doi:10.7326/M23-1073

Our Comments on Insanitary Conditions in the Preparation, Packing, and Holding of Tattoo Inks and the Risk of Microbial Contamination FDA Draft Guidance

September 11, 2023


We appreciate the opportunity to comment and support FDA’s proposed rule regarding: “Insanitary Conditions in the Preparation, Packing, and Holding of Tattoo Inks and the Risk of Microbial Contamination: Guidance for Industry Draft Guidance.”

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

Due to the growing rate of Americans getting tattoos and increased reports of infections related to contaminated tattoo ink, we agree this is an important public health issue that needs to be addressed. Microbial contamination of tattoo inks can occur in nearly 50% of inks on the market in the United States, which can include organisms that are known to cause serious infection and are highly resistant to antibiotics.1  We support the FDA’s objectives of ensuring that ink products are unadulterated and holding manufacturers accountable for contaminated products.

While the act of tattooing is primarily regulated by state, local, and tribal public health authorities, the FDA has the authority to regulate tattoo ink. In addition to microbial contamination, pigments have been found to contain potentially toxic chemicals, heavy metals, degradants, printer toner, car paint, and other substances that were not intended to be used on the human body.We agree that the FDA needs to provide guidance that will better support state, local, and tribal public health agencies to help address the growing public health burden of unsafe tattoo ink. This is especially relevant as many local tattooing regulations have recently been found to be outdated as well as inconsistent.

Accordingly, we recommend that the FDA provides explicit guidance regarding the labeling of tattoo inks. While tattoo ink manufacturers are required to include ingredient and safety risks as part of the labeling requirements under the Fair Packaging and Labeling Act, these labels are rarely seen by consumers since the ink is often purchased in bulk by tattoo studios.3 We strongly urges the FDA to require that user-friendly labels for tattoo ink be made available online to consumers prior to getting tattoos; preferably, in a consumer checklist that they must sign, so that they have the information they need to make informed decisions on the risks of tattooing.

We also recommend that the FDA include clear, understandable guidance regarding the water and dilution techniques that should be used to achieve color variation in tattoo studios. This is of particular importance as non-sterile dilution techniques were a primary cause of the nontuberculous mycobacterial skin infection outbreak that was referenced in FDA’s draft guidance. A common practice for tattoo studios is to use distilled or reverse osmosis water for dilution. However, these are non-sterile techniques, and the FDA should prohibit such techniques and instead require and explain the importance of sterile dilution techniques.

We are also concerned about the voluntary reporting system of contaminated ink products, which primarily relies on consumers. This places the burden of contamination identification and reporting on the consumer rather than the manufacturer, and also undermines the responsibility of the manufacturer to ensure that their products are unadulterated. In addition, since consumers are rarely aware of existing reporting mechanisms, the FDA should require that tattoo studios educate consumers on how to report adverse events caused by contaminated ink. We also agree with the FDA’s recommendation that tattoo ink and ink components be tested for microbial contamination and that tattoo establishments be required to discard contaminated products. Although we are concerned that the lack of proposed manufacture accountability and enforcement mechanisms, traceability, and regulatory incentives will lead to noncompliance, having such requirements will increase the risk of lawsuits for noncompliance, and that will serve as an incentive to comply with FDA requirements.

It is estimated that nearly one-third of Americans have a tattoo with reports of microbial contamination at a staggering 49%1,4 Thus, there is a great need to better regulate tattoo ink and raise awareness among the public about the risks of unsafe tattoo ink. We support the objective of the FDA in helping manufacturers to identify and discard adulterated ink to better protect public health. However, we recommend that ink labels be made readily available to consumers and sterile dilution techniques are included in the final guidance. We also strongly recommend that the FDA develop an information toolkit to increase consumer awareness regarding contamination reporting systems in tattoo studios, while working to build robust mechanisms for manufacturer reporting, traceability, and accountability.

As noted above, in addition to microbial contamination, pigments have been found to contain potentially toxic chemicals, heavy metals, degradants, printer toner, car paint, and other substances that were not intended to be used on the human body. The rate of ink contamination with unsafe substances that include but are not limited to microbial contamination has been reported as high as 67%.5 Therefore, we strongly urge the FDA to expand the regulation of all types of dangerous substances in this draft guidance or develop a similar draft guidance specifically to reduce the risks caused by these other dangerous substances.


References:

  1. Nho, SW et al. “Microbiological Survey of Commercial Tattoo and Permanent Makeup Inks Available in the United States.” Journal of Applied Microbiology, 124: 1294-1302 (2018).
  2. “NEHA Response to Request from FDA for Good Manufacturing Practices on Tattooing Inks and Pigments.” 2023.
  3. Association of Food and Drug Officials, Body Art Committee. “Tattoo Ink and Permanent Makeup Labeling Guide.” 2019.
  4. Pew Research Center. “32% of Americans have a tattoo, including 22% who have more than one.” 2023.
  5. Bonadonna, Lucia. “Survey of Studies on Contamination of Marketed Tattoo Inks.” Karger. 2015.

Our Comments on the FDA Proposed Guidance Regarding the Registration and Listing of Cosmetic Product Facilities and Products

September 7, 2023


We appreciate the opportunity to comment on the Food and Drug Administration proposed guidance: Registration and Listing of Cosmetic Product Facilities and Products; Draft Guidance for Industry.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

We strongly support the purpose and requirements included in the Modernization of Cosmetics Regulation Act of 2022 (MoCRA), which was part of the Consolidated Appropriations Act, 2023 (Pub. L. 117-328) related to the regulation of cosmetic products. These regulations are long overdue and an essential first step toward protecting public health through the disclosure of the ingredients in these ubiquitous products and the registration of the facilities that make these products. Research has documented scientific concerns about the presence of endocrine disrupting chemicals in cosmetics and their effect on consumers’ health.[1],[2],[3] Some hormone disruptors such as phthalates and parabens are found in a wide range of cosmetic products. Other hormone disrupting substances are used in specific cosmetics, such as triclosan in toothpaste and mouthwash; this chemical ingredient was previously banned from soap products by the FDA in 2016. It is essential that the public be made aware of the potential for cumulative exposure to substances in many different makeups, creams, and other cosmetic products used every day.

We are very supportive of the requirements included in MoCRA, but have four recommendations to improve the proposed guidance:

  • We are concerned that the FDA does not plan to transfer the voluntary cosmetics registration program to this new system. We agree that previous submissions to the voluntary cosmetics registration program fail to satisfy the registration and listing requirements, since that information differs from the information required to be submitted under MoCRA. However, there is likely to be substantial overlap of information. We recommend that these entities should be required to register their facilities and submit product listings even if they voluntarily provided similar information previously. If information is not transferred, where will previously submitted voluntary information be stored? Will it be available to the public?
  • Regarding the requirements set for a product listing, we strongly urge that all fragrance ingredients be required to be listed. Fragrance ingredients in self-care products such as shower gels, shampoos, body lotions, and shaving creams are often labeled “unscented.” This is because manufacturers are not obligated to label the fragrance in the ingredient list if the amount added is just enough to cover the scent of other ingredients versus giving the product a noticeable scent.[4] This is not an appropriate justification. All fragrance ingredients added to the product, no matter how minimal, should be included in the product listing. It is not enough to simply list the product as containing “fragrance” or “flavor” as is required under section 701.3 of title 21, Code of Federal Regulations. A more detailed ingredient list is essential and would not jeopardize trade secrets since according to the guidance document, brand names will not be disclosed publicly.
  • Regarding the requirements set for a facility registration, we support the requirements listed in the guidance but also recommend the disclosure of the amount of the product manufactured or processed in each facility in the year prior to the initial registration. Production levels should also be included in each renewal of registration biennially.
  • According to the guidance, the “FDA requests that individuals submitting registration and listing information to attest to the accuracy and veracity of the information submitted.” The guidance does not specify how violations or inaccuracies in the registrations and product listings will be enforced.  It is essential the manufacturers comply with the requirements in order to ensure transparency, and enforcement is necessary to achieve that goal.

1. Ejaredar, M., Nyanza, E., Eycke, K., Dewey, D. (2015). Phthalate Exposure and Childrens Neurodevelopment: A Systematic Review. Environ Res 142:51-60.

2. Diamanti-Kandarakis, E., Bourquioqnon, J., Giudice, L., et al. (2009). Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocr Rev 30(4):293-342.

3. Harley, K., Kogut, K., Madrigal, D., Cardenas, M., et al. (2016) Reducing Phthalate, Paraben, and Phenol Exposure from Personal Care Products in Adolescent Girls: Findings from the HERMOSA Intervention Study. Environ Health Perspect In Press.

4. Sun, A. (2023) Everything you need to know to choose safe cosmetic products. National Center for Health Research. https://www.center4research.org/cosmetics-safety-regulations-law-tips/

Our Comments on the FDA Notice Regarding Changes to Third-Party Vendors for Risk Evaluation and Mitigation Strategies (REMS)

July 19, 2023


We are pleased to have the opportunity to share our views with the Food and Drug Administration (FDA) on their notice regarding Changes to Third-Party Vendors for Risk Evaluation and Mitigation Strategies (REMS).

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

Implementing changes in REMS has the potential to cause significant disruptions in the operations of any REMS program, including the ability for prescribers and patients to interact with the tools necessary to fulfill the various REMS requirements. These disruptions can undermine patients’ ability to access a drug in ways that minimize risks. Since the FDA does not approve third-party REMS administrators, or play a major role in the initial development of REMS with elements to assure safe use (ETASU), it is essential that the FDA closely monitors any changes in REMS plans to make sure they are appropriate and yield beneficial outcomes.

We strongly urge that the FDA require drug sponsors and their REMS administrators to test proposed changes to REMS systems prior to implementation with those that actively engage with the system, including but not limited to physicians, patients, and pharmacists. This will ensure that the REMS program will have the intended impact. A less-than-rigorous approach to studying the efficacy of REMS defeats the purpose of REMS and fails to protect patients from predictable harm. The FDA REMS for Transmucosal immediate-release fentanyl (TIRF) drugs and the REMS for Extended Release/Long Acting (ER/LA) opioids provide important examples of how improper implementation of REMS can harm patients. The HHS IG found numerous failures for both these REMS programs, at a time when these REMS were especially important because of the opioid epidemic.1 For example, manufacturers consistently missed the REMS’ targets for training ER/LA prescribers, and the FDA was blamed for not giving manufacturers sufficient time to respond to FDA’s requests for better data before their next assessments were due. As a result, the REMS for ER/LA opioids was changed to primarily measure voluntary prescriber training to educate about risks, a decision that also failed to adequately protect patients.

We also strongly recommend that the sponsor and/or the REMS administrator conduct a Failure Modes and Effects Analysis (FMEA) to identify and plan for system failures. This includes providing for adequate support services in the event that the system fails to work as intended following full implementation of an altered REMS system. Part of the planning should include provisions for an emergency suspension of the REMS or specific parts of the REMS.

Additionally, beyond testing a REMS modification with stakeholders, FDA should require stakeholder input from prescribers in all stages of developing, implementing, and tracking a REMS modification related to changes to third party vendors. This will require greater transparency between drug sponsors, REMS administrators, and stakeholders.

In numerous REMS, the FDA has faced measurement challenges, such as a lack of baseline data and limited surveillance data. These metrics are essential for the sponsor to include when evaluating whether a REMS system was successfully and efficiently implemented. It is also essential to collect data on which types of health professionals are involved in implementing a specific REMS. For REMS that involve training of health professionals, there must be a record of the percentage of prescribers being trained, the percentage who start training who complete it, and what percentage that complete the training will answer training questions correctly.

Finally, we strongly recommend that all future REMS agreements that the FDA enters into with manufacturers and their vendors, require that deidentified REMS data be made available to appropriate outside stakeholders. The availability of this data will reassure the public, patients, and health care providers that each REMS is accomplishing its intended outcomes and promoting the safe use of drugs while minimizing harm, especially serious harm.

  1. U.S. Department of Health and Human Services Office of Inspector General. (2020). FDA’s Risk Evaluation and Mitigation Strategies: Uncertain Effectiveness in Addressing the Opioid Crisis. https://oig.hhs.gov/oei/reports/OEI-01-17-00510.pdf

Our Comments on the FDA’s Use of Generally Accepted Medical Knowledge Draft Guidance

July 24, 2023


We are pleased to have the opportunity to share our views with the Food and Drug Administration (FDA) on their Guidance: Generally Accepted Scientific Knowledge in Applications for Drug and Biological Products: Nonclinical Information.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

We support the efforts of the FDA to remain flexible and provide a more open application of scientific and regulatory judgment when conducting nonclinical studies that determine in vitro safety and efficacy. We recognize that this has the potential to streamline product development as well as avoid unnecessary animal testing, decrease costs, and hasten new drug approval time.  However, we predict that this will result in some sponsors providing insufficient data to show the safety, toxicology, and efficacy profile of a drug.

For that reason, we do not recommend using Generally Accepted Scientific Knowledge (GASK) as the sole source of nonclinical data in New Drug Applications (NDAs) or Biologic License Applications (BLAs). Instead, GASK should only be used to support sponsor data and should not replace the vital research that is needed to create a robust safety and efficacious drug profile.

Permitting GASK as the sole or primary evidence would often create a level of ambiguity regarding a drug’s true pharmacologic, distributive, and toxicologic effects. We support sponsor communication that is clear and data that are unequivocal, so that potential harms are minimized. We strongly encourage that the GASK used be: 1) long-standing, 2) uncontroversial, and 3) scientifically robust.  However, we note that even when the generally accepted scientific knowledge being relied upon is uncontroversial, long-standing, and scientifically robust, the external application of that information by the sponsor may be inappropriate. For example, even when a drug’s mechanism of action or the biologic pathway that a drug acts on is well understood, the drug should still be tested to assure that there are no downstream or unanticipated effects when in vitro to the full extent possible, and not solely rely on GASK.

In conclusion, we appreciate the opportunity to comment and support the efforts of the FDA to streamline product development and avoid unnecessary animal testing, decrease costs, and hasten new drug approval time. However, this must be better balanced with the need for sponsors to provide clear, unambiguous data regarding the pharmacologic, safety, and effectiveness profile of new drugs and not use GASK as a means of replacing vital research. To that end, we strongly urge the FDA to revise the proposed GASK guidance to require comprehensive and precise language on when using GASK by the sponsor is appropriate.

Testimony of Diana Zuckerman at the CMS Meeting Regarding Transitional Coverage for Emerging Technologies

August 1, 2023


I’m Dr. Diana Zuckerman, president of the National Center for Health Research and Cancer Prevention and Treatment Fund.  Our Center is a public health think tank that focuses on policies and programs that increase the safety and effectiveness of medical products.

We support the goals of the TCET program, but we see an enormous disconnect between the types of evidence that FDA requires for breakthrough devices, especially for 510k devices, and the CED standards that CMS requires for coverage.  We hear a lot about flexibility from FDA and industry but not enough about scientific evidence of safety or effectiveness.  Innovation should be defined to require that a device is proven to be better, not just newer.  We urge CMS to work with industry to make it clear that CMS evidence standards of clinical benefit are very different from the standards required by CDRH.  And we urge CMS to urge companies to provide the evidence needed to be worthy of CMS coverage.

Let’s remember that the standards for FDA for devices are not proof of safety or effectiveness, but rather the “reasonable assurance of safety and effectiveness.”  And often that “reasonable assurance” is not so reassuring.

I want to reiterate the previous comment that even when the FDA requires clinical data, many types of Medicare beneficiaries are under-represented:  older patients, people of color, and women.

I want to thank CMS for this effort to improve access to safe and effective medical products and urge CMS to hold firm to its standard for coverage based on scientific evidence that all medical products are proven to be reasonable and necessary for Medicare patients.

Our Comments on FDA Guidance Regarding Decentralized Clinical Trials for Drugs, Biological Products, and Devices

August 1, 2023


We are pleased to have the opportunity to share our views with the Food and Drug Administration (FDA) on their draft guidance regarding Decentralized Clinical Trials (DCTs) for Drugs, Biological Products, and Devices.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

DCTs have the potential to increase inclusion of underserved or rural communities and patients who are home-bound. It reduces geographic barriers by enabling patients to participate in clinical trials even if they do not live near a study site. This is much more convenient than traveling to a conventional study for medical interventions, data collection, assessments, and follow-up visits. However, the FDA and those conducting DCTs must also recognize how they could inadvertently reduce the enrollment of diverse populations when relying on digital health technologies (DHTs). The inability to access DHTs or lack of familiarity or comfort with DHTs could limit or prevent enrollment of older adults and children, participants living in rural areas, people who speak a language other than English, and people who have lower literacy skills or lower income. We recommend that FDA revise the guidance to incorporate the following strategies when implementing DCTs, including those that use DHTs:

  1. The guidance should incorporate information on how patients who decide to use their own DHTs during DCTs differ from those individuals who are provided a DHT during the study. Patients who regularly use these tools before study participation may differ in terms of several baseline health characteristics, vary in socioeconomic status, or have different health habits than those who do not have DHTs. Data recorded during a trial should include information on a participant’s prior device experience, as well as reasons for use, and include these variables in study analysis, as prior experience with a device could affect outcomes.
  2. DCTs using DHTs should consider and plan for the consistent availability and use of the same DHTs over time, even if newer versions of a device are introduced, as these updates could affect trial performance. Additionally, DHTs that require software on a participant’s phone or computer could undergo multiple app updates over the course of the study, with the potential to add new features that affect data input. Investigators must plan to follow-up with participants whenever major software updates occur.
  3. The FDA guidance mentions that sponsors should consider syncing information recorded by DHTs across different platforms. Digital health sources such as electronic health record (EHR) portals or portals linking data from personal digital devices, can be disconnected during the course of the DCT and require significant additional effort to reconnect. These disconnections can come from password changes and security issues which can result in the loss of data, which may be temporary or permanent depending on the willingness or ability of the participant to reconnect. Planning for this possibility is essential to ensure comprehensive data capture. Study teams should regularly review the completeness and quality of the DHT data over the course of the study to reduce missing data.
  4. The guidance mentions that, “training should be provided to all parties (e.g., trial personnel, local HCPs, and trial participants)” related to the software used in DCTs. This should apply to all DHTs and, as appropriate, should include caregivers who may assist study participants during DCTs.
  5. Although FDA states that researchers “should attempt” to collect data regarding healthcare services provided outside the study site. This does not adequately provide explicit directions on how to provide information regarding unexpected or routine visits to non-study sites, such as an ER visit for an adverse event that may or may not be obviously related to the clinical trial. The FDA guidance recommended that providers outside of the clinical trial not be included in the task log, which tracks health care providers that perform trial-related activities. However, if that information is not collected and evaluated, then significant information about safety issues would inevitably be missed. FDA should explicitly address how potentially important information should be included in the task log and re-evaluate the need to include these data points.

Biden’s Crackdown on ‘Junk’ Plans: Minimal Impact on Payers

Jesus Mesal, Health Payer Specialist, July 14, 2023


The Biden administration’s proposed restrictions on short-term private health plans aim to protect consumers, but they raise questions about the future value potential of a thriving market segment and do little to quell the controversy about insurance criticized by some as “junk.”

Short-term plans offer flexible coverage periods, such as 30 days or three years, and cost 50% to 80% less than individual market coverage. They are not regulated to the same extent as plans offered in the Affordable Care Act insurance marketplaces and can, for example, exclude pre-existing conditions or limit the number of visits or coverage amounts.

The proposal from the Department of Health and Human Services, the Labor Department’s Employee Benefits Security Administration, and the Internal Revenue Service would restrict them to three months, or to four months at a maximum.

These “misleading insurance products” can “trick consumers into buying products that provide little or no coverage when they need it most,” says a joint statement from the agencies.

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The plans, devised as a way for consumers to plug short-term gaps in coverage, have remained a source of political contention since the ACA was enacted in 2010. In 2016, the Obama administration limited their coverage period to three months to address concerns that consumers might choose these plans over comprehensive coverage under the ACA.

Two years later, former President Donald Trump reversed the rule, arguing that consumers should have choice. He extended the allowable duration of short-term plans to a year, with option for consumers to renew them for up to three years. Unlike the ACA’s once-a-year open-enrollment period, these plans are accessible at any time during the year.

Growing market

Since the policy swing, the short-term health insurance market has emerged as a thriving segment experiencing significant growth. The firm Persistence Market Research reports that its value reached $41.1billion in 2022, with the Trump administration rule change playing a substantial role in this expansion.

Mixed opinions

Democratic lawmakers have long advocated for measures to limit the impact of short-term plans. They argue that these lower-cost plans provide minimal coverage and have the potential to lure Americans away from more-comprehensive ACA plans.

The proposed rule could increase ACA marketplace enrollment by an estimated 60,000 individuals in the years2026, 2027, and 2028. Enrollment in ACA plans hit 16.3 million people this year, according to HHS.

They are called ‘junk’ plans for a reason,” said Diana Zuckerman, president of the National Center for Health Research. Zuckerman questioned why the Biden administration took so long to take this step and does not agree with the argument that having one of these plans is better than having no coverage at all. Short-term plans end up being more expensive for Americans because many people cannot afford the bills they receive when they do not have coverage for emergencies, she said.

“When more people have high-quality health insurance, we are all better protected. These plans do not provide the 10 essential health benefits required by the ACA,” she told Health Payer Specialist. “People claim they have a choice, but what we have observed is that due to misleading marketing, many customers do not fully understand what they are purchasing, and it ends up costing millions of dollars for all Americans.”

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