FDA Comment Guidance

Friends of Maisie,

The FDA has re-opened comments on proposed packaging changes for a variety of medications, including opioids. We are urging you to consider submitting a comment either as an individual, or on behalf of a group/organization you work for/represent. Links to the comment submission site are immediately below, further information from us is also below, including optional language for submitting comments, if you need assistance. Comments are due by February 1st, 2021.

Link to FDA Docket Information

Link to Submit Comments

Link to SUPPORT Act (reference section 3032)

We are contacting you as you have, in some way, participated in the telling of Maisie’s story. You may be family or a close friend, you may be a member of the medical community, you may be a public servant, you may be a member of the media or someone interviewed or contacted regarding Maisie’s story, or you may represent a group or organization we have worked with. Maybe you are all or none of those things, but we needed to start with contacting you.

As part of the SUPPORT Act of 2019 (Section 3032), the FDA was given the authority over drug packaging and disposal. Specifically, the authority to mandate fixed quantity (or unit of use) packaging. Commonly, this is known as blister packaging.

Plainly, we will never be able to directly answer the question on what could have saved Maisie’s life. We do believe layers of protection that were not present could have tipped the odds in her favor, or at least prevented the negligence of the person who dropped the methadone pill that killed our daughter.

Blister packaging is that layer of protection, and the FDA already has the authority to act on this today. Rightfully so, they are exploring the benefits and issues of taking such action.

Reading comments from 2019, pharmaceutical organizations are mostly against this change. In our opinion, it is entirely due to costs and profit margins, despite what their public comments say. With any significant change, there will be an adjustment patients will need to make, but this packaging change in no way disrupts their access to medication they need and options exist to help the small percentage patients who cannot use blister packaging effectively. We encourage you to view the comments from the original comment period in 2019 as well as supporting materials and decide for yourself.

Your comments, informed by your experiences with our family or the data you have from your work around the opioid epidemic can positively affect and inform the FDA to make these packaging changes. To be clear, opinions alone will not make the FDAs decision. Our hope is that Maisie’s story, combined with data, professional expertise, studies, and facts will move packaging safety forward to create a safer place for everyone.

The Upstate NY Poison Center took over 19,000 calls in 2019, and roughly one call a week of a child ingesting an opioid. That is one region in one state. Families are impacted by inefficient and unsafe practices, and our family was devastated with the death of Maisie.

On our website supporting Maisie’s memory, www.purplelightproject.com, we have added materials to utilize for submitting a comment. We hope you take the time to communicate with the FDA, share this opportunity with your network, or both.

This opportunity for change with the FDA is not the only area we have interest in pursuing. Locally to the Monroe County New York Region, we are anticipating Maisie’s Law to be passed in early 2021. There are New York State bills we will advocate on behalf of, and at the federal level we believe the Poison Prevention Packaging Act, written in 1970, is out of date and out of touch with the modern advancements as well as the functional use of medication today.

Again, we hope and urge you to participate as well as to share this information in your network.

Love,

The Gillan Family

FDA Docket Posting

SUPPORT Act Language

Unit-Dose Packaging of Iron Supplements and Reduction of Iron Poisoning in Young Children

FDA Information on Methadone Tablets

This is the full text version, you may consider using parts relevant to your opinions or experience:

January XX, 2021

Stephen Hahn, MD

Commissioner

Food and Drug Administration

C/O Dockets Management Staff (HFA-305)

5630 Fishers Lane, Rm. 1061

Rockville, MD 20852

RE: Docket No. FDA-2019-N-1845, “Fixed-Quantity Unit-of-Use Blister Packaging for Certain Immediate-Release Opioid Analgesics for Treatment of Acute Pain; Establishment of a Public Docket; Request for Comments"

Dear Commissioner Hahn:

On behalf of ____________, I write to provide input on the U.S. Food and Drug Administration’s (FDA) request for comments on a potential modification to the Opioid Analgesic Risk Evaluation and Mitigation Strategy (OA REMS) to require that certain solid, oral dosage forms of immediate-release (IR) opioid analgesics commonly prescribed for treatment of acute pain be made available in fixed-quantity unit-of-use blister packaging for outpatient dispensing.

_______ is supportive of expanding the use of unit-dose packaging and believes more must be done to reduce the risk of unintentional ingestion, diversion, and overdose.

________ shares the FDA’s serious concern about unintentional child opioid ingestion, and in reducing inappropriate access to opioids. Opioids were involved in over 47,600 overdose deaths in 2015, a number that has increased nearly sixfold since 1999.¹ Drug overdoses of all kinds led to over 70,000 deaths in 2017, ² causing more deaths than car crashes.³ These fatalities are the inflection point of a much larger trend of higher incidence of substance use disorders (SUDs) affecting millions of U.S. families and negatively impacting child health and well-being.

The opioid epidemic’s toll is due, in part, to access by children to prescription opioid drug products. In the last two decades, nearly nine thousand children and adolescents died from opioid poisonings, with the mortality rate increasing nearly threefold.⁴ This is an alarming increase, and we are concerned that this number will only grow as the epidemic continues its scourge. One study found that children of mothers prescribed opioids are at a substantially increased risk of opioid toxicity.⁵

________ is encouraged that FDA is exploring ways to prevent unintentional ingestion of opioids by young children. We respectfully offer the following feedback on this proposal, including suggestions to strengthen it in ways that can reduce child and adolescent morbidity and mortality resulting from unintentional child ingestion and adolescent use of diverted opioids.

Unintentional Ingestion of Opioids by Young Children is a Public Health Threat

Young children face a serious risk of poisoning morbidity and mortality from unintended opioid ingestion. A recent study in Pediatrics examined 2004 to 2015 data on opioid-related hospitalizations among children in children’s hospitals, finding that child opioid-related hospitalizations rose from 797 in 2004 to 1,504 in 2015. Over one-third of those hospitalizations were among children younger than 6, highlighting the significant need for protections against unintentional ingestion by young children.⁶ Public education and other measures are insufficient to address this issue. Policies to design out the hazard of unintentional ingestion through child-resistant unit-dose packaging are essential to reduce unintended child access to opioids.

Unit-of-use packaging for solid medications is an evidence-based, effective child-resistant packaging intervention that can reduce the risk of unintentional ingestion. A sole mechanism, such as a child resistant cap for the entire container, is not the solution for high-risk ingestion hazards. Significant poisoning from high-risk drugs occurs after the ingestion of a small number of therapeutic doses. Typically, fewer than five doses of such substances can result in serious adverse outcomes, including fatality.

Passive prevention interventions such as unit-dose blister packages have been shown to be more effective than conventional child-resistant caps. A study⁷ by Dr. Milton Tenenbein of the impacts of unit-dose packaging for iron supplements showed a decrease in the incidence of non intentional ingestion of a specific drug by young children and a decrease in mortality from poisoning by this drug after the introduction of unit-dose packaging. There was a decrease in the incidence of iron ingestion and a dramatic decrease in the number of deaths due to iron poisoning.8 Unit-dose packaging is a highly effective intervention, and should be considered for all medications with a high hazard for morbidity and mortality when taken as an overdose. Opioid analgesic products meet the criteria of particularly high-risk substances, and are a prime candidate for unit-dose packaging.

Applying these Requirements to More Potent Opioid Products Will Prevent Pediatric Poisoning

This proposal is directed toward lower-potency opioids, but omits drugs that are responsible for most of the opioid morbidity and nearly all of its mortality. The AAP encourages FDA to expand the requirement to drugs with high rates of morbidity and mortality, such as buprenorphine. Focusing first on the oral solid opioids that have the greatest poisoning morbidity and mortality would increase the public health benefits of the intervention. AAP supports greatly expanding the use of blister packaging to address those opioid products most associated with morbidity and mortality from poisoning. While we appreciate the progress outlined in this initial proposal, limiting its application to just seven commonly prescribed products is not a sufficient response to the unique child health threat posed by unintentional opioid ingestion.

Blister Packaging Requirements Provide Public Health Benefits

To turn the tide on the alarming increases in unintentional ingestion of opioids by children 5 and under, it is imperative that FDA require more effective child-resistant packaging for all opioid medications. AAP is encouraged that FDA is considering an OA REMS requirement that certain IR opioid analgesics commonly prescribed for the treatment of acute pain be available in blister packaging. This intervention will help prevent unintentional ingestion, diversion, and abuse. However, concerns of unintentional child ingestion exist far beyond this intervention’s target population of opioid-naïve patients with acute pain. Research from the U.S. Centers for Disease Control and Prevention (CDC) shows the efficacy of unit-dose packaging for buprenorphine and naloxone, prescriptions not currently included in the proposal:

Accounting for prescribing frequency, [emergency department (ED)] visits for unsupervised buprenorphine/naloxone ingestions declined 65.3%, from an estimated 28.2 ED visits per 100,000 dispensed prescriptions during 2008–2010 to an estimated 9.8 per 100,000 dispensed prescriptions during 2013–2015 (p = 0.011).The approximate two thirds reduction in the rate of ED visits by children for buprenorphine/naloxone ingestions as the proportion of prescriptions dispensed in unit-dose packaging increased to over 80%, suggests that packaging/formulation changes might reduce pediatric ingestions. A study of poison center calls for pediatric buprenorphine/naloxone exposures also found a significantly lower rate of calls involving film strips in unit-dose packaging, compared with tablets in multi-dose bottles (6). Other factors potentially contributing to the rate reduction include increased counseling of patients on safe use and storage (7) and a decline in pediatric medication ingestions overall (22% from 2010 to 2013) (8). ⁹

AAP appreciates the proposed use of OA REMS modification to require packaging changes rather than relying on guidance for this important public health intervention. We urge FDA to require unit dose blister packaging for all such opioid products. Blister packaging is a well-known and well established solution already in use,so requiring this intervention for solid, oral dosage forms of opioids would be a straightforward undertaking. We encourage FDA to work with the Consumer Product Safety Commission (CPSC) to ensure that all such blister packaging must meet the CPSC standards for child resistance outlined under the Poison Prevention Packaging Act.

Ongoing Monitoring of Packaging Modifications is Necessary

In addition to requiring that additional high-risk solid opioids be available in blister packaging, FDA should consider steps to encourage uptake and increase access to this packaging. AAP supports requiring application holders to periodically report on the production of their blister package configurations to track the use of these products. FDA should also consider requiring that a certain fraction of marketed products be in blister package configurations to encourage the broader use of these products. FDA should adopt additional measures as needed to ensure that the required blister packaging is sufficiently available and protective of children’s health.

Finally, it is critical to underscore that child-resistant does not mean child-proof. Child-resistant packaging is simply a first-line defense in preventing a child from accessing poisonous substances. Continued vigilance and regulatory oversight by FDA is critical to both public awareness of, and manufacturer efforts to prevent, unintentional ingestion of opioids.

Conclusion

Thank you for the opportunity to comment on the FDA's consideration of opioid packaging safety improvements. The agency is in a position to prevent thousands of ED visits and many deaths in the youngest children by promulgating a regulation for child-resistant packaging of opioid products. We urge the FDA to put this regulation into place expeditiously, and to closely monitor its success in preventing harm to children. We look forward to working with you to ensure that children and adolescents are protected from unintentional ingestion and inappropriate access to opioids. If we can be of further assistance, please contact ____________

Sincerely,

Name

Title

Organization

1 - National Center for Health Statistics. National Vital Statistics System, Mortality. Retrieved from https://www.cdc.gov/nchs/data/databriefs/db329_tables-508.pdf#page=4.

2 - Drug Overdose Deaths. U.S. Centers for Disease Control and Prevention.

https://www.cdc.gov/drugoverdose/data/statedeaths.html. Published December 19, 2018. Accessed July 16, 2019.

3 - Early estimate of motor vehicle traffic fatalities in 2017. National Highway Traffic Safety Administration. https://crashstats.nhtsa.dot.gov/Api/Public/ViewPublication/812542. Published May 2018. Accessed July 16, 2019.

4 - Gaither JR, Shabanova V, Leventhal JM. US national trends in pediatric deaths from prescription and illicit opioids, 1999-2016. JAMA Netw Open. Published online December 28, 20181(8):e186558. doi:10.1001/jamanetworkopen.2018.6558

5 - Finkelstein Y, Macdonald EM, Gonzalez A, Sivilotti MLA, Mamdani MM, Juurlink DN, Canadian Drug Safety And Effectiveness Research Network (CDSERN). Overdose risk in children of young women prescribed opioids. Pediatrics. Mar 2017, 139 (3) e20162887; DOI: 10.1542/peds.2016-2887.

6 - Kane, J. et al (2018). Opioid-related critical care resource uses in U.S. children’s hospitals. Pediatrics. 141;4. Retrieved from http://pediatrics.aappublications.org/content/141/4/e20173335.

7 - Tenebein M, et al. Unit-dose packaging of iron supplements and reduction of iron poisoning in young children. Arch Pediatr Adolesc Med. 2005;159:557-560.

8 - Ibid.

9 - Pediatric Emergency Department Visits for Buprenorphine/Naloxone Ingestion – United States, 2008 – 2015. MMWR / October 21, 2016 / Vol. 65 / No. 41 US Department of Health and Human Services/Centers for Disease Control and Prevention.

January XX, 2021

Stephen Hahn, MD

Commissioner

Food and Drug Administration

C/O Dockets Management Staff (HFA-305)

5630 Fishers Lane, Rm. 1061

Rockville, MD 20852

RE: Docket No. FDA-2019-N-1845, “Fixed-Quantity Unit-of-Use Blister Packaging for Certain Immediate-Release Opioid Analgesics for Treatment of Acute Pain; Establishment of a Public Docket; Request for Comments"

Dear Commissioner Hahn:

On behalf of our late daughter, Maisie Lucienne Gillan, we urge you to take action in packaging safety and technology advancements to mandate blister packaging for any medication lethal to an infant or child. These medications, known as “one pill kills,” are over-prescribed in high quantities, we have personally seen up to 90 pills. The packaging is intended as safe, but the functional use of the prescription and its traditional pill bottle container creates untold opportunities for mishandling, miscounting, and access to children.

Our daughter, at a neighbor’s home, came across a methadone pill no one even knew was missing. Hours later she was dead, and it took an autopsy to understand why. From the criminal justice system to the current regulatory environment around opioids and patient safety, our daughter was failed at every turn, cast off as an unforeseeable tragedy.

Between 1999 and 2017, more than 9,000 children and teenagers died from opioid poisoning in the United States, including 650 children under 5 years old, according to the Centers for Disease Control and Prevention. These are tragedies that left 9,000 parents to bury their children.

We can do better and we must do better. Layers of protection are available to protect patients from harming themselves or others. Blister packaging alone may not have saved our daughter’s life, but that layer of protection would have clearly identified a pill as missing, or it may never have been lost in the first place.

We know we are an anecdote that must be supported with data. We know that data of efficacy in blister packaging exists through various JAMA studies, including those of iron supplements, as well as research produced within the FDA. We offer the attached, names redacted snapshot. It is the investigator's notes attempting to reconcile the 90 pills given to the negligent adult who lost a pill that killed our daughter. A 3 month supply. It only took one pill to kill her. The notes also indicate that the prescription, tamper proof bottle is not used. Pills were always transferred to a pill carrier.

Please, we are begging you. Use our story with the studies, facts, and research from other institutions and organizations and make this change. Lives are at stake, and too many, including Maisie’s, have already been lost.

Sincerely,

Adam Gillan, Maisie’s father

MaryBeth Gillan, Maisie’s mother

Rhona Gillan, Maisie’s sister

Conway Gillan, Maisie’s brother