Focus on the FDA
Where do things currently stand on issues that concern dermatologists?
Feature
By Emily Margosian, assistant editor, September 1, 2021
Since its founding in 1906 during Theodore Roosevelt’s presidency, what is now known as the U.S. Food and Drug Administration (FDA) has been tasked with protecting America’s public health by ensuring the safety and efficacy of human and veterinary drugs, biological products, medical devices, food, and cosmetics. As the oldest comprehensive consumer protection agency in the federal government, the purview of the FDA covers several key areas of dermatologic practice.
This month, DermWorld takes a look at recent FDA activities on issues affecting dermatology, such as compounding, indoor tanning, sunscreen ingredients, and drug shortages and access.
Compounding
In 2013, Congress passed the Drug Quality and Security Act (DQSA), which tightened the FDA’s oversight of compounding facilities, and gave the FDA the green light to take steps to restrict physician in-office compounding and office-use compounding. Initially, the FDA’s interpretation of the DQSA resulted in the FDA issuing a draft guidance that threatened dermatologists’ ability to prepare drugs in the clinical setting, such as buffered lidocaine and reconstituted botulinum toxin.
However, in November 2020, the FDA loosened restrictions on compounding in physician offices, with a decision to not act against physicians who compound drug products for in-office administration. “It doesn’t mean that there’s a rule on the books saying that physicians can compound drug products in-office, it’s just saying that the FDA is not going to take any action against physicians who choose to do so,” explained AJ Custard, JD, AADA manager of regulatory policy. “The implication is that with guidance like that on the books — indicating that action won’t be taken — physicians can safely compound and administer medicines that their patients need within their office.”
Currently, the AADA is also conducting a research project evaluating the safety of in-office prepared buffered lidocaine. This initiative is a key part of the Academy’s ongoing advocacy efforts surrounding compounding, according to Leslie Stein Lloyd, JD, IOM, CAE, AADA director of public policy and healthcare economics. “This project is critical to be able to demonstrate to the FDA, the CDC, the United States Pharmacopeia, and to state legislators, that it’s safe for dermatologists to buffer lidocaine in their offices, and that the lidocaine they buffer is also stable and not contaminated, which has been the basis of the concerns that these agencies have had over compounding,” she explained. “The Academy has been very active in working with the AMA, other specialties, and our sister societies on this issue. The AADA Compounding Workgroup has also been active in advocating to ensure that the FDA was very clear that they were not going to be enforcing this rule against physicians, so it’s a big step forward. It really takes the issue of compounding in a physician’s office off of the plate of the FDA for now and turns the attention to where the next set of actions from a regulatory standpoint are: the United States Pharmacopeia. That’s where our lab testing is really geared toward — we’re setting the groundwork to have a specific exemption from all of these onerous standards for buffered lidocaine that’s prepared in the physician office.”
Compounding toolkit
Learn more about compounding, and access interactive tools to help ensure the type of compounding you are performing is in compliance with FDA regulations.
Additionally, in March 2021, the FDA proposed adding quinacrine as a bulk drug substance for the 503B bulks list to compound drug products for the treatment of cutaneous lupus erythematosus (CLE). This was a result of the AADA’s multi-year effort to improve access to quinacrine hydrochloride through targeted advocacy including testimony at the 2016 FDA Compounding Advisory Committee hearing, meetings, and comment letters, both directly and in collaboration with other organizations.
Currently, quinacrine is in short supply due to problems with the manufacturing pipeline. Exclusion of quinacrine on the bulks list would mean the drug would not be available to patients in the U.S. While the potential addition of quinacrine to the bulks list will not improve the supply issue, it does preserve the ability of the substance to be prepared for patients with CLE, explained Custard. “Adding quinacrine to the bulk substance list improves access for drugs to be made in the United States. This is essentially adding an additional pathway for this drug to be made and created within the country.”
The implications of this decision are significant for dermatologists and their lupus patients, according to Stein Lloyd. “It’s a big access issue, and we have worked and advocated for a long time for quinacrine to be added to the bulk substance list through collaboration with the Lupus Foundation and other organizations.”
iPLEDGE: Changes are coming
Dermatologists can expect some changes to the FDA’s iPLEDGE program as early as this year, said Leslie Stein Lloyd, JD, IOM, CAE, AADA director of public policy and healthcare economics. “Modernizing iPLEDGE has been a big priority for the Academy for a long time. Our iPLEDGE Work Group recently met with the Assistant Secretary of HHS, Dr. Rachel Levine, to talk about the barriers that exist with the current iPLEDGE program.”
The AADA recommended the following changes to the iPLEDGE program to improve successful treatment with isotretinoin and to improve compliance with birth control protocols:
Reduce attestation frequency for patients who are not able to become pregnant.
For patients who are not able to become pregnant, reduce frequency of confirmation requirements. Monthly appointments are currently required.
Allow medication refills in between confirmations.
More frequent visits and monitoring would be based on clinician/patient preferences.
Improve iPLEDGE classification scheme.
iPLEDGE’s three-pronged approach to classification of patients — as females who can become pregnant, females who cannot become pregnant, or male, all on the basis of sex assigned at birth — unnecessarily complicates care of transgender, non-binary, and other gender-diverse persons. A classification model focused on childbearing potential alone (e.g., person who can become pregnant, person who cannot become pregnant), ensures equity and inclusion across all populations.
Improve contraceptive options and counseling.
Optimize educational material regarding the relative effectiveness of contraception methods, encourage the use of long-acting reversible contraception (LARC)
Provide additional information on how to obtain emergency contraception.
Allow alternative/flexible options for follow-up evaluation of patients.
Allow clinicians to use flexible options for patient counseling and follow-up, including store-and-forward telemedicine (highly effective in managing other inflammatory skin diseases), telephone or video visits, and secure messaging.
The Academy’s request to reclassify patients who cannot become pregnant has been granted and is underway. iPLEDGE program sponsors are in the process of updating the program so that patients will be classified as “patients who can become pregnant” or “patients who cannot become pregnant.” The modification is expected to take effect later this year.
“We may see more updates as early as this fall on some changes to iPLEDGE,” said AJ Custard, JD, AADA manager of regulatory policy. “We’re definitely moving the needle in that area. Just having people at the top of the administration aware that this is something they need to reform, is something we’re very passionate about.”
Indoor tanning
While many states have implemented legislation banning indoor tanning for individuals under 18, action at the federal level has remained elusive despite long-term advocacy efforts. Although the AADA decided to not raise the issue with the Trump administration because of its emphasis on reducing regulations, there has been some recent traction to finalize a nationwide under-18 ban within the Biden administration.
“For now, the FDA’s main priority is still the COVID-19 public health emergency until the situation becomes more tolerable,” explained Custard. “However, we just learned that Congresswoman Carolyn Maloney (N.Y.-12) is submitting a letter to the FDA and Acting FDA Commissioner Dr. Janet Woodcock, urging her to finalize the proposed indoor tanning rule. We would love to see this go through as quickly as possible; we’re just unsure of the timing, given that Dr. Woodcock’s current priority is still COVID-19. We’ll see if the letter can have any impact with the right backing and signatures to push it through. It’s already been commented on, and it has received over 1,500 comments from us and other member societies. So, it just needs to be finalized.”
Are teens tanning less?
Signs point to progress, but more work remains. Read more.
Sunscreen ingredients
While the FDA has been regulating sunscreen since the beginning of the monograph system in 1972, guidance on new ingredients has continued to evolve in the roughly 50 years since — albeit at a slow pace.
In 2019, the FDA released its most recent proposed rule for the OTC sunscreen final monograph, which addresses sunscreen active ingredients’ safety and dosage forms, sun protection factor (SPF), and broad-spectrum requirements. The 2019 proposed rule requests that sunscreen manufacturers provide additional safety and effectiveness data on 12 sunscreen ingredients: oxybenzone, octinoxate, avobenzone, cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octisalate, octocrylene, padimate O, and sulisobenzone. It also proposed:
To raise the maximum proposed SPF value on sunscreen labels from SPF 50+ to SPF 60+.
To require sunscreens with an SPF value of 15 or higher to provide broad-spectrum protection. As SPF increases for broad-spectrum products, the extent of protection against UVA radiation should also increase.
That dosage forms that are generally recognized as safe and effective (GRASE) for use as sunscreens include sprays, oils, lotions, creams, gels, butters, pastes, ointments, and sticks.
That products that combine sunscreens with insect repellents are not GRASE.
That wipes, towelettes, body washes, shampoos, and other dosage forms be categorized as new drugs.
Requiring the front of the sunscreen package to list the active ingredients.
To revise the formats for SPF, broad spectrum, and water resistance statements.
While the FDA originally set a deadline of Nov. 26, 2019, to issue the final rule as directed under the Sunscreen Innovation Act (SIA), a new deadline was established after the passage of the Coronavirus Aid, Relief, and Economic Stimulus (CARES) Act in March 2020, which included a legislative initiative to reform the monograph that regulates sunscreen ingredients. “What this did was streamline the process to get new sunscreen products approved by the FDA and onto the market,” explained Custard. “Essentially, the CARES Act established that a modernized process needs to be in place, and the final monograph needs to be published within a certain timeline.”
Sunscreens on trial
Dermatologists discuss the debate about the effects of sunscreen ingredients on the environment. Read more.
According to Custard, the FDA has shown encouraging signs that it’s on track to issue a final OTC sunscreen monograph by fall of this year. “The most recent step forward was in May 2021, when the FDA published a notice of intent to prepare an environmental impact statement. That means they’re really preparing to begin work on issuing the final sunscreen order if they’re starting to consider the environmental impact.”
According to Stein Lloyd, the passage of the CARES Act has significantly streamlined the sunscreen approval process — to the benefit of both manufacturers and consumers. “Namely, they have the ability to meet with the FDA in a way that is more protective of their interests, thus there is more of an incentive for them to partner with the FDA. That is really important, because the goal here is for them to move as quickly as possible. If there’s robust conversation between the FDA and manufacturers, that is good for everybody,” she explained. “The CARES Act also included some changes to the classification system. Which again, is very good for bringing new products or formulations over from Europe. So, we’re expecting there to be a lot more activity now that the CARES Act has passed, although there is a three- to six-month backlog because of COVID.”
FDA Dermatologic and Ophthalmic Drugs Advisory Committee
One opportunity for dermatologists to get involved at the federal level with public health efforts that directly relates to the specialty is through the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee. The FDA uses advisory committees and panels to obtain independent expert advice on scientific, technical, and policy matters.
The Dermatologic and Ophthalmic Drugs Advisory Committee meets on an ad hoc basis, at FDA’s request, to provide input on the safety and effectiveness of marketed and investigational drugs for the treatment of dermatologic and ophthalmic disorders. The dermatologic and ophthalmic portions of the Committee meet separately. There are nine voting members in the fields of dermatology, ophthalmology, internal medicine, pathology, immunology, epidemiology, or statistics. However, there are often temporary members who bring expertise related to the specific issue being addressed. More information about the application process and criteria are available on the FDA website.
“Serving on the committee offers dermatologists an opportunity to provide advice to the FDA to assist in its decision making,” said Kenneth Katz, MD, MSc, MSCE, FAAD, a dermatologist at Kaiser Permanente in San Francisco, and the chairperson for the dermatology group for the Dermatologic and Ophthalmic Drugs Advisory Committee. “As committee members, we dermatologists can use our clinical training and experience to offer expert perspectives on risks and benefits of specific medicines or other important dermatology-related questions on which the FDA requests input. The FDA benefits from our perspectives — and ultimately, so do our patients.”
To learn more about the committee and its recent activities, visit the FDA website.
Drug shortages and access
Drug shortages can occur for a variety of reasons including manufacturing and quality problems, delays, and discontinuations. The FDA reports drug shortage information provided by manufacturers on its Drug Shortages webpage. Additionally, the American Society of Health-System Pharmacists (ASHP) also publishes drug shortage bulletins, which include more detailed commentary on reasons for the shortage.
Drugs in dermatology currently in shortage include:
Sodium bicarbonate
Lidocaine hydrochloride (Xylocaine®)
Lidocaine hydrochloride (Xylocaine®) with epinephrine
Bacteriostatic 0.9% sodium chloride vials
In September 2020, the Trump administration issued a final rule and FDA guidance for industry creating two new pathways for the safe importation of drugs from Canada and other countries. President Biden supported prescription drug importation during his campaign, however, the final rule authorizing states to create importation programs was the subject of a lawsuit challenging the rule based on safety and other concerns. “The Biden administration filed a motion in federal court to dismiss the lawsuit that would prevent it, so it seems like they’re in favor,” said Custard, “The temporary injunction that prevented the order from being implemented has expired, and thus, OMB has begun reviewing the order to weigh the overall consequences of the rules before it proceeds — both costs and benefits.”
Should the rule go forward, its impact on dermatology is likely to be limited, however. “Biologics are excluded from drugs that can be imported; importation plans will not help people struggling with the cost of certain types of drugs,” explained Custard.
To address drug shortage issues, the AADA took several steps in 2020 to advocate for improved access, including expressing support for the Mitigating Emergency Drug Shortages (MEDS) Act, which is intended to address drug shortages by providing additional authority to the FDA to ensure a stable supply of medications, as well as the Preventing Drug Shortages Act, which would help address critical drug shortages that can lead to substitution of recommended treatments with alternative therapies, compromising or delaying critical medical procedures, and rationing drug doses. Learn more about AADA drug shortage advocacy efforts.
Take action: Drug shortages letter
Help your patients advocate by providing them with a template letter to use when advocating to their local lawmakers about the severity of the ongoing drug shortage. Access the template letter (Word download).
