
[Federal Register Volume 79, Number 36 (Monday, February 24, 2014)]
[Notices]
[Pages 10168-10172]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-03884]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-N-0202]


Over-The-Counter Drug Monograph System--Past, Present, and 
Future; Public Hearing

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public hearing; request for comments.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
announcing a public hearing to obtain input on the Over-The-Counter 
(OTC) Drug Review (sometimes referred to as the OTC Monograph Process, 
OTC Monograph, or OTC Drug Review). The Agency would like input on how 
to improve or alter the current OTC Monograph Process for reviewing 
nonprescription drugs (sometimes referred to as OTC drugs) marketed 
under the OTC Drug Review. This public hearing is being held to obtain 
information and comments from the public on the strengths and 
weaknesses of the current OTC Monograph Process, and to obtain and 
discuss ideas about modifications or alternatives to this process.

[[Page 10169]]


DATES: Public Hearing: The public hearing will be held on March 25 and 
26, 2014, from 9 a.m. to 4 p.m. The meeting may be extended or may end 
early depending on the level of public participation. Register to 
attend or provide oral testimony at the meeting by March 12, 2014. See 
Registration and Request To Provide Oral Testimony for information on 
how to register or make an oral presentation at the meeting. Written or 
electronic comments will be accepted until May 12, 2014.

ADDRESSES: The public hearing will be held at FDA's White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31, rm. 1503A, Silver Spring, MD 20993-
0002. Entrance for the public meeting participants (non-FDA employees) 
is through Building 1 where routine security check procedures will be 
performed. For parking and security information, please refer to http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.

FOR FURTHER INFORMATION CONTACT: Mary Gross, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Silver Spring, MD 20903-0002, 301-796-3519, FAX: 301-847-8753, 
mary.gross@fda.hhs.gov; or Georgiann Ienzi, Center for Drug Evaluation 
and Research, 10903 New Hampshire Ave., Silver Spring, MD 20903-0002, 
301-796-3515, FAX: 301-595-7910, georgiann.ienzi@fda.hhs.gov.
    Registration and Request To Provide Oral Testimony: The public 
hearing is free and seating will be on a first-come, first-served 
basis. If you wish to attend the public hearing or make an oral 
presentation, see section IV of this notice (Attendance and/or 
Participation in the Public Hearing) for information on how to register 
and the deadline for registration. For those who cannot attend in 
person, information about how to access a live Webcast of the meeting 
will be located at: http://www.fda.gov/Drugs/NewsEvents/ucm380446.htm.
    Comments and Transcripts: Interested persons may submit either 
electronic comments regarding this document to http://www.regulations.gov or written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852. You should annotate and organize your 
comments to identify the specific questions identified by the topic to 
which they refer. It is only necessary to send one set of comments. 
Identify comments with the docket number found in brackets in the 
heading of this document. Received comments may be seen in the Division 
of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, 
and will be posted to the docket at http://www.regulations.gov.
    Transcripts of the hearing will be available for review at the 
Division of Dockets Management and at http://www.regulations.gov 
approximately 45 days after the hearing. A transcript also will be 
available in either hard copy or on CD-ROM after submission of a 
Freedom of Information request. Send requests to the Division of 
Freedom of Information (ELEM-1029), Office of Management Programs, Food 
and Drug Administration, 12420 Parklawn Dr., Element Bldg., Rockville, 
MD 20857.

SUPPLEMENTARY INFORMATION:  FDA is announcing a public hearing to 
obtain input on the OTC Drug Review. We believe that the OTC Drug 
Review needs a critical examination at this juncture to examine whether 
and how to modernize its processes and regulatory framework. The Agency 
is interested in exploring ways to re-engineer the process of 
regulating OTC drugs that are currently regulated under the OTC 
Monograph Process to, among other things, create a process that is more 
efficient and more responsive to newly emerging information and 
evolving science, and to allow for more rapid product innovation where 
appropriate.

I. Background

    FDA has been assessing the OTC Monograph Process and, in 
particular, has been considering how effectively the monograph system 
is functioning in today's world, 40 years after its inception, from the 
scientific, policy, and process perspectives. We are now soliciting 
opinions about whether and how to modernize the process for the future.

A. The Past: OTC Drug Review Implementation and Accomplishments

1. OTC Drug Review Regulatory Framework
    FDA's regulations in 21 CFR part 330 describe the conditions for a 
drug to be considered generally recognized as safe and generally 
recognized as effective (GRAS/GRAE) and not misbranded. If a drug meets 
each of the conditions contained in part 330, as well as each of the 
conditions contained in any applicable OTC drug monograph, and other 
applicable regulations, it is considered GRAS/GRAE and not misbranded, 
and is not required by FDA to obtain approval of a new drug application 
(NDA) under section 505 of the FD&C Act (21 U.S.C. 355).
    The lengthy notice and comment rulemaking procedures for evaluating 
each therapeutic category are set forth at Sec.  330.10. These 
regulations require a three part regulatory rulemaking process 
including the publication of an Advanced Notice of Proposed Rulemaking, 
a Tentative Final Monograph (TFM) or Proposed Rule, and a Final 
Monograph or Final Rule to establish the conditions under which drugs 
under the OTC Drug Review are considered GRAS/GRAE and are not 
misbranded. FDA does not require OTC products conforming to the 
conditions of a final monograph and other applicable regulations to 
have approved NDAs prior to marketing. As a corollary, it has also 
generally been FDA's enforcement approach since the early days of the 
OTC Drug Review to not pursue regulatory action against OTC products 
marketed in conformance with the conditions proposed in a TFM. (See 
Compliance Policy Guide Section 450.200 Drugs--General Provisions and 
Administrative Procedures for Recognition as Safe and Effective at: 
http://www.fda.gov/iceci/compliancemanuals/compliancepolicyguidancemanual/ucm074388.htm).
2. Accomplishments of FDA's OTC Drug Review
    The OTC Drug Review has been successful in a variety of ways. Under 
the OTC Drug Review, FDA was able to evaluate the safety and efficacy 
of thousands of OTC drug products by therapeutic category, instead of 
reviewing NDAs for each drug product. FDA has issued final monographs 
for the majority of the original drug categories (see 21 CFR parts 331 
to 361) and over 150 TFMs. The final rules cover large segments of the 
OTC marketplace. Examples include fluoride toothpastes, acne products, 
and topical antifungals. As a result of the OTC Drug Review, thousands 
of OTC drugs that FDA determined are GRAS/GRAE and not misbranded are 
regulated under final monographs and continue to be available to 
consumers, and numerous other OTC drugs that were considered unsafe, 
ineffective, or both, have been removed from the market.

B. The Present: Challenges and Changed Landscapes

    Our examination, however, has revealed significant challenges 
associated with the OTC Drug Review as it functions today. When we look 
at how rapidly science now evolves and the impact this has had on the 
emergence of drug safety issues and on drug development, it is clear to 
us that

[[Page 10170]]

questions need to be asked about whether this impact necessitates a 
more agile and responsive process than the OTC Drug Review allows. When 
the OTC Monograph Process was initially established and implemented in 
the early 1970s, the multistep rulemaking strategy was thought to be an 
effective and efficient approach to reviewing large categories of 
active ingredients in drug products at the same time given what was the 
current thinking about the known science related to these ingredients. 
Indeed, the questions we are raising in this notice about the OTC Drug 
Review become all the more important to the public health when we 
compare the statutory changes that have been made to update the 
regulation of prescription NDA drugs to address the scientific advances 
in evaluating drug safety. These changes give FDA the ability to 
quickly obtain new information and take administrative action as needed 
efficiently and effectively.
    We have identified what we believe are the biggest challenges to 
efficiently and effectively regulating under the OTC Drug Review. We 
are also interested in feedback that identifies any other scientific or 
regulatory challenges associated with the OTC Drug Review that are not 
described here.
    We believe that the biggest challenges of the current system are:
     The large number of products marketed under the OTC Drug 
Review for which there are not yet final monographs,
     limitations on FDA's ability to require, for example, new 
warnings or other labeling changes to address emerging safety or 
effectiveness issues for products marketed under the OTC Drug Review in 
a timely and effective manner, and
     the inability of the OTC Drug Review to easily accommodate 
innovative changes to products regulated under the OTC Drug Review.
1. Monographs That Have Not Been Finalized
    The OTC Drug Review is one of the largest and most complex 
regulatory undertakings ever at FDA. It now consists of approximately 
88 simultaneous rulemakings in 26 broad categories that encompass 
hundreds of thousands of OTC drug products marketed in the United 
States and some 800 active ingredients for over 1,400 different 
ingredient uses. However, several significant segments of the OTC 
marketplace are still not covered by final monographs, and these 
products may lack sufficient data for FDA to determine whether they are 
safe, effective, or both. Under the enforcement approach we have been 
using since the early days of the OTC Drug Review, most of these 
products have remained on the market pending finalization of their 
monograph. Over the years, it has become clear that one unintended 
consequence of this enforcement approach is that it creates negative 
incentives for those who manufacture or market these OTC drugs to 
conduct studies or otherwise respond to safety concerns as to do so may 
hasten a determination that their product is not GRAS/GRAE.
2. Emerging Safety Concerns, Evolving Science, and Product Formulation
    The OTC Monograph Process also presents challenges to FDA's ability 
to respond to emerging safety issues, keep pace with evolving science, 
and ensure the consistent safety and effectiveness of varying 
formulations.
    a. New safety concerns can arise before or after a monograph is 
finalized. The OTC Drug Monograph Process is not agile enough to 
quickly change a monograph to address new safety concerns that may be 
identified during the rulemaking process or after a monograph is 
finalized (e.g., the addition of a warning into the monograph 
regulation, narrowing of an indication in the monograph regulation, or 
removal of an active ingredient from the monograph). Although the 
Agency may be able to take some actions to deal with safety issues that 
emerge, in order to change the monograph under the current process FDA 
engages in a lengthy rulemaking process. This process for changing a 
monograph is not well-adapted to address new safety issues with the 
speed and agility that are necessary to serve the public health.
    b. Keeping Pace with Evolving Science. As we have already 
described, the OTC Drug Review is not able to easily keep pace with 
evolving science. When the OTC Drug Review was established, it was 
generally thought that safety and effectiveness evaluations for the 
various active ingredients would be fairly straightforward and would 
not necessarily need continuous reexamination over time. Forty years 
later we know that information and data regarding medicine and science 
are changing at increasingly rapid rates. For example, scientific 
advancements have changed what is known about how drugs act in the body 
and in turn, how drugs are evaluated by FDA. These changes cannot be 
reflected under the OTC Drug Review in an efficient or timely manner. 
For example, many drug products regulated under the OTC Drug Review are 
indicated for use by children and are labeled with dosing instructions 
for this population. For most OTC monograph products, the information 
and data available at the time the initial advisory review panels 
established by FDA evaluated the various active ingredients, in the 
1970s, lacked specific data on use in children and infants. FDA did 
what was scientifically customary at the time, and extrapolated known 
data to use in children by simply reducing adult doses by a percentage. 
For most monographs that include specific labeling for use in the 
pediatric population, the pediatric dosing instructions were developed 
in this manner. The science of pharmacokinetics has advanced over the 
years and, as a result, the preferred approach to pediatric dosing has 
changed. Ideally, data from actual use in the pediatric population 
would be needed for an indication for use in children.
    In addition, with some categories of OTC drugs, changes in patterns 
of use take place which, in turn, impact consumer exposure to the 
drugs. Exposure patterns are a key component of any safety and 
effectiveness assessment. The current process of changing a monograph 
does not contain an efficient mechanism to assess or address these 
kinds of changes to exposure patterns.
    c. Product Formulation. Under the OTC Drug Review, the monographs 
set forth the conditions under which a specific active ingredient used 
in a drug product is GRAS/GRAE and not misbranded. The monographs, 
however, generally do not dictate what other non-active ingredients can 
be added, or other aspects of the formulation (other than the general 
requirement that they be safe and suitable and not interfere with the 
effectiveness of the preparation, see Sec.  330.1(e)). Thus, under the 
OTC Drug Review, products in their final formulation are not 
specifically evaluated by the Agency to ensure product safety, 
effectiveness, and consistency. Although FDA regulations require that 
inactive ingredients not interfere with the safety or efficacy of the 
drug product, for drug products marketed under the OTC Drug Review, FDA 
generally does not receive information about specific varying 
formulations that it can use to ensure that the final finished drug 
products meet the standards for safety and effectiveness.
3. Limited Opportunity for Innovation
    Eligibility for the OTC Drug Review is limited to active 
ingredients that were on the market in their specific dosage forms at 
the inception of the OTC Drug

[[Page 10171]]

Review, and products that have become eligible under the Time and 
Extent Application process set forth at Sec.  330.14. Thus, when 
manufacturers develop new combinations of ingredients or new dosage 
forms (e.g. dissolving films or tablets), the OTC Drug Review is not 
facile in accommodating these types of changes. Due to these changes, 
products that are not eligible for consideration under the OTC Drug 
Review would otherwise require an NDA prior to marketing.

II. The Future: Modernizing the OTC Drug Review

    In light of the challenges posed by the OTC Drug Review, FDA 
believes it is time for considering ideas for modernizing the 
regulation of drugs under the OTC Drug Review. We are interested in 
hearing ideas for changes to the existing OTC Monograph Process or 
ideas for its replacement with an entirely new regulatory or statutory 
framework.
    In developing suggestions for change, FDA notes that many of the 
OTC Drug Review's present day challenges are systemic, and thus cannot 
be addressed solely by increasing resources. In this section, we 
identify some preliminary ideas for potential changes to the OTC 
Monograph Process. Although none of these ideas appear likely to lead 
to a comprehensive solution, we are sharing them as a starting point 
for a discussion on modernizing the OTC Drug Review. Our summary of 
these initial ideas here is not intended to define the limits of the 
kind of changes that might be proposed. We are interested in hearing a 
full range of ideas, including novel ideas for new regulatory 
frameworks.
    Suggestions and other comments from the public need not be 
comprehensive to be useful. FDA is interested in ideas that may not 
solve every problem, but do address one or more of them. Ideally, a 
comprehensive solution (made up of a single proposal or a group of 
proposed solutions) would address all the challenges of the current 
system. We believe that an ideal, comprehensive solution would:
     Use modern standards for safety and efficacy,
     provide an efficient mechanism for finalizing the status 
of drug products that are currently marketed under pending TFMs,
     allow for innovative changes to drug products,
     provide FDA with the ability to respond promptly to 
emerging safety or effectiveness concerns,
     allow FDA to easily and quickly require additional 
information or data necessary to develop pediatric labeling where 
appropriate, and
     allow FDA to obtain final formulation information about 
individual products or readily establish final formulation testing 
standards.
    We recognize that the preliminary concepts we discuss in this 
document touch upon some, but not all, of the challenges we have 
identified. In addition, these ideas are not necessarily limited to 
approaches for which FDA has existing statutory authority. These 
preliminary ideas are:
     Identifying a streamlined process that would allow prompt 
resolution of existing TFMs,
     issuing monographs by administrative order,
     issuing regulations to require product specific 
information and expanding the use of guidances, and
     expanding the NDA deviation process.
    We invite the public to comment on these potential options, but we 
also encourage comments that propose other ideas.

A. Promptly Resolve Existing Tentative Final Monographs Pursuant to a 
Streamlined Process

    FDA is considering ways to more efficiently bring TFMs to closure. 
We are interested in ideas for developing streamlined processes under 
which the Agency could promptly finalize the existing TFMs.

B. Issue Monographs by Administrative Order

    This idea would involve establishing a process similar to that 
enacted by the Food and Drug Administration Safety and Innovation Act 
(FDASIA) (Pub. L. 112-144) for device reclassifications. FDASIA changed 
the process by which devices are reclassified under section 513(e) of 
the FD&C Act from notice and comment rulemaking to an administrative 
order process (see 21 U.S.C. 360c(e)(1)(A)(i)). Under this model, 
monographs could be established by administrative order, after issuance 
of a proposed order for comment.

C. Issuing Regulations To Require Product Specific Information and 
Expanding the Use of Guidances

    FDA could issue new regulations that would require that 
manufacturers submit, prior to marketing, limited information about 
individual products that will be using active ingredients that have 
been determined to be GRAS/GRAE. The individual product information 
requested might be similar to, but less detailed than, what is required 
under an NDA and could include, for example, labeling, and quality and 
pharmacokinetic information. FDA could then issue guidances 
recommending the types of information FDA would be seeking. FDA's use 
of guidances under this framework could increase the Agency's 
flexibility to address specific product issues as they arise.

D. Expand the NDA Deviation Process

    The OTC Drug Review regulations provide a process for approving a 
drug product that complies with the conditions of a final monograph 
except for a deviation (Sec.  330.11). In this instance, a sponsor can 
apply for an NDA deviation by submitting an NDA showing that the 
product complies with the conditions of the monograph except for the 
deviation and providing the necessary data to demonstrate the safety 
and effectiveness of the product with the deviation. For example, an 
OTC monograph may not cover certain dosage forms of a monograph 
ingredient. The manufacturer of a proposed different dosage form could 
submit an NDA that relies on the final monograph to demonstrate the 
safety and efficacy for the drug except for the differences related to 
the change in dosage form. The NDA would also need to include the 
appropriate data to demonstrate the safety and effectiveness of the new 
dosage form. The approved NDA would be specific only to the NDA sponsor 
and would not amend the monograph.
    Industry has not utilized the NDA deviation process as a pathway to 
marketing very often. The Agency is interested in learning why this is 
and whether there are changes that could be made to the existing NDA 
deviation process that would make it a more attractive alternative for 
industry and that could allow marketing of additional drug products 
without having to submit a full NDA.

III. Scope of the Public Hearing

    FDA is holding this public hearing to seek input on possible ways 
to modernize the OTC Monograph Process in order to make the process 
more responsive to emerging safety information and scientific advances. 
We would like feedback from a variety of interested members of the 
public, including consumers; industry; and pharmacists, physicians, and 
other members of the medical community. FDA is interested in obtaining 
information and public comment in the following areas:

[[Page 10172]]

A. Strengths and Weaknesses of the Existing OTC Drug Review

     What aspects of the OTC Drug Review continue to function 
effectively?
     Which aspects of the OTC Drug Review are most in need of 
change?
     Are there additional mechanisms to eligibility for the OTC 
Drug Review that could be explored? If so, what should be the 
parameters of eligibility?
     Why is the NDA deviation process rarely used by industry? 
Are there changes to that process that would make it a more appealing 
and appropriate alternative pathway?

B. Preliminary Concepts for Modernization Described in This Document

    We welcome views on the following preliminary concepts identified 
by FDA for modernizing the OTC Drug Review:
     Ideas for a streamlined process that would allow us to 
promptly resolve all TFMs.
     Issue monographs by administrative order.
     Issue regulations to require product specific information 
and expand the use of guidances.
     Expand the NDA deviation process.

C. Your Suggestions for Modifications or Alternatives to the OTC Drug 
Review

     What alternatives or changes to the OTC Drug Review would 
modernize or improve FDA's regulation of monograph drugs?
     What changes can facilitate speedier finalization of the 
remaining monographs?
     How can the Agency most expeditiously address emerging 
safety issues for drugs regulated under the OTC Drug Review?
     Are there specific changes to the OTC Drug Review that the 
Agency could employ to address the lack of pediatric data for some 
final monographs?
     Should the only alternative to marketing an OTC drug under 
an OTC monograph be an NDA or abbreviated NDA approval? If not, what 
could another alternative be?
     Are there other regulatory mechanisms (not necessarily 
used for the regulation of drug products) that are used by other 
agencies in the United States or in other countries that FDA could 
consider using to regulate OTC drugs products?

IV. Attendance and/or Participation in the Public Hearing

    The public hearing is free and seating will be on a first-come, 
first-served basis. If you wish to make an oral presentation during the 
hearing, you must register by submitting either an electronic or a 
written request by 5 p.m. on March 12, 2014, to Mary Gross or Georgiann 
Ienzi (see FOR FURTHER INFORMATION CONTACT). Submit electronic requests 
to CDEROTCMONOGRAPH@fda.hhs.gov. We recommend that you register early 
because seating is limited. You must provide your name, title, business 
affiliation (if applicable), address, telephone and fax numbers, email 
address, and type of organization you represent (e.g., industry, 
consumer organization, etc.). You also should submit a brief summary of 
the presentation, including the discussion topic(s) that will be 
addressed and the approximate time requested for your presentation. FDA 
encourages individuals and organizations with common interests to 
coordinate and give a joint, consolidated presentation. Registrants 
will receive confirmation once they have been accepted to attend the 
meeting. FDA may limit both the number of participants from individual 
organizations and the total number of attendees based on space 
limitations. Registered presenters should check in before the hearing.
    Participants should submit a copy of each presentation to Mary 
Gross or Georgiann Ienzi (see FOR FURTHER INFORMATION CONTACT) no later 
than 5 p.m. on March 12, 2014. We will file the hearing schedule, 
indicating the order of presentation and the time allotted to each 
person, with the Division of Dockets Management (see Comments and 
Transcripts). FDA will post an agenda of the public hearing and other 
background material at least 3 days before the public hearing and 
additional information will be available at: http://www.fda.gov/Drugs/NewsEvents/ucm380446.htm (select this hearing from the events list).
    We will mail, email, or telephone the schedule to each participant 
before the hearing. In anticipation of the hearing presentations moving 
ahead of schedule, participants are encouraged to arrive early to 
ensure their designated order of presentation. Participants who are not 
present when called risk forfeiting their scheduled time.
    If you need special accommodations due to a disability, contact 
Mary Gross or Georgiann Ienzi (see FOR FURTHER INFORMATION CONTACT) at 
least 7 days in advance of the hearing.

V. Notice of Hearing Under 21 CFR Part 15

    The Commissioner of Food and Drugs is announcing that the public 
hearing will be held in accordance with part 15 (21 CFR part 15). The 
hearing will be conducted by a presiding officer, who will be 
accompanied by FDA senior management from the Office of the 
Commissioner and the relevant centers.
    Under Sec.  15.30(f), the hearing is informal and the rules of 
evidence do not apply. No participant may interrupt the presentation of 
another participant. Only the presiding officer and panel members may 
question any person during or at the conclusion of each presentation 
(Sec.  15.30(e)). Public hearings under part 15 are subject to FDA's 
policy and procedures for electronic media coverage of FDA's public 
administrative proceedings (21 CFR part 10, subpart C) (Sec.  
10.203(a)). Under Sec.  10.205, representatives of the electronic media 
may be permitted, subject to certain limitations, to videotape, film, 
or otherwise record FDA's public administrative proceedings, including 
presentations by participants. The hearing will be transcribed as 
stipulated in Sec.  15.30(b). (See section VII for more details.) To 
the extent that the conditions for the hearing as described in this 
document conflict with any provisions set out in part 15, this notice 
acts as a waiver of those provisions as specified in Sec.  15.30(h).

    Dated: February 19, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-03884 Filed 2-21-14; 8:45 am]
BILLING CODE 4160-01-P


