August 8, 2005

Division of Documents Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane

Room 1061

Rockville, MD 20852

RE: Docket No. 2005D-0062

Dear Sir/Madam:

Thank you for the opportunity to comment on the draft guidance to
industry on the FDA's "Drug Watch" for Emerging Drug Safety Information.
The American Pharmacists Association (APhA), founded in 1852 as the
American Pharmaceutical Association, represents more than 53,000
practicing pharmacists, pharmaceutical scientists, student pharmacists,
pharmacy technicians, and others interested in advancing the profession.
APhA, dedicated to helping all pharmacists improve medication use and
advance patient care, is the first-established and largest association
of pharmacists in the United States.

The safety of prescription and over-the-counter drugs is obviously of
vital interest to pharmacists as we are committed to helping patients
use their medications safely and effectively. Pharmacists, other health
care providers, and patients rely on the Food and Drug Administration
(FDA) to regulate the safety of medications.

APhA appreciates the Agency's commitment to improve drug safety through
the implementation of new safety measures to detect, assess, manage, and
communicate the risks and benefits of prescription drugs. The new Drug
Watch website is just one of the Agency's efforts to better communicate
information on potential medication-related risks to health care
professionals and the public. APhA supports the creation of the Drug
Watch page within the FDA's website. Publishing emerging safety data may
provide health care professionals and consumers with additional
information with which to make important health care decisions.

APhA offers the following comments for the Agency's consideration as the
FDA develops the Drug Watch website.

**I. Introduction**

Lines 23-25: According to the draft guidance, inclusion on the Drug
Watch website should not be construed as a statement by the Agency that
a particular drug is dangerous or inappropriate for use. Inclusion on
the website is only intended to signify that the FDA is examining
emerging safety

information on the product. To ensure that visitors to the Drug Watch
website understand the purpose of the information provided, and do not
prematurely conclude that drug products included on the site are too
dangerous for use, APhA recommends that the website include a basic
overview in consumer-friendly language explaining how drugs are
identified for inclusion on the site and what inclusion means. The
website should also direct consumers with questions or concerns about a
drug product to talk to their physician or pharmacist. In addition, for
drugs that have serious side effects when stopped abruptly, the website
should include a warning to that effect and direct consumers to talk to
their physician or pharmacist before stopping the medication.

Lines 39-40: APhA agrees with the Agency's proposal to continue to
communicate information on confirmed safety risks with health care
professionals and the public through more traditional means such as
provider letters and public health advisors. The Agency must continue to
communicate this information through more active means. For confirmed
safety risks, it would be inappropriate to rely on a passive
communication system such as the Drug Watch website that requires
providers or consumers to seek out the information.

**II. Background**

Lines 59-68: The guidance document includes a discussion on the Agency's
decision to provide potential drug risk information to health care
professionals and consumers as the information emerges. According to the
guidance, the FDA intends to post "emerging safety information before we
have fully determined its significance or taken final regulatory
action." Because the FDA will have to decide whether the information
warrants inclusion on the Drug Watch "while the Agency is evaluating its
significance", we risk the inclusion of too much uninterpreted or
unconfirmed information on the website. APhA is concerned that visitors
to the website may not fully understand that safety risks included on
the Drug Watch are [potential]{.underline} risks and that no direct
relationship has yet been confirmed. To reduce the opportunity for
confusion or misinterpretation, APhA recommends that the Agency
strengthen the disclaimer on the website about the posted information.
The FDA must emphasize that the information is still under evaluation
and that no final decision has been made.

**III. Discussion**

***A. What information will be posted?***

Lines 80-110: According to the draft guidance, the Agency is considering
posting information on newly observed, serious adverse events associated
with use of a drug, information on significant emerging risks that may
be associated with a drug, and information on new risk minimization
procedures on the Drug Watch website. APhA agrees with the Agency's
assessment that these three types of information are appropriate for
inclusion on the Drug Watch website. We also recommend that the Agency
organize the information posted on the website according to those three
categories. Drug products included on the Drug Watch should be
categorized or labeled as either an adverse event associated with use of
a drug, an emerging risk that may be associated with a drug, or as
information on new risk minimization procedures. Posting and labeling
drug products by the type of emerging safety risk may help health care
professionals and consumers better understand the type of potential
safety issue in question, and may help ensure that visitors to the
website do not misunderstand the posted information.

Lines 85-86: The draft guidance includes proposed text to alert visitors
to information on newly observed, serious adverse events. The sample
language states, "FDA is investigating postmarketing reports of renal
failure in elderly patients treated with Drug A, but a causal
relationship has not been established." APhA is concerned that consumers
visiting the website may not fully understand the term

"causal relationship." We recommend that the Agency consider whether
another term (such as "direct relationship") would be more appropriate
or the Agency should consider adding a brief explanation explaining the
term.

Lines 130-131: The draft guidance states that the Agency will update
information on the Drug Watch as soon as new information becomes
available or specific issues are resolved. APhA recommends that the
Agency allow visitors to sign up to receive an e-mail notification when
information on the website has been updated. (The notification system
could be modeled on the system currently used by the Centers for
Medicare and Medicaid Services to notify visitors when a response to a
Frequently Asked Question on its website has been updated). The creation
of an opt-in electronic notification system will help ensure that health
care professionals and the public are aware of the most up-to-date
information available.

Footnote 5: The draft guidance contains a discussion of the Agency's
plan to intensify its existing "Patient Information Sheets" and
"Healthcare Professional Information Sheets" programs. According to the
guidance document, the FDA intends to create Healthcare Professional
Information Sheets on all new molecular entities and some existing
drugs. The sheets will include links to information on the Drug Watch
website when available. APhA supports this initiative. We do, however,
have questions regarding the Agency's plan to create Patient Information
Sheets for all drugs which would contain emerging safety information
when available. Based upon the Consumer Drug Information Sheets
currently posted on the FDA website, it appears that these documents
contain general information on the drug product such as the drug's
indication, precautions, and possible side effects -- information that
is similar to some of the required elements for Consumer Medication
Information (CMI) developed by the private sector. Because the Agency is
developing Patient Information Sheets on all drugs, and the included
information mirrors some of the information included in CMI, what
relationship does the Agency see between the two? For example, are the
Patient Information Sheets an acceptable source of information for CMI?
How are the Patient Information Sheets being developed? Will the Patient
Information Sheets meet the Keystone criteria for CMI -- which has been
recognized by the Agency as the standard for evaluating the quality of
patient information? APhA requests that the FDA address the issue of
Patient Information Sheets and provide a detailed explanation of their
purpose, the information they will contain, and their relationship to
CMI.

***B. How will FDA decide which drugs will be included on the Drug
Watch?***

Lines 201-203: The Drug Safety Oversight Board will be responsible for
determining what drug-specific information should be included on the
Drug Watch website. According to the draft guidance, the Drug Safety
Oversight Board may also consult chairs from FDA Advisory Committees,
other external scientific experts, and consumer and patient
representatives. APhA supports the Agency's intention to expand the
decision-making process to individuals outside of the Drug Safety
Oversight Board which is solely comprised of representatives from the
FDA and two additional federal regulatory agencies. However, we urge the
Agency to require the Drug Safety Oversight Board to consult with
outside experts -- including pharmacists, the medication experts on the
health care team -- when evaluating emerging safety information.

***C. How will drugs be removed from the Drug Watch?***

Lines 208-209: The Agency intends to remove drugs from the Drug Watch as
safety issues are resolved. According to the guidance document,
resolution may include revising a product's labeling to address

safety concerns, other steps to adequately communicate information to
health care professionals and patients, or when it has been determined
that no new safety concern exists. While APhA understands

the FDA's rationale for removing drug products when the Agency believes
the safety issue has been resolved, we caution the Agency against
completely removing the drug product from the website. Completely
removing the drug product and its original safety concern from the
website will prevent health care professionals and consumers from easily
learning whether the safety concerns were validated or if no causal
relationship was found. Removing the drug from the website will also
prevent visitors from determining what action the Agency took to
mitigate any confirmed risks. It is important that visitors to the
website know what action the Agency took to resolve an issue. For
example, if the Agency resolves a potential safety issue and removes the
drug product from the website, a health care professional will not know
if the product was removed because no causal relationship was found, or
if a the product was removed because the product's labeling was revised
to address the safety concern. Knowing that the potential issue was
resolved is not adequate in this situation -- the website must reflect
what action was taken. Instead or completely removing the drug product
from the Drug Watch, we recommend that the Agency move these drug
products to a separate part of the Drug Watch website or mark the safety
concerns as "resolved". The website should also include a brief overview
of the original safety concern, whether or not a causal relationship was
confirmed, and what actions the Agency took based on that determination.

***D. Will sponsors be notified that a drug will be placed on the Drug
Watch?***

Lines 216-217: The FDA intends to notify product sponsors "shortly
before" posting emerging safety information about their drugs on the
website. APhA agrees that the Agency should notify product sponsors
before posting information about their products on the Drug Watch.
However, we question the Agency's decision to notify sponsors "shortly
before" the first posting. The use of the term "shortly before" implies
that the Agency may delay notifying product sponsors until the decision
to post the safety concerns has been finalized. APhA requests that the
Agency clarify the timeframe for involving the product sponsor in the
evaluation of emerging safety concerns. Product sponsors should be
notified that the Agency is evaluating possible safety concerns at the
beginning of the evaluation process. By notifying product sponsors at
the beginning of the process, the product sponsor can assist the Agency
with the evaluation efforts through the provision of clinical trial
information, additional data obtained since the product's approval, and
adverse event reports that were submitted directly to the drug
manufacturer. While the Drug Safety Oversight Board makes the final
decision to post information on the Drug Watch, notifying and requesting
relevant information from the product sponsor at the beginning of the
process will help ensure that the FDA has the necessary information to
make an appropriate decision.

***E. How will the Drug Watch affect the promotion of prescription
drugs?***

Lines 234-240: According to the draft guidance, information included on
the Drug Watch will not constitute substantial evidence or substantial
clinical experience to support a comparative safety or effectiveness
claim. The document continues to state that comparative claims based on
information contained on the Drug Watch "may be considered false or
misleading". APhA requests that the Agency strengthen this section of
the guidance document by changing "[may]{.underline} be considered false
or misleading" to "[will]{.underline} be considered false and
misleading". The Agency must explicitly prohibit drug manufacturers with
competing drug products from using information contained on the Drug
Watch to claim or suggest that their product is safer and/or more
effective than the product under evaluation by the FDA.

In closing, we reiterate our support for the Agency's commitment to
evaluate and improve its approach to drug safety issues. The creation of
a Drug Watch website is a good first step toward ensuring that health
care professionals and patients have access to the most up-to-date and
accurate product

information. By providing access to emerging safety data, prescribers,
pharmacists, and their patients will be able to work together to select
the most appropriate and safest medication therapy to meet the patient's
specific health care needs. However, we must reiterate our concern that
visitors to the website may prematurely conclude that drug products
included on the Drug Watch are too dangerous for use. To ensure that
health care professionals and consumers understand the purpose of the
Drug Watch, we urge the Agency to include a brief overview on the drug
selection process and a prominent disclaimer that the Drug Watch
includes potential safety risks that have not been proven or confirmed.
We offer our assistance to the FDA as it works to finalize the Drug
Watch program and moves forward with additional initiatives to improve
drug safety. The Association and our members stand ready to play a
greater role in ensuring that medications are prescribed and used
appropriately. Ensuring the public's health and safety, especially with
respect to medication use, is the pharmacist's, and APhA's, highest
priority.

Thank you for your consideration of the views of the nation's
pharmacists. Please contact Susan K. Bishop, Associate Director,
Regulatory Affairs, at 202-429-7538 or SBishop@APhAnet.org, or Susan C.
Winckler, Vice President, Policy & Communications and Staff Counsel, at
202-429-7533 or SWinckler@APhAnet.org, with any questions.

Sincerely,

![](media/image1.png)John A. Gans, PharmD

Executive Vice President

cc: Susan C. Winckler, RPh, Esq, Vice President, Policy & Communications
and Staff Counsel

Susan K. Bishop, MA, Associate Director, Regulatory Affairs