CENTER FOR DRUG EVALUATION AND RESEARCH
`
`APPROVAL PACKAGE FOR:
`
`APPLICATION NUMBER
`
`21-344
`
`Administrative Documents
`
`

`

`EXCLUSIVITY SUMMARY for NDA #
`
`21-344
`
`SUPPL #
`
`Trade Name
`
`FASLODEX (fulvestrant) Injection Generic Name
`
`Applicant Name AstraZeneca Pharmaceuticals
`
`HFD- 150
`
`Approval Date
`
`4-26-02
`
`PART I:
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1.An exclusivity determination will be made for all original
`applications, but only for certain supplements. Complete
`Parts II and III of this Exclusivity Summary only if you
`answer "YES"
`to one or more of the following questions about
`the submission.
`
`a)Is it an original NDA?
`
`YES/ x /
`
`NO /
`
`b) Is it an effectiveness supplement? YES /
`
`/
`
`NO /
`
`/
`
`/
`
`If yes, what
`
`type(SE1, SE2, etc.)?
`
`c)Did it require the review of clinical data other than to
`support a safety claim or change in labeling related to
`safety?
`(If it required review only of bioavailability
`or bioequivalence data, answer "NO.")
`
`YES /.X_/
`
`NO /___/
`
`If your answer is "no" because you believe the study is a
`bioavailability study and,
`therefore, not eligible for
`exclusivity, EXPLAIN why it is a bioavailability study,
`including your reasons for disagreeing with any arguments
`made by the applicant that the study was not simply a
`bioavailability study.
`
`If it is a supplement requiring the review of clinical
`data but it is not an effectiveness supplement, describe
`the change or claim that is supported by the clinical
`data:
`
`Page 1
`
`

`

`d)Did the applicant request exclusivity?
`
`is "yes," how many years of
`If the answer to (d)
`exclusivity did the applicant request?
`
`YES /_x_/ NO /
`
`/
`
`e)Has pediatric exclusivity been granted for this Active
`Moiety?
`
`YES /_/
`
`NO /___/
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO
`
`DIRECTLY TO THE SIGNATURE BLOCKS ON Page 9.
`
`2 Has a product with the same active ingredient(s), dosage form,
`strength, route of administration, and dosing schedule
`previously been approved by FDA for the same use? (Rx to OTC)
`Switches should be answered No — Please indicate as such).
`
`/‘\
`
`If yes, NDA #
`
`Drug Name
`
`YES /__/
`
`NO /_§_/
`
`IF THE ANSWER TO QUESTION 2 IS "YES,“ GO DIRECTLY TO THE
`
`SIGNATURE BLOCKS ON Page 9.
`
`3. Is this drug product or indication a DESI upgrade?
`
`YES /____/
`
`NO /_§_/
`
`IF THE ANSWER TO QUESTION 3 IS "YES,“ G0 DIRECTLY To THE
`
`SIGNATURE BLOCKS ON Page 9
`upgrade).
`
`(even if a study was required for the
`
`Page 2
`
`

`

`
`PART II: FIVEcYEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`
`(Answer either #1 or #2, as appropriate)
`
`1.Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any
`drug product containing the same active moiety as the drug
`under consideration? Answer "yes" if the active moiety
`(including other esterified forms, salts, complexes, chelates
`or clathrates) has been previously approved, but this
`particular form of the active moiety, e.g.,
`this particular
`ester or salt
`(including salts with hydrogen or coordination
`bonding) or other non—covalent derivative (such as a complex,
`chelate, or clathrate) has not been approved. Answer "no" if
`the compound requires metabolic conversion (other than
`deesterification of an esterified form of the drug)
`to produce
`an already approved active moiety.
`
`YES /_/ NO /_§_/
`
`If "yes," identify the approved drug product(s) containing the
`active moiety, and,
`if known,
`the NDA #(s).
`
`NDA #
`
`NDA #
`
`NDA #
`
`2. Combination product.
`
`If the product contains more than one active moiety (as
`defined in Part II, #1), has FDA previously approved an
`application under section 505 containing any 222 of the active
`moieties in the drug product?
`If, for example,
`the
`combination contains one never-before-approved active moiety
`and one previously approved active moiety, answer "yes."
`(An
`active moiety that is marketed under an OTC monograph, but
`that was never approved under an NDA,
`is considered not
`previously approved.)
`
`YES /__/
`
`NO /l_/
`
`Page 3
`
`

`

`If "yes," identify the approved drug product(s) containing the
`active moiety, and, if known,
`the NDA #(s).
`
`NDA #
`
`NDA #
`
`NDA #
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS “NO," GO
`DIRECTLY TO THE SIGNATURE BLOCKS ON Page 9.
`IF "YES.'I GO TO PART
`III.
`
`PART III: THREE-YEAR EXCLUSIVITY FOR NDA'S AND SUPPLEMENTS
`
`To qualify for three years of exclusivity, an application or
`supplement must contain "reports of new clinical investigations
`(other than bioavailability studies) essential to the approval of
`the application and conducted or sponsored by the applicant."
`This section should be completed only if the answer to PART II,
`Question 1 or 2, was "yes."
`
`1.Does the application contain reports of clinical
`investigations?
`(The Agency interprets "clinical
`investigations" to mean investigations conducted on humans
`other than bioavailability studies.)
`If the application
`contains clinical investigations only by virtue of a right of
`reference to clinical investigations in another application,
`answer "yes," then skip to question 3(a).
`If the answer to
`3(a)
`is "yes" for any investigation referred to in another
`application, do not complete remainder of summary for that
`investigation.
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS 0N Page 9.
`
`YES /_/
`
`NO /_/
`
`2. A clinical investigation is "essential to the approval" if the
`Agency could not have approved the application or supplement
`without relying on that investigation. Thus,
`the
`investigation is not essential to the approval if 1) no
`clinical investigation is necessary to support the supplement
`or application in light of previously approved applications
`(i.e.,
`information other than clinical trials, such as
`bioavailability data, would be sufficient to provide a basis
`
`Page 4
`
`

`

`for approval as an ANDA or 505(b)(2) application because of
`what is already known about a previously approved product), or
`2)
`there are published reports of studies (other than those
`conducted or sponsored by the applicant) or other publicly
`available data that independently would have been sufficient
`to support approval of the application, without reference to
`the clinical investigation submitted in the application.
`
`For the purposes of this section, studies comparing two
`products with the same ingredient(s) are considered to be
`bioavailability studies.
`
`(a)
`
`is a
`In light of previously approved applications,
`clinical investigation (either conducted by the
`applicant or available from some other source,
`including the published literature) necessary to
`support approval of the application or supplement?
`
`YES /_/
`
`NO /_/
`
`If "no," state the basis for your conclusion that a
`clinical trial is not necessary for approval AND GO
`DIRECTLY TO SIGNATURE BLOCK ON Page 9:
`
`(b) Did the applicant submit a list of published studies
`relevant to the safety and effectiveness of this drug
`product and a statement that the publicly available
`data would not
`independently support approval of the
`application?
`
`is "yes," do you personally
`If the answer to 2(b)
`(1)
`know of any reason to disagree with the applicant's
`conclusion?
`If not applicable, answer NO.
`
`YES /___/
`
`NO /
`
`/
`
`YES /___/
`
`NO /__/
`
`If yes, explain:
`
`Page 5
`
`

`

`is "no," are you aware of
`If the answer to 2(b)
`(2)
`published studies not conducted or sponsored by the
`applicant or other publicly available data that
`could
`independently demonstrate the safety and effectiveness
`of this drug product?
`
`YES /___/
`
`NO /_/
`
`If yes, explain:
`
`(c)
`
`If the answers to (b)(1) and (b)(2) were both "no,"
`identify the clinical investigations submitted in the
`application that are essential to the approval:
`
`Investigation #1, Study #
`
`Investigation #2, Study #
`
`Investigation #3, Study #
`
`investigations must be "new"
`3. In addition to being essential,
`to support exclusivity.
`The agency interprets "new clinical
`investigation" to mean an investigation that 1) has not been
`relied on by the agency to demonstrate the effectiveness of a
`previously approved drug for any indication and 2) does not
`duplicate the results of another investigation that was relied
`on by the agency to demonstrate the effectiveness of a
`previously approved drug product, i.e., does not redemonstrate
`something the agency considers to have been demonstrated in an
`already approved application.
`
`(a)
`
`For each investigation identified as "essential to the
`approval," has the investigation been relied on by the
`agency to demonstrate the effectiveness of a previously
`approved drug product?
`(If the investigation was relied
`on only to support the safety of a previously approved
`drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`Investigation #3
`
`YES /
`
`YES /
`
`YES /
`
`/
`
`/
`
`/
`
`NO /
`
`NO /
`
`NO /
`
`/
`
`/
`
`/
`
`If you have answered "yes" for one or more
`investigations,
`identify each such investigation and the
`NDA in which each was relied upon:
`
`Page 6
`
`

`

`NDA #
`NDA #
`NDA #
`
`Study #
`Study #
`Study #
`
`(b)
`
`For each investigation identified as "essential to the
`approval," does the investigation duplicate the results
`of another investigation that was relied on by the agency
`to support the effectiveness of a previously approved
`drug product?
`
`Investigation #1
`
`Investigation #2
`
`Investigation #3
`
`YES /
`
`YES /
`
`YES /
`
`/
`
`/
`
`/
`
`NO /
`
`NO /
`
`NO /
`
`/
`
`/
`
`/
`
`If you have answered "yes" for one or more
`investigations,
`identify the NDA in which a similar
`investigation was relied on:
`
`NDA #
`
`NDA #
`
`NDA #
`
`Study #
`
`Study #
`
`Study #
`
`(c)
`
`identify each
`If the answers to 3(a) and 3(b) are no,
`"new“ investigation in the application or supplement that
`is essential to the approval
`(i e.,
`the investigations
`listed in #2(c),
`less any that are not "new“):
`
`Investigation #__, Study #
`
`Investigation #__, Study #
`
`Investigation #_., Study #
`
`. To be eligible for exclusivity, a new investigation that is
`essential to approval must also have been conducted or
`sponsored by the applicant. An investigation was "conducted
`or sponsored by" the applicant if, before or during the
`conduct of the investigation, 1)
`the applicant was the sponsor
`of the IND named in the form FDA 1571 filed with the Agency,
`or 2)
`the applicant
`(or its predecessor in interest) provided
`substantial support for the study. Ordinarily, substantial
`support will mean providing 50 percent or more of the cost of
`the study.
`
`Page 7
`
`

`

`(a)
`
`For each investigation identified in response to
`question 3(C): if the investigation was carried out
`under an IND, was the applicant identified on the FDA
`1571 as the sponsor?
`
`Investigation #1
`
`IND #
`
`YES
`
`/
`
`/
`
`NO /
`
`/ Explain:
`
`Investigation #2
`
`IND #
`
`YES /
`
`/
`
`NO /
`
`/ Explain:
`
`._._._._...._._._
`
`(b)
`
`For each investigation not carried out under an IND or
`for which the applicant was not identified as the
`sponsor, did the applicant certify that it or the
`applicant's predecessor in interest provided
`substantial support for the study?
`
`Investigation #1
`
`YES /
`
`/ Explain
`
`NO /
`
`/ Explain
`
`Investigation #2
`
`YES /
`
`/ Explain
`
`NO /
`
`/ Explain
`
`Page 8
`
`

`

`(c) Notwithstanding an answer of "yes" to (a) or (b), are
`there other reasons to believe that the applicant
`should not be credited with having "conducted or
`sponsored" the study?
`(Purchased studies may not be
`used as the basis for exclusivity. However,
`if all
`rights to the drug are purchased (not just studies on
`the drug),
`the applicant may be considered to have
`sponsored or conducted the studies sponsored or
`conducted by its predecessor in interest.)
`
`YES /___/
`
`NO /
`
`/
`
`If yes, explain:
`
`
`
`fis7—“——‘—_‘
`
`Signature of Preparer
`Title:
`
`Date
`
`Signature of Office or Division Director
`
`Date
`
`49/
`
`CC:
`
`Archival NDA
`
`/Division File
`HFD-
`/RPM
`HFD-
`HFD-OSB/Mary Ann Holovac
`HFD—lO4/PEDS/T.Crescenzi
`
`Form OGD-011347
`
`Revised 8/7/95; edited 8/8/95; revised 8/25/98, edited 3/6/00
`
`Page 9
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Amy Baird
`4/25/02 01:20:20 PM
`
`Richard Pazdur
`
`4/25/02 05:34:54 PM
`
`

`

`(Complete for all original applications and all efficacy supplements)
`NOTE: A new Pediatric Page must be completed at the time of each action even though one was prepared at the
`time of the last action.
`
`PEDIATRIC PAGE
`
`NDA/BLA #
`
`21-344
`
`Supplement #
`
`Circle one: SE1
`
`SE2 SE3 SE4 SE5 SE6
`
`RFD-150 Trade and generic names/dosage form: Faslodex (fulvestrant) Iniection Action: Ag AE NA
`
`Applicant AstraZeneca Pharmaceuticals
`
`Therapeutic Class
`
`1P
`
`N/A
`lndicationls) previously approved
`Pediatric information in labeling of approved indication(s) is adequate X
`
`inadequate _
`
`Proposed indication in this application: Faslodex is indicated for the treatment of hormone receptor postive
`metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
`
`FOR SUPPLEMENTS, ANSWER THE FOLLOWING QUESTIONS IN RELATION TO THE PROPOSED INDICATION.
`
`IS THE DRUG NEEDED IN ANY PEDIATRIC AGE GROUPS? _Yes (Continue with questions) _No (Sign and
`return the form)
`
`WHAT PEDIATRIC AGE GROUPS IS THE DRUG NEEDED?
`
`(Check all that apply)
`
`”Neonates (Birth-1monthl _lnfants (1month-2yrs) _Children (2-12yrs) _Adolecents(12-16yrs)
`
`PEDIATRIC LABELING IS ADEQUATE FOR ALL PEDIATRIC AGE GROUPS. Appropriate information has
`_ 1.
`been submitted in this or previous applications and has been adequately summarized in the labeling to permit
`satisfactory labeling for all pediatric age groups. Further information is not required.
`
`__ __ 2.
`PEDIATRIC LABELING IS ADEQUATE FOR CERTAIN AGE GROUPS. Appropriate information has been
`(
`submitted in this or previous applications and has been adequately summarized in the labeling to permit
`satisfactory labeling for certain pediatric age groups (e.g., infants, children, and adolescents but not
`neonates). Further information is not required.
`
`PEDIATRIC STUDIES ARE NEEDED. There is potential for use in children, and further information is
`_ 3.
`required to permit adequate labeling for this use.
`
`A new dosing formulation is needed, and applicant has agreed to provide the appropriate
`a.
`formulation.
`
`A new dosing formulation is needed. however the sponsor is either not willing to provide it or is in
`b.
`negotiations with FDA.
`
`_ c.
`
`The applicant has committed to doing such studies as will be required.
`(1) Studies are ongoing.
`(2) Protocols were submitted and approved.
`(3) Protocols were submitted and are under review.
`
`(4) If no protocol has been submitted, attach memo describing status of discussions.
`
`If the sponsor is not willing to do pediatric studies, attach copies of FDA's written request that
`d.
`such studies be done and of the sponsor's written response to that request.
`
`PEDIATRIC STUDIES ARE NOT NEEDED. The drug/biologic product has little potential for use in
`4.
`pediatric patients. Attach memo explaining why pediatric studies are not needed.
`
`If none of the above apply, attach an explanation, as necessary.
`( _ 5.
`ARE THERE ANY PEDIATRIC PHASE IV COMMITMENTS IN THE ACTION LETTER? _ Yes
`ATTACH AN EXPLANATION FOR ANY OF THE FOREGOING ITEMS, AS NECESSARY.
`
`X No
`
`

`

`This page was completed based on information from
`le.g.. medical review, medical officer, team leader).
`
`the medical review
`
`/34
`
`Signature of Preparer and Title
`
`Date
`
`cc: Orig NDAIBLA # 21-344
`HFD-‘I5OIDiv File
`
`NDA/BLA Action Package
`HFD-960/ Peds Team
`(revised 1-14-02)
`FOR QUESTIONS ON COMPLETING THIS FORM CONTACT, PEDIATRIC TEAM, HFD-960, 4-7337
`
`

`

`Office of Drug Safety
`
`Memo
`
`To:
`
`Richard Pazdur, MD.
`
`Director, Division of Oncology Drug Products
`HFD-l 50
`
`From:
`
`Nora Roselle, PharmD.
`
`Safety Evaluator, Office of Drug Safety
`HFD-400
`
`Through:
`
`Carol Holquist, R.Ph.
`Deputy Director, Division of Medication Errors and Technical Support
`HFD—400
`
`Jerry Phillips, R.Ph.
`Associate Director, Office of Drug Safety
`HFD-400
`
`CC:
`
`Amy Baird
`Project Manager, Division of Oncology Drug Products
`HFD-l 50
`
`Date:
`
`March 4, 2002
`
`Re:
`
`ODS Consult 01-0229-2; Faslodex (Fulvestrant Injection); NDA 21-344
`
`This memorandum is in response to a February 27, 2002, request from your Division to prepare a Phase IV
`Commitment for the proposed proprietary name, Faslodex. The proposed proprietary name, Faslodex, was found
`unacceptable by ODS in the initial name review on January 14, 2002 (Consult 01-0229). In addition, DMETS
`provided a response to a January 22, 2002 request from the sponsor, AstraZeneca, to reconsider the acceptability of
`the proprietary name Faslodex or accept an alternative name of FaslodeXV- DMETS did not recommend the use of
`either proprietary name in the January 29, 2002 memorandum (Consult 01-0229-1).
`
`In an internal meeting on February 27, 2002 between DMETS and your Division, an agreement was made to consider
`the proposed proprietary name, Faslodex, acceptable with the following Phase IV comrniUnent incorporated into the
`final approval package.
`
`

`

`Phase IV Commitment:
`
`The sponsor will submit all error reports, both potential and actual, that occur with the drug Faslodex for a period of
`two years following the date of drug approval. Potential errors include any reports of potential circumstances or
`events that have the capacity to cause error and should be reported in a quarterly summary. Actual errors include any
`preventable event that reached the patient and caused harm or reached the patient and did not cause harm.
`Additionally, the sponsor will report actual errors that occurred but did not reach the patient, such as if the wrong drug
`was prepared but system checks prevented the drug from reaching the patient or being administered to the patient. All
`actual errors should be submitted as a 15-day report regardless of patient outcome. The sponsor will agree to provide
`yearly reports of potential and actual errors occurring with the drug, Faslodex, to the Agency for two years following
`the date of drug approval.
`
`Ifyou have any questions or need clarification, please contact the medication errors project manager, Sammie Beam
`at 301-827-3242.
`
`APPEARS nus w
`0N ORIGINAL AV
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Nora L. Roselle
`
`3/4/02 11:09:48 AM
`CSO
`
`Carol Holquist
`3/4/02 11:14:50 AM
`PHARMACIST
`
`Jerry Phillips
`3/5/02 08:15:20 AM
`DIRECTOR
`
`

`

`Office of Drug Safety
`
`NIEMO
`
`To:
`
`Richard Pazdur, MD.
`
`Director, Division of Oncology Drug Products
`HFD-l 50
`
`From:
`
`Carol Holquist
`Deputy Director, Division of Medication Errors and Technical Support, HFD-400
`
`Through:
`
`Jerry Phillips, RPh
`Associate Director, Office of Drug Safety, HFD-400
`
`CC:
`
`Amy Baird, Project Manager
`Division of Oncology Drug Products, HFD-ISO
`
`Date:
`
`January 29, 2002
`
`Re:
`
`ODS Consult 01-0229-1; Faslodex (Fulvestrant Injection), NDA #: 21-344
`
`This memorandum is in response to a January 22, 2002, request from the sponsor, AstraZeneca, to reconsider
`the acceptability of the proprietary name Faslodex or accept an alternative name of Faslodex ~' The sponsor
`believes that medication errors will not result from the use of the trade name Faslodex because of the following
`significant differences between Faslodex and the product trade names Zoladex and Casodex.
`
`Differences in dosage form and dosing schedule:
`
`0 Sponsor Comment #1
`There is a significant difference in the dosage form of CASODEX and FOSAMAX compared to
`FASLODEX. Both CASODEX and FOSAMAX are administered orally as one tablet daily and one tablet
`daily or weekly, respectively, whereas FASLODEX is dosed intramuscularly on a monthly basis.
`
`DMETS Response
`Generally, one would assume that based on these differences in dosage form of these two
`products the potential for medication errors would be low. However, post-marketing experience
`has demonstrated that having differing dosage forms does not eliminate the potential for error.
`The Agency has received a number of medication error reports that describe administration of
`the wrong drug despite that fact that one drug was a tablet and the other an injection. We have
`also received reported cases of oral solutions administered intravenously. Therefore, based on
`
`o Page 1
`
`

`

`previous post~marketing experience, DMETS does not believe that differences in dosage forms
`or routes of administration necessarily eliminate any potential for confusion when the names
`clearly sound or look alike to a currently marketed drug product.
`
`6 Sponsor Comment #2
`There is a significant difference between the parenteral dosage forms of FASLODEX and ZOLADEX.
`FASLODEX is an intramuscular injectable solution administered in the buttock, whereas ZOLADEX is a
`subcutaneous injectable solid depot administered in the abdomen. The needle gauge size for the two is also
`different. FASLODEX is administered intramuscularly via a 23—gauge SafetyGlideTM needle and ZOLADEX
`is administered in a disposable syringe device fitted with a l6-gauge hypodermic needle. A health care
`professional will not administer via the intramuscular route using the ZOLADEX l6-gauge hypodermic
`needle.
`
`DllflfTS Response:
`The sponsor notes the difference in administration sites (abdomen vs. buttock) and needle size would
`eliminate the chance of these products being misadministered. However, this statement is unfounded as the
`Agency has one reported error (ISR 3735202-0) where in fact Zoladex was administered in the buttocks rather
`than the abdomen.
`
`9 Sponsor Comment #3
`There are significant dosing schedule differences between FASLODEX and ZOLADEX. FASLODEX is
`administered 250 mg monthly (either as a single 5 mL injection or two 2.5 mL injections), whereas
`ZOLADEX is given at 3.6 mg monthly or 10.8 mg every three months.
`
`DME TS Response
`We believe the dosing schedule between Zoladex and Faslodex can be quite similar, Both
`Zoladex and Faslodex can be administered on a “once monthly” dosing schedule. Although
`Zoladex is available in two strengths, only one strength (3.6 mg) is indicated for the “once
`monthly” dosing regimen. Therefore, a prescription with a SIG of “once monthly as directed”
`may not include the corresponding strength. Moreover, confounding factors such as overlapping
`indications of use (antineoplastics used in breast cancer), injectable dosage forms, and single use
`syringes exponentially increase the potential for confusion between the two products.
`
`Differences in storage reguirernents:
`
`0 Sponsor Comment #4
`The storage location for FASLODEX is different than the other three products that OPDRA has cited as being
`too similar. FASLODEX must be refrigerated. The other products are stored at room temperature.
`
`DME TS Response
`Storage differences are not an essential factor in the assurance of correct product selection.
`Medication errors due to sound-alike/look—alike name confusion usually occur upon initial
`receipt of the prescription. Practitioners cognitively misinterpret the drug product then proceed
`to dispense, transcribe or administer the incorrect drug product as they believe this is what was
`intended to be ordered. Upon filling the prescription, the practitioner would proceed to the area
`in which the incorrect drug product is stored rather than the location of the intended drug
`product.
`
`O Page2
`
`

`

`Differences in dispensing practices:
`
`0 Sponsor Comment #5
`AstraZeneca estimates that approximately 80% of FASLODEX will be given in the Oncologist office setting.
`Approximately 15% of FASLODEX will be given in the hospital setting, and less then 2% will be in the retail
`pharmacy setting. Since 80% of the FASLODEX patients will not require a prescription and will be
`administered drug in an office setting by a nurse, the risk of medication errors will be minimal.
`
`DMETS Response
`Errors can occur in any practice setting. According to the sponsor, approximately 17% of Faslodex
`prescriptions will be dispensed from one of the usual practice settings, hospital or retail. Thus, increasing the
`number of individuals involved in the medication distribution system. Given the number of variables in these
`types of distribution systems the likelihood of confusion can be high.
`
`0 Sponsor Comment #6
`CASODEX and FOSAMAX are dispensed to a patient from a pharmacy. According to ——— _‘
`m of CASODEX units are sold to the retail pharmacy. FASLODEX will be
`and ZOLADEXis administered almost exclusivelyin a hospital setting (in or out-patient), or in an outpatient
`clinic setting (oncologist or urologist’ 5 office).
`
`DA/ETS Response
`The sponsor has previously acknowledged that Faslodex will be dispensed from both a retail and hospital
`setting. Given the look-alike and sound-alike similarities of these product names, in addition to the
`commonalties cited above, this overlap in dispensing enviromnents only increases the potential for the
`occurrence of a medication error.
`
`0 Sponsor Comment#7
`Urologists and their nurses are very familiar with the unique features of ZOLADEX administration set forth
`above, including dose and adminisnation technique. This process is very difi'erent from the intramuscular
`injection procedure FASLODEX requires. As a result, patients and nurses, as well as physicians, would be
`very unlikely to confuse the two products.
`
`DIVE}TS Response
`As stated in the response to comment number two above, product nuances are often overlooked and can result
`in improper administration of the product.
`
`Differences in patient profiles:
`0 Sponsor Comment #8
`Whereas FASLODEX is expected to be indicated for postmenopausal women with advanced breast cancer,
`ZOLADEX is primarily used in men with prostate cancer (3.6 and 10.8 mg). In the _ ‘-—
`~f— of the patients who received ZOLADEX from a physician were men.
`
`DIVETS Response
`Zoladex is also indicated for treatment of breast cancer in women. Irregardless of the percentage of patient
`population this may represent, there is a risk of overlap between patient populations increasing the likelihood
`of confusion. Additionally, the sponsor has not addressed the potential risk associated with inadvertent
`administration of Faslodex to a man.
`
`O Page 3
`
`

`

`0 Sponsor Comment #9
`According to
`
`-—'~
`f‘
`
`I of CASODEX prescriptions are written for men, with just
`over ‘9 written for women. Therefore, the likelihood of a FASLODEX female patient receiving CASODEX
`is minimal.
`
`DIVETS Response
`See response to comment eight above.
`
`Differences in visual appearance:
`
`0 Sponsor Comment #10
`There are significant differences in the visual appearance of FASLODEX versus ZOLADEX. In addition to
`differences in the size, shape, and color of the cartons, FASLODEX, a solution, is packaged with 1 or 2 pre-
`filled syringes in a clear plastic tray. ZOLADEX is a solid depot in a syringe, which is packaged in a brightly
`colored aluminum pouch. Artwork from the packaging for FASLODEX (2 x 2.5 mL and
`l x 5 mL pre-filled syringe) cartons, ZOLADEX (3.6 mg and 3-Month 10.8 mg) cartons and CASODEX
`carton are provided in Appendix B. Although not included in Appendix B, the FOSAMAX carton is green
`and yellow.
`
`BMTS Response
`Differences such as those outlined above may not always aid in product distinction especially if it is the first
`time a patient receives or a practitioner administers the product. Post-marketing reports of medication errors
`often times describe cases in which the products looked different to the practitioner or patient however they
`continued to administer the product because they thought it was a generic substitute.
`
`
`Other:
`
`.
`0 Sponsor Comment #1 1
`Prior to January 15, 2002 discussion, FDA officials never suggested that the tradename FASLODEX might be
`confused with names of the other approved pharmaceutical products. The trade name FASLODEX was first
`used in correspondence to FDA in December 1996, and first appeared in scientific literature in July 1997
`(Howell A. New endocrine agents. British Journal of Cancer 1997; 76 (Suppl): 13, Abs SP27).
`
`DMETS Response
`DMETS begins the review of a proprietary name upon official consult fi'om the review Division.
`Faslodex was not submitted to DMETS for review and comment until November, 21, 2001. Therefore, we
`cannot comment further on the timeliness of the submission of the proposed name to the Agency.
`
`o Page 4
`
`

`

`Additionally, the sponsor has requested consideration of the alternate name, Faslodex — We do not believe
`the addition of the modifier —' will adequately address the sound-alike or look-alike concerns associated with
`Zoladex. Prescriptions for Faslodexdmay be misinterpreted as Zoladex IM. Although the recommended
`route of administration of Zoladex is SQ, we have evidence that the product has been administered in the
`buttocks, a site often reserved for [M injections. Furthermore, physicians may not always remember to include
`the modifier on the prescription.
`
`In summary, the applicant has failed to provide persuasive data or evidence (i.e., independent analysis of the
`proposed name utilizing a larger sample size) to minimize the Agency’s concern with regard to potential
`medication errors between Faslodex and Zoladex/Casodex. Based on the lack of supportive data such as an
`independent analysis of the name and post-marketing experience, DMETS does not recommend the use of the
`proprietary name Faslodex.
`
`APPEARS mus WAY
`0N ORIGINAL
`
`o Page 5
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Carol Holquist
`1/29/02 04:18:51 PM
`PHARMACIST
`
`Jerry Phillips
`1/29/02 05:05:00 PM
`DIRECTOR
`
`

`

`CONSULTATION RESPONSE
`
`DIVISION OF MEDICATION ERRORS AND TECHNICAL SUPPORT
`OFFICE OF DRUG SAFETY
`
`(ODS; HFD-400)
`
`
`
`
`
`
`
`
`DATE RECEIVED: 11/21/01
`
`DUE DATE: 01/18/01
`
`ODS CONSULT #: 01-0229
`
`TO:
`
`Richard Pazdur, MD.
`
`
`
`
`
`
`
`Director, Division of Oncology Drug Products
`HFD-l 50
`
`THROUGH: Amy Baird
`Project Manager
`
`
`
`
`HFD- l 50
`
`PRODUCT NAME:
`NDA SPONSOR: AstraZeneca Pharmaceuticals
`Faslodex (fulvestrant) Injection
`
`
`125 mg/2.5 mL, 250 mg/5 mL
`
`NDA #: 21-344
`
`
`
`SAFETY EVALUATOR: Nora Roselle, PhamiD
`
`
`
`In response to a consult from the Division of Oncology Drug Products
`SUMMARY:
`(HFD-l 50), the Division of Medication Errors and Technical Support (DMETS) conducted a review of the
`proposed proprietary name “Faslodex” to determine the potential for confusion with approved proprietary and
`established names as well as sendin names.
`
`
`
`
`
`DMETS RECOMMENDATION:
`
`
`DMETS does not recommend the use of the proprietary name, Faslodex.
`In addition, DMETS recommends
`
`implementation of the labeling revisions outlined in section III of this review to minimize potential errors with the
`use of this nroduct.
`
`
`
`
`
` Carol Holquist, RPh
`Jerry Phillips, RPh
`Associate Director
`
`
`Office of Drug Safety
`Center for Drug Evaluation and Research
`Food and Dru Administration
`
`
`
`
`
`Deputy Director,
`Division of Medication Errors and Technical Support
`Office of Drug Safety
`Fax:
`Phone: (301 827-3242
`
`
`
`(301 443-5161
`
`
`
`

`

`Division of Medication Errors and Technical Support
`Office of Drug Safety
`RFD-400; Rm. 15B32
`Center for Drug Evaluation and Research
`
`PROPRIETARY NAME REVIEW
`
`DATE OF REVIEW:
`
`January 14, 2002
`
`NBA NUMBER:
`
`21-344
`
`NAME OF DRUG:
`
`Faslodex (fulvestrant) Injection
`125 mg/2.5 mL, 250 mg/5 mL
`
`NDA HOLDER:
`
`AstraZeneca Pharmaceuticals
`
`1.
`
`INTRODUCTION:
`
`This consult was written in response to a request from the Division of Oncology Drug Products (HFD-
`150), for assessment of the tradename “Faslodex”, regarding potential name confusion with other
`proprietary/generic drug names.
`
`PRODUCT INFORMATION
`
`“Faslodex” is the proposed name for fulvestrant, an intramuscular injection indicatedin
`Dr‘ait:
`
`~ ‘
`
`Faslodex” is suppliedin sterile single patient pre--filled syringes
`containing 50 mg/mL fulvestrant, either as a single 5 mL or two concurrent 2 5 mL injections to deliver
`the required monthly dose. “Faslodex” is administered as an intramuscular injection of 250 mg once
`monthly.
`
`II.
`
`RISK ASSESSMENT:
`
`The medication error staff of DMETS conducted a search of several standard published drug product
`reference texts2as well as several FDA databases3 for existing drug names which sound alike or
`look alike to Faslodex to a degree where potential confusion between drug names could occur under
`the usual clinical practice settings. A search of the electronic online version of the US. Patent and
`Trademark Office’s Text and Image Database was also conducted“. The Saegis5 Phanna-In-Use
`database was searched for drug names with potential for confusion. An expert panel discussion was
`
`' MICROMEDEX Healthcare Intranet Series, 2000, MICROMEDEX, Inc., 6200 South Syracuse Way, Suite 300, Englewood, Colorado
`80! l 1—4740, which includes the following published texts: DrugDex, Poisindex, Martindale (Parfitt K (Ed), Martindale: The Complete
`Drug Reference. London: Pharmaceutical Press. Electronic version), Index Nominum, and PDR/Physician’s Desk Reference (Medical
`Economics Company Inc, 2000).
`2 Facts and Comparisons, online v