CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`
`
`
`APPLICATION NUMBER:
`
`
`761145Orig1s000
`
`
`
`OTHER REVIEW(S)
`
`
`

`

`FOOD AND DRUG ADMINISTRATION
`
`
`
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`
`
`****Pre-decisional Agency Information****
`Memorandum
`Date:
` April 24, 2020
`
`To:
`Kimberly Scott, RN, BSN, OCN, Senior Regulatory Project Manager
`
` Division of Hematologic Malignancies 2 (DHM2)
`
`
`
` Stacy Shord, PharmD, BCOP, Associate Director for Labeling, (DHM2)
`
`
`
`
`
`From:
`
`CC:
`
`Subject:
`
`Adesola Adejuwon, PharmD, Regulatory Review Officer
`
`
` Office of Prescription Drug Promotion (OPDP)
`
`Kevin Wright, PharmD, Team Leader, OPDP
`
`
`
`
`OPDP Labeling Comments for DARZALEX FASPROTM (daratumumab
`
`
`and hyaluronidase-fihj) injection, for subcutaneous use
`
`BLA:
`
`761145
`
`
`In response to DHM2 consult request dated September 8, 2019, OPDP has reviewed the
`proposed product labeling (PI) and patient package insert (PPI) for the original BLA
`
`
`
`submission for DARZALEX FASPROTM (daratumumab and hyaluronidase-fihj) injection, for
`subcutaneous use (Darzalex Faspro).
`
`PI and PPI: OPDP’s comments on the proposed labeling are based on the draft PI received by
`
`
`
`electronic mail from DHM2 (Kimberly Scott) on April 17, 2020 and are provided below.
`
`
`
`A combined OPDP and Division of Medical Policy Programs (DMPP) review was completed,
`
`
`
`
`
`
`and comments on the proposed PPI were sent under separate cover on April 24, 2020.
`
`
`
`Thank you for your consult. If you have any questions, please contact Adesola Adejuwon at
`
`
`(240) 402-5773 or Adesola.Adejuwon@fda.hhs.gov.
`
`
`
`
`Reference ID: 4598070Reference ID: 4753174
`
`27 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately
`following this page
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`ADESOLA F ADEJUWON
`04/24/2020 07:06:48 PM
`
`
`
`Reference ID: 4598070Reference ID: 4753174
`
`

`

` Department of Health and Human Services
`
`
`Public Health Service
`
`Food and Drug Administration
`
`Center for Drug Evaluation and Research
`
`Office of Medical Policy
`
`
`
`
`PATIENT LABELING REVIEW
`
`
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`April 24, 2020
`
`Kimberly Scott, RN, BSN, OCN
`Senior Regulatory Project Manager
`
`Division of Hematologic Malignancies 2 (DHM2)
`
`LaShawn Griffiths, MSHS-PH, BSN, RN
`Associate Director for Patient Labeling
`
`
`Division of Medical Policy Programs (DMPP)
`
`Morgan Walker, PharmD, MBA, CPH
`Senior Patient Labeling Reviewer
`Division of Medical Policy Programs (DMPP)
`Adesola Adejuwon, PharmD, MBA
`Regulatory Review Officer
`Office of Prescription Drug Promotion (OPDP)
`Review of Patient Labeling: Patient Package Insert (PPI)
`
`Drug Name (established
`name):
`
`DARZALEX FASPRO (daratumumab and hyaluronidase-
`fihj)
`
`Dosage Form and
`
`Route:
`Application
`Type/Number:
`Applicant:
`
`injection, for subcutaneous use
`
`BLA 761145
`
`Janssen Research and Development, LLC.
`
`
`
`Reference ID: 4597434Reference ID: 4753174
`
`

`

`1
`
`INTRODUCTION
`
`On July 12, 2019, Janssen Biotech, Inc. submitted for the Agency’s review an
`original Biologic License Application (BLA) 761145 DARZALEX FASPRO
`
`(daratumumab and hyaluronidase-fihj). This original BLA proposes to support the
`use of subcutaneous daratumumab co-formulated with recombinant human
`
`
`hyaluronidase for the treatment of adult patients with multiple myeloma.
`
`
`
`This collaborative review is written by the Division of Medical Policy Programs
`
`
`
`
`
`(DMPP) and the Office of Prescription Drug Promotion (OPDP) in response to a
`request by the Division of Hematology Products (DHP) on September 6, 2019 for
`
`DMPP and OPDP to review the Applicant’s proposed Patient Package Insert (PPI)
`for DARZALEX FASPRO (daratumumab and hyaluronidase-fihj).
`
`2 MATERIAL REVIEWED
`x Draft DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) PPI received
`on July 12, 2019, and received by DMPP and OPDP on April 16, 2020.
`x Draft DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) Prescribing
`
`Information (PI) received on July 12, 2019, and received by DMPP and OPDP on
`
`April 16, 2020.
`
`3 REVIEW METHODS
`To enhance patient comprehension, materials should be written at a 6th to 8th grade
`
`
`
`
`reading level, and have a reading ease score of at least 60%. A reading ease score of
`60% corresponds to an 8th grade reading level.
`
`Additionally, in 2008 the American Society of Consultant Pharmacists Foundation
`(ASCP) in collaboration with the American Foundation for the Blind (AFB)
`published Guidelines for Prescription Labeling and Consumer Medication
`
`Information for People with Vision Loss. The ASCP and AFB recommended using
`fonts such as Verdana, Arial or APHont to make medical information more
`accessible for patients with vision loss.
`In our collaborative review of the PPI we:
`simplified wording and clarified concepts where possible
`x
`
`ensured that the PPI is consistent with the Prescribing Information (PI)
`x
`removed unnecessary or redundant information
`x
`ensured that the PPI is free of promotional language or suggested revisions to
`x
`ensure that it is free of promotional language
`
`ensured that the PPI meets the criteria as specified in FDA’s Guidance for
`
`Useful Written Consumer Medication Information (published July 2006)
`
`x
`
`4 CONCLUSIONS
`
`
`
`Reference ID: 4597434Reference ID: 4753174
`
`

`

`The PPI is acceptable with our recommended changes.
`
`
`
`5 RECOMMENDATIONS
` x Please send these comments to the Applicant and copy DMPP and OPDP on the
`correspondence.
`x Our collaborative review of the PPI is appended to this memorandum. Consult
`DMPP and OPDP regarding any additional revisions made to the PI to determine
`
`
`
`if corresponding revisions need to be made to the PPI.
`
`Please let us know if you have any questions.
`
`
`
`Reference ID: 4597434Reference ID: 4753174
`
`5 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS)
`immediately following this page
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`MORGAN A WALKER
`04/24/2020 08:31:49 AM
`
`ADESOLA F ADEJUWON
`04/24/2020 08:48:35 AM
`
`LASHAWN M GRIFFITHS
`04/24/2020 09:22:21 AM
`
`
`
`Reference ID: 4597434Reference ID: 4753174
`
`

`

`MEMORANDUM
`
`REVIEW OF REVISED LABEL AND LABELING
`
`Division of Medication Error Prevention and Analysis (DMEPA)
`
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`
`Office of Surveillance and Epidemiology (OSE)
`
`Center for Drug Evaluation and Research (CDER)
`
`
`Date of This Memorandum:
`March 30, 2020
`Requesting Office or Division:
`Division of Hematologic Malignancies 2 (DHM 2)
`Application Type and Number: BLA 761145
`Product Name and Strength:
`Darzalex Faspro (daratumumab and hyaluronidase-fihj)
`Injection, 1,800 mg and 30,000 units/15 mL
`Janssen Research & Development, LLC
`2019-1486-2 and 2019-1490-2
`Nicole Iverson, PharmD, BCPS
`Hina Mehta, PharmD
`
`Applicant/Sponsor Name:
`OSE RCM #:
`DMEPA Safety Evaluator:
`DMEPA Team Leader:
`
`PURPOSE OF MEMORANDUM
`1
`The Applicant submitted revised carton labeling received on March 20, 2020 for Darzalex
`Faspro. We reviewed the revised carton labeling for Darzalex Faspro (Appendix A) to determine
`if it is acceptable from a medication error perspective. The revisions are in response to
`recommendations that we made during a previous label and labeling review.a We determined
`the container label was acceptable in our previous label and labeling review memo.
`
` CONCLUSION
`2
`The Applicant implemented all of our recommendations and we have no additional
`recommendations at this time.
`
`a Iverson N. Human Factors Label and Labeling Review Memo for Darzalex Faspro (BLA 761145). Silver Spring (MD):
`FDA, CDER, OSE, DMEPA (US); 2020 MAR 11. RCM No.: 2019-1486-1 and 2019-1490-1.
`1
`
`
`
`Reference ID: 4583008Reference ID: 4753174
`
`1 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately
`following this page
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`NICOLE F IVERSON
`03/30/2020 07:58:37 AM
`
`HINA S MEHTA
`04/01/2020 01:57:20 PM
`
`
`
`Reference ID: 4583008Reference ID: 4753174
`
`

`

`MEMORANDUM
`
`REVIEW OF REVISED LABEL AND LABELING
`
`Division of Medication Error Prevention and Analysis (DMEPA)
`
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`
`Office of Surveillance and Epidemiology (OSE)
`
`Center for Drug Evaluation and Research (CDER)
`
`
`Date of This Memorandum:
`March 11, 2020
`Requesting Office or Division:
`Division of Hematologic Malignancies 2 (DHM 2)
`Application Type and Number: BLA 761145
`Product Name and Strength:
`Darzalex Faspro (daratumumab and hyaluronidase-fihj)
`Injection, 1,800 mg and 30,000 units/15 mL
`Janssen Research & Development, LLC
`2019-1486-1 and 2019-1490-1
`Nicole Iverson, PharmD, BCPS
`Hina Mehta, PharmD
`
`Applicant/Sponsor Name:
`OSE RCM #:
`DMEPA Safety Evaluator:
`DMEPA Team Leader:
`
`PURPOSE OF MEMORANDUM
`1
`The Applicant submitted revised container label and carton labeling received on March 9, 2020
`for Darzalex Faspro. We reviewed the revised container label and carton labeling for Darzalex
`Faspro (Appendix A) to determine if they were acceptable from a medication error perspective.
`The revisions are in response to recommendations that we made during a previous label and
`
`labeling review.a
`
` CONCLUSION
`2
`The revised container label is acceptable from a medication error perspective; however the
`revised carton labeling is unacceptable from a medication error perspective. The
`administration time is missing on principal display panel of the carton labeling, which may help
`mitigate administration errors.
`
`3 RECOMMENDATIONS FOR JANSSEN RESEARCH & DEVELOPMENT, LLC
`We recommend the following be implemented prior to approval of this BLA:
`A. Carton Labeling
`
`a Smith J. Label and Labeling Review for Darzalex Faspro (BLA 761145). Silver Spring (MD): FDA, CDER, OSE, DMEPA
`(US); YYYY MON DD. RCM No.: XXXX-XX.
`
`1
`
`
`
`Reference ID: 4573559Reference ID: 4753174
`
`

`

`1.
`
`In your use-related risk analysis, you have acknowledged the potential clinical
`consequence of administering Darazalex Faspro as an intravenous infusion,
`which may cause an overdose and lead to adverse events (e.g. infusion reaction).
`Considering this risk, we have determined that including the administration time
`on the principal display panel of the carton labeling should be used as a
`mitigation strategy to help prevent wrong route administration errors.
`Therefore, we recommend you revise the statement, “For Subcutaneous Use
`Only” to “For Subcutaneous Use Only. Administer subcutaneous injection over 3
`to 5 minutes.” on the principal display panel of the carton labeling.
`
`
`
`
`Reference ID: 4573559Reference ID: 4753174
`
`2
`
`
`2 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately
`following this page
`
`

`

`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
`
`NICOLE F IVERSON
`03/11/2020 10:07:28 AM
`
`HINA S MEHTA
`03/13/2020 05:55:37 PM
`
`
`
`Reference ID: 4573559Reference ID: 4753174
`
`

`

`
`
`HUMAN FACTORS LABEL AND LABELING REVIEW
`Division of Medication Error Prevention and Analysis (DMEPA)
`
`Office of Medication Error Prevention and Risk Management (OMEPRM)
`
`Office of Surveillance and Epidemiology (OSE)
`
`Center for Drug Evaluation and Research (CDER)
`
`
`*** This document contains proprietary information that cannot be released to the public***
`
`Date of This Review:
`January 21, 2020
`Requesting Office or Division:
`Division of Hematologic Malignancies 2 (DHM 2)
`Application Type and Number: BLA 761145
`Product Name, Dosage Form,
`Darzalex Faspro (daratumumab and hyaluronidase-xxxx)
`and Strength:
`Injection, 1,800 mg and 30,000 units/15 mL)
`Product Type:
`Multi-Ingredient Product
`Rx or OTC:
`Prescription (Rx)
`Applicant/Sponsor Name:
`Janssen Research & Development, LLC.
`FDA Received Date:
`July 12, 2019 and November 13, 2019
`OSE RCM #:
`2019-1486 and 2019-1490
`DMEPA Safety Evaluator:
`Nicole Iverson, PharmD, BCPS
`DMEPA Team Leader:
`Hina Mehta, PharmD
`DMEPA Associate Director:
`Mishale Mistry, PharmD, MPH
`DMEPA Associate Director for
`Quynh Nhu Nguyen, MS
`Human Factors:
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`1
`
`

`

`
`
`•
`
`•
`
`1 REASON FOR REVIEW
`As part of the approval process for BLA 761145 Darzalex Faspro (daratumumab and
`hyaluronidase-xxxx) injection, 1,800 mg and 30,000 units/15 mL), this review evaluates the
`proposed container label, carton labeling, Patient Information, Prescribing Information (PI) Use-
`Related Risk Analysis, and Human Factors (HF) study results for areas that may lead to
`medication errors.
`1.1 PRODUCT BACKGROUND
`Darzalex (daratumumab) approved under BLA 761036 on November 16, 2015 is indicated for
`the treatment of adult patients with multiple myeloma:
`in combination with lenalidomide and dexamethasone in newly diagnosed patients who are
`•
`ineligible for autologous stem cell transplant and in patients with relapsed or refractory
`multiple myeloma who have received at least one prior therapy.
`in combination with bortezomib, melphalan and prednisone in newly diagnosed patients
`who are ineligible for autologous stem cell transplant.
`in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed
`patients who are eligible for autologous stem cell transplant.
`in combination with bortezomib and dexamethasone in patients who have received at least
`one prior therapy.
`in combination with pomalidomide and dexamethasone in patients who have received at
`least two prior therapies including lenalidomide and a proteasome inhibitor.
`• as monotherapy, in patients who have received at least three prior lines of therapy
`including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-
`refractory to a PI and an immunomodulatory agent.
`Darzalex is currently available as 100 mg/5 mL and 400 mg/20 mL single-dose vials for
`intravenous infusion. The recommended dose of Darzalex is 16 mg/kg actual body weight
`according to a dosing schedule (see Appendix A).
`The proposed product, Darzalex Faspro is a co-formulation of the currently approved Darzalex
`
`(daratumumab) and recombinant hyaluronidase. Darzalex Faspro
`is administered as a fixed dose (1,800 mg and 30,000
`units/15 mL) subcutaneously in the abdomen over 3 to 5 minutes (see Appendix A).
`
`•
`
`•
`
`1.2 REGULATORY HISTORY RELATED TO THE PROPOSED PRODUCT’S HUMAN FACTORS
`DEVELOPMENT PROGRAM
`We provided written HF comments to Janssen through a Type C meeting on September 20,
`2016 under IND 125541, recommending they submit a comprehensive risk analysis and plans
`for a HF validation study.
`
`2
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`(b) (4)
`
`

`

`
`
`Subsequently, in a briefing package for a Type C meeting on June 28, 2018a, Janssen submitted
`a CMC Information Amendment which included a clinical product risk assessment.
`We provided additional HF comments to Janssen through a Type C meeting on December 13,
`2018 under IND 125541, reiterating that they submit a comprehensive risk analysis for the
`proposed daratumumab/recombinant human hyaluronidase subcutaneous formulation as a part of
`the BLA submission.
`On August 8, 2019, Janssen submitted a use-related risk analysis, product differentiation and
`label comprehension HF study report, which is the subject of this review.
`
`2 MATERIALS REVIEWED
`We considered the materials listed in Table 1 for this review. The Appendices provide the
`methods and results for each material reviewed.
`Table 1. Materials Considered for this Label and Labeling Review
`Appendix Section
`Material Reviewed
`(for Methods and Results)
`A
`B
`C
`
`Product Information/Prescribing Information
`Previous DMEPA Reviews
`Use-Related Risk Analysis and Human Factors
`Study Report
`ISMP Newsletters*
`FDA Adverse Event Reporting System (FAERS)*
`Other
`Labels and Labeling
`N/A=not applicable for this review
`*We do not typically search FAERS or ISMP Newsletters for our label and labeling reviews
`unless we are aware of medication errors through our routine postmarket safety surveillance
`
`D
`E – N/A
`F- N/A
`G
`
`3 OVERALL ASSESSMENT OF THE MATERIALS REVIEWED
`The sections below provide our evaluation of the summary of the study design, product
`differentiation and label comprehension study results, PI, container label, carton labeling for
`the proposed Darzalex Faspro injection.
`
`a DMEPA was not consulted and did not review the risk assessment at that time.
`
`3
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`

`

`
`
`3.1 SUMMARY OF STUDY DESIGN
`The study design followed a simulated use methodology with the goal to ensure the intended
`users can differentiate between the product presentations, by selecting the correct medication,
`correct dose strength, and identify the correct route of administration. The study also
`evaluated comprehension of the product’s carton labeling, vial label, and PI to assess the user’s
`understanding of dosing and administration procedures. The study included 16 pharmacists/
`pharmacy technicians as well as 16 nurses. The study evaluated two differentiation tasks: 1) A
`pharmacist/pharmacy technician identifies the correct product among the two presentations of
`Darzalex and one presentation of Darzalex Faspro based on a prescription; and 2) a nurse
`verifies the medication supplied by the pharmacy by checking it against the prescription.
`Following the differentiation tasks, all participants completed a label comprehension
`questionnaire assessing the user’s understanding of label and labeling for Darzalex Faspro. For
`any observed errors, the moderator probed for root cause and subjective feedback of the use
`error to determine root cause. We find the overall methodology acceptable.
`
`3.2 ANALYSIS OF PRODUCT DIFFERENTIATION AND LABEL COMPREHENSION STUDY RESULTS
`All participants completed the product differentiation tasks successfully. Table 2 describes the
`errors/close calls/use difficulties observed in the label comprehension study, the Sponsor’s
`reporting of the results and proposed mitigations, and DMEPA’s analyses and
`recommendations.
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`4
`
`

`

`Table 2: Summary and Analyses of Study Results
`
`Tasks (include Number and Description of
`C for critical
`Failures/Use Errors, Close
`and E for
`Calls and Use Difficulties
`essential)
`Question #7
`What should
`you inspect
`the vial
`contents for?
`
`Close calls =6
`Two nurses (P6 and P9), one
`pharmacist (P20), and one
`pharmacy technician (P22)
`provided a partial answer (i.e.
`product color, colorless to
`yellow, etc.) in response to
`the questions.
`Two nurses (P21 and P 24) did
`not understand the question.
`
`Use error= 1
`One pharmacist (P1) provided
`a partial answer.
`
`
`
`Sponsor’s Root Cause Analysis
`
`Sponsor’s Discussion
`of Mitigation
`Strategies
`
`DMEPA’s Analysis and
`Recommendations
`
`Close calls
`Did not understand the question
`(P9)
`After the question was clarified
`answers from these participants
`included particulate matter (P6,
`P20 and P22). Question 7 was
`clarified to, “What should you
`inspect the vial contents for prior
`to injection?”
`The participants provided answers
`based on experience. Participants
`were able to provide the correct
`answer when instructions were
`clarified to base answers on the PI,
`Carton, and Vial.
`Use error
`One participant (P1) initially
`provided a partially correct answer
`to the question which was not
`clarified.
`
`A mitigation strategy We note that lack of inspection of
`was not required as
`the vial contents could result in
`the use errors were
`use of product that has
`primarily due to how
`unacceptable product quality.
`the question was
`Participants were able to state the
`asked. No further
`correct information once the
`changes are required
`question was clarified.
`to improve the
`Our review of Section 2.4
`saliency of the
`Preparation, Storage, and
`information.
`Administration of the PI concluded
`that the information is available as
`it indicates, “Parenteral drug
`products should be inspected
`visually for particulate matter and
`discoloration prior to
`administration, whenever solution
`and container permit. Do not use if
`opaque particles, discoloration or
`other foreign particles are
`present.”
`Inspecting the solution prior to
`administration is considered best
`practice for all products
`
`5
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`

`

`Tasks (include Number and Description of
`C for critical
`Failures/Use Errors, Close
`and E for
`Calls and Use Difficulties
`essential)
`
`
`
`Sponsor’s Root Cause Analysis
`
`Sponsor’s Discussion
`of Mitigation
`Strategies
`
`DMEPA’s Analysis and
`Recommendations
`
`Use error= 1
`One nurse provided the
`incorrect answer (P9)
`
`Question #8
`What material
`of syringe is
`this product
`compatible
`with?
`
`Participant replied “unsure”
`because they were not able to find
`the answer. When shown the
`location of the information, the
`participant said that the content
`was clear.
`
`Current location of
`material compatibility
`in the PI is most
`optimal and similar to
`that for other
`injectable
`prescription drugs.
`No further changes
`are required to
`improve the saliency
`of the information.
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`administered parenterally. We do
`not have any recommendations to
`further mitigate the risk and we
`find the residual risk acceptable.
`Failure to use the proper syringe
`can result in administration of a
`product with degraded quality.
`The participant provided an
`incorrect answer because they
`were unable to find the
`information. However, once
`shown the information, they
`understood the content.
`Our review of Section 2.4
`Preparation, Storage, and
`Administration of the PI concluded
`that compatibility information is
`available as it indicates,
`“DARZALEX Faspro is compatible
`with polypropylene or
`polyethylene syringe material;
`polypropylene, polyethylene, or
`polyvinyl chloride (PVC)
`subcutaneous infusion sets; and
`stainless steel transfer and
`
`6
`
`

`

`Tasks (include Number and Description of
`C for critical
`Failures/Use Errors, Close
`and E for
`Calls and Use Difficulties
`essential)
`
`
`
`Sponsor’s Root Cause Analysis
`
`Sponsor’s Discussion
`of Mitigation
`Strategies
`
`DMEPA’s Analysis and
`Recommendations
`
`Question #9
`What material
`of winged
`infusion set is
`this product
`compatible
`with?
`
`Use errors= 2
`One nurse (P9) provided the
`incorrect answer.
`One pharmacy technician did
`not provide an answer (P23).
`
`One participant (P9) provided
`incorrect answer (“polypropylene
`barrel with polypropylene or
`polyethylene plunger”) because
`they could not locate the correct
`information (“PVC”). When shown
`the location of the correct
`information, the participant said
`that the content was clear.
`Another participant (P23) could
`not find the information. When
`shown the location of the
`information, the participant said
`that the content was clear.
`
`Current location of
`material compatibility
`in the PI is most
`optimal and similar to
`that for other
`injectable
`prescription drugs.
`No further changes
`are required to
`improve the saliency
`of the information.
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`injection needles.” Based on the
`root cause analysis and subjective
`feedback, we recommend
`including a sub-heading,
`“Preparation” to bring prominence
`to the preparation instructions.
`This may help to minimize the risk
`for this instruction being
`overlooked.
`Failure to use the correct infusion
`set may result in administration of
`a product with degraded quality.
`We note that participants
`provided incorrect answers
`because they were unable to find
`the information. However, once
`shown the information, they
`understood the content.
`Our review of Section 2.4
`Preparation, Storage, and
`Administration of the PI concluded
`that compatibility information is
`available as it indicates,
`“DARZALEX Faspro is compatible
`with polypropylene or
`
`7
`
`

`

`Tasks (include Number and Description of
`C for critical
`Failures/Use Errors, Close
`and E for
`Calls and Use Difficulties
`essential)
`
`
`
`Sponsor’s Root Cause Analysis
`
`Sponsor’s Discussion
`of Mitigation
`Strategies
`
`DMEPA’s Analysis and
`Recommendations
`
`polyethylene syringe material;
`polypropylene, polyethylene, or
`polyvinyl chloride (PVC)
`subcutaneous infusion sets; and
`stainless steel transfer and
`injection needles.” Based on the
`root cause analysis and subjective
`feedback, we recommend
`including a sub-heading,
`“Preparation” to bring prominence
`to the preparation instructions.
`This may help to minimize the risk
`for this instruction being
`overlooked.
`Failure to properly store the
`product may result in
`administration of a product with
`degraded quality. One participant
`was able to state the correct
`information once the question was
`clarified. The other participant
`was unable to find the
`information. However, once
`shown the information, they
`understood the content.
`
`8
`
`Question #10
`How long can
`the product
`be stored at
`ambient
`temperature
`after transfer
`to the
`syringe?
`
`Close call = 1
`One nurse (P2) did not
`understand the question.
`
`Use error=1
`One nurse (P27) did not
`provide an answer.
`
`Close call
`One participant (P2) responded
`“24 hours” and asked for further
`clarification of the question.
`Question was clarified to mean
`time period “after transfer to the
`syringe”. With this clarification,
`participant provided correct
`answer (“4 hours”).
`
`Per feedback from
`study participants to
`improve flow of
`information in section
`2.4 of the PI, storage
`information was
`relocated to precede
`the Administration
`section. This update
`is minor and does not
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`

`

`Tasks (include Number and Description of
`C for critical
`Failures/Use Errors, Close
`and E for
`Calls and Use Difficulties
`essential)
`
`
`
`Sponsor’s Root Cause Analysis
`
`Use error
`Another participant (P27) left the
`answer blank because they could
`not find the answer. When shown
`the location of the answer, the
`participant said that the content
`was clear but suggested that
`information be moved to precede
`the Administration” steps.
`
`Sponsor’s Discussion
`of Mitigation
`Strategies
`
`require further
`validation.
`
`Question #11 Use errors= 4
`What can be
`Two nurses (P31 and N6), one
`done to
`pharmacist (P1), and one
`prevent
`pharmacy technician (P23)
`clogging?
`provided an incorrect answer.
`
`One participant (P1) provided
`“Equilibrate to ambient
`temperature”.
`
`One participant (N6) responded
`with “Pause or slow down delivery
`for pain or 2nd site”.
`
`Per feedback from
`study participants to
`improve flow of
`information in section
`2.4 of the PI,
`information about
`what to do if the
`needle clogged was
`relocated to precede
`the Administration
`section. This update
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`DMEPA’s Analysis and
`Recommendations
`
`Our review of Section 2.4
`Preparation, Storage, and
`Administration of the PI concluded
`that information is available as it
`indicates, “If the syringe
`containing DARZALEX Faspro is not
`used immediately, store the
`DARZALEX Faspro solution for up
`to 4 hours at ambient temperature
`and ambient light.” We do not
`have any recommendations to
`mitigate the risk for this use error
`and we find the residual risk
`acceptable.
`Failure to prevent clogging may
`result in no dose or delay in dose
`administration if the syringe clogs.
`We note that participants
`provided incorrect answers
`because they were unable to find
`the information. One participant
`stated this instruction was not
`where they expected it because it
`was buried after a sentence of a
`different topic. However, once
`
`9
`
`

`

`Tasks (include Number and Description of
`C for critical
`Failures/Use Errors, Close
`and E for
`Calls and Use Difficulties
`essential)
`
`Sponsor’s Discussion
`of Mitigation
`Strategies
`
`is minor and does not
`require further
`validation.
`
`
`
`Sponsor’s Root Cause Analysis
`
`Another participant (P23)
`responded “Never redraw”.
`One participant P31 responded
`“Administer over 3-5 minutes, do
`not freeze, or let sit for more than
`4 hours”.
`All participants (P1, N6, P23, P31)
`did not notice instructions to
`attach needle or infusion set
`immediately prior to injection.
`P23 stated that this instruction
`was not where they expected it; it
`was buried after a sentence of a
`different topic and was not
`noticed. When shown the location
`of the information, all participants
`understood the information.
`
`DMEPA’s Analysis and
`Recommendations
`
`shown the information, they
`understood the content.
`Per feedback from the study
`participants, the Applicant
`relocated the statement, “To avoid
`needle clogging, attach the
`hypodermic injection needle or
`subcutaneous infusion set to the
`syringe immediately prior to
`injection.” to precede the
`Administration section (in the
`“Preparation” section).
`Our review of Section 2.4
`Preparation, Storage, and
`Administration of the PI conclude
`this information has been
`relocated to precede the
`administration section.
`The Applicant determined that this
`change can be implemented
`without further validation. Based
`on our post marketing experience
`with similar products, we agree
`with the Applicant’s mitigation
`
`10
`
`
`
`Reference ID: 4548924Reference ID: 4753174
`
`

`

`Tasks (include Number and Description of
`C for critical
`Failures/Use Errors, Close
`and E for
`Calls and Use Difficulties
`essential)
`
`Question #15 Use errors= 2
`How should
`One pharmacist (P20) and
`you dispose of
`one pharmacy technician
`waste
`(P23) provided an incorrect
`material?
`answer.
`
`
`
`Sponsor’s Root Cause Analysis
`
`Sponsor’s Discussion
`of Mitigation
`Strategies
`
`DMEPA’s Analysis and
`Recommendations
`
`Both participants were unable to
`locate information on how to
`dispose of waste material. P20
`responded with “chemo waste”
`and P23 responded red/blue bin”
`per their facility regulations. When
`shown the location of the
`information, both participants
`understood the information but
`indicated that it was not where
`they expected; it was at the end of
`the entire section with no header.
`
`Current location of
`disposal instructions
`in the PI is most
`optimal. No further
`changes are required
`to improve the
`saliency of the
`information.
`
`strategy. We do not have any
`recommendations to further
`mitigate the risk and we find the
`residual risk acceptable.
`Failure to dispose of waste
`material appropriately may result
`in improper disposal of the
`product. We note that
`participants provided incorrect
`answers because they were unable
`to find the information. However,
`once shown the information, they
`understood the content.
`Our review of Section 2.4
`Preparation, Storage, and
`Administration of the PI concluded
`that disposal information is
`available as it indicates, “Any
`waste material should be disposed
`in accordance with local
`requ