83 FR 47623 - Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing; Guidance for Industry and Food and Drug Administration Staff; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 183 (September 20, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 183 (September 20, 2018)
| Page Range | 47623-47625 | |
| FR Document | 2018-20472 |
[Federal Register Volume 83, Number 183 (Thursday, September 20, 2018)] [Notices] [Pages 47623-47625] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-20472] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2015-D-2167] Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing; Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance entitled ``Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing.'' The United States Pharmacopeia (USP) drug substance monograph for Heparin Sodium, and drug product monographs for Heparin Lock Flush Solution and Heparin Sodium Injection, recently have undergone several revisions following serious and fatal events related to the use of heparin sodium products. Investigation of heparin product overdose errors identified the expression of drug strength in the labels as a major contributing factor in these errors. This guidance document addresses these safety concerns by clarifying new expectations for labeling with regard to the revised heparin USP monographs, as well as outlining safety testing recommendations. DATES: The announcement of the guidance is published in the Federal Register on September 20, 2018. ADDRESSES: You may submit either electronic or written comments on Agency guidances at any time as follows: Electronic Submissions Submit electronic comments in the following way:Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your [[Page 47624]] comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov. If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ``Written/Paper Submissions'' and ``Instructions''). Written/Paper Submissions Submit written/paper submissions as follows: Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ``Instructions.'' Instructions: All submissions received must include the Docket No. FDA-2015-D-2167 for ``Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing.'' Received comments will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday. Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ``confidential.'' Any information marked as ``confidential'' will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.thefederalregister.org/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)). An electronic copy of the guidance document is available for download from the internet. See the SUPPLEMENTARY INFORMATION section for information on electronic access to the guidance. Submit written requests for a single hard copy of the guidance document entitled ``Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing'' to the Office of the Center Director, Guidance and Policy Development, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5431, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your request. FOR FURTHER INFORMATION CONTACT: Andrew Yeatts, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 1643, Silver Spring, MD 20993-0002, 301-796-4539. SUPPLEMENTARY INFORMATION: I. Background The USP \1\ heparin monographs have recently undergone several revisions following serious and fatal events related to the use of heparin sodium products. Investigation of heparin product overdose errors identified the expression of drug strength in the labels as a major contributing factor in these errors. This guidance document addresses these safety concerns by clarifying new expectations for labeling with regard to the revised heparin USP monographs, as well as outlining safety testing recommendations. --------------------------------------------------------------------------- \1\ USP is a scientific nonprofit organization that develops standards for the identity, strength, quality, and purity of drugs and drug ingredients marketed in the United States. These standards are published in USP's official compendia, U.S. Pharmacopeia and National Formulary. --------------------------------------------------------------------------- In addition, the outbreak of serious and often fatal events due to heparin contamination with over-sulfated chondroitin sulfate in 2008 led the USP to include in its monograph additional testing of heparin source material to ensure its quality and purity. This guidance also outlines use of conformance to the monograph in premarket submissions, specifically testing and documentation requirements and/or recommendations contained in the current USP monographs and the guidance document ``Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for Quality'' (https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291390.pdf).\2\ --------------------------------------------------------------------------- \2\ The Agency updates guidances periodically. To make sure you have the most recent version of this guidance, check the FDA guidance page at https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. --------------------------------------------------------------------------- FDA considered comments received on the draft guidance that appeared in the Federal Register of July 9, 2015 (80 FR 39440). FDA revised the guidance as appropriate in response to the comments. II. Significance of Guidance This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the current thinking of FDA on ``Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing.'' It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. This guidance is not subject to Executive Order 12866. III. Electronic Access Persons interested in obtaining a copy of the guidance may do so by downloading an electronic copy from the internet. A search capability for all Center for Devices and Radiological Health guidance documents is available at https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. This [[Page 47625]] guidance is also available at https://www.regulations.gov. Persons unable to download an electronic copy of ``Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing'' may send an email request to CDRH-Guidance@fda.hhs.gov to receive an electronic copy of the document. Please use the document number 1817 to identify the guidance you are requesting. IV. Paperwork Reduction Act of 1995 This guidance refers to previously approved collections of information. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collections of information in the following FDA regulations and guidance have been approved by OMB as listed in the following table: ------------------------------------------------------------------------ 21 CFR part; guidance; or FDA OMB control form Topic No. ------------------------------------------------------------------------ 211............................ Current good 0910-0139 manufacturing practice for finished pharmaceuticals. 807, subpart E................. Premarket notification. 0910-0120 814, subparts A through E...... Premarket approval..... 0910-0231 814, subpart H................. Humanitarian Device 0910-0332 Exemption. 812............................ Investigational Device 0910-0078 Exemption. ``De Novo Classification De Novo classification 0910-0844 Process (Evaluation of process. Automatic Class III Designation)''. 801............................ Medical Device Labeling 0910-0485 Regulations. 803............................ Medical Devices; 0910-0437 Medical Device Reporting; Manufacturer reporting, importer reporting, user facility reporting, distributor reporting. 820............................ Quality System (QS) 0910-0073 Regulation. ------------------------------------------------------------------------ Dated: September 17, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-20472 Filed 9-19-18; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 83, No. 183 / Thursday, September 20, 2018 / Notices 47623
SUPPLEMENTARY INFORMATION: November 27, 2019, and November 27, Dated: September 14, 2018.
2020, respectively. Leslie Kux,
I. Background In section 582(a)(5)(A) of the FD&C Associate Commissioner for Policy.
FDA is announcing the availability of Act, Congress directed FDA to issue [FR Doc. 2018–20503 Filed 9–19–18; 8:45 am]
a guidance for industry entitled guidance specifying ‘‘whether and BILLING CODE 4164–01–P
‘‘Grandfathering Policy for Packages and under what circumstances product that
Homogenous Cases of Product Without is not labeled with a product identifier
a Product Identifier.’’ On November 27, and that is in the pharmaceutical supply DEPARTMENT OF HEALTH AND
2013, the Drug Supply Chain Security chain at the time at the time of the HUMAN SERVICES
Act (DSCSA) (Title II of Pub. L. 113–54) effective date of the requirements of
was signed into law. Section 202 of the [section 582] shall be exempted’’ from Food and Drug Administration
DSCSA added section 582 to the FD&C the product tracing requirements [Docket No. FDA–2015–D–2167]
Act (21 U.S.C. 360eee–1), which discussed previously. The guidance
established product tracing addresses this requirement. As Heparin-Containing Medical Devices
requirements for manufacturers, explained in the guidance, only and Combination Products:
repackagers, wholesale distributors, and packages and homogenous cases of Recommendations for Labeling and
dispensers. The DSCSA phases in its product that are in the pharmaceutical Safety Testing; Guidance for Industry
requirements over a 10-year period. distribution supply chain at the time of and Food and Drug Administration
A critical set of phased product the effective date of the requirements of Staff; Availability
tracing requirements outlined in section section 582 are eligible for
582 of the FD&C Act relates to the grandfathering under section AGENCY: Food and Drug Administration,
product identifier. Among its 582(a)(5)(A) of the FD&C Act. HHS.
provisions, section 582 of the FD&C Act In the Federal Register of November ACTION: Notice of availability.
requires that each package and 27, 2017 (82 FR 56033), FDA issued a
homogenous case of product in the notice announcing the availability of the SUMMARY: The Food and Drug
pharmaceutical distribution supply draft version of this guidance. The Administration (FDA or Agency) is
chain bear a product identifier that is comment period for the draft guidance announcing the availability of a final
encoded with the product’s ended January 26, 2018. FDA received guidance entitled ‘‘Heparin-Containing
standardized numerical identifier, lot approximately 10 comments on the draft Medical Devices and Combination
number, and expiration date by specific guidance. In response to received Products: Recommendations for
dates. Under the statute, manufacturers comments or on its own initiative, FDA Labeling and Safety Testing.’’ The
were required to begin affixing or made several changes. The most United States Pharmacopeia (USP) drug
imprinting a product identifier to each significant change FDA made was to substance monograph for Heparin
package and homogenous case of a revise the grandfathering exemption to Sodium, and drug product monographs
product intended to be introduced into include products repackaged by a for Heparin Lock Flush Solution and
commerce no later than November 27, repackager before November 27, 2018. Heparin Sodium Injection, recently have
2017. Repackagers are required to do the FDA made this change in response to undergone several revisions following
same no later than November 27, 2018. comments indicating that repackagers serious and fatal events related to the
Sections 582(c)(2), (d)(2), and will need time beyond November 27, use of heparin sodium products.
(e)(2)(A)(iii) of the FD&C Act restrict 2018, to sell such product. In addition, Investigation of heparin product
trading partners’ ability to engage in FDA made editorial and formatting overdose errors identified the
transactions involving packages and changes to improve clarity. expression of drug strength in the labels
homogenous cases of product that are This guidance is being issued as a major contributing factor in these
not labeled with a product identifier consistent with FDA’s good guidance errors. This guidance document
after specific dates. Beginning practices regulation (21 CFR 10.115). addresses these safety concerns by
November 27, 2018, repackagers may The guidance represents the current clarifying new expectations for labeling
not engage in a transaction involving a thinking of FDA on ‘‘Grandfathering with regard to the revised heparin USP
package or homogenous case of a Policy for Packages and Homogenous monographs, as well as outlining safety
product that is not encoded with a Cases of Product Without a Product testing recommendations.
product identifier. Similar restrictions Identifier.’’ It does not establish any DATES: The announcement of the
go into effect for wholesale distributors rights for any person and, with the guidance is published in the Federal
and dispensers on November 27, 2019, exception of specified material in Register on September 20, 2018.
and November 27, 2020, respectively. section IV, is not binding on FDA or the ADDRESSES: You may submit either
In addition, section 582 of the FD&C public. You can use an alternative electronic or written comments on
Act requires trading partners to verify approach if it satisfies the requirements Agency guidances at any time as
product identifiers on packages and of the applicable statutes and follows:
homogenous cases starting on November regulations. This guidance is not subject
27, 2017, for manufacturers (section to Executive Order 12866. Electronic Submissions
582(b)(4)); on November 27, 2019, for Submit electronic comments in the
wholesale distributors (section II. Electronic Access following way:
582(c)(4)); on November 27, 2020, for Persons with access to the internet • Federal eRulemaking Portal:
dispensers (section 582(d)(4)); and on may obtain the guidance at https:// https://www.regulations.gov. Follow the
amozie on DSK3GDR082PROD with NOTICES1
November 27, 2018, for repackagers www.fda.gov/Drugs/Guidance instructions for submitting comments.
(section 582(e)(4)). Manufacturers, ComplianceRegulatoryInformation/ Comments submitted electronically,
repackagers, wholesale distributors, and Guidances/default.htm, https:// including attachments, to https://
dispensers are also required to verify the www.fda.gov/BiologicsBloodVaccines/ www.regulations.gov will be posted to
product identifier of a saleable returned GuidanceComplianceRegulatory the docket unchanged. Because your
package or sealed homogenous case on Information/Guidances/default.htm, or comment will be made public, you are
November 27, 2017, November 27, 2018, https://www.regulations.gov. solely responsible for ensuring that your
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![Federal Register / Vol. 83, No. 183 / Thursday, September 20, 2018 / Notices 47625
guidance is also available at https:// to receive an electronic copy of the subject to review by the Office of
www.regulations.gov. Persons unable to document. Please use the document Management and Budget (OMB) under
download an electronic copy of number 1817 to identify the guidance the Paperwork Reduction Act of 1995
‘‘Heparin-Containing Medical Devices you are requesting. (44 U.S.C. 3501–3520). The collections
and Combination Products: IV. Paperwork Reduction Act of 1995 of information in the following FDA
Recommendations for Labeling and regulations and guidance have been
This guidance refers to previously
Safety Testing’’ may send an email approved by OMB as listed in the
approved collections of information.
request to CDRH-Guidance@fda.hhs.gov following table:
These collections of information are
OMB
21 CFR part; guidance; or FDA form Topic control No.
211 ..................................................................... Current good manufacturing practice for finished pharmaceuticals ................... 0910–0139
807, subpart E ................................................... Premarket notification ......................................................................................... 0910–0120
814, subparts A through E ................................ Premarket approval ............................................................................................. 0910–0231
814, subpart H ................................................... Humanitarian Device Exemption ......................................................................... 0910–0332
812 ..................................................................... Investigational Device Exemption ....................................................................... 0910–0078
‘‘De Novo Classification Process (Evaluation of De Novo classification process ........................................................................... 0910–0844
Automatic Class III Designation)’’.
801 ..................................................................... Medical Device Labeling Regulations ................................................................. 0910–0485
803 ..................................................................... Medical Devices; Medical Device Reporting; Manufacturer reporting, importer 0910–0437
reporting, user facility reporting, distributor reporting.
820 ..................................................................... Quality System (QS) Regulation ......................................................................... 0910–0073
Dated: September 17, 2018. Electronic Submissions information submitted, marked and
Leslie Kux, Submit electronic comments in the identified, as confidential, if submitted
Associate Commissioner for Policy. following way: as detailed in ‘‘Instructions.’’
[FR Doc. 2018–20472 Filed 9–19–18; 8:45 am] • Federal eRulemaking Portal: Instructions: All submissions received
BILLING CODE 4164–01–P https://www.regulations.gov. Follow the must include the Docket No. FDA–
instructions for submitting comments. 2017–D–2232 for ‘‘Product Identifier
Comments submitted electronically, Requirements Under the Drug Supply
DEPARTMENT OF HEALTH AND including attachments, to https:// Chain Security Act—Compliance
HUMAN SERVICES www.regulations.gov will be posted to Policy.’’ Received comments will be
the docket unchanged. Because your placed in the docket and, except for
Food and Drug Administration comment will be made public, you are those submitted as ‘‘Confidential
solely responsible for ensuring that your Submissions,’’ publicly viewable at
[Docket No. FDA–2017–D–2232]
comment does not include any https://www.regulations.gov or at the
Product Identifier Requirements Under confidential information that you or a Dockets Management Staff between 9
the Drug Supply Chain Security Act— third party may not wish to be posted, a.m. and 4 p.m., Monday through
Compliance Policy; Guidance for such as medical information, your or Friday.
anyone else’s Social Security number, or • Confidential Submissions—To
Industry; Availability
confidential business information, such submit a comment with confidential
AGENCY: Food and Drug Administration, information that you do not wish to be
as a manufacturing process. Please note
HHS. made publicly available, submit your
that if you include your name, contact
ACTION: Notice of availability. information, or other information that comments only as a written/paper
identifies you in the body of your submission. You should submit two
SUMMARY: The Food and Drug copies total. One copy will include the
Administration (FDA or Agency) is comments, that information will be
posted on https://www.regulations.gov. information you claim to be confidential
announcing the availability of a final with a heading or cover note that states
guidance for industry entitled ‘‘Product • If you want to submit a comment
with confidential information that you ‘‘THIS DOCUMENT CONTAINS
Identifier Requirements Under the Drug CONFIDENTIAL INFORMATION.’’ The
Supply Chain Security Act— do not wish to be made available to the
public, submit the comment as a Agency will review this copy, including
Compliance Policy.’’ This guidance the claimed confidential information, in
describes FDA’s intention with regard to written/paper submission and in the
manner detailed (see ‘‘Written/Paper its consideration of comments. The
enforcement of the Drug Supply Chain second copy, which will have the
Security Act (DSCSA) provision Submissions’’ and ‘‘Instructions’’).
claimed confidential information
requiring manufacturers to begin Written/Paper Submissions redacted/blacked out, will be available
affixing or imprinting product Submit written/paper submissions as for public viewing and posted on
identifiers on their products beginning follows: https://www.regulations.gov. Submit
November 27, 2017. This guidance • Mail/Hand delivery/Courier (for both copies to the Dockets Management
finalizes the draft guidance issued on written/paper submissions): Dockets Staff. If you do not wish your name and
amozie on DSK3GDR082PROD with NOTICES1
July 3, 2017. Management Staff (HFA–305), Food and contact information to be made publicly
DATES: The announcement of the Drug Administration, 5630 Fishers available, you can provide this
guidance is published in the Federal Lane, Rm. 1061, Rockville, MD 20852. information on the cover sheet and not
Register on September 20, 2018. • For written/paper comments in the body of your comments and you
ADDRESSES: You may submit either submitted to the Dockets Management must identify this information as
electronic or written comments on Staff, FDA will post your comment, as ‘‘confidential.’’ Any information marked
Agency Guidance at any time as follows: well as any attachments, except for as ‘‘confidential’’ will not be disclosed
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Document Created: 2018-09-20 02:09:11
Document Modified: 2018-09-20 02:09:11
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice of availability. | |
| Dates | The announcement of the guidance is published in the Federal Register on September 20, 2018. | |
| Contact | Andrew Yeatts, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 1643, Silver Spring, MD 20993-0002, 301-796-4539. | |
| FR Citation | 83 FR 47623 |
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