81 FR 43211 - Elemental Impurities in Drug Products; Draft Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 81, Issue 127 (July 1, 2016)
Food and Drug Administration
Federal Register Volume 81, Issue 127 (July 1, 2016)
| Page Range | 43211-43212 | |
| FR Document | 2016-15704 |
[Federal Register Volume 81, Number 127 (Friday, July 1, 2016)] [Notices] [Pages 43211-43212] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2016-15704] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2016-D-1692] Elemental Impurities in Drug Products; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS.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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Elemental Impurities in Drug Products.'' This draft guidance provides recommendations regarding the control of elemental impurities of human drug products marketed in the United States consistent with implementation of International Council for Harmonisation (ICH) guidance for industry ``Q3D Elemental Impurities.'' This draft guidance will also assist manufacturers of compendial drug products in responding to the issuance of the United States Pharmacopeia (USP) requirement for the control of elemental impurities. DATES: Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by August 30, 2016. ADDRESSES: You may submit comments as follows: Electronic Submissions Submit electronic comments in the following way:Federal eRulemaking Portal: http://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to http://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 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 http://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): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Division of Dockets Management, 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.'' [[Page 43212]] Instructions: All submissions received must include the Docket No. FDA-2016-D-1692 for Elemental Impurities in Drug Products. Received comments will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management 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 http://www.regulations.gov. Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002; or the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document. FOR FURTHER INFORMATION CONTACT: John Kauffman, Center for Drug Evaluation and Research (HFD-920), Food and Drug Administration, 645 S. Newstead Ave., St. Louis, MO 63110, 314-539-2168; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911. SUPPLEMENTARY INFORMATION: I. Background FDA is announcing the availability of a draft guidance for industry entitled ``Elemental Impurities in Drug Products.'' This draft guidance provides recommendations regarding the control of elemental impurities of human drug products marketed in the United States consistent with implementation of ICH Q3D. The draft guidance will also assist manufacturers of compendial drug products in responding to the issuance of the USP requirement for the control of elemental impurities. USP introduced new limits and analytical procedures for elemental impurities in General Chapters Elemental Impurities--Limits and Elemental Impurities--Procedures. Their primary goals are to (1) set limits for acceptable levels of elemental impurities in finished drug products, and (2) update the methodology used to test for elemental impurities in drug products to include modern analytical procedures. ICH Q3D contains recommendations for manufacturers of human drugs and biologics on applying a risk-based approach to control elemental impurities and permitted daily exposure. USP worked closely with ICH to align its new General Chapters with ICH Q3D. Because elemental impurities pose toxicological concerns and do not provide any therapeutic benefit to the patient, their levels in drug products should be controlled within acceptable limits. In general, FDA recommends that the manufacturer of any U.S. marketed drug product follow ICH Q3D recommendations to establish appropriate procedures for identifying and controlling elemental impurities in the drug product based on risk assessment and product-specific considerations, unless the drug product must comply with USP-NF requirements. This draft guidance outlines approaches for implementation of USP, and ICH Q3D in new and existing products. This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA on elemental impurities in drug products. 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. II. The Paperwork Reduction Act of 1995 This draft guidance refers to previously approved collections of information that 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 21 CFR part 314 for submitting NDAs and ANDAs, including supplemental applications and annual reports, have been approved under OMB control number 0910-0001. The collections of information in 21 CFR part 211 and part 212 (CGMPs) have been approved under OMB control numbers 0910-0139 and 0910-0667. III. Electronic Access Persons with access to the Internet may obtain the document at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or http://www.regulations.gov. Dated: June 27, 2016. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2016-15704 Filed 6-30-16; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 81, No. 127 / Friday, July 1, 2016 / Notices 43211
with a heading or cover note that states development, phase 3 trial consistent with implementation of
‘‘THIS DOCUMENT CONTAINS considerations, and safety International Council for Harmonisation
CONFIDENTIAL INFORMATION.’’ The considerations in the development of (ICH) guidance for industry ‘‘Q3D
Agency will review this copy, including antiviral drug products used to treat or Elemental Impurities.’’ This draft
the claimed confidential information, in prevent recurrent herpes labialis guidance will also assist manufacturers
its consideration of comments. The lesions. of compendial drug products in
second copy, which will have the This draft guidance is being issued responding to the issuance of the United
claimed confidential information consistent with FDA’s good guidance States Pharmacopeia (USP) requirement
redacted/blacked out, will be available practices regulation (21 CFR 10.115). for the control of elemental impurities.
for public viewing and posted on http:// The draft guidance, when finalized, will DATES: Although you can comment on
www.regulations.gov. Submit both represent the current thinking of FDA any guidance at any time (see 21 CFR
copies to the Division of Dockets on developing drugs for the treatment 10.115(g)(5)), to ensure that the Agency
Management. If you do not wish your and prevention of recurrent herpes considers your comment on this draft
name and contact information to be labialis. It does not establish any rights guidance before it begins work on the
made publicly available, you can for any person and is not binding on final version of the guidance, submit
provide this information on the cover FDA or the public. You can use an either electronic or written comments
sheet and not in the body of your alternative approach if it satisfies the on the draft guidance by August 30,
comments and you must identify this requirements of the applicable statutes 2016.
information as ‘‘confidential.’’ Any and regulations. ADDRESSES: You may submit comments
information marked as ‘‘confidential’’ II. The Paperwork Reduction Act of as follows:
will not be disclosed except in 1995
accordance with 21 CFR 10.20 and other Electronic Submissions
applicable disclosure law. For more This guidance refers to previously Submit electronic comments in the
information about FDA’s posting of approved collections of information that following way:
comments to public dockets, see 80 FR are subject to review by the Office of • Federal eRulemaking Portal: http://
56469, September 18, 2015, or access Management and Budget (OMB) under www.regulations.gov. Follow the
the information at: http://www.fda.gov/ the Paperwork Reduction Act of 1995 instructions for submitting comments.
regulatoryinformation/dockets/ (44 U.S.C. 3501–3520). The collections Comments submitted electronically,
default.htm. of information in 21 CFR part 312 have including attachments, to http://
Docket: For access to the docket to been approved under OMB control www.regulations.gov will be posted to
read background documents or the number 0910–0014. the docket unchanged. Because your
electronic and written/paper comments III. Electronic Access comment will be made public, you are
received, go to http:// solely responsible for ensuring that your
Persons with access to the Internet comment does not include any
www.regulations.gov and insert the
may obtain the draft guidance at either confidential information that you or a
docket number, found in brackets in the
http://www.fda.gov/Drugs/Guidance third party may not wish to be posted,
heading of this document, into the
ComplianceRegulatoryInformation/ such as medical information, your or
‘‘Search’’ box and follow the prompts
Guidances/default.htm or http:// anyone else’s Social Security number, or
and/or go to the Division of Dockets
www.regulations.gov. confidential business information, such
Management, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. Dated: June 27, 2016. as a manufacturing process. Please note
Submit written requests for single Leslie Kux, that if you include your name, contact
copies of the draft guidance to the Associate Commissioner for Policy. information, or other information that
Division of Drug Information, Center for [FR Doc. 2016–15698 Filed 6–30–16; 8:45 am] identifies you in the body of your
Drug Evaluation and Research, Food BILLING CODE 4164–01–P
comments, that information will be
and Drug Administration, 10001 New posted on http://www.regulations.gov.
Hampshire Ave., Hillandale Building, • If you want to submit a comment
4th Floor, Silver Spring, MD 20993– DEPARTMENT OF HEALTH AND with confidential information that you
0002. Send one self-addressed adhesive HUMAN SERVICES do not wish to be made available to the
label to assist that office in processing public, submit the comment as a
your requests. See the SUPPLEMENTARY Food and Drug Administration written/paper submission and in the
INFORMATION section for electronic manner detailed (see ‘‘Written/Paper
[Docket No. FDA–2016–D–1692]
access to the draft guidance document. Submissions’’ and ‘‘Instructions’’).
FOR FURTHER INFORMATION CONTACT: Elemental Impurities in Drug Products; Written/Paper Submissions
Regina Alivisatos, Center for Drug Draft Guidance for Industry;
Submit written/paper submissions as
Evaluation and Research, Food and Availability
follows:
Drug Administration, 10903 New AGENCY: Food and Drug Administration, • Mail/Hand delivery/Courier (for
Hampshire Ave., Bldg. 22, Rm. 6340, HHS. written/paper submissions): Division of
Silver Spring, MD 20993–0002, 301– ACTION: Notice of availability. Dockets Management (HFA–305), Food
796–1500. and Drug Administration, 5630 Fishers
SUMMARY: The Food and Drug
asabaliauskas on DSK3SPTVN1PROD with NOTICES
SUPPLEMENTARY INFORMATION: Lane, Rm. 1061, Rockville, MD 20852.
Administration (FDA or Agency) is • For written/paper comments
I. Background announcing the availability of a draft submitted to the Division of Dockets
FDA is announcing the availability of guidance for industry entitled Management, FDA will post your
a draft guidance for industry entitled ‘‘Elemental Impurities in Drug comment, as well as any attachments,
‘‘Recurrent Herpes Labialis: Developing Products.’’ This draft guidance provides except for information submitted,
Drugs for Treatment and Prevention.’’ recommendations regarding the control marked and identified, as confidential,
This guidance addresses nonclinical of elemental impurities of human drug if submitted as detailed in
development, early phases of clinical products marketed in the United States ‘‘Instructions.’’
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![43212 Federal Register / Vol. 81, No. 127 / Friday, July 1, 2016 / Notices
Instructions: All submissions received Food and Drug Administration, 10903 must comply with USP–NF
must include the Docket No. FDA– New Hampshire Ave., Bldg. 71, Rm. requirements. This draft guidance
2016–D–1692 for Elemental Impurities 3128, Silver Spring, MD 20993–0002. outlines approaches for implementation
in Drug Products. Received comments Send one self-addressed adhesive label of USP, and ICH Q3D in new and
will be placed in the docket and, except to assist that office in processing your existing products.
for those submitted as ‘‘Confidential requests. See the SUPPLEMENTARY This draft guidance is being issued
Submissions,’’ publicly viewable at INFORMATION section for electronic consistent with FDA’s good guidance
http://www.regulations.gov or at the access to the draft guidance document. practices regulation (21 CFR 10.115).
Division of Dockets Management FOR FURTHER INFORMATION CONTACT: John The draft guidance, when finalized, will
between 9 a.m. and 4 p.m., Monday Kauffman, Center for Drug Evaluation represent the current thinking of FDA
through Friday. and Research (HFD–920), Food and on elemental impurities in drug
• Confidential Submissions—To Drug Administration, 645 S. Newstead products. It does not establish any rights
submit a comment with confidential Ave., St. Louis, MO 63110, 314–539– for any person and is not binding on
information that you do not wish to be 2168; or Stephen Ripley, Center for FDA or the public. You can use an
made publicly available, submit your Biologics Evaluation and Research, alternative approach if it satisfies the
comments only as a written/paper Food and Drug Administration, 10903 requirements of the applicable statutes
submission. You should submit two New Hampshire Ave., Bldg. 71, Rm. and regulations.
copies total. One copy will include the 7301, Silver Spring, MD 20993–0002,
information you claim to be confidential II. The Paperwork Reduction Act of
240–402–7911. 1995
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS SUPPLEMENTARY INFORMATION:
This draft guidance refers to
CONFIDENTIAL INFORMATION’’. The I. Background previously approved collections of
Agency will review this copy, including information that are subject to review by
FDA is announcing the availability of
the claimed confidential information, in the Office of Management and Budget
its consideration of comments. The a draft guidance for industry entitled
‘‘Elemental Impurities in Drug (OMB) under the Paperwork Reduction
second copy, which will have the Act of 1995 (44 U.S.C. 3501–3520). The
claimed confidential information Products.’’ This draft guidance provides
recommendations regarding the control collections of information in 21 CFR
redacted/blacked out, will be available part 314 for submitting NDAs and
for public viewing and posted on http:// of elemental impurities of human drug
products marketed in the United States ANDAs, including supplemental
www.regulations.gov. Submit both applications and annual reports, have
copies to the Division of Dockets consistent with implementation of ICH
Q3D. The draft guidance will also assist been approved under OMB control
Management. If you do not wish your number 0910–0001. The collections of
name and contact information to be manufacturers of compendial drug
products in responding to the issuance information in 21 CFR part 211 and part
made publicly available, you can 212 (CGMPs) have been approved under
provide this information on the cover of the USP requirement for the control
of elemental impurities. OMB control numbers 0910–0139 and
sheet and not in the body of your 0910–0667.
comments and you must identify this USP introduced new limits and
information as ‘‘confidential.’’ Any analytical procedures for elemental III. Electronic Access
information marked as ‘‘confidential’’ impurities in General Chapters
Elemental Impurities—Limits and Persons with access to the Internet
will not be disclosed except in may obtain the document at http://www.
accordance with 21 CFR 10.20 and other Elemental Impurities—Procedures.
Their primary goals are to (1) set limits fda.gov/Drugs/GuidanceCompliance
applicable disclosure law. For more RegulatoryInformation/Guidances/
information about FDA’s posting of for acceptable levels of elemental
impurities in finished drug products, default.htm, http://www.fda.gov/
comments to public dockets, see 80 FR BiologicsBloodVaccines/Guidance
56469, September 18, 2015, or access and (2) update the methodology used to
test for elemental impurities in drug ComplianceRegulatoryInformation/
the information at: http://www.fda.gov/ Guidances/default.htm, or http://
regulatoryinformation/dockets/ products to include modern analytical
procedures. ICH Q3D contains www.regulations.gov.
default.htm.
Docket: For access to the docket to recommendations for manufacturers of Dated: June 27, 2016.
read background documents or the human drugs and biologics on applying Leslie Kux,
electronic and written/paper comments a risk-based approach to control Associate Commissioner for Policy.
received, go to http:// elemental impurities and permitted [FR Doc. 2016–15704 Filed 6–30–16; 8:45 am]
www.regulations.gov and insert the daily exposure. USP worked closely BILLING CODE 4164–01–P
docket number, found in brackets in the with ICH to align its new General
heading of this document, into the Chapters with ICH Q3D.
‘‘Search’’ box and follow the prompts Because elemental impurities pose DEPARTMENT OF HEALTH AND
and/or go to the Division of Dockets toxicological concerns and do not HUMAN SERVICES
Management, 5630 Fishers Lane, Rm. provide any therapeutic benefit to the
1061, Rockville, MD 20852. patient, their levels in drug products Food and Drug Administration
Submit written requests for single should be controlled within acceptable
copies of the draft guidance to the limits. In general, FDA recommends that [Docket No. FDA–2016–D–1662]
asabaliauskas on DSK3SPTVN1PROD with NOTICES
Division of Drug Information, Center for the manufacturer of any U.S. marketed
Drug Evaluation and Research, Food drug product follow ICH Q3D Vulvovaginal Candidiasis: Developing
and Drug Administration, 10001 New recommendations to establish Drugs for Treatment; Draft Guidance
Hampshire Ave., Hillandale Building, appropriate procedures for identifying for Industry; Availability
4th Floor, Silver Spring, MD 20993– and controlling elemental impurities in AGENCY: Food and Drug Administration,
0002; or the Office of Communication, the drug product based on risk HHS.
Outreach and Development, Center for assessment and product-specific
ACTION: Notice.
Biologics Evaluation and Research, considerations, unless the drug product
VerDate Sep<11>2014 19:05 Jun 30, 2016 Jkt 238001 PO 00000 Frm 00031 Fmt 4703 Sfmt 4703 E:\FR\FM\01JYN1.SGM 01JYN1](https://thefederalregister.org/doc/81_FR_43338/page/2.svg)
Document Created: 2016-07-14 11:37:40
Document Modified: 2016-07-14 11:37:40
| 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 | Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by August 30, 2016. | |
| Contact | John Kauffman, Center for Drug Evaluation and Research (HFD-920), Food and Drug Administration, 645 S. Newstead Ave., St. Louis, MO 63110, 314-539-2168; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911. | |
| FR Citation | 81 FR 43211 |
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