83 FR 39103 - Elemental Impurities in Drug Products; Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 153 (August 8, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 153 (August 8, 2018)
| Page Range | 39103-39105 | |
| FR Document | 2018-16984 |
[Federal Register Volume 83, Number 153 (Wednesday, August 8, 2018)] [Notices] [Pages 39103-39105] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-16984] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2016-D-1692] Elemental Impurities in Drug Products; 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 final guidance for industry entitled ``Elemental Impurities in Drug Products.'' This guidance finalizes the draft guidance issued July 1, 2016, which provides recommendations regarding the control of elemental impurities of human drug products marketed in the United States consistent with the implementation of International Council for Harmonisation (ICH) guidance for industry entitled ``Q3D Elemental Impurities'' (ICH Q3D). This 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: The announcement of the guidance is published in the Federal Register on August 8, 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 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 [[Page 39104]] 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-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 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)). Submit written requests for single copies of this 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 to the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research (CBER), 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 guidance document. FOR FURTHER INFORMATION CONTACT: Danae Christodoulou, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 21, Rm. 2602, Silver Spring, MD 20993-0002, 301- 796-1342; 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 guidance for industry entitled ``Elemental Impurities in Drug Products.'' This 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 guidance will also assist manufacturers of compendial drug products in responding to the issuance of the USP chapters for the control of elemental impurities. USP introduced new limits and analytical procedures for elemental impurities in General Chapters <232> Elemental Impurities--Limits and <233> 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-National Formulary requirements. This guidance outlines approaches for implementation of USP <232>, <233>, and ICH Q3D in new and existing products. This guidance finalizes the draft guidance issued July 1, 2016 (81 FR 43211). Since the draft guidance was issued, USP <232> was harmonized with ICH Q3D with respect to the all elements and their limits. Originally, prior to issuance of the draft guidance, USP <232> included a fraction (15) of elemental impurities (EIs) listed in ICH Q3D. A number of stakeholder comments to the draft guidance referred to the update and harmonization of USP <232> with ICH Q3D, which is now reflected in the final guidance. In addition, a number of stakeholder comments requested clarification regarding the applicability of the guidance to biologics license applications (BLAs). The final guidance now states that ``for control of EIs in approved or pending BLAs, see ICH Q3D.'' This differs from the draft, where it was stated that the guidance pertained to biotechnology products covered by new drug applications (NDAs). 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 ``Elemental Impurities in Drug Products.'' It does not establish any rights for any person and is not binding on FDA or the public. [[Page 39105]] 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. II. Paperwork Reduction Act of 1995 This 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 abbreviated new drug applications, including supplemental applications and annual reports, have been approved under OMB control number 0910-0001. The collections of information in 21 CFR parts 211 and 212 (current good manufacturing practices) have been approved under OMB control numbers 0910-0139 and 0910-0667. III. Electronic Access Persons with access to the internet may obtain the guidance at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or https://www.regulations.gov. Dated: August 3, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-16984 Filed 8-7-18; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 83, No. 153 / Wednesday, August 8, 2018 / Notices 39103
Therefore, approval of the DEPARTMENT OF HEALTH AND DATES:Approval is withdrawn as of
applications listed in the table, and all HUMAN SERVICES September 7, 2018.
amendments and supplements thereto, FOR FURTHER INFORMATION CONTACT:
is hereby withdrawn as of September 7, Food and Drug Administration
Florine P. Purdie, Center for Drug
2018. Introduction or delivery for [Docket No. FDA–2018–N–2702] Evaluation and Research, Food and
introduction into interstate commerce of Drug Administration, 10903 New
products without approved new drug Merck Sharp & Dohme Corporation, et Hampshire Ave., Bldg. 51, Rm. 6248,
applications violates section 301(a) and al.; Withdrawal of Approval of Four Silver Spring, MD 20993–0002, 301–
(d) of the Federal Food, Drug, and New Drug Applications 796–3601.
Cosmetic Act (21 U.S.C. 331(a) and (d)).
AGENCY: Food and Drug Administration, SUPPLEMENTARY INFORMATION: The
Drug products that are listed in the table holders of the applications listed in the
HHS.
that are in inventory on September 7, table have informed FDA that these drug
2018 may continue to be dispensed ACTION: Notice.
products are no longer marketed and
until the inventories have been depleted SUMMARY: The Food and Drug have requested that FDA withdraw
or the drug products have reached their Administration (FDA or Agency) is approval of the applications under the
expiration dates or otherwise become withdrawing approval of four new drug process described in § 314.150(c) (21
violative, whichever occurs first. applications (NDAs) from multiple CFR 314.150(c)). The applicants have
Dated: August 3, 2018. applicants. The holders of the also, by their requests, waived their
Leslie Kux, applications notified the Agency in opportunity for a hearing. Withdrawal
writing that the drug products were no of approval of an application or
Associate Commissioner for Policy.
longer marketed and requested that the abbreviated application under
[FR Doc. 2018–16985 Filed 8–7–18; 8:45 am] approval of the applications be § 314.150(c) is without prejudice to
BILLING CODE 4164–01–P withdrawn. refiling.
Application No. Drug Applicant
NDA 005619 ............ Aminohippurate Sodium (PAH) 20% sterile solution Injec- Merck Sharp & Dohme Corp., Subsidiary of Merck & Com-
tion, 2 grams in 10 milliliter (mL) vials. pany, Inc., 1 Merck Dr., P.O. Box 100, Whitehouse Sta-
tion, NJ 08889.
NDA 008506 ............ Hydrocortone (hydrocortisone) Tablets USP, 10 milligrams Do.
(mg) and 20 mg.
NDA 011891 ............ Durabolin (nandrolone phenpropionate) Injection, 25 mg/mL Organon USA, Inc., Subsidiary of Merck & Company, Inc.,
and 50 mg/mL. 2000 Galloping Hill Rd., Kenilworth, NJ 07033.
NDA 020301 ............ Ortho-Cept (desogestrel and ethinyl estradiol) Tablets USP, Janssen Pharmaceuticals, Inc., 920 U.S. Hwy. 202, P.O.
0.15 mg/0.03 mg (21-Day and 28-Day Regimens). Box 300, Raritan, NJ 08869–0602.
Therefore, approval of the DEPARTMENT OF HEALTH AND (USP) requirement for the control of
applications listed in the table, and all HUMAN SERVICES elemental impurities.
amendments and supplements thereto, DATES: The announcement of the
is hereby withdrawn as of September 7, Food and Drug Administration guidance is published in the Federal
2018. Introduction or delivery for [Docket No. FDA–2016–D–1692] Register on August 8, 2018.
introduction into interstate commerce of ADDRESSES: You may submit either
products without approved new drug Elemental Impurities in Drug Products; electronic or written comments on
applications violates section 301(a) and Guidance for Industry; Availability Agency guidances at any time as
(d) of the Federal Food, Drug, and AGENCY: Food and Drug Administration, follows:
Cosmetic Act (21 U.S.C. 331(a) and (d)). HHS. Electronic Submissions
Drug products that are listed in the table ACTION: Notice of availability.
that are in inventory on September 7, Submit electronic comments in the
2018 may continue to be dispensed SUMMARY: The Food and Drug following way:
until the inventories have been depleted Administration (FDA or Agency) is • Federal eRulemaking Portal:
or the drug products have reached their announcing the availability of a final https://www.regulations.gov. Follow the
expiration dates or otherwise become guidance for industry entitled instructions for submitting comments.
violative, whichever occurs first. ‘‘Elemental Impurities in Drug Comments submitted electronically,
Products.’’ This guidance finalizes the including attachments, to https://
Dated: August 3, 2018. draft guidance issued July 1, 2016, www.regulations.gov will be posted to
Leslie Kux, which provides recommendations the docket unchanged. Because your
Associate Commissioner for Policy. regarding the control of elemental comment will be made public, you are
[FR Doc. 2018–16982 Filed 8–7–18; 8:45 am] impurities of human drug products solely responsible for ensuring that your
BILLING CODE 4164–01–P
marketed in the United States consistent comment does not include any
with the implementation of confidential information that you or a
sradovich on DSK3GMQ082PROD with NOTICES
International Council for Harmonisation third party may not wish to be posted,
(ICH) guidance for industry entitled such as medical information, your or
‘‘Q3D Elemental Impurities’’ (ICH Q3D). anyone else’s Social Security number, or
This guidance will also assist confidential business information, such
manufacturers of compendial drug as a manufacturing process. Please note
products in responding to the issuance that if you include your name, contact
of the United States Pharmacopeia information, or other information that
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![Federal Register / Vol. 83, No. 153 / Wednesday, August 8, 2018 / Notices 39105
You can use an alternative approach if of information has been submitted to the includes a ‘‘Supplemental Data Sheet,’’
it satisfies the requirements of the Office of Management and Budget Form FDA 3427, and a ‘‘General Device
applicable statutes and regulations. This (OMB) for review and clearance under Classification Questionnaire,’’ Form
guidance is not subject to Executive the Paperwork Reduction Act of 1995. FDA 3429. Both forms contain a series
Order 12866. DATES: Fax written comments on the of questions concerning the safety and
collection of information by September effectiveness of the device type.
II. Paperwork Reduction Act of 1995
7, 2018. In the Federal Register of March 25,
This guidance refers to previously ADDRESSES: To ensure that comments on 2014 (79 FR 16252), FDA issued a
approved collections of information that the information collection are received, proposed rule that would eliminate the
are subject to review by the Office of OMB recommends that written need for Forms FDA 3427 and 3429.
Management and Budget (OMB) under comments be faxed to the Office of However, because the proposed rule has
the Paperwork Reduction Act of 1995 Information and Regulatory Affairs, not been finalized, we continue to
(44 U.S.C. 3501–3520). The collections OMB, Attn: FDA Desk Officer, Fax: 202– include the forms in the burden
of information in 21 CFR part 314 for 395–7285, or emailed to oira_ estimate for this information collection.
submitting NDAs and abbreviated new submission@omb.eop.gov. All The reclassification provisions of the
drug applications, including comments should be identified with the FD&C Act serve primarily as a vehicle
supplemental applications and annual OMB control number 0910–0138. Also for manufacturers to seek
reports, have been approved under OMB include the FDA docket number found reclassification from a higher to a lower
control number 0910–0001. The in brackets in the heading of this class, thereby reducing the regulatory
collections of information in 21 CFR document. requirements applicable to a particular
parts 211 and 212 (current good device type, or to seek reclassification
manufacturing practices) have been FOR FURTHER INFORMATION CONTACT:
from a lower to a higher class, thereby
approved under OMB control numbers Amber Sanford, Office of Operations,
increasing the regulatory requirements
0910–0139 and 0910–0667. Food and Drug Administration, Three
applicable to that device type. If
White Flint North, 10A–12M, 11601
III. Electronic Access approved, petitions requesting
Landsdown St., North Bethesda, MD
classification from class III to class II or
Persons with access to the internet 20852, 301–796–8867, PRAStaff@
class I provide an alternative route to
may obtain the guidance at either fda.hhs.gov.
market in lieu of premarket approval for
https://www.fda.gov/Drugs/ SUPPLEMENTARY INFORMATION: In class III devices. If approved, petitions
GuidanceCompliance compliance with 44 U.S.C. 3507, FDA requesting reclassification from class I
RegulatoryInformation/Guidances/ has submitted the following proposed or II, to a different class, may increase
default.htm, or https://www.fda.gov/ collection of information to OMB for requirements.
BiologicsBloodVaccines/ review and clearance. In the Federal Register of March 07,
GuidanceCompliance 2018 (83 FR 9743), FDA published a 60-
RegulatoryInformation/Guidances/ Reclassification Petitions for Medical
Devices day notice requesting public comment
default.htm or https:// on the proposed collection of
www.regulations.gov. OMB Control Number 0910–0138— information. FDA received one
Dated: August 3, 2018. Extension comment.
Leslie Kux, Under sections 513(e) and (f), 514(b), The comment supports continued use
Associate Commissioner for Policy. 515(b), and 520(l) of the Federal Food, of Forms FDA 3427 and FDA 3429.
[FR Doc. 2018–16984 Filed 8–7–18; 8:45 am] Drug, and Cosmetic Act (FD&C Act) (21 Specifically, the commenter is
BILLING CODE 4164–01–P U.S.C. 360c(e) and (f), 360d(b), 360e(b), addressing the issue of discontinuing
and 360j(l)) and part 860 (21 CFR part the forms as previously referenced,
860), subpart C, FDA has the wherein FDA issued a proposed rule (79
DEPARTMENT OF HEALTH AND responsibility to collect data and FR 16252) to eliminate the need for the
HUMAN SERVICES information contained in forms. Because FDA is not
reclassification petitions. The discontinuing use of the forms at this
Food and Drug Administration reclassification provisions of the FD&C time, and this comment relates to the
Act allow any person to petition for proposed rule (79 FR 16252) and not to
[Docket No. FDA–2011–N–0776] the information collection itself, we
reclassification of a device from any of
the three classes, i.e., I, II, and III, to make no changes to this information
Agency Information Collection collection based on the comment.
another class. The reclassification
Activities; Submission for Office of The Center for Devices and
content regulation (§ 860.123) requires
Management and Budget Review; Radiological Health (CDRH) has
the submission of valid scientific
Comment Request; Reclassification continually maintained contact with
evidence demonstrating that the
Petitions for Medical Devices industry. Informal communications
proposed reclassification will provide a
AGENCY: Food and Drug Administration, reasonable assurance of safety and concerning the importance and effect of
HHS. effectiveness of the device type for its reclassification are provided primarily
ACTION: Notice. indications for use. through trade organizations, and via
The reclassification procedure CDRH’s website (https://www.fda.gov/
sradovich on DSK3GMQ082PROD with NOTICES
SUMMARY: The Food and Drug regulation requires the submission of MedicalDevices/default.htm).
Administration (FDA or we) is specific data when a manufacturer is FDA estimates the burden of this
announcing that a proposed collection petitioning for reclassification. This collection of information as follows:
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Document Created: 2018-08-08 02:05:03
Document Modified: 2018-08-08 02:05:03
| 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 August 8, 2018. | |
| Contact | Danae Christodoulou, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 21, Rm. 2602, Silver Spring, MD 20993-0002, 301- 796-1342; 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 | 83 FR 39103 |
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