83 FR 54597 - Considerations for the Development of Dried Plasma Products Intended for Transfusion; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 210 (October 30, 2018)

Page Range		54597-54598
FR Document		2018-23637

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft document entitled ``Considerations for the Development of Dried Plasma Products Intended for Transfusion; Draft Guidance for Industry.'' This guidance is intended to assist manufacturers, sponsors, and applicants developing dried plasma products intended for transfusion in order to facilitate the availability of safe and effective dried plasma products in the United States. The draft guidance document provides considerations for the successful development and licensing of dried plasma products and for the approval of devices used to manufacture dried plasma. The guidance includes recommendations on optimal sources of input plasma; manufacturing and product quality, including product characterization; packaging and reconstitution; clinical studies; and device submissions.

Federal Register, Volume 83 Issue 210 (Tuesday, October 30, 2018)

[Federal Register Volume 83, Number 210 (Tuesday, October 30, 2018)]
[Notices]
[Pages 54597-54598]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2018-23637]

[[Page 54597]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-3759]

Considerations for the Development of Dried Plasma Products
Intended for Transfusion; Draft Guidance for Industry; Availability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 document entitled ``Considerations for the
Development of Dried Plasma Products Intended for Transfusion; Draft
Guidance for Industry.'' This guidance is intended to assist
manufacturers, sponsors, and applicants developing dried plasma
products intended for transfusion in order to facilitate the
availability of safe and effective dried plasma products in the United
States. The draft guidance document provides considerations for the
successful development and licensing of dried plasma products and for
the approval of devices used to manufacture dried plasma. The guidance
includes recommendations on optimal sources of input plasma;
manufacturing and product quality, including product characterization;
packaging and reconstitution; clinical studies; and device submissions.

DATES: Submit either electronic or written comments on the draft
guidance by January 28, 2019 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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 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-2018-D-3759 for ``Considerations for the Development of Dried
Plasma Intended for Transfusion; Draft Guidance for Industry.''
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 the draft guidance 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 the office in
processing your requests. The draft guidance may also be obtained by
mail by calling CBER at 1-800-835-4709 or 240-402-8010. See the
SUPPLEMENTARY INFORMATION section for electronic access to the draft
guidance document.

FOR FURTHER INFORMATION CONTACT: Jonathan McKnight, 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 document entitled
``Considerations for the Development of Dried Plasma Products Intended
for Transfusion; Draft Guidance for Industry.'' Plasma is a critical
component of early transfusion therapy in the management of traumatic
hemorrhage. Plasma can replenish various coagulation proteins that are
consumed during the coagulopathy that can accompany traumatic injury.
Because plasma products intended for transfusion such as fresh frozen
plasma (FFP), plasma frozen within 24 hours after phlebotomy (PF24),
and plasma frozen within 24 hours after phlebotomy held at room
temperature up to 24 hours after phlebotomy (PF24, RT24) are stored
frozen, these products need to be thawed prior to transfusion. This
limits

[[Page 54598]]

or prevents the use of plasma in settings where freezers and other
support equipment are unavailable (e.g. battlefields, remote locations,
and other austere settings) and may lead to delayed administration.
Dried plasma (such as freeze-dried or spray-dried plasma) offers the
potential to address these challenges by providing a product that is
stable at ambient temperatures and can be rapidly reconstituted and
transfused.
Recent clinical studies have demonstrated promising efficacy and
safety of dried plasma, particularly in military applications, and
dried plasma products are available for limited use in Germany, South
Africa, and France. This guidance is intended to assist manufacturers,
sponsors, and applicants developing dried plasma products intended for
transfusion in order to facilitate the availability of safe and
effective dried plasma products in the United States.
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 considerations
for the development of dried plasma products intended for transfusion.
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.

II. Paperwork Reduction Act of 1995

This draft guidance refers to previously approved collections of
information 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 211 have been approved
under OMB control number 0910-0139; the collections of information in
21 CFR part 312 have been approved under OMB control number 0910-0014;
the collections of information in 21 CFR part 601 have been approved
under OMB control number 0910-0338; the collections of information in
21 CFR part 610 have been approved under OMB control numbers 0910-0116,
0910-0139, and 0910-0338; the collections of information in 21 CFR part
630 have been approved under OMB control number 0910-0116; the
collections of information in 21 CFR part 640 have been approved under
OMB control number 0910-0116; the collections of information in 21 CFR
part 812 have been approved under OMB control number 0910-0078; and the
collections of information in 21 CFR part 814 have been approved under
OMB control number 0910-0231.

III. Electronic Access

Persons with access to the internet may obtain the draft guidance
at either https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or
https://www.regulations.gov.

Dated: October 25, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-23637 Filed 10-29-18; 8:45 am]
BILLING CODE 4164-01-P

54598 Federal Register / Vol. 83, No. 210 / Tuesday, October 30, 2018 / Notices

or prevents the use of plasma in settings the collections of information in 21 CFR relying in part on the Agency’s previous
where freezers and other support part 814 have been approved under findings of safety and effectiveness for
equipment are unavailable (e.g. OMB control number 0910–0231. ROXICODONE (oxycodone HCl IR
battlefields, remote locations, and other tablets (NDA 021011)) (Ref. 1).
III. Electronic Access PMRS’s product contains excipients,
austere settings) and may lead to
delayed administration. Dried plasma Persons with access to the internet including a dye blend, that have
(such as freeze-dried or spray-dried may obtain the draft guidance at either solubility in common solvents,
plasma) offers the potential to address https://www.fda.gov/BiologicsBlood including water and ethanol, similar to
these challenges by providing a product Vaccines/GuidanceCompliance the solubility of the active
that is stable at ambient temperatures RegulatoryInformation/Guidances/ pharmaceutical ingredient (API). PMRS
and can be rapidly reconstituted and default.htm or https:// contends that a solution prepared from
transfused. www.regulations.gov. its product for subcutaneous or
Recent clinical studies have Dated: October 25, 2018. intravenous injection will look
demonstrated promising efficacy and relatively ‘‘impure’’ compared to a
Leslie Kux,
safety of dried plasma, particularly in solution prepared from Roxicodone and
Associate Commissioner for Policy.
military applications, and dried plasma will have a dark, opaque,
products are available for limited use in [FR Doc. 2018–23637 Filed 10–29–18; 8:45 am]
‘‘contaminated-looking’’ appearance,
Germany, South Africa, and France. BILLING CODE 4164–01–P
providing both a ‘‘visual deterrent’’ and
This guidance is intended to assist a ‘‘chemical deterrent’’ to abuse by
manufacturers, sponsors, and applicants injection (Refs. 2 and 3).1 PMRS
developing dried plasma products DEPARTMENT OF HEALTH AND
provided in vitro data intended to show
intended for transfusion in order to HUMAN SERVICES
that a solution prepared for injection
facilitate the availability of safe and would have these qualities but provided
Food and Drug Administration
effective dried plasma products in the no data or literature supporting the
United States. [Docket No. FDA–2018–N–0188] conclusion that people who inject
This draft guidance is being issued opioids would, in fact, be deterred from
consistent with FDA’s good guidance Denial of Hearing Request Regarding
injecting such a solution (Ref. 2).
practices regulation (21 CFR 10.115). Proposal To Refuse To Approve a New PMRS also provided in vitro data
The draft guidance, when finalized, will Drug Application for Oxycodone intended to demonstrate that its product
represent the current thinking of FDA Hydrochloride Immediate-Release would be more difficult to grind into
on considerations for the development Abuse-Deterrent Formulation, Oral particle sizes suitable for snorting
of dried plasma products intended for Capsules, 5 Milligrams, 15 Milligrams, compared to ROXICODONE but
transfusion. It does not establish any and 30 Milligrams; Order Refusing provided no data from studies in human
rights for any person and is not binding Approval subjects to evaluate the pharmacokinetic
on FDA or the public. You can use an or pharmacodynamic properties of the
AGENCY: Food and Drug Administration,
alternative approach if it satisfies the product following abuse via the nasal
HHS.
requirements of the applicable statutes route (Ref. 1).2 Nonetheless, PMRS
and regulations. This guidance is not ACTION: Notice.
proposed labeling for its product
subject to Executive Order 12866. SUMMARY: The Chief Scientist is denying representing that it has abuse-deterrent
II. Paperwork Reduction Act of 1995 a request for a hearing regarding the properties (Ref. 4).
proposal by the Center for Drug On November 16, 2017, CDER issued
This draft guidance refers to
Evaluation and Research (CDER) of the a complete response letter to PMRS
previously approved collections of
Food and Drug Administration (FDA or under § 314.110(a) (21 CFR 314.110(a))
information subject to review by the
Agency) to refuse to approve a new drug stating that the NDA could not be
Office of Management and Budget
(OMB) under the Paperwork Reduction application submitted by
Act of 1995 (44 U.S.C. 3501–3520). The Pharmaceutical Manufacturing Research 1 With respect to the purported ‘‘chemical

Services, Inc. (PMRS) for oxycodone deterrent’’ aspect of its product, we note that
collections of information in 21 CFR PMRS’s claims that its product resists physical and
part 211 have been approved under hydrochloride (HCl) immediate-release chemical ‘‘extraction’’ appear to rest on a
OMB control number 0910–0139; the (IR) capsules, 5 milligrams (mg), 15 mg, misunderstanding of how that term is used in the
collections of information in 21 CFR and 30 mg in its present form. The Chief context of abuse-deterrent opioids. PMRS appears
Scientist denies approval. to be using the term ‘‘extraction’’ to mean that it is
part 312 have been approved under difficult to separate the API from the excipients in
OMB control number 0910–0014; the DATES: The order is applicable October solution, not that it is difficult to prepare a solution
collections of information in 21 CFR 30, 2018. that contains the API. In fact, PMRS’s data show
that the oxycodone in its formulation can be readily
part 601 have been approved under FOR FURTHER INFORMATION CONTACT: extracted in commonly available solvents into a
OMB control number 0910–0338; the Nathan R. Sabel, Office of Scientific solution physically suitable for injection. These
collections of information in 21 CFR Integrity, Food and Drug data show that more of the API could be extracted
part 610 have been approved under Administration, 10903 New Hampshire from oxycodone HCl IR capsules (approximately 98
percent of the API) than from ROXICODONE
OMB control numbers 0910–0116, Ave., Bldg. 1, Rm. 4206, Silver Spring, (approximately 90–91 percent) in both small and
0910–0139, and 0910–0338; the MD 20993, 301–796–8588. medium volume extraction and at ambient and high
collections of information in 21 CFR SUPPLEMENTARY INFORMATION: temperatures (Refs. 1 and 2).
2 While PMRS initially intended for the product
part 630 have been approved under
khammond on DSK30JT082PROD with NOTICES

OMB control number 0910–0116; the I. Procedural Background to confer resistance to grinding to particle sizes
suitable for snorting (Ref. 7), PMRS has conceded,
collections of information in 21 CFR PMRS submitted new drug based on the results of its testing, that the
part 640 have been approved under application (NDA) 209155 for formulation should not be considered to have this
OMB control number 0910–0116; the oxycodone HCl IR capsules, 5 mg, 15 property. See Ref. 2 at 12–13 (‘‘Because of the
decrease in particle size distribution after grinding
collections of information in 21 CFR mg, and 30 mg, under section 505(b)(2) as the drug product ages, resistance to grinding
part 812 have been approved under of the Federal Food, Drug, and Cosmetic cannot be considered as one of the characteristics
OMB control number 0910–0078; and Act (FD&C Act) (21 U.S.C. 355(b)(2)), of [PMRS’ product]’’).

VerDate Sep<11>2014 17:34 Oct 29, 2018 Jkt 247001 PO 00000 Frm 00033 Fmt 4703 Sfmt 4703 E:\FR\FM\30OCN1.SGM 30OCN1

Document Created: 2018-10-30 00:43:43
Document Modified: 2018-10-30 00:43:43

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		Submit either electronic or written comments on the draft guidance by January 28, 2019 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.
Contact		Jonathan McKnight, 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 54597

83 FR 54597 - Considerations for the Development of Dried Plasma Products Intended for Transfusion; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 83, Issue 210 (October 30, 2018)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration