Professional Documents
Culture Documents
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42580 Federal Register / Vol. 70, No. 141 / Monday, July 25, 2005 / Notices
FDA has the authority under section Written procedures for these evaluations • Section 211.105(b)—Major
701(a) of the act (21 U.S.C. 371(a)) to are to be established and include equipment must be identified by a
issue regulations for the efficient provisions for a review of a distinctive identification number or
enforcement of the act regarding CGMP representative number of batches and, code that must be recorded in the batch
procedures for manufacturing, where applicable, records associated production record to show the specific
processing, and holding drugs and drug with the batch; provisions for a review equipment used in the manufacture of
products. The CGMP regulations help of complaints, recalls, returned or each batch of a drug product. In cases
ensure that drug products meet the salvaged drug products; and where only one of a particular type of
statutory requirements for safety and investigations conducted under equipment exists in a manufacturing
have their purported or represented § 211.192 for each drug product. facility, the name of the equipment may
identity, strength, quality, and purity The specific recordkeeping be used in lieu of a distinctive
characteristics. The information requirements provided in table 1 of this identification number or code.
collection requirements in the CGMP document are as follows: • Section 211.122(c) —Records must
regulations provide FDA with the • Section 211.34—Consultants be maintained for each shipment
necessary information to perform its advising on the manufacture, received of each different labeling and
duty to protect public health and safety. processing, packing, or holding of drug packaging material indicating receipt,
CGMP requirements establish products must have sufficient examination, or testing.
accountability in the manufacturing and education, training, and experience to • Section 211.130(e)—Inspection of
processing of drug products, provide for advise on the subject for which they are packaging and labeling facilities must be
meaningful FDA inspections, and retained. Records must be maintained made immediately before use to assure
enable manufacturers to improve the stating the name, address, and that all drug products have been
quality of drug products over time. The qualifications of any consultants and the removed from previous operations.
CGMP recordkeeping requirements also type of service they provide. Inspection must also be made to assure
serve preventive and remedial purposes, • Section 211.67(c)—Records must be that packaging and labeling materials
and provide crucial information if it is kept of maintenance, cleaning, not suitable for subsequent operations
necessary to recall a drug product. sanitizing, and inspection as specified have been removed. Results of
The general requirements for in §§ 211.180 and 211.182. inspection must be documented in the
recordkeeping under part 211 (21 CFR • Section 211.68—Appropriate batch production records.
part 211) are set forth in § 211.180. Any controls must be exercised over • Section 211.132(c)—Certain retail
production, control, or distribution
computer or related systems to assure packages of OTC drug products must
record associated with a batch and
that changes in master production and bear a statement that is prominently
required to be maintained in
control records or other records are placed so consumers are alerted to the
compliance with part 211 must be
instituted only by authorized personnel. specific tamper-evident feature of the
retained for at least 1 year after the
• Section 211.68(a)—Records must be package. The labeling statement is
expiration date of the batch and, for
maintained of calibration checks, required to be so placed that it will be
certain over-the-counter (OTC) drugs, 3
inspections, and computer or related unaffected if the tamper-resistant feature
years after distribution of the batch
system programs for automatic, of the package is breached or missing.
(§ 211.180(a)). Records for all
components, drug product containers, mechanical, and electronic equipment. If the tamper-evident feature chosen is
closures, and labeling are required to be • Section 211.68(b)—All appropriate one that uses an identifying
maintained for at least 1 year after the controls must be exercised over all characteristic, that characteristic is
expiration date and 3 years for certain computers or related systems and required to be referred to in the labeling
OTC products (§ 211.180(b)). control data systems to assure that statement.
All part 211 records must be readily changes in master production and • Section 211.132(d)—A request for an
available for authorized inspections controls records or other records are exemption from packaging and labeling
during the retention period instituted only by authorized persons. requirements by a manufacturer or
(§ 211.180(c)), and such records may be • Section 211.72—Filters for liquid packer is required to be submitted in the
retained either as original records or as filtration used in the manufacture, form of a citizen petition under 21 CFR
true copies (§ 211.180(d)). In addition, processing, or packing of injectable drug 10.30.
21 CFR 11.2(a) provides that ‘‘[f]or products intended for human use must • Section 211.137—Requirements
records required to be maintained but not release fibers into such products. regarding product expiration dating and
not submitted to the agency, persons • Section 211.80(d)—Each container compliance with 21 CFR 201.17 are set
may use electronic records in lieu of or grouping of containers for forth.
paper records or electronic signatures in components or drug product containers • Section 211.160(a)—The
lieu of traditional signatures, in whole or closures must be identified with a establishment of any specifications,
or in part, provided that the distinctive code for each lot in each standards, sampling plans, test
requirements of this part are met.’’ To shipment received. This code must be procedures, or other laboratory control
the extent this electronic option is used, used in recording the disposition of mechanisms, including any change in
the burden of maintaining paper records each lot. Each lot must be appropriately such specifications, standards, sampling
should be substantially reduced, as identified as to its status. plans, test procedures, or other
should any review of such records. • Section 211.100(b)—Written laboratory control mechanisms, must be
In order to facilitate improvements production and process control drafted by the appropriate
and corrective actions, records must be procedures must be followed in the organizational unit and reviewed and
maintained so that data can be used for execution of the various production and approved by the quality control unit.
evaluating, at least annually, the quality process control functions and must be These requirements must be followed
standards of each drug product to documented at the time of performance. and documented at the time of
determine the need for changes in drug Any deviation from the written performance. Any deviation from the
product specifications or manufacturing procedures must be recorded and written specifications, standards,
or control procedures (§ 211.180(e)). justified. sampling plans, test procedures, or
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Federal Register / Vol. 70, No. 141 / Monday, July 25, 2005 / Notices 42581
other laboratory control mechanisms • Section 211.194—Explains and conform to standards or specifications,
must be recorded and justified. describes laboratory records that must to insure that reprocessed batches
• Section 211.165(e)—The accuracy, be retained. conform with all established standards,
sensitivity, specificity, and • Section 211.196—Specifies the specifications, and characteristics;
reproducibility of test methods information that must be included in • Section 211.122(a)—Receipt,
employed by a firm must be established records on the distribution of the drug. identification, storage, handling,
and documented. Such validation and • Section 211.198—Specifies and sampling, examination, and/or testing of
documentation may be accomplished in describes the handling of all complaint labeling and packaging materials;
accordance with § 211.194(a)(2). files received by the applicant. • Section 211.125(f)—Control
• Section 211.166(c)—Homeopathic • Section 211.204—Specifies that procedures for the issuance of labeling;
drug product requirements are set forth. records be maintained of returned and • Section 211.130—Packaging and
• Section 211.173—Animals used in salvaged drug products and describes label operations, prevention of mixup
testing components, in-process the procedures involved. and cross contamination, identification
materials, or drug products for • Written procedures, referred to here and handling of filed drug product
compliance with established as standard operating procedures containers that are set aside and held in
specifications must be maintained and (SOPs), are required for many part 211 unlabeled condition, and identification
controlled in a manner that assures their records. The current SOP requirements of the drug product with a lot or control
suitability for their intended use. They were initially provided in a final rule number that permits determination of
must be identified, and adequate published in the Federal Register of the history of the manufacture and
records must be maintained showing the September 29, 1978 (43 FR 45014), and control of the batch;
history of their use. are now an integral and familiar part of • Section 211.142—Warehousing;
• Section 211.180(e)—Written records the drug manufacturing process. The • Section 211.150—Distribution of
required by part 211 must be major information collection impact of drug products;
maintained so that data can be used for SOPs results from their creation. • Section 211.160—Laboratory
evaluating, at least annually, the quality Thereafter, SOPs need to be periodically controls;
standards of each drug product to updated. A combined estimate is • Section 211.165(c)—Testing and
determine the need for changes in drug provided in table 1 of this document. release for distribution;
product specifications or manufacturing The 25 SOP provisions under part 211 • Section 211.166(a)—Stability testing;
or control procedures. Written in the combined maintenance estimate • Section 211.167—Special testing
procedures must be established and include: requirements;
followed for such evaluations and must • Section 211.22(d)—Responsibilities • Section 211.180(f)—Notification of
include provisions for a representative and procedures of the quality control responsible officials of investigations,
number of batches, whether approved or unit; recalls, reports of inspectional
unapproved or rejected, and a review of • Section 211.56(b)—Sanitation observations, and any regulatory actions
complaints, recalls, returned or salvaged procedures; relating to good manufacturing practice;
• Section 211.56(c)—Use of suitable • Section 211.198(a)—Written and oral
drug products, and investigations
rodenticides, insecticides, fungicides, complaint procedures, including quality
conducted under § 211.192 for each
fumigating agents, and cleaning and control unit review of any complaint
drug product. sanitizing agents;
• Section 211.180(f)—Procedures must involving specifications failures, and
• Section 211.67(b)—Cleaning and serious and unexpected adverse drug
be established to assure that the maintenance of equipment;
responsible officials of the firm, if they experiences;
• Section 211.68(a)—Proper • Section 211.204—Holding, testing,
are not personally involved in or performance of automatic, mechanical,
immediately aware of such actions, are and reprocessing of returned drug
and electronic equipment; products; and
notified in writing of any investigations • Section 211.80(a)—Receipt,
conducted under § 211.198, § 211.204, • Section 211.208—Drug product
identification, storage, handling, salvaging.
or § 211.208, any recalls, reports of sampling, testing, and approval or
inspectional observations issued, or any Although most of the CGMP
rejection of components and drug provisions covered in this document
regulatory actions relating to good product containers or closures; were created many years ago, there will
manufacturing practices brought by • Section 211.94(d)—Standards or
FDA. be some existing firms expanding into
specifications, methods of testing, and
• Section 211.182—Specifies new manufacturing areas and startup
methods of cleaning, sterilizing, and
requirements for equipment cleaning firms that will need to create SOPs. As
processing to remove pyrogenic
records and the use log. provided in table 1 of this document,
properties for drug product containers
• Section 211.184—Specifies and closures; FDA is assuming that approximately
requirements for component, drug • Section 211.100(a)—Production and 100 firms will have to create up to 25
product container, closure, and labeling process control; SOPs for a total of 2,500 records, and
records. • Section 211.110(a)—Sampling and the agency estimates that it will take 20
• Section 211.186—Specifies master testing of in-process materials and drug hours per recordkeeper to create 25 new
production and control records products; SOPs, for a total of 50,000 hours.
requirements. • Section 211.113(a)—Prevention of The burden estimates for the
• Section 211.188—Specifies batch objectionable microorganisms in drug recordkeeping requirements in table 1 of
production and control records products not required to be sterile; this document are based on the
requirements. • Section 211.113(b)—Prevention of following factors: (1) FDA’s institutional
• Section 211.192—Specifies the microbiological contamination of drug experience regarding creation and
information that must be maintained on products purporting to be sterile, review of such procedures and similar
the investigation of discrepancies found including validation of any sterilization recordkeeping requirements; and (2)
in the review of all drug product process; data provided to FDA to prepare an
production and control records by the • Section 211.115(a)—System for economic analysis of the potential
quality control staff. reprocessing batches that do not economic impact of the May 3, 1996,
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42582 Federal Register / Vol. 70, No. 141 / Monday, July 25, 2005 / Notices
proposed rule entitled ‘‘Current Good The May 3, 1996, proposed rule In the Federal Register of March 28,
Manufacturing Practice: Proposed revising part 211 CGMP requirements 2005 (70 FR 15628), FDA published a
Amendment of Certain Requirements for would require additional SOPs. Cost 60-day notice requesting public
Finished Pharmaceuticals’’ (61 FR estimates for those additional SOPs comment on the information collection
20104). Annual SOP maintenance is were included in the proposed rule, but provisions. No comments were received.
estimated to involve 1 hour annually are not included here. Any comments
FDA estimates the burden of this
per SOP, totaling 25 hours annually per on those estimates will be evaluated in
recordkeeper. any final rule based on that proposal. collection of information as follows:
SOP Maintenance
(See list of 25
SOPs in the
SUPPLE-
MENTARY IN-
FORMATION
section of this
document) 4,184 1 4,184 25 104,600
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Federal Register / Vol. 70, No. 141 / Monday, July 25, 2005 / Notices 42583
Total 848,625
1 There are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: July 20, 2005. • E-mail: HSAC@dhs.gov. Include DEPARTMENT OF THE INTERIOR
Jeffrey Shuren, docket number in the subject line of the
Assistant Commissioner for Policy. message. Central Utah Project Completion Act
[FR Doc. 05–14698 Filed 7–21–05; 11:48 am] • Fax: (202) 772–9718. AGENCY: Office of the Assistant
BILLING CODE 4160–01–S
• Mail: Katie Knapp, Homeland Secretary—Water and Science, Interior.
Security Advisory Council, Department ACTION: Notice of Availability of a Final
of Homeland Security, Washington, DC Environmental Assessment (EA) and
DEPARTMENT OF HOMELAND Finding of No Significant Impact
20528.
SECURITY (FONSI) for the execution of a lease of
Docket: For access to the docket to power privilege contract and the
Office of the Secretary read background documents or construction, operation, and
[Docket No. DHS–2005–0053] comments received, go to http:// maintenance of a non-federal
www.epa.gov/feddocket. You may also hydroelectric generation facility on
Homeland Security Advisory Council access the Federal eRulemaking Portal Jordanelle Dam, Wasatch County, Utah,
at http://www.regulations.gov. pursuant to the lease.
AGENCY:Office of the Secretary, DHS.
Notice of Federal Advisory
ACTION: FOR FURTHER INFORMATION CONTACT: For SUMMARY: Pursuant to Section 102(2)(C)
Committee Meeting. additional information concerning the of the National Environmental Policy
meeting, please contact Mike Miron or Act (NEPA) of 1969, as amended; Public
SUMMARY: The Homeland Security Katie Knapp of the HSAC Executive Law 102–575, Central Utah Project
Advisory Council (HSAC) will hold a Staff Member via email at Completion Act (CUPCA), as amended;
teleconference for the purposes of HSAC@dhs.gov, or via phone at (202) a July 2, 1999, Federal Register notice
receiving a report and recommendations 692–4283. (FR Doc. 99–16852); and a March 19,
from a HSAC Task Force, and holding
2004, Federal Register notice (FR Doc.
member deliberations. The HSAC will SUPPLEMENTARY INFORMATION: Public
04–6175); the Department of the Interior
receive a final report from the HSAC Attendance: Members of the public may
is making available a Final EA and
Private Sector Information Sharing Task register to dial in and listen to this
FONSI for the execution of a lease of
Force, Chaired by Mayor Patrick teleconference by contacting the power privilege contract and the
McCrory, Mayor of Charlotte, North Department officials listed above no construction, operation, and
Carolina. The Task Force will report on later than 5 p.m., e.d.t., on Friday, maintenance of a non-federal
the topic of information sharing with August 5, 2005, via e-mail at hydroelectric generation facility on
the Private Sector. Following the Task HSAC@dhs.gov, or via phone at (202) Jordanelle Dam, Bonneville Unit,
Force report, the HSAC will hold 692–4283. Upon registration, Central Utah Project and associated
deliberations and discussions among instructions for the dial in will be power transmission lines and facilities.
HSAC members. provided. Persons with hearing Through a competitive selection process
DATES: This meeting will be held via disabilities who desire to obtain a the joint application of the Central Utah
teleconference on Wednesday, August transcript of the teleconference must Water Conservancy District (District)
10, 2005, and will begin at 3:05 p.m. request that the Department produce and Heber Light and Power (HL&P) was
e.d.t. and provide a verbatim transcript based selected as the potential lessee to
ADDRESSES: If you desire to submit upon special needs due to a physical develop hydropower at Jordanelle Dam.
comments, they must be submitted by impairment at the time of registration. Construction and generation of power
August 5, 2005. Comments must be Absent any such request, the will be accomplished by the non-federal
identified by DHS–2005–0053 and may Department may not produce a verbatim partnership of the District and HL&P
be submitted by one of the following transcript of the meeting. through a lease of power privilege with
methods: Dated: July 19, 2005.
the United States. A lease contract will
• EPA Federal Partner EDOCKET be executed among the District, HL&P,
Web Site: http://www.epa.gov/ Kathryn Knapp, and the Department, which defines the
feddocket. Follow instructions for Special Assistant, Homeland Security development, operation, and
submitting comments on the Web site. Advisory Council, U.S. Department of maintenance of a hydroelectric
• Federal eRulemaking Portal: http:// Homeland Security. generation facility at Jordanelle Dam,
www.regulations.gov. Follow the [FR Doc. 05–14603 Filed 7–20–05; 3:00 pm] consistent with the purposes and
instructions for submitting comments. BILLING CODE 4410–10–P operations of the Bonneville Unit.
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