21
Code of Federal Regulations
Parts
211
Subpart
J-Records and Reports
§ 211.180 General requirements.
(a) Any production, control, or distribution record that is
required to be maintained in compliance with this part and is specifically
associated with a batch of a drug product shall be retained for at least 1 year
after the expiration date of the batch or, in the case of certain OTC drug
products lacking expiration dating because they meet the criteria for exemption
under § 211.137, 3 years after distribution of the batch.
(b) Records shall be maintained for all components, drug product
containers, closures, and labeling for at least 1 year after the expiration
date or, in the case of certain OTC drug products lacking expiration dating
because they meet the criteria for exemption under § 211.137, 3
years after distribution of the last lot of drug product incorporating the
component or using the container, closure, or labeling.
(c) All records required under this part, or copies of such
records, shall be readily available for authorized inspection during the
retention period at the establishment where the activities described in such
records occurred. These records or copies thereof shall be subject to
photocopying or other means of reproduction as part of such inspection. Records
that can be immediately retrieved from another location by computer or other electronic
means shall be considered as meeting the requirements of this paragraph.
(d) Records required under this part may be retained either as
original records or as true copies such as photocopies, microfilm, microfiche,
or other accurate reproductions of the original records. Where reduction
techniques, such as microfilming, are used, suitable reader and photocopying
equipment shall be readily available.
(e) Written records required by this part shall be maintained so
that data therein can be used for evaluating, at least annually, the quality
standards of each drug product to determine the need for changes in drug
product specifications or manufacturing or control procedures. Written
procedures shall be established and followed for such evaluations and shall
include provisions for:
(1) A review of a representative number of batches, whether
approved or rejected, and, where applicable, records associated with the batch.
(2) A review of complaints, recalls, returned or salvaged drug
products, and investigations conducted under § 211.192 for
each drug product.
(f) Procedures shall be established to assure that the responsible
officials of the firm, if they are not personally involved in or immediately
aware of such actions, are notified in writing of any investigations conducted
under §§ 211.198, 211.204, or 211.208 of these regulations, any recalls, reports of inspectional
observations issued by the Food and Drug Administration, or any regulatory
actions relating to good manufacturing practices brought by the Food and Drug
Administration. [43 FR 45077, Sept. 29, 1978, as amended at 60 FR 4901, Jan.
20, 1995]
§ 211.182 Equipment cleaning and use log.
A written record of major equipment cleaning, maintenance (except
routine maintenance such as lubrication and adjustments), and use shall be
included in individual equipment logs that show the date, time, product, and
lot number of each batch processed. If equipment is dedicated to manufacture of
one product, then individual equipment logs are not required, provided that
lots or batches of such product follow in numerical order and are manufactured
in numerical sequence. In cases where dedicated equipment is employed, the
records of cleaning, maintenance, and use shall be part of the batch record.
The persons performing and double-checking the cleaning and maintenance shall
date and sign or initial the log indicating that the work was performed.
Entries in the log shall be in chronological order.
§ 211.184 Component, drug product container, closure, and labeling
records.
These records shall include the following:
(a) The identity and quantity of each shipment of each lot of
components, drug product containers, closures, and labeling; the name of the
supplier; the supplier's lot number(s) if known; the receiving code as
specified in § 211.80; and the date of receipt. The name and location of the prime
manufacturer, if different from the supplier, shall be listed if known.
(b) The results of any test or examination performed (including
those performed as required by §
(c) An individual inventory record of each component, drug product
container, and closure and, for each component, a reconciliation of the use of
each lot of such component. The inventory record shall contain sufficient
information to allow determination of any batch or lot of drug product
associated with the use of each component, drug product container, and closure.
(d) Documentation of the examination and review of labels and
labeling for conformity with established specifications in accord with §§ 211.122(c)
and 211.130(c).
(e) The disposition of rejected components, drug product
containers, closure, and labeling.
§ 211.186 Master production and control records.
(a) To assure uniformity from batch to batch, master production
and control records for each drug product, including each batch size thereof,
shall be prepared, dated, and signed (full signature, handwritten) by one
person and independently checked, dated, and signed by a second person. The
preparation of master production and control records shall be described in a
written procedure and such written procedure shall be followed.
(b) Master production and control records shall include:
(1) The name and strength of the product and a description of the
dosage form;
(2) The name and weight or measure of each active ingredient per
dosage unit or per unit of weight or measure of the drug product, and a
statement of the total weight or measure of any dosage unit;
(3) A complete list of components designated by names or codes sufficiently
specific to indicate any special quality characteristic;
(4) An accurate statement of the weight or measure of each
component, using the same weight system (metric, avoirdupois, or apothecary)
for each component. Reasonable variations may be permitted, however, in the
amount of components necessary for the preparation in the dosage form, provided
they are justified in the master production and control records;
(5) A statement concerning any calculated excess of component;
(6) A statement of theoretical weight or measure at appropriate
phases of processing;
(7) A statement of theoretical yield, including the maximum and
minimum percentages of theoretical yield beyond which investigation according
to § 211.192 is required;
(8) A description of the drug product containers, closures, and packaging
materials, including a specimen or copy of each label and all other labeling
signed and dated by the person or persons responsible for approval of such
labeling;
(9) Complete manufacturing and control instructions, sampling and
testing procedures, specifications, special notations, and precautions to be
followed.
§ 211.188 Batch production and control records.
Batch production and control records shall be prepared for each
batch of drug product produced and shall include complete information relating
to the production and control of each batch. These records shall include:
(a) An accurate reproduction of the appropriate master production
or control record, checked for accuracy, dated, and signed;
(b) Documentation that each significant step in the manufacture,
processing, packing, or holding of the batch was accomplished, including:
(1) Dates;
(2) Identity of individual major equipment and lines used;
(3) Specific identification of each batch of component or
in-process material used;
(4) Weights and measures of components used in the course of
processing;
(5) In-process and laboratory control results;
(6) Inspection of the packaging and labeling area before and after
use;
(7) A statement of the actual yield and a statement of the
percentage of theoretical yield at appropriate phases of processing;
(8) Complete labeling control records, including specimens or copies
of all labeling used;
(9) Description of drug product containers and closures;
(10) Any sampling performed;
(11) Identification of the persons performing and directly
supervising or checking each significant step in the operation;
§ 211.192 Production record review.
All drug product production and control records, including those
for packaging and labeling, shall be reviewed and approved by the quality
control unit to determine compliance with all established, approved written
procedures before a batch is released or distributed. Any unexplained
discrepancy (including a percentage of theoretical yield exceeding the maximum
or minimum percentages established in master production and control records) or
the failure of a batch or any of its components to meet any of its
specifications shall be thoroughly investigated, whether or not the batch has
already been distributed. The investigation shall extend to other batches of
the same drug product and other drug products that may have been associated
with the specific failure or discrepancy. A written record of the investigation
shall be made and shall include the conclusions and
followup.
§ 211.194 Laboratory records.
(a) Laboratory records shall include complete data derived from
all tests necessary to assure compliance with established specifications and
standards, including examinations and assays, as
follows:
(1) A description of the sample received for testing with
identification of source (that is, location from where sample was obtained),
quantity, lot number or other distinctive code, date sample was taken, and date
sample was received for testing.
(2) A statement of each method used in the testing of the sample.
The statement shall indicate the location of data that establish that the
methods used in the testing of the sample meet proper standards of accuracy and
reliability as applied to the product tested. (If the method employed is in the
current revision of the United States Pharmacopeia, National Formulary,
Association of Official Analytical Chemists, Book of Methods,{2} or in other
recognized standard references, or is detailed in an approved new drug
application and the referenced method is not modified, a statement indicating
the method and reference will suffice). The suitability of all testing methods
used shall be verified under actual conditions of use.
{2} Copies may be obtained from: Association of Official
Analytical Chemists, 2200 Wilson Blvd., Suite 400, Arlington, VA 22201-3301.
(3) A statement of the weight or measure of sample used for each
test, where appropriate.
(4) A complete record of all data secured in the course of each
test, including all graphs, charts, and spectra from laboratory
instrumentation, properly identified to show the specific component, drug
product container, closure, in-process material, or drug product, and lot
tested.
(5) A record of all calculations performed in connection with the
test, including units of measure, conversion factors, and equivalency factors.
(6) A statement of the results of tests and how the results
compare with established standards of identity, strength, quality, and purity
for the component, drug product container, closure, in-process material, or
drug product tested.
(7) The initials or signature of the person who performs each test
and the date(s) the tests were performed.
(8) The initials or signature of a second person showing that the
original records have been reviewed for accuracy, completeness, and compliance
with established standards.
(b) Complete records shall be maintained of any modification of an
established method employed in testing. Such records shall include the reason
for the modification and data to verify that the modification produced results
that are at least as accurate and reliable for the material being tested as the
established method.
(c) Complete records shall be maintained of any testing and
standardization of laboratory reference standards, reagents, and standard
solutions.
(d) Complete records shall be maintained of the periodic
calibration of laboratory instruments, apparatus, gauges, and recording devices
required by § 211.160(b)(4).
(e) Complete records shall be maintained of all stability testing
performed in accordance with §211.166.
[43 FR 45077, Sept. 29, 1978, as amended at 55 FR 11577, Mar. 29,
1990]
§ 211.196 Distribution records.
Distribution records shall contain the name and strength of the
product and description of the dosage form, name and address of the consignee,
date and quantity shipped, and lot or control number of the drug product. For
compressed medical gas products, distribution records are not required to
contain lot or control numbers.
(Approved by the Office of Management and Budget under control
number 0910-0139)
[49 FR 9865, Mar. 16, 1984]
§ 211.198 Complaint files.
(a) Written procedures describing the handling of all written and
oral complaints regarding a drug product shall be established and followed. Such
procedures shall include provisions for review by the quality control unit, of
any complaint involving the possible failure of a drug product to meet any of its
specifications and, for such drug products, a determination as to the need for
an investigation in accordance with § 211.192.
Such procedures shall include provisions for review to determine whether the
complaint represents a serious and unexpected adverse drug experience which is
required to be reported to the Food and Drug Administration in accordance with
§ 310.305 of this chapter.
(b) A written record of each complaint shall be maintained in a
file designated for drug product complaints. The file regarding such drug
product complaints shall be maintained at the establishment where the drug product
involved was manufactured, processed, or packed, or such file may be maintained
at another facility if the written records in such files are readily available
for inspection at that other facility. Written records involving a drug product
shall be maintained until at least 1 year after the expiration date of the drug
product, or 1 year after the date that the complaint was received, whichever is
longer. In the case of certain OTC drug products lacking expiration dating
because they meet the criteria for exemption under § 211.137,
such written records shall be maintained for 3 years after distribution of the
drug product.
(1) The written record shall include the following information,
where known: the name and strength of the drug product, lot number, name of
complainant, nature of complaint, and reply to complainant.
(2) Where an investigation under § 211.192 is
conducted, the written record shall include the findings of the investigation
and followup. The record or copy of the record of the investigation shall be maintained
at the establishment where the investigation occurred in accordance with § 211.180(c).
(3) Where an investigation under § 211.192 is
not conducted, the written record shall include the reason that an
investigation was found not to be necessary and the name of the responsible
person making such a determination.
[43 FR 45077, Sept. 29, 1978, as amended
at 51 FR 24479, July 3, 1986]
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