6. DOCUMENTATION AND RECORDS

6. DOCUMENTATION AND RECORDS
6.1 Documentation System and Specifications
6.10 All documents related to the manufacture of intermediates or APIs should be prepared, reviewed, approved and distributed according to written procedures. Such documents can be in paper or electronic form.
6.11 The issuance, revision, superseding and withdrawal of all documents should be controlled with maintenance of revision histories.
6.12 A procedure should be established for retaining all appropriate documents (e.g., development history reports, scale-up reports, technical transfer reports, process validation reports, training records, production records, control records, and distribution records). The retention periods for these documents should be specified.
6.13 All production, control, and distribution records should be retained for at least 1 year after the expiry date of the batch. For APIs with retest dates, records should be retained for at least 3 years after the batch is completely distributed.
6.14 When entries are made in records, these should be made indelibly in spaces provided for such entries, directly after performing the activities, and should identify the person making the entry. Corrections to entries should be dated and signed and leave the original entry still readable.
6.15 During the retention period, originals or copies of records should be readily available at the establishment where the activities described in such records occurred. Records that can be promptly retrieved from another location by electronic or other means are acceptable.
6.16 Specifications, instructions, procedures, and records can be retained either as originals or as true copies such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records. Where reduction techniques such as microfilming or electronic records are used, suitable retrieval equipment and a means to produce a hard copy should be readily available.
6.17 Specifications should be established and documented for raw materials, intermediates where necessary, APIs, and labelling and packaging materials. In addition, specifications may be appropriate for certain other materials, such as process aids, gaskets, or other materials used during the production of intermediates or APIs that could critically impact on quality. Acceptance criteria should be established and documented for in-process controls.
6.18 If electronic signatures are used on documents, they should be authenticated and secure.
6.2 Equipment Cleaning and Use Record
6.20 Records of major equipment use, cleaning, sanitization and/or sterilization and maintenance should show the date, time (if appropriate), product, and batch number of each batch processed in the equipment, and the person who performed the cleaning and maintenance.
6.21 If equipment is dedicated to manufacturing one intermediate or API, then individual equipment records are not necessary if batches of the intermediate or API follow in traceable sequence. In cases where dedicated equipment is employed, the records of cleaning, maintenance, and use can be part of the batch record or maintained separately.
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
6.3 Records of Raw Materials, Intermediates, API Labelling and Packaging Materials
6.30 Records should be maintained including:
− The name of the manufacturer, identity and quantity of each shipment of each batch of raw materials, intermediates or labelling and packaging materials for API's; the name of the supplier; the supplier's control number(s), if known, or other identification number; the number allocated on receipt; and the date of receipt;
− The results of any test or examination performed and the conclusions derived from this;
− Records tracing the use of materials;
− Documentation of the examination and review of API labelling and packaging materials for conformity with established specifications; and
− The final decision regarding rejected raw materials, intermediates or API labelling and packaging materials.
6.31 Master (approved) labels should be maintained for comparison to issued labels.
6.4 Master Production Instructions (Master Production and Control Records)
6.40 To ensure uniformity from batch to batch, master production instructions for each intermediate and API should be prepared, dated, and signed by one person and independently checked, dated, and signed by a person in the quality unit(s).
6.41 Master production instructions should include:
− The name of the intermediate or API being manufactured and an identifying document reference code, if applicable;
− A complete list of raw materials and intermediates designated by names or codes sufficiently specific to identify any special quality characteristics;
− An accurate statement of the quantity or ratio of each raw material or intermediate to be used, including the unit of measure. Where the quantity is not fixed, the calculation for each batch size or rate of production should be included. Variations to quantities should be included where they are justified;
− The production location and major production equipment to be used;
− Detailed production instructions, including the:
− sequences to be followed,
− ranges of process parameters to be used,
− sampling instructions and in-process controls with their acceptance criteria, where appropriate,
− time limits for completion of individual processing steps and/or the total process, where appropriate; and
− expected yield ranges at appropriate phases of processing or time;
− Where appropriate, special notations and precautions to be followed, or cross-references to these; and
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
− The instructions for storage of the intermediate or API to assure its suitability for use, including the labelling and packaging materials and special storage conditions with time limits, where appropriate.
6.5 Batch Production Records (Batch Production and Control Records)
6.50 Batch production records should be prepared for each intermediate and API and should include complete information relating to the production and control of each batch. The batch production record should be checked before issuance to assure that it is the correct version and a legible accurate reproduction of the appropriate master production instruction. If the batch production record is produced from a separate part of the master document, that document should include a reference to the current master production instruction being used.
6.51 These records should be numbered with a unique batch or identification number, dated and signed when issued. In continuous production, the product code together with the date and time can serve as the unique identifier until the final number is allocated.
6.52 Documentation of completion of each significant step in the batch production records (batch production and control records) should include:
− Dates and, when appropriate, times;
− Identity of major equipment (e.g., reactors, driers, mills, etc.) used;
− Specific identification of each batch, including weights, measures, and batch numbers of raw materials, intermediates, or any reprocessed materials used during manufacturing;
− Actual results recorded for critical process parameters;
− Any sampling performed;
− Signatures of the persons performing and directly supervising or checking each critical step in the operation;
− In-process and laboratory test results;
− Actual yield at appropriate phases or times;
− Description of packaging and label for intermediate or API;
− Representative label of API or intermediate if made commercially available;
− Any deviation noted, its evaluation, investigation conducted (if appropriate) or reference to that investigation if stored separately; and
− Results of release testing.
6.53 Written procedures should be established and followed for investigating critical deviations or the failure of a batch of intermediate or API to meet specifications. The investigation should extend to other batches that may have been associated with the specific failure or deviation.
6.6 Laboratory Control Records
6.60 Laboratory control records should include complete data derived from all tests conducted to ensure compliance with established specifications and standards, including examinations and assays, as follows:
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
− A description of samples received for testing, including the material name or source, batch number or other distinctive code, date sample was taken, and, where appropriate, the quantity and date the sample was received for testing;
− A statement of or reference to each test method used;
− A statement of the weight or measure of sample used for each test as described by the method; data on or cross-reference to the preparation and testing of reference standards, reagents and standard solutions;
− A complete record of all raw data generated during each test, in addition to graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific material and batch tested;
− A record of all calculations performed in connection with the test, including, for example, units of measure, conversion factors, and equivalency factors;
− A statement of the test results and how they compare with established acceptance criteria;
− The signature of the person who performed each test and the date(s) the tests were performed; and
− The date and signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards.
6.61 Complete records should also be maintained for:
− Any modifications to an established analytical method;
− Periodic calibration of laboratory instruments, apparatus, gauges, and recording devices;
− All stability testing performed on APIs; and
− Out-of-specification (OOS) investigations.
6.7 Batch Production Record Review
6.70 Written procedures should be established and followed for the review and approval of batch production and laboratory control records, including packaging and labelling, to determine compliance of the intermediate or API with established specifications before a batch is released or distributed.
6.71 Batch production and laboratory control records of critical process steps should be reviewed and approved by the quality unit(s) before an API batch is released or distributed. Production and laboratory control records of non-critical process steps can be reviewed by qualified production personnel or other units following procedures approved by the quality unit(s).
6.72 All deviation, investigation, and OOS reports should be reviewed as part of the batch record review before the batch is released.
6.73 The quality unit(s) can delegate to the production unit the responsibility and authority for release of intermediates, except for those shipped outside the control of the manufacturing company.