日期：2018-02-11 / 人气： / 来源：http://www.rzfanyi.com/ 作者：译声翻译公司美国FDA原料药生产质量管理规范(中部分 中英文）
4.4 Containment 4.4 限制
4.40 Dedicated production areas, which can include facilities, air handling equipment and/or process equipment, should be employed in the production of highly sensitizing materials, such as penicillins or cephalosprins.
4.41 The use of dedicated production areas should also be considered when material of an infectious nature or high pharmacological activity or toxicity is involved (e.g., certain steroids or cytotoxic anti-cancer agents) unless validated inactivation and/or cleaning procedures are established and maintained.
4.42 Appropriate measures should be established and implemented to prevent cross-contamination from personnel and materials moving from one dedicated area to another. 4.42 应当建立并实施相应的措施，防止由于在各专用区域间流动的人员和物料而造成的交叉污染。
4.43 Any production activities (including weighing, milling, or packaging) of highly toxic nonpharmaceutical materials, such as herbicides and pesticides, should not be conducted using the buildings and/or equipment being used for the production of APIs. Handling and storage of these highly toxic nonpharmaceutical materials should be separate from APIs.
4.5 Lighting 4.5 照明
4.50 Adequate lighting should be provided in all areas to facilitate cleaning, maintenance, and proper operations.
4.6 Sewage and Refuse 4.6 排污和垃圾
4.60 Sewage, refuse, and other waste (e.g., solids, liquids, or gaseous by-products from manufacturing) in and from buildings and the immediate surrounding area should be disposed of in a safe, timely, and sanitary manner. Containers and/or pipes for waste material should be clearly identified.
4.7 Sanitation and Maintenance 4.7 卫生和保养
4.70 Buildings used in the manufacture of intermediates and APIs should be properly maintained and repaired and kept in a clean condition.
4.71 Written procedures should be established assigning responsibility for sanitation and describing the cleaning schedules, methods, equipment, and materials to be used in cleaning buildings and facilities.
4.72 When necessary, written procedures should be established for the use of suitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents to prevent the contamination of equipment, raw materials, packaging/labeling materials, intermediates, and APIs.
5. PROCESS EQUIPMENT 5. 工艺设备
5.1 Design and Construction 5.1 设计和结构
5.10 Equipment used in the manufacture of intermediates and APIs should be of appropriate design and adequate size, and suitably located for its intended use, cleaning, sanitation (where appropriate), and maintenance.
5.11 Equipment should be constructed so that surfaces that contact raw materials, intermediates, or APIs do not alter the quality of the intermediates and APIs beyond the official or other established specifications.
5.12 Production equipment should only be used within its qualified operating range.
5.13 Major equipment (e.g., reactors, storage containers) and permanently installed processing lines used during the production of an intermediate or API should be appropriately identified.
5.14 Any substances associated with the operation of equipment, such as lubricants, heating fluids or coolants, should not contact intermediates or APIs so as to alter the quality of APIs or intermediates beyond the official or other established specifications. Any deviations from this practice should be evaluated to ensure that there are no detrimental effects on the material’s fitness for use. Wherever possible, food grade lubricants and oils should be used.
5.15 Closed or contained equipment should be used whenever appropriate. Where open equipment is used, or equipment is opened, appropriate precautions should be taken to minimize the risk of contamination.
5.16 A set of current drawings should be maintained for equipment and critical installations (e.g., instrumentation and utility systems).
5.2 Equipment Maintenance and Cleaning 5.2 设备保养和清洁
5.20 Schedules and procedures (including assignment of responsibility) should be established for the preventative maintenance of equipment.
5.21 Written procedures should be established for cleaning equipment release for use in the manufacture of intermediates and APIs. Cleaning procedures should contain sufficient details to enable operators to clean each type of equipment in a reproducible and effective manner. These procedures should include:
5.21 应当制订设备清洗及允许用于中间体和原料药生产的书面程序。清洁程序应当尽量详细，使操作者能对各类设备进行可重复的、有效 的清洗。这些程序应当包括：
5.22 Equipment and utensils should be cleaned, stored, and, where appropriate, sanitized or sterilized to prevent contamination or carry-over of a material that would alter the quality of the intermediate or API beyond the official or other established specifications.
5.23 Where equipment is assigned to continuous production or campaign production of successive batches of the same intermediate or API, equipment should be cleaned at appropriate intervals to prevent build-up and carry-over of contaminants (e.g., degradants or objectionable levels of microorganisms).
5.24 Nondedicated equipment should be cleaned between production of different materials to prevent cross-contamination.
5.25 Acceptance criteria for residues and the choice of cleaning procedures and cleaning agents should be defined and justified.
5.26 Equipment should be identified as to its contents and its cleanliness status by appropriate means.
5.3 Calibration 5.3 校验
5.30 Control, weighing, measuring, monitoring, and testing equipment critical for ensuring the quality of intermediates or APIs should be calibrated according to written procedures and an established schedule.
5.31 Equipment calibrations should be performed using standards traceable to certified standards, if they exist.
5.32 Records of these calibrations should be maintained. 5.32 校验记录应当加以保存。
5.33 The current calibration status of critical equipment should be known and verifiable.
5.34 Instruments that do not meet calibration criteria should not be used.
5.35 Deviations from approved standards of calibration on critical instruments should be investigated to determine if these could have had an effect on the quality of the intermediates(s) or API(s) manufactured using this equipment since the last successful calibration.
5.4 Computerized Systems 5.4 计算机控制系统
5.40 GMP-related computerized systems should be validated. The depth and scope of validation depends on the diversity, complexity, and criticality of the computerized application.
5.41 Appropriate installation and operational qualifications should demonstrate the suitability of computer hardware and software to perform assigned tasks.
5.42 Commercially available software that has been qualified does not require the same level of testing. If an existing system was not validated at time of installation, a retrospective validation could be conducted if appropriate documentation is available.
5.43 Computerized system should have sufficient controls to prevent unauthorized access or changes to data. There should be controls to prevent omissions in data (e.g., system turned off and data not captured). There should be a record of any data change made, the previous entry, who made the change, and when the change was made.
5.44 Written procedures should be available for the operation and maintenance of computerized system.
5.45 Where critical data are being entered manually, there should be an additional check on the accuracy of the entry. This can be done by a second operator or by the system itself.
5.46 Incidents related to computerized system that could affect the quality of intermediates or APIs or the reliability of records or test results should be recorded and investigated.
5.47 Changes to computerized system should be made according to a change procedure and should be formally authorized, documented, and tested. Records should be kept of all changes, including modifications and enhancements made to the hardware, software, and any other critical component of the system. These records should demonstrate that the system is maintained in a validated state.
5.48 If system breakdowns or failures would result in the permanent loss of records, a back-up system should be provided. A means of ensuring data protection should be established for all computerized system.
5.49 Data can be recorded by a second means in addition to the computer system.
6. DOCUMENTATION AND RECORDS 6. 文件和记录
6.1 Documentation System and Specifications 6.1 文件系统和质量标准
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 by maintaining 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 legible.
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 labeling 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 affect 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.6.18如果文件采用电子签名，它们应当经过证实，并且确保其安全可靠。
6.2 Equipment cleaning and Use Record 6.2 设备的清洁和使用记录
6.20 Records of major equipment use, cleaning, sanitation, 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, individual equipment records are not necessary if batches of intermediate or API follow in traceable sequence. In case where dedicated equipment is employed, the records of cleaning, maintenance, and use can be part of the batch record or maintained separately.
6.3 Records of Raw Materials, Intermediates, API Labeling 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 labeling 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
6.30 需保存的记录应当包括： 每次到货的每批原料、中间体、原料药标签和包装材料的生产商的名称，标识和数量;供应商的名称、供应商的管理编号，或其它识别号码;物料接收编号和接收日期;
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).
6.5 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 ensure 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 production code together with the date and time can serve as the unique identifier until the final number is allocated.
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. 6.53 应当建立并执行一种书面程序，对在符合规格上有重大偏差或不合格的一批中间体或原料药进行调查。调查还应当延伸到与这批失误或偏差有关的其它批号。
6.6 Laboratory Control Records 6.6 实验室控制记录
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:
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
The date and signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards 6.60 实验室控制记录应当包括从为了确保符合规定的规格和标准所做的所有测试中得到的下列完整的数据，包括下列检验和测定：
6.7 Batch Production Record Review 6.7批生产记录审核
6.70 Written procedures should be established and followed for the review and approval of batch production and laboratory control records, including packaging and labeling, 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 noncritical 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.
7. MATERIALS MANAGEMENT 7. 物料管理
7.1 General Controls 7.1 控制通则
7.10 There should be written procedures describing the receipt, identification, quarantine, storage, handling, sampling, testing, and approval or rejection of materials.
7.11 Manufacturers of intermediates and/or APIs should have a system for evaluating the suppliers of critical materials.
7.12 Materials should be purchased against an agreed specification, from a supplier, or suppliers, approved by the quality unit(s).
7.13 If the supplier of a critical material is not the manufacturer of that material, the name and address of that manufacturer should be known by the intermediate and/or API manufacturer.7.13 如果关键物料的供应商不是该物料的生产商，原料药或中间体的生产商应当获知该物料生产商的名称和地址。
7.14 Changing the source of supply of critical raw materials should be treated according to Section 13, Change Control.
7.2 Receipt and Quarantine 7.2接收和待验
7.20 Upon receipt and before acceptance, each container or grouping of containers of materials should be examined visually for correct labeling (including correlation between the name used by the supplier and the in-house name, if these are different), container damage, broken seals and evidence of tampering or contamination. Materials should be held under quarantine until they have been sampled, examined, or tested, as appropriate, and released for use.
7.21 Before incoming materials are mixed with existing stocks (e.g., solvents or stocks in silos), they should be identified as correct, tested, if appropriate, and released. Procedures should be available to prevent discharging incoming materials wrongly into the existing stock.
7.22 If bulk deliveries are made in nondedicated tankers, there should be assurance of no cross-contamination from the tanker. Means of providing this assurance could include one or more of the following:
7.23 Large storage containers and their attendant manifolds, filling, and discharge lines should be appropriately identified.
7.24 Each container or grouping of containers (batches) of materials should be assigned and identified with a distinctive code, batch, or receipt number. This number should be used in recording the disposition of each batch. A system should be in place to identify the status of each batch.
7.3 Sampling and Testing of Incoming Production Materials 7.3 进厂物料的取样与测试
7.30 At least one test to verify the identity of each batch of material should be conducted, with the exception of the materials described below. A supplier’s certificate of analysis can be used in place of performing other tests, provided that the manufacturer has a system in place to evaluate suppliers.
7.31 Supplier approval should include an evaluation that provides adequate evidence (e.g., past quality history) that the manufacturer can consistently provide material meeting specifications. Complete analyses should be conducted on at least three batches before reducing in-house testing. However, as a minimum, a complete analysis should be performed at appropriate intervals and compared with the certificates of analysis. Reliability of certificates of analysis should be checked at regular intervals.
7.32 Processing aids, hazardous or highly toxic raw materials, other special materials, or materials transferred to another unit within the company’s control do not need to be tested if the manufacturer’s certificate of analysis is obtained, showing that these raw materials conform to established specifications. Visual examination of containers, labels, and recording of batch numbers should help in establishing the identity of these materials. The lack of on-site testing for these materials should be justified and documented.
7.33 Samples should be representative of the batch of material from which they are taken. Sampling methods should specify the number of containers to be sampled, which part of the container to sample, and the amount of material to be taken from each container. The number of containers to sample and the sample size should be based on a sampling plan that takes into consideration the criticality of the material, material variability, past quality history of the supplier, and the quality needed for analysis.
7.34 Sampling should be conducted at defined locations and by procedures designed to prevent contamination of the material sampled and contamination of other materials.
7.35 Containers from which samples are withdrawn should be opened carefully and subsequently reclosed. They should be marked to indicate that a sample has been taken.
7.4 Storage 7.4储存
7.40 Materials should be handled and stored in a manner to prevent degradation, contamination, and cross-contamination.
7.41 Materials stored in fiber drums, bags, or boxes should be stored off the floor and, when appropriate, suitably spaced to permit cleaning and inspection.
7.42 Materials should be stored under conditions and for a period that have no adverse effect on their quality, and should normally be controlled so that the oldest stock is used first.
7.43 Certain materials in suitable containers can be stored outdoors, provided identifying labels remain legible and containers are appropriately cleaned before opening and use.
7.44 Rejected materials should be identified and controlled under a quarantine system designed to prevent their unauthorized use in manufacturing.
7.5 Re-evaluation 7.5重新评估
7.50 Materials should be re-evaluated, as appropriate, to determine their suitability for use (e.g., after prolonged storage or exposure to heat or humidity).
8. PRODUCTION AND IN-PROCESS CONTROLS 8. 生产和过程控制
8.1 Production Operations 8.1 生产操作
8.10 Raw materials for intermediate and API manufacturing should be weighed or measured under appropriate conditions that do not affect their suitability for use. Weighing and measuring devices should be of suitable accuracy for the intended use.
8.11 If a material is subdivided for later use in production operations, the container receiving the material should be suitable and should be so identified that the following information is available:
8.12 Critical weighing, measuring, or subdividing operations should be witnessed or subjected to an equivalent control. Prior to use, production personnel should verify that the materials are those specified in the batch record for the intended intermediate or API.
8.13 Other critical activities should be witnessed or subjected to an equivalent control.
8.14 Actual yields should be compared with expected yields at designated steps in the production process. Expected yields with appropriate ranges should be established based on previous laboratory, pilot scale, or manufacturing data. Deviations in yield associated with critical process steps should be investigated to determine their impact or potential impact on the resulting quality of affected batches.
8.15 Any deviation should be documented and explained. Any critical deviation should be investigated.
8.16 The processing status of major units of equipment should be indicated either on the individual units of equipment or by appropriate documentation, computer control systems, or alternative means.
8.17 Materials to be reprocessed or reworked should be appropriately controlled to prevent unauthorized use.
8.2 Time Limits 8.2 时限
8.20 If time limits are specified in the master production instruction (see 6.40), these time limits should be met to ensure the quality of intermediates or APIs. Deviations should be documented and evaluated. Time limits may be inappropriate when processing to a target value (e.g., pH adjustment, hydrogenation, drying to predetermined specification) because completion of reactions or processing steps are determined by in-process sampling and testing.
8.21 Intermediates held for further processing should be stored under appropriate conditions to ensure their suitability for use.
8.3 In-process Sampling and Controls 8.3 工序间的取样和控制
8.30 Written procedures should be established to monitor the progress and control the performance of processing steps that cause variability in the quality characteristics of intermediates and APIs. In-process controls and their acceptance criteria should be defined based on the information gained during the developmental stage or from historical data.
8.31 The acceptance criteria and type and extent of testing can depend on the nature of the intermediate or API being manufactured, the reaction or process step being conducted, and the degree to which the process introduces variability in the product’s quality. Less stringent in-process controls may be appropriate in early processing steps, whereas tighter controls may be appropriate for later processing steps (e.g., isolation and purification steps).
8.32 Critical in-process controls (and critical process monitoring), including control points and methods, should be stated in writing and approved by the quality unit(s).
8.33 In-process controls can be performed by qualified production department personnel and the process adjusted without prior quality unit(s) approval if the adjustments are made within pre-established limits approved by the quality unit(s). All test and results should be fully documented as part of the batch record.
8.34 Written procedures should describe the sampling methods for in-process materials, intermediates, and APIs. Sampling plans and procedures should be based on scientifically sound sampling practices.
8.35 In-process sampling should be conducted using procedures designed to prevent contamination of the sampled material and other intermediates or APIs. Procedures should be established to ensure the integrity of samples after collection.
8.36 Out-of-specification (OOS) investigations are not normally needed for in-process tests that are performed for the purpose of monitoring and/or adjusting the process.
8.4 Blending Batches of Intermediates or APIs 8.4 中间体或原料药的混批
8.40 For the purpose of this document, blending is defined as the process of combining materials within the same specification to produce a homogeneous intermediate or API. In-process mixing of fractions from single batches (e.g., collecting several centrifuge loads from a single crystallization batch) or combining fractions from several batches for further processing is considered to be part of the production process and is not considered to be blending.
8.41 Out-of-specification batches should not be blended with other batches for the purpose of meeting specifications. Each batch incorporated into the blend should have been manufactured using an established process and should have been individually tested and found to meet appropriate specifications prior to blending.
8.43 Blending processes should be adequately controlled and documented, and the blended batch should be tested for conformance to established specifications, where appropriate.
8.44 The batch record of the blending process should allow traceability back to the individual batches that make up the blend.
8.45 Where physical attributes of the API are critical (e.g., APIs intended for use in solid oral dosage forms or suspensions), blending operations should be validated to show homogeneity of the combined batch. Validation should include testing of critical attributes (e.g., particle size distribution, bulk density, and tap density) that may be affected by the blending process.
8.46 If the blending could adversely affect stability, stability testing of the final blended batches should be performed.
8.47 The expiry or retest date of the blended batch should be based on the manufacturing date of the oldest tailings or batch in the blend.
8.5 Contamination Control 8.5 污染控制
8.50 Residual materials can be carried over into successive batches of the same intermediate or API if there is adequate control. Examples include residue adhering to the wall of a micronizer, residual layer of damp crystals remaining in a centrifuge bowl after discharge, and incomplete discharge of fluids or crystals from a processing vessel upon transfer of the material to the next step in the process. Such carryover should not result in the carryover of degradants or microbial contamination that may adversely alter the established API impurity profile.
8.51 Production operations should be conducted in a manner that prevents contamination of intermediates or APIs by other materials.
8.52 Precautions to avoid contamination should be taken when APIs are handled after purification. 8.52 处理精制后的原料药应当采取预防污染的措施。
9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES
9.1 General 9.1 总则
9.10 There should be written procedures describing the receipt, identification, quarantine, sampling, examination, and/or testing, release, and handling of packaging and labeling materials.
9.11 Packaging and labeling materials should conform to established specifications. Those that do not comply with such specifications should be rejected to prevent their use in operations for which they are unsuitable.
9.12 Records should be maintained for each shipment of labels and packaging materials showing receipt, examination, or testing, and whether accepted or rejected.
9.2 Packaging Materials 9.2 包装材料
9.20 Containers should provide adequate protection against deterioration or contamination of the intermediate or API that may occur during transportation and recommended storage.
9.21 Containers should be clean and, where indicated by the nature of the intermediate or API, sanitized to ensure that they are suitable for their intended use. These containers should not be reactive, additive, or absorptive so as to alter the quality of the intermediate or API beyond the specified limits.
9.22 If containers are reused, they should be cleaned in accordance with documented procedures, and all previous labels should be removed or defaced.
9.3 Label Issuance and Control 9.3 标签发放与控制
9.30 Access to the label storage areas should be limited to authorized personnel.
9.31 Procedures should be established to reconcile the quantities of labels issued, used, and returned and to evaluate discrepancies found between the number of containers labeled and the number of labels issued. Such discrepancies should be investigated, and the investigation should be approved by the quality unit(s).
9.32 All excess labels bearing batch numbers or other batch-related printing should be destroyed. Returned labels should be maintained and stored in a manner that prevents mix-ups and provides proper identification.
9.33 Obsolete and out-dated labels should be destroyed.
9.34 Printing devices used to print labels for packaging operations should be controlled to ensure that all imprinting conforms to the print specified in the batch production record.
9.35 Printed labels issued for a batch should be carefully examined for proper identity and conformity to specifications in the master production record. The results of this examination should be documented.
9.36 A printed label representative of those used should be included in the batch production record. 9.36 批生产记录中应当附一张代表那些所用标签的印制好的标签。
9.4 Packaging and Labeling Operations 9.4 包装和贴签操作
9.40 There should be documented procedures designed to ensure that correct packaging materials and labels are used.
9.41 Labeling operations should be designed to prevent mix-ups. There should be physical or spatial separation from operations involving other intermediates or APIs.
9.42 Labels used on containers of intermediates or APIs should indicate the name or identifying code, batch number, and storage conditions when such information is critical to ensure the quality of intermediate or API.
9.43 If the intermediate or API is intended to be transferred outside the control of the manufacturer’s material management system, the name and address of the manufacturer, quantity of contents, special transport conditions, and any special legal requirements should also be included on the label. For intermediates or APIs with an expiry date, the expiry date should be indicated on the label and certificate of analysis. For intermediates or APIs with a retest date, the retest date should be indicated on the label and/or certificate of analysis.
9.44 Packaging and labeling facilities should be inspected immediately before use to ensure that all materials not needed for the next packaging operation have been removed. This examination should be documented in the batch production records, the facility log, or other documentation system.
9.45 Packaged and labeled intermediates or APIs should be examined to ensure that containers and packages in the batch have the correct label. This examination should be part of the packaging operation. Results of these examinations should be recorded in the batch production or control records.
9.46 Intermediate or API containers that are transported outside of the manufacturer’s control should be sealed in a manner such that, if the seal is breached or missing, the recipient will be alerted to the possibility that the contents may have been altered.
- 技术顾问协议（中英文翻译模板） 02-11