Training materials for SOP standard operating instructions

Basic knowledge of standard operating procedures

Standard Operating Procedure (SOP) is an important part of all kinds of standardized management certification and product certification, and all industries have SOP requirements. What is SOP? Simply put, SOP is a comprehensive set of operating instructions. Good SOP is a necessary condition to ensure the quality of products or services. SOP is not only a set of technical models, but also covers management ideas, management concepts and management means. Because mature industries have clear management norms and certification systems, the standardization and maturity of their SOPs are relatively high, and it is difficult to have evidence to compile SOPs. Because there is no mature laboratory management and certification system at present, it is a bit blind to write SOP in inspection work.

First of all, SOP has industry characteristics, and different industries have different SOPs. As far as inspection work is concerned, instruments and reagents have SOPs, and each item has its own different SOPs, not to mention that bacteria and biochemical immunity also have different SOPs, that is, different items in the same subject also have different SOPs. Therefore, the inspection SOP is not one, but a set.

Second, SOP should be detailed, that is, as long as it is related to the project, it should be detailed and comprehensive, including all possible details. Taking the pilot's operating rules as an example, the first competition is "sitting down", which shows the meticulous coverage of SOP. SOP is not a simple operation instruction, but a practical operation encyclopedia, which should be a reference book. An ideal SOP should make an ignorant person become an expert after learning.

Thirdly, SOP is not only a detailed work instruction, but also a part of management norms, which also contains quality control and management concepts, and even can see the staffing situation.

Although the specific contents of SOP in different industries are different, there are certain logical connections, so it is very valuable to learn from the particularly similar SOP requirements in other industries. Take pharmaceutical production SOP as an example, its requirements are required by GMP certification. According to GMP, the emphasis of its SOP is attached.

Drawing on the key points of drug SOP, the inspection SOP should include:

1. Operating procedures: operating procedures of experiments and instruments, acquisition of experimental instruments and post-experiment treatment, cleaning of experimental platform, treatment of experimental material overflow, etc.

2. Quality control: the quality control of experiments and instruments, such as the quality control quantity of experiments (high, medium and low? ), instrument calibration (personnel, time, methods, etc. ), maintenance, original records of experiments, etc. The original record of the experiment is very important. Besides patient data, the important means to find and solve problems should also include environmental parameters (weather conditions, temperature and humidity, etc.). ), the instrument used, the nature and quality of the sample, the manufacturer and batch number of the reagent, the quality control results of the same batch and the treatment methods (such as re-inspection, re-pumping, and sending reports). , as detailed as possible.

3. Judgment and handling of abnormal results: indicators for judging abnormal results, methods and procedures for analyzing and handling reasons. For example, is it an abnormal result or an experimental error or mistake? How to judge? What is the normal range of samples? If the specimens with abnormal range are handled, will they be re-examined or contacted with clinic more or less?

4. Process: It should include sample sending and receiving, report sending and receiving audit, quality and instrument problem handling, etc. There should be clear technological procedures. Such as who receives the specimen, who sends the report, how long it takes to receive it, how long it takes to send it, to whom it is received, and the procedures for reporting instrument failures.

5. Quality indicators, acceptance and storage of reagents and samples: whoever comes in will check, how to store, and whether the storage quality is guaranteed. Such as: who will monitor the temperature of the storage refrigerator, who will give an early warning when the reagent fails, and how often to replant the standard bacteria.

6. Personnel responsibilities: Personnel responsibilities are clearly reflected in the process, such as who to report the broken instrument, who to handle it, who to review the report form, what the experimental operators have to deal with and what to report to the supervisor. Of course, it is better to have personnel training SOP.

The preparation of inspection SOP can be based on the instrument operation manual and reagent instructions, as well as the upstream and downstream contents, such as sample collection and processing, abnormal result processing, etc. , according to the situation of the department as the SOP of the project or instrument. The SOP of each project is basically completed by SOP of sample collection, report distribution, reagent purchase, acceptance and warehousing, and distribution.

Appendix:

Key contents of SOP for pharmaceutical production:

1 Treatment of deviation

Explain in detail when and how there may be deviation from the expected results and conclusions, such as the yield is beyond the expected range, the product does not meet the specifications, the reaction conditions do not meet the specific parameters, and the equipment standards are unqualified. , conducted a study, what measures and procedures have been taken, and whether it is reasonable. Scientific experiment demonstration, approval, etc.

2 internal audit

Describe as clearly as possible how, when and by whom to conduct internal audit, why to conduct internal audit, and what methods and procedures to adopt.

3 external audit

Describe the frequency and reasons for auditing suppliers (raw materials, packaging materials, etc.). ) and the agreement (contract) used. The simplest and clearest way is to ask the supplier to fill out a self-designed form containing the above contents and go through the examination and approval procedures.

4 Quality audit procedures

Describe how and who will review and approve the batch records, process inspection and final API inspection data, for which the quality assurance department (QA) must be ultimately responsible before the finished products enter the market.

Five people were sent to the production department for intermediate process test.

Describe the regulations and standards that production personnel must meet when conducting intermediate tests in the process, such as checking the PH value of the solution before extraction.

6 standard specifications

Describe the personnel, departments and procedures responsible for reviewing and approving the quality standards of new raw materials, intermediates and drugs. If the quality standard changes, the review and approval of the procedure shall also be described in this standard operating procedure.

7 Approval of inspection procedures

Describe the personnel, departments and inspection procedures responsible for inspection procedures. This inspection procedure may be a national legal standard, such as the inspection procedures of China Pharmacopoeia, US Pharmacopoeia and National Pharmacopoeia, but if such procedures do not exist or are not applicable to specific raw materials, other relevant inspection methods can be used.

8 Approval of control in process specification

A program that describes the decisive program used to control the inspection in the process.

9 Verification Manual and Report

Describe the requirements for issuing, reviewing and approving process verification manuals and reports.

10 change control

Describe the work, audit and approval procedures that must be completed when the process, inspection method, in-process inspection and equipment are changed or will be changed.

1 1 sampling regulations

Describe how to notify the quality control department and how to collect, identify and transport samples to the quality control room.

12 approval of standard reference materials

Describe the personnel and departments that select and approve the reference substance for the relevant process flow.

13 analysis, research and evaluation

Describe the personnel and departments that select and approve the analysis, research and evaluation of related technical processes.

14 approval of test article

Describe the personnel and departments that select and approve samples for the relevant process flow, including relevant laboratory reports.

15 entrusted production materials audit

Describe how to test and use intermediates produced by third parties.

16 stability test

Describe the stability test procedure, including conditions, frequency, data review and documents.

17 contractor's evaluation and approval

Describe how to select, evaluate and approve contractors, such as entrusting external inspection when it is impossible within the enterprise.

18 batch record review

Describe how the production records are reviewed and signed, and by whom.

19 complaint review

Describe how to handle customer complaints, from acceptance to evaluation and finally to response.

20 Use of materials exceeding specifications

Describe when materials outside the specifications are allowed and what the approval procedures include.

2 1 Use of returned materials

Describe what must be done when using returned materials, and when it is acceptable or unacceptable.

22 SOP regular audit

Describe how often SOP is audited (usually every two years), who audits and who participates in the approval of the audit process.

23 the establishment of training records

Describe who received the training, what kind of training they received, by whom, and where the training documents are kept.

Purchasing, receiving, testing and storage of raw materials, intermediates, packaging materials and drugs.

Describe how all materials are arranged, when they are received, inspection procedures (such as labeling), storage location and method (storage location is separated from qualified materials, such as waiting area), and relocation after inspection (qualified area or unqualified area). The restocking and identification steps also apply to intermediates and drugs.

25 Disposal of unqualified materials

Describe how nonconforming materials are returned to suppliers (for example, notifying suppliers and preparing documents when purchasing) and where they are stored before being shipped out.

26 label control

Describe how labels are printed, stored, controlled and transported to production departments and other related departments when necessary. (Note: The area where labels are stored must be avoided, and the number of labels must be strictly controlled. )

27 Work clothes replacement

Describe who must change into work clothes (for example, operators wear uniforms and supervisors wear lab clothes), when and where to change clothes, and how often to distribute and change work clothes.

Control of gas supply and water supply system

Describe the use frequency of ventilation and all water supply systems, who is responsible for the inspection and the contents of the inspection (including its process, deionized water that meets the specifications of microbial analysis and endotoxin).

29 Identification of piping system in laboratory and production area

Describe the system used to identify all laboratory and production area pipelines, which can be a mixture of color codes, arrows, written instructions, labels, etc.

Cleaning procedures for production equipment, appliances and containers

Describe the proven and approved methods for cleaning each piece of equipment. If the procedure for cleaning several reaction tanks is the same, the procedure describing this cleaning can include cleaning all reaction tanks. )

3 1 Maintenance of production equipment

Describe what each Takuwa needs to do to keep the equipment running normally. It is necessary to make a record of each piece of equipment and explain what was done at the last maintenance time and who maintained it. )

Protection and inspection of equipment use

Describe how the equipment that is idle between uses is preserved, and the inspection that must be carried out before it is used again, and record the longest idle time (no more than 10 days or it is necessary to clean it again).

33 cleaning verification procedures

Describe how to develop cleaning verification procedures, who will review and approve these procedures, and where documents and records are kept. (The content should include the interval frequency of residue, detergent and biological load control. )

34 equipment calibration

Describe what equipment is calibrated, how often it is reviewed, by whom, how to mark it, and where the records are kept.

35 Unused or calibrated unqualified equipment.

Describe how to identify unused equipment that needs maintenance due to unqualified verification.

Verification of computer system

Some standards stipulate when computer systems are used in production and when they need to be verified. The main contents to be verified include: the operation of the system, measures taken to prevent faults, error check, record correction, restart and data recovery, change permission, change record, electronic signature, accurate check of manually entered data, data backup, user rights, etc.

37 equipment log

A log describing which devices are used and which products are produced. Note: This is unnecessary for special equipment. These contents have generally been included in the batch production records.

38 Preservation of main production and control records

Describe how to save and control the main production records (blank batch records) and analysis records (quality control inspection procedures), and require that the main production records should be kept in appropriate places by the quality assurance department.

39 the preservation of complete production and control records

Describe how to keep complete production records (complete batch records) and analysis test records (analysis reports). Complete batch records and analytical test reports shall be kept and controlled by the Quality Assurance Department.

Re-inspection cycle of all raw materials and intermediates

Explain in detail how often and which raw materials must be re-inspected. For example, after hydrochloric acid is qualified, the approval is valid for two years. If all the materials have not been used up by then, the rest must be rechecked before use. After passing, it can be postponed, otherwise it will be invalid.

4 1 multi-batch product mixing

Describe how to mix multiple batches of products. If mixed batch is to be carried out, each batch must be inspected and all standard parameters must be passed before it can be mixed with other batches of products. Mixing multiple batches of APIs should be avoided unless absolutely necessary.

42 API label identification

Describe how to label the finished product. A copy of the label should be included in the SOP. (The surface of the label is damaged and cannot be used. )

Traceability of 43 batches of products

Describe the system and operating procedures that can be tracked when a given batch of raw materials or intermediates has problems after use. If the relevant materials are to be recovered, the system needs to be more rigorous.

Once unqualified products are found, raw materials, intermediates and APIs shall be re-sampled and re-inspected.

Detailed description of raw materials, intermediates or APIs once found unqualified, under what circumstances should be reinspected, including how to reinspect and allow reuse.

Validate 45 analytical programs

Describe the characteristics that should be considered when verifying analytical methods, including accuracy, precision, specificity, detection limit, quantitative limit, linearity, range and breadth.

Inform customers of changes in established production and process control procedures.

Describe how and when to inform customers whether the established production and control procedures are to be changed or expected to be changed. It should be noted that minor changes, major changes and major changes should be distinguished.

Inspection and certification of reworked APIs

When the reworked API is inspected and qualified, any differences need to be analyzed. For example, critically analyze and evaluate the standards that lead to API disqualification.

48 Mixing of Newly Prepared and Recovered Solvents

Describe how to preserve and use newly prepared and recovered solvents. It is very inappropriate to mix the newly prepared and recovered solvents in the storage barrel. They can only be used in a batch of products, and can only be used as qualified products according to their respective specifications before use.

Recover 49 APIs

Describe what must be done and who to notify when it is decided that recycling is necessary.

50 drugs are used in clinical trials.

This paper describes the quality control measures and good manufacturing practices of clinical trial drug production. Note: The quality standard is the same as the medicinal raw materials used in regular production.