1.GMP defective - Institutions and personnel ...................................................................................................................................

1.Submit the responsibilities of sampling and inspection of intermediate products to the production department.

2.Training implementation is not in place, the training pertinence is poor. The new employee operates independently without mastering the operational skills.

3.Production management, quality management personnel are few, when someone asks for leave it can not be managed in time.

4.Special posts (such as Chinese medicinal materials inspection) lack of experienced person.

5.The quality transfer recipient has not received the corresponding training.

6.Maintenance personnel entering the clean area are not trained in microbiology knowledge.

7.For outsiders entering areas(rooms)of different cleanliness levels,no on-site guidance on personal hygiene and changing clothes is provided.

8.Clean clothes are not numbered, and different clean levels of clothes are cleaned and sorted together.

 

 2.GMP defective - Plant and facilities ...............................................................................................................................................

1.The functional area is small, the storage of production materials and the personnel operation space is not enough, which is easy to cause confusion and cross-pollution.

2.Failure to repair the plant according to the maintenance plan, and relevant records cannot be provided.

3.Plant renovation drawings are not controlled, there is no version number, and the revision records cannot be traced.

4.The plant design is unreasonable, and the storage area is also used as a

human circulation channel.  

5.The risk assessment of the shared plant facilities and equipment of multiple products is not sufficient.

6.No record of newly installed equipment and facilities or hardware renovation, no verification, modification of documents, and personnel training after renovation. 

7.During online production, the processed materials are placed on the same pad as the unprocessed materials, and the container has no material name.

8.The temperature and humidity monitoring points are not representative.The temperature, humidity and pressure difference exceed the standard, no appropriate treatment measures have been taken, and not implemented according to the deviation management system, and the record is not consistent with the actual situation.

9.The air flow type of the dust producing room is not confirmed, which can not fully prove that the dust in the area is not discharged.

10.The diameter of the sewer pipe is too small, and the sewage discharge overflows to the surrounding ground.The sink and cover plate are too small, and the water seal is too shallow to form a water seal.

11.The dust removal capacity of the dust removal facilities in the workshop is not enough, the method is not correct, and the dust removal effect is not good.

12.There is no reference to clean area management for the crushing room of Chinese herbal decoction pieces directly used as medicine and the entry and exit rooms of personnel and materials.

13.No effective physical isolation was taken between the different packaging lines in the packaging area.

14.Toxic decoction piece storehouse are glass doors and windows, which don’t meet the requirements for safe storage.

15.The acceptance, distribution and delivery areas can not effectively ensure that the materials and products are not affected by the outside world (such as snow and rain).

16.Sampling in production and quality control areas, no written procedures were established to prevent pollution, cross-contamination, confusion and errors.

17.Labs for biological verification, microbes, and radioisotopes were not set up separately.

18.The exhaust in the positive control chamber was not properly treated.

19.Dissolution tester and water tester are stored in the same chamber.

20.The storage room and the drinking water room in the quality control area are located in the operation area, which affects the operation.

 

 3.GMP defective - device management .............................................................................................................................................

1.The equipment installation position is close to the exhaust outlet, affecting the air flow type and increasing the risk of pollution.

2.Equipment maintenance, maintenance records and equipment operation records are inconsistent, and the equipment is both in operation and maintenance at the same time.

3.The accuracy of electronic scale can not meet the feeding accuracy of individual materials in the post.

4.Measure the sample using an electronic balance, load the sample with the reset function, and then remove the weighed sample, the number shows the plural value.

5.Maintain the equipment in the production process without taking the necessary protective measures.

6.At the end of production, the abrasive tools were disassembled and found to be damaged individually, and the quality tracking of the products produced in the early stage was not carried out.

7.The corresponding deviation analysis of maintenance and maintenance is insufficient, or not according to the change control procedures.

8.After replacing the new silicone tube with the peristaltic pump of the boiling granulator, the shot rate was not re-confirmed, resulting in an inaccurate shot amount during the granulation process, and the pellets were not easy to tablet

9.The cleaned equipment, containers and parts shall be placed in the same room as the equipment, containers and parts to be cleaned, and are not effectively isolated.

10.The key meters and control equipment used for production and inspection are not conducted according to the inspection cycle.

11.The marking information of metering device and control equipment is not cleaned or wrong.

12.The design of the sampling point is unreasonable, and the water quality monitoring is not representative.

13.Pure water pipeline design is unreasonable, with a blind pipe of more than 6 times the pipe diameter.

14.The hydrophobic sterilization filter installed in the pure water storage tank was not replaced in the specified period, or had no replacement record.

15.Pure water conveying pipelines have low points that cannot be emptied (such as buried underground).

16.Multiple workshops share one set of water-making system, and the storage tanks are operated separately in parallel.When a workshop stops production, the storage and distribution pipelines of the pure water system stops running, and no evaluation and regulation are made for the cleaning, sterilization and reconfirmation of the stopped system before it can be used again, and the stopped part forms a blind end, which is easy to breed microorganisms.

17.The deviation in the operation of the pure water system has not been analyzed and dealt with.

18.There is no preventive maintenance plan and procedures for equipment, and temporary methods are used for equipment maintenance.

19.The equipment is not operating within the specified standard range.For example, the mixing amount of the mixer exceeds the standard amount specified by the equipment.

20.The production capacity of the equipment does not match the actual product output.

 

 4.GMP defective - Materials and products .......................................................................................................................................

1.Materials are not issued on a “first in, first out” basis.

2.For materials that receive multiple batches at one time, they are mixed into one batch for sampling, inspection and release.

3.No check or identification item by piece, nor supplier site data audit.

4.The labels on the packaging of the purchased Chinese medicinal materials have no original labels such as origin, source and harvest date.

5.During the storage process, the storage temperature of the warehouse temperature control system fails, and the material quality is not evaluated and continues to be used for production.

6.The storage period of an intermediate product is not verified and is not supported by the data.Use materials beyond the reinspection period for production.

7.A label of a material is affixed to the outer packaging bucket cover, and the bucket cover is easily confused with other materials.

8.Labels of different varieties and specifications are stored in the same storage cabinet, and it is easy to use wrong without labeling.

9.No balance accounting of the amount of label issued, used and returned.

10.The unqualified intermediate products are not marked prominently, and no special isolation area is set up.

11.The validity period of the recycling batch product was not determined according to the earliest batch in the recycling treatment.

12.The rework process control parameters of individual products are inconsistent with the process.

13.After a certain batch of products are reprocessed, they are only inspected according to the conventional inspection items and released after passing them.The Quality Department did not evaluate the reprocessed products.

14.The return products of the same batch of different return channels are not stored and recorded separately.

15.In the clean verification of the production equipment shared by the enterprise varieties, the impact of toxic medicinal materials is not taken into account in the selection of reference substances.The equipment cleaning verification results do not fully demonstrate whether the common equipment will affect the cleaning.

 

 5.GMP defective - Confirmation and verification ............................................................................................................................

1.The enterprise has established the calculation standard of product pile density in the registration standard of drug registration declaration materials, but its process verification acceptance standard is only set to meet the requirements of Chinese Pharmacopoeia (2010 edition), and the heap density standards as met in the registration file were not included in the criteria.

2.The number of screened raw material was considered as the key process parameter but is not included in the process validation protocol.

3.After changing the speed of the mixer, no reconfirmation of material uniformity after mixing.

4.In the cleaning verification,the direct wipe sampling method was used to sample the residue after cleaning the equipment, but the wiping sampling method did not perform the test of the sampling recovery rate.

5.A total of three crude drug were produced on the same production line, and one crude drug was selected as the representative to perform cleaning verification, but the cleaning process of this crude drug is different from the other two.

6.The temperature controlled during the product production process verification is not consistent with the actual production control temperature recorded in the batch production record.

7.The verification record content is incomplete and lacks originality.

8.When there is a deviation in the verification process,relevant supplementary instructions and records for non-deviation processing.

9.The verification was not implemented in strict accordance with the contents of the verification scheme, and the change instructions were not made.

10.The number of sterilized items loaded on the steam sterilizer verification is inconsistent with the number of sterilized items loaded during the actual use of the sterilizer.

 

16.GMP defective - File management ...............................................................................................................................................

1.The process flow in the process procedure is inconsistent with the registered process.

2.The operating procedures are simple and are not operable.

3.The quality standard of enterprise products only implements the current pharmacopoeia standard, and did not implement the registration standard.

4.The revision of the document was not implemented in accordance with the procedures, not regularly reviewed and revised as required, and no relevant records of revision.

5.Some records do not have enough spaces.When there is an error in filing in the record, the modified data is small and difficult to read.

6.Due to busy operation and other reasons, failure to fill in the operation records and sign in time and then write memoirs afterwards.

7.To stick the automatic print record behind the batch record, the automatic print record is not signed by the operator.Thermal printing data is not copied, the data is not easy to save.

8.Production post records will be changed at will, and the person's signature and date are not changed at the change place.

9.After the change of an equipment, the batch production volume increased, the corresponding process procedures were not formulated or revised, and the process was not re-verified.

10.The packaging requirements for different specifications of the same product are not specified in the process procedures.

11.The temperature and humidity of the operation process are not specified in the process procedure of a icing sheet.

12.For products with special storage conditions requirements, the process procedures do not stipulate the storage conditions and storage time of packaging products.

13.Batch record design is more complex, need to be filled in more text content, not easy to record and easy to error.

14.Field records were replaced with blank paper and transcribed afterwards.

15.Power failure or equipment failure, production failure for several hours, the batch record is not truthfully recorded, and it is not reported according to the deviation handling procedure.

16.Deviation occurring in the package are not documented in the batch package record.

 

 7.GMP defective - Quality control and quality assurance ................................................................................................................

1.The working reference substance used in the laboratory cannot be traced to the source, and the relevant information of the national legal reference substance cannot be provided in the calibration record. The self-made reference substance has not been used regularly to prove the stability of its titer or content within the validity period.

2.The sampling management is not standard, and the corresponding sampling operation procedures are not formulated according to different dosage forms and different packages; the use of untreated sample containers will affect the test effect.

3.In the identification test for a product, the standard is the added milliliters (ml) of a certain reagent, the inspection record of the enterprise is a formatted record, and the accurate number of reagents added in the reagent operation is not recorded.

4.The national standard revised the standard of a certain piece of agent, increased the relevant material inspection, and the enterprises directly adopted the national standard method, and did not verify the necessary methods.

5.The results of intermediate product content of a preparation exceeded the standards stipulated by the enterprise, but were not investigated and processed.

6.The storage condition of a product is kept at room temperature, but the enterprise keeps the product in the shade.The sample retention conditions are inconsistent with the provisions.

7.An expiry date is not specified for a working control, or an expiry date is specified but the necessary verification and validation have not been carried out.

8.The results and data of the continuous stability investigation of a certain product have not formed a complete report, nor has it been reviewed by the person in charge of quality management.

9.The enterprise commissioned a third-party laboratory to conduct a product stability inspection, but only issued an inspection report, and failed to provide a detailed test plan, test records and qualification certificate.

10.The recording and judgment of the key parameters are not scientific, and no detailed changes of the indicators are recorded, so the trend cannot be analyzed.

11.The enterprise changed the raw material supplier, the evaluation data after the implementation of the change was insufficient, and the product stability after the implementation of the change was not investigated.

12.The model and specification of the chromatographic column used in the analysis method of a certain product have changed, and the change was not approved according to the analysis method.

13.In the annual deviation ledger of the enterprise, the reasons of the deviation are attributed to the operation error of employees.The corrective and preventive measures are to train employees, and the training content is related to equipment labeling.

14.During the summer, the temperature and humidity of the finished product warehouse deviate from the specified requirements, the warehouse has only recorded simple notes, not reported to the quality department, and not managed according to the deviation management standards.

15.The supplier can provide multiple specifications of a material with different quality standards, but the qualified supplier information provides no material specifications in the material supplier.

16.Site audit records are not detailed, including necessary instruments, equipment and personnel.Just marked with Yes and No in a formatted record table.

17.The supplier's production condition has changed greatly, and it was not reevaluated.

18.The retrospective analysis data of quality were not comprehensive, and no clear corrective measures were established for the adverse trends found.

19.The electronic data integrity defects:

（1）HPLC and other instrument workstations have no audit tracking function

（2）The computer connected to the device has a username and password, and the workstation software is not set

（3）The computer display date does not match the actual date

（4）The EXICL calculation table used for the content determination was not validated

（5）The batch test incentive map did not match with the map on the workstation, and the records were deleted and changed

（6）The enterprise has not established the computer system management procedures, and has stipulated the responsibilities and authority of the use and management personnel, as well as the corresponding requirements of data entry, review, backup and storage.

 

 8.GMP defective - Manufacturing management ...............................................................................................................................

1.The actual production batch exceeds the maximum batch specified in the process procedures.

2.The formulation product uses recovery calculations instead of mass balance calculations.

3.When the final mixing hopper is discharged, it is not tightly sealed with the receiving hopper, and there is dust diffusion, which is easy to cause cross-contamination.

4.Unidentified containers or tools exist on the production site.

5.There is no design to prevent wrong connection, and the operation is not reviewed by the personnel.

6.After cleaning, the inner wall of the hopper remains watery, or touched.

7.There is no sealing inspection and control item of aluminum-plastic packaging materials.

8.No inspection method and frequency of oral solid preparation for the effectiveness of waste removal device

9.The information content of the production status indication is incomplete, and the "theoretical output" is not indicated.

10.The containers are not numbered and have poor traceability and cannot determine whether cleaning has been performed.

11.The online testing equipment used to check for missed labeling is not tested regularly and has no test records.

12.Repackaging behavior is found in the deviation investigation and processing records, but the repackaging content and records are not reflected in the batch packaging records.

13.The enterprise stipulates that the intermediate inspection frequency of the packaging process is twice per shift, but there is no inspection time in the inspection record, and the traceability cannot be realized.

14.The process procedure is inconsistent with the original registration and declaration process.Change production process without authorization; batch production records not according to actual production process.Contradictions occur between the production record data.

 

 9.GMP defective -Product shipping and recall .................................................................................................................................

1.The returned products have been resold without strict evaluation by the quality department according to the operating procedures.

2.The returned products have been resold without strict evaluation by the quality department according to the operating procedures.

3.Only the production date and validity period of one batch of products are indicated on the outer box.

4.Wrong box record, box batch number does not consistent with the product production date.

5.The recalled products are not graded, and the process record of the recall products is incomplete.

6.The recalled product does not guarantee a clear striking logo on each packaging container.

 

 10.GMP defective -self-checking .......................................................................................................................................................

1.The effect of organizing regular self-inspection is poor, and the relevant responsibilities of all departments in the self-inspection group are not clearly defined.

2.There is no rectification plan for the self-inspection, and the rectification measures have not been implemented.

3.The quality audit of an enterprise is not enough to confirm that a quality system effectively meets the target requirements of its quality system.

4.The self-inspection report is incomplete, and the description of the defects is incomplete and unclear.

5.No defect inspection, and detailed corrective and preventive measures for deviations found in self-inspection.

6.No changes to the original system, such as new shade library, deployment of inspection instruments, etc.

7.Modify process parameters directly, no analysis and process verification; modify documents directly, without relevant verification.