CN106022668A - Risk assessment system for confirmation and verification - Google Patents

Abstract

The invention provides a risk assessment system for confirmation and verification. The system is composed of 18 different risk assessment tables, a work procedure for making a risk assessment report and a work template. During system risk assessment, after the 18 assessment tables of the system are filled in, the work procedure of the system makes the risk assessment report according to the risk assessment report template pre-made for the system. On the basis of the tables, the system can generate a confirmation and verification scheme, a confirmation and verification record, a confirmation and verification report, a confirmation and verification review assessment plan, a confirmation and verification data audit and a confirmation and verification review assessment report for a user according to system template design. The system is suitable for production and monitoring of industrial products for people, the workload of confirmation and verification data writing by the user can be greatly reduced, it is ensured that the confirmation and verification content is completely consistent with the requirements of risk assessment data, and quality risks are effectively controlled.

Description

A kind of for confirming and the risk evaluating system of checking

Technical field

This patent is applicable to production and the quality management of people's industrial products, it is provided that a kind of quality risk assessment system, rule Generalized people is with industry production and the risk assessment of quality management and the work based on risk assessment, as confirmed and testing Card, maintaining, verification calibration, sampling detection plan, Trend Analysis Program.

Background technology

Risk management is a special management art, and complete management process includes: risk identification, Risk communication, wind Danger control, Risk communication, risk examination & verification.Since it is 20 years in the past with people with the combination of industry production and quality management Thing." Good Manufacturing Practice and Quality Control of Drug " (revision in 2010) is widely applied quality risk in pharmacy and medical instruments field Management is as one of basic tool.Although the work of universal risky assessment and pattern exist, but during specifically used, Risk assessment, quality risk management itself lack of standardization, specific to people with industry production and quality management field, it is necessary to The quality risk being carried out specification industrial field by the design of a kind of system is managed.Up to the present performance is, neither one phase The risk assessment management mode available to ripe specialty or industry standard.

Confirm and verify the certification supervision and the effective quality monitoring instrument of association being as pharmaceutical production.But by At present, confirm to be mainly on network the technical data imitating or somewhat transforming formation each other with checking, and as regulator, Also concrete confirmation and checking detailed rules and regulations it are formed without, specific in the implementation process of enterprise, mainly by checking on-the-spot public procurator Judge.Although as effective quality monitoring instrument, the most effectively managing in supervision aspect.

Drug's GMP specification is pointed out, confirms that the degree with checking is formulated according to the result of risk assessment with scope.This results in Confirmation and the congenital defect of verification management, during because cut-off confirms to complete with checking, confirm the quality wind related to checking The Risk Management Process of danger factor preferably at most completes risk control, but the assessment of risk control measure, the communication of risk, wind The examination & verification of danger does not has the work of completing technology aspect.

The medication economics message chapter " basing oneself upon " the confirming and checking " of quality risk management " that Shi Zhengguo delivers is pointed out: include DQ, IQ, OQ, PQ interior each " confirming and checking " stage be all control and reduce a measure of quality risk, one to plan The evaluation measures of drug quality risk control measure taked, an evidence having official document to prove.So " confirm with Checking " it is exactly a step of quality risk management, or perhaps intend, in order to assess, the drug quality risk control measure taked And the test carried out, one section of interlude checking or check.In " confirming and checking " implementation process, it should concrete to this project The measure of " quality risk management ", control main points, important reference record is estimated, be identified through these tests, inspection and The result of inspection, the monitoring record of parameter can effectively assess the implementation result of taked drug quality risk control measure With can reduce degree and the effectiveness thereof of quality risk, certainly complete to assess drug quality risk management at " confirming and checking " After record needed for control measure, the collection of formal evidence, in addition it is also necessary to the follow-up risk assessment after control, the ditch of quality risk The work of the aspects such as siphunculus reason.From the point of view of quality risk management view, only complete follow-up risk control measure reevaluate, matter The examination & verification of amount risk and communication process, " confirming and checking " activity is only and is finally completed, and can guarantee " confirming and checking " Result can effectively be used, and drug quality risk control measure just can well be carried out.

By such combing, the angle in quality risk management to the definition of " confirming and checking " is: a kind of collection is commented Estimate the required record of effect and the test of data evidence, the inspection of the quality risk control measure that drug quality risk management is intended performing Or Survey Operations, this kind of activity has ultimately formed a set of may be used for and has assessed drug quality risk control measure effect and quality wind Danger reduces the formal clerking of degree, and this record may certify that relevant drug quality risk is controlled effectively, can Take under this quality risk slave mode (namely continuous verification state) of respective quality risk control measure with proof, Can be continual and steady realize certain specific technique purpose, the purpose of technological operation can meet intended purpose or purposes.

By this definition, can be clearly seen that, due to the drug quality risk control measure taked, formed Record, the needs such as control measures of risk adapt with the rank of quality risk, naturally, this adapt with quality risk rank Test, check and check, the most just constitute degree and the scope of " confirming and checking ".This namely drug's GMP specification to " confirm With checking " the cause of quality risk principle of management.

The article " slightly discussing confirmation and checking that quality risk guides " that Shi Zhengguo, Meng Quanke deliver at " Shandong chemical industry " is clearly Risk-oriented confirm the technical data composition with checking system:

Part I: quality risk is assessed, to confirming comprehensively to specifically describe with identifying object to carry out risk assessment afterwards, In general, including systematic influence assessment, parts criticality assessment and the Cause and Effect matrix risk assessment of GMP key element.Comment in risk On the basis of estimating, formulate about verification calibration, confirm with demonstration plan, equipment maintenance, sampling and quality testing plan, become Potential analysis plan etc..

Part II: confirm and proof scheme, implements confirmation and checking meter that Part I risk assessment is formulated comprehensively Stroke, it is divided into and designs confirmation, installation confirmation, operation confirmation, confirming performance four-stage.Need exist for it is emphasized that need to include in Confirm more than traditional equipment or the operational elements with checking scope, and should be all of key element of GMP, including Qualification such as operator, sampling personnel confirms.

Part III: confirm and checking logging template design.It is to set specially owing to confirming a lot of records being suitable for checking Meter, it is therefore desirable to will confirm that and the record specialized designs verified out, and confirm and other quality managements of using in checking The record of system forms the record material confirmed and needed for checking together.The design that above-mentioned record design and record are filled in is both needed to Quality system to be met is to record management, the relevant requirement of file management.

Part IV: confirm the summary with checking report and confirm and checking report.According to confirming and the answering of Verification Project Miscellaneous degree decides whether to form report summaries, and the test confirmed with checking, inspection are carried out comprehensive combing, necessary number According to analyzing, managing requirement etc..

Part V: confirm and checking implementation record.After confirming to report with checking, should include relevant to validation test All of record material, such as inspection record, test record, examining report and the statistic data of data.The most receivable Record electronic bits of data.

Part VI: confirm the review plan with Verification Project.Because quality risk management needs to look back assessment, need Want the plan of bond quality risk assessment, list concrete about verification calibration, maintaining, sample and monitor, trend analysis, Looking back assessment plan and looking back the relevant requirement assessed of validation test result, provides the application table looking back assessment.It should be understood that Need to understand department and the personnel looking back assessment result in detail.

Part VII: confirm the examination & verification approval with checking report.This part should include according to confirming and the result need File, the revision of record to be revised, train, examination & verification situation, confirm and examination & verification situation, confirmation and the validation test of checking report During about change and the examination & verification situation of deviation, the demonstration plan again of confirmation again etc. of formulation.Audit qualified after, provide confirm with The checking certificate of competency.

By the support of the technical data of above-mentioned seven parts, the confirmation of ability difficulty action accomplishment risk management aspect and checking Management.In other words, confirmation and the verification management system of Erecting and improving, at least need in terms of above-mentioned seven confirming and testing The management of card is planned comprehensively.Before verifying year or confirming again to verify again, all should assess, according to looking back, the requirement planned, Form the report looking back assessment.

Summary of the invention

The confirmation that the research of this patent be have accumulated over for many years and verification management experience, based on installations and facilities confirmation with Checking, and confirming and during verification management, completing a whole set of quality risk management program.Clearly define the people of specification With industry production and the general risk assessment of supervision-confirm the work system with checking-trend retrospective analysis.

A kind of for confirming and the risk evaluating system of checking, 18 different risk assessment forms, making risk comment Estimate working procedure and the working template composition of report, it is adaptable to production and the supervision of people's industrial products use, and this system is permissible The confirmation being significantly reduced user writes workload with verifying data, and guarantees to confirm that the content with checking provides with risk assessment The requirement of material is completely the same, helps user that main attention is focused among concrete quality risk management, effectively controls quality Risk.

Described 18 different risk assessment forms are respectively as follows: the basic condition table confirmed with Verification Project；It is applicable to produce The systematic influence assessment table of system；It is applicable to the classification assessment table of analytical tool；Parts criticality assessment table；The inefficacy of parts Mode evaluation table；The decomposition assessment table of production technology；The failure mode evaluation table of production technology；Project GMP key element and quality refer to Target decomposes assessment table；The failure mode evaluation table of project GMP key element and quality index；Quality risk control plan summary table；System The verification calibration planning chart of system parts；The maintaining planning chart of system unit；The cleaning of project and use monitoring plan table；If Meter confirms (DQ) planning chart；Install and confirm (IQ) planning chart；Run and confirm (OQ) planning chart；Confirming performance (PQ) planning chart；Take Sample plan and Trend Analysis Program table；Confirm to assess planning chart with Verification Project.

The working template of described Risk Assessment Report is described and form by the basic of the risk assessment form different to 18 Collectively constituting of Position Design, basic description and the position of form in the Risk Assessment Report of system are the form bodies with bookmark Existing, template is a complete document, after utilizing the establishment of working procedure completion report, to the catalogue in template and header, page Digital content i.e. can get complete Risk Assessment Report after being updated.

Described confirmation is to be designed according to corresponding LISP program LISP with the working procedure of the risk evaluating system of checking Working procedure, it is possible to achieve the Data Enter from above table to template, thus realize on the basis of working registration form, quickly accurate Confirmation that true establishment risk assessment project is corresponding and checking material, including Risk Assessment Report, confirm and proof scheme, really Recognize with checking record design, confirm with checking report summaries, confirm with checking report, confirm with checking implementation record, confirm with Checking look back assessment plan, confirm with checking data verification, confirm with checking look back assessment report.

The feature composition of the working template of described Risk Assessment Report includes: the content of risk assessment includes systematic influence Property assessment, and parts criticality assessment following closely, the assessment of process operations, the assessment of GMP key element, at risk identification and wind After the assessment of danger, by each risk elements identified being carried out the overall planning of risk control, assess risk elements control The practical plans of system, including verification calibration, maintaining, cleaning-sterilizing requirement and the requirement of process-monitor, confirm and verify, take Sample plan and trend analysis.

The risk assessment of this patent is divided into following several stages: the preparation of risk assessment (preparation of technical data and The description of evaluation object), systematic influence assessment (production equipment) or experimental facilities classification assessment, risk assessment (critical component Assessment and FMEA assessment, production operation operation assessment and FEMA assessment, GMP key element and about quality index assessment and FMEA assesses), the formulation of risk control measure (verify and calibrate, maintenance, cleaning-sterilizing and production monitoring, confirm with Checking, sampling detection and trend retrospective analysis, these risk control measures or carry out clearly in related management file, or In Risk Assessment Report clearly).Above-mentioned work process can illustrate with the workflow diagram of this system.It is specifically shown in this The accompanying drawing of patent.

After completing the filling in of above-mentioned risk assessment form, the working procedure arranged by system, in technical data template Relevant position carry out in the replacement of perhaps form, it is possible to quickly obtain meeting the technical data of laws and regulations requirement, at least include: Risk Assessment Report, confirm with proof scheme, confirm with checking record design, confirm with checking report summaries, confirm with checking Report, confirm with checking implementation record, confirm with checking look back assessment plan, confirm with checking data verification, confirm with Assessment report is looked back in checking.

This patent (including: the medication economics message chapter that Shi Zheng state delivers " bases oneself upon quality risk pipe at disclosed article " confirming and checking " of reason "；Article " the confirmation that slightly opinion quality risk guides that Shi Zhengguo, Meng Quanke deliver at " Shandong chemical industry " With checking ") theoretical research on the basis of, carried out substantial amounts of actual rehearsal, carried out creating in rehearsal and improved.Concrete body Now in.

(1) design the specification form system of risk assessment, be embodied in that the preparatory stage in risk assessment, bright Really evaluation object is described the requirement of content, the control meter after risk identification, risk assessment, to each risk elements Drawing and carry out combing, the most specifically implement to go among corresponding work plan, this work is by increasing " table 09, quality wind Danger control plan summary table " complete.

(2) according on disclosed Research foundation, having worked out the template of Risk Assessment Report, specification people is raw with industrial products The workout content of the Risk Assessment Report produced and supervise and form.

(3) docking risk assessment form and the computer program of corresponding report data are developed.

(4) above-mentioned assessment form is integrated with working template, computer program, defined work system, used Person can directly form corresponding document information on the basis of risk assessment form.Greatly alleviate the document preparation of enterprise Workload.The mutual relation of these work is simply discussed by presently disclosed research, is not related to its concrete operation And combination.

(5) this patent is concerned with the concrete application of the confirmation of risk-oriented and proof theory, particularly risk assessment, really Recognize and being connected of checking, different confirm and the realization of the content consistencies of statement in verifying data.

Beneficial effect

(1) use uniprocessor version risk evaluating system after, quality risk can assess by manufacturing enterprise, staff training, confirmation and Checking, production scene and organization of production, maintaining, verification calibration, sampling detection, the trend analysis coordinating and unifying is got up.Due to Native system can the guarantees risk evaluation result of height and the concordance of other work, after utilizing this quality risk assessment system, Enterprise can play and confirm to act on the preview of production scene, organization of production with commander with checking, and the energy of management is focused on Risk assessment and effective control aspect of risk.

(2) for regulator, after this system development is formed network data base system, by the production of enterprise, storage Core standby, transhipment confirms to carry out unified standard with Verification Project by this system, by confirming and can well demonstrate Solve the actual management level of enterprise, by the comparison of risk management, can find that trade management is not enough in time.Make the prison of industry Pipe, not in the substantial amounts of inspection of needs, reduces the unnecessary wasting of resources, has ensured supervision effect and product quality.

(3) production and the supervision that are applicable to people's industrial products use, and this system can be significantly reduced the confirmation of user Write workload with verifying data, and guarantee that the content confirming with verifying is completely the same with the requirement of risk assessment data, side Help user that main attention is focused among concrete quality risk management, effectively control quality risk.

Accompanying drawing explanation

Fig. 1 is the working-flow figure of the present invention；

Fig. 2 is the Cause and Effect matrix pattern of GMP key element of the present invention assessment.

Detailed description of the invention

The risk evaluating system of this patent is made up of three parts, is discussed by this embodiment and confirms and the wind of checking The composition of system is assessed in danger, as concrete system operation programs or the design of working template, and can be according to concrete exploitation Platform is the most flexible, although within the protection domain of this patent, but is not that this patent can comprehensive list really.

Part I: confirm and the table section of the risk evaluating system verified.

This patent discusses the tissue of risk assessment form with EXCEL form, is not the form group said and can not use other Knit risk assessment form, eventually form, as long as can be combined with copy editor's software, the sets of tables that the software of document report combines Form of knitting is all acceptable.The form of this patent has a following feature:

(1) line number of each form of this patent is can be according to the increase in demand of actual items, and grammatically wrong sentence is confined to this The quantity that example is given.Having unlimited ductility, specifically, filling in of these forms can be the form of unitem, Can also be risk assessment summary sheet or perhaps the risk management storehouse of all items.

(2) form of this patent is arranged according to its order numbered, and according to the relation between form, system is being filled in a form Time can provide example, or by the corresponding information Auto-writing of above form to current assessment form.

(3) there is dependency relation in the form of this patent, should be relevant in the operating process of inserting line or deletion row The synchronous operation function of connection form, such as, in all forms relevant to parts, as long as inserting in parts key evaluation table Entering a profession or delete capable operation, other association table should carry out the simultaneously operating of relevant position by program at corresponding site, The arrangement of parts order of the association table after guaranteeing inserting line or deleting row and the order of related content do not change.

(4) sheet paradigm of this patent organizational form in EXCEl is: whole forms organizes a book In file；2. organize according to the order of this example, and worksheet be named, as " table 01 ", " table 02-1 " ..., " table 18 ".3. first being classified as A row, second is classified as B row.3rd is classified as C row, the like.Comprise the first behavior of gauge outfit 1, the second behavior 2, the like.

Table 01, confirms the basic condition table with Verification Project (risk assessment project)

Particular content in form, such as the file needed, composition of personnel, the division of technical data, can be according to enterprise Concrete condition adjusted, but do not affect the composition of this patent, technology use.

Table 02-1, systematic influence assessment table (being applicable to production system)

This table is applicable to the system or equipment of production and application, the 1 to 7 of evaluation problem, belongs to the assessment of computerized system.Problem 8 to 16 belong to systematic influence assessment literary composition slightly longer, the design of evaluation problem can be adjusted according to specific circumstances.

Table 02-2, classification assessment table (being applicable to analytical tool)

Wherein: whether Q19 instrument is for GMP scope.The data that Q20 instrument or instrument produce directly affect made product originally Body or product quality, purity, the decision-making of titer.Whether this instrument of Q21 has measurement performance.Whether this instrument of Q22 enters after buying Row user calibrates.Whether the use of this instrument of Q23 uses observational method with the more alternate manner of external demand.Whether this instrument of Q24 is measured Numerical value or control physical parameter.Whether Q25 has a single computer in order to control instrument or to gather data Q26 instrument Whether it is used for measuring certain technological parameter or providing one measuring or calculating data.Q27 instrument is the need of changing spare part/consumptive material Or instrument supplier suggestion carries out preventive maintenance maintenance.

Table 03, parts criticality assessment table

This table, with industrial steam pipeline as example, can according to circumstances supplement perfect.Wherein: Q28 parts are used for proving whether symbol Close the regulation of registered technique；The normal operating of Q29 parts or control have directly impact to product quality；Q30 parts are sent out Raw fault or alarm condition have directly impact to product quality or effect；The information of these parts of Q31 be registered as batch record, Criticize clearance data or a part for other GMP associated documents；Q32 parts directly contact with product or product composition；Q33 parts are used In controlling to affect the key process parameter of product quality, and to the performance of control system without independent checking；Q34 parts are used In creating or keeping certain system core state.

Table 04, the failure mode evaluation table of parts

Table 05, the decomposition assessment table of production technology

Sequence number	Operating procedure	Operation describes, such as purpose and parameter	Impact on quality describes	Management main points	Perform file or reference material
						001	PLC control panel logs in	Operation purpose and affecting parameters 001	Step affects description 001	Step management 001
002	PLC control panel is reported to the police and is eliminated	Operation purpose and affecting parameters 002	Step affects description 002	Step management 002
						003	PLC control panel parameter is arranged	Operation purpose and affecting parameters 003	Step affects description 003	Step management 003
004	PLC control panel parameter query	Operation purpose and affecting parameters 004	Step affects description 004	Step management 004
						005	PLC control panel sensitivity test	Operation purpose and affecting parameters 005	Step affects description 005	Step management 005

Table 06, the failure mode evaluation table of production technology

Table 07, the decomposition assessment table of project GMP key element and quality index

Table 08, the failure mode evaluation table of project GMP key element and quality index

Table 09, quality risk control plan summary table

Table 10, the verification calibration planning chart of system unit

Sequence number

Component names

Measurement scope

Range

Verification calibration steps

Verification calibration criterion of acceptability

Verification calibration cycle

Verification calibration plan

001

Parts 001

Method of calibration 001

Verification standard 001

Check-verifying period 001

Verification plan 001

002

Parts 002

Method of calibration 002

Verification standard 002

Check-verifying period 002

Verification plan 002

003

Parts 003

Method of calibration 003

Verification standard 003

Check-verifying period 003

Verification plan 003

Table 11, the maintaining planning chart of system unit

Sequence number	Component names	The content of maintaining	The criterion of acceptability of maintaining	Maintenance cycle	The secondary requirements of maintaining
						001	Parts 001	Maintenance content 001	Maintenance criterion 001	Maintenance period 001	Safeguard auxiliary 001
002	Parts 002	Maintenance content 002	Maintenance criterion 002	Maintenance period 002	Safeguard auxiliary 002
						003	Parts 003	Maintenance content 003	Maintenance criterion 003	Maintenance period 003	Safeguard auxiliary 003

Table 12, the cleaning of project and use monitoring plan table

Sequence number	Operating procedure or GMP element name	Cleaning requirement	Sterilization or sterilizing requirement	The monitoring method of technological parameter and record	The precision of process-monitor and limit
						001	Operating procedure 001	Cleaning requires 001	Sterilization requires 001	Monitoring method 001	Monitoring accuracy and limit 001
002
						003
004

Table 13, design confirms (DQ) planning chart

Table 14, installs and confirms (IQ) planning chart

Table 15, runs and confirms (OQ) planning chart

Table 16, confirming performance (PQ) planning chart

Table 17, sampling plan and Trend Analysis Program table

Sequence number

Monitoring object oriented

The sample ID of monitoring

Need the index of detection

Accept standard

Waning limit

Correction limit

Trend Analysis Program

001

Operating procedure 001

Sample ID 001

Monitoring index 001

Sample standard 001

Waning limit 001

Correction limit 001

Trend plan 001

002

Operating procedure 002

Sample ID 002

Monitoring index 002

Sample standard 002

Waning limit 002

Correction limit 002

Trend plan 002

003

Operating procedure 003

Sample ID 003

Monitoring index 003

Sample standard 003

Waning limit 003

Correction limit 003

Trend plan 003

Table 18, confirms to assess planning chart with Verification Project.

Part II: the template part of system.

This part with the template-setup of Risk Assessment Report as example, the deletion developing principle of other Data templates of system Similar.Horizontal line therein represents the ground floor bookmark of bookmark this content entitled and arranges, and arranges that to represent bookmark entitled with shading The second layer bookmark of this content is arranged.

In the homepage of template information, specify confirming and the composition of checking System Documents of risk-oriented, include: (1) matter Amount Risk Assessment Report；(2) confirmation and proof scheme；(3) confirm and checking record design (template)；(4) confirm and checking report Accuse summary；(5) confirm and checking report (in full)；(6) confirm and checking implementation record；(7) the review assessment with checking is confirmed Plan；(8) examination & verification with verifying data and the certificate of competency are confirmed；(9) confirm and the review assessment report of checking.By overstriking or The mode of risk illustrates which part of the data that currently belongs to.Indicate the basic condition confirmed with Verification Project, such as: confirm simultaneously With Verification Project title, confirm with Verification Project numbering, confirm with verifying data numbering, confirm with Authentication-Type, device name, Device numbering, use department, make employment, administrative man.

The situation of this set data is illustrated by the title page in data, and content is:

For guaranteeing to confirm and checking, risk assessment content and the concordance of form of presentation thereof.Same confirmation and the matter of Verification Project Amount risk (review) assessment report, confirm with proof scheme, confirm with verify record design (template) three data should enter simultaneously Row examination & approval.

The confirmation of same confirmation and Verification Project and checking report summaries, confirm to report (in full) with checking, confirm and test The data of the assessment plan of looking back, confirmation and the examination & verification of verifying data and the certificate of competency that demonstrate,prove implementation record, confirm and verify should be same Time examination & approval.If desired, other files being associated revised and logging template should also be included.

After above-mentioned cover strcution and explanation, it it is the catalogue of data.Content to headerfooter, it is special that this patent does not do Requirement.The template of the Risk Assessment Report of this patent is as follows:

1 drafts, audits and ratifies

Following signature represents that you take part in the risk assessment of this project, and has read over this Risk Assessment Report, detailed Solution wherein content, and be to perform risk control measure to get ready.

After the approval of this Risk Assessment Report, should perform in strict accordance with the methods and procedures wherein specified, and to producing Deviation itemized record and rectified a deviation.

Risk assessment object factory

2.1 risk assessment object general introductions

Confirm to describe with identifying object (to include: the 1. model number of evaluation object, position, composition and functional characteristics；2. purposes and Use the description of parameter；3. use flow process and use the description of state such as load mode；4. maintaining brief account situation；5. change And file recension；6. deviation and investigation thereof describe, and the correction preventive measure of necessity；7. confirm and the management of checking Requirement；8. confirm and the general introduction of checking situation).

The content of risk assessment and foundation

Confirmation and checking are one of risk control measures during quality risk management.Confirming and the implementation process of checking In, risk control plan detailed including the confirmation and demonstration plan in each stage should be formulated according to the result of risk assessment.

Confirm that the risk assessment data being suitable for checking includes: systematic influence assessment, parts criticality assessment, operation stream Journey risk assessment, the risk assessment of GMP key element Cause and Effect matrix.

Include the higher GMP managing risk that confirms just to anticipate with verification management category in, should carry out quality risk assessment, control, Link up, the entire flow of examination & verification manages.Should be according to looking back assessment before before annual quality retrospective analysis and confirming again/verifying again Plan carries out looking back assessment, improves the quality risk assessment content confirmed with Verification Project if desired.And build based on this The quality risk data base of production management.

Risk assessment

2.3.1 basic parameter sets and RPN(risk factor) value calculating

The setting of drug quality risk basic parameter see table:

Score value	Probability of happening (P)	The severity (S) of harm	(D) can be estimated
				1	Occur hardly.	Product quality is had little to no effect, can ignore.	Directly detected by instrument or have warning to arrange.
2	Probability is the least.	Product quality is produced remote-effects, is likely to result in the wasting of resources.	Can be found by conventional manual's detection every time.
				3	Occur once in a while.	Product quality is produced minimal effect, such as packaging external appearance etc..	Can there is artificial measurement indirectly every time.
4	Occurrence frequency is high.	Have influence on product quality, cause contamination of products, make product not meet quality criteria requirements, violate GMP principle.	Periodically manual detection can find.
				5	Occurrence frequency is the highest, often occurs.	Directly contribute contamination of products, serious violation GMP clause.	Uncertain burst, at present without suitable detection means.

The severity S of the calculating of RPN value: RPN=probability of happening P × harm × D can be estimated

2.3.1 defining of risk class

2.3.2.1 low risk: RPN≤15, risk is relatively low, occurs for risk when of can taking measures or be suitable Basic reason improve.

2.3.2.2 moderate risk: 15 < RPN≤24, risk is medium, should formulate CAPA timetable, is timely completed CAPA and arranges Execute.

2.3.2.3 high risk: RPN>24, excessive risk, it is impossible to accept, should take immediately CAPA measure be reduced to RPN< 24。

When 2.3.2.4 endangering severity (S) more than 3, also should there is reliable risk control measure.

Parameter data

2.4.1 Good Manufacturing Practice and Quality Control of Drug (revision in 2010).

2.4.2 current edition Chinese Pharmacopoeia.

2.4.3 pharmaceutical technology checking enforcement manual, He Guoqiang edits, Chemical Industry Press, in November, 2012.

2.4.4 PDA technical report 44: gnotobiosis quality risk manages, 2008.

2.4.5 systematic influence evaluation procedure (reference number of a document :) 1.

2.4.6 parts criticality assessment code (reference number of a document :) 1.

2.4.7 FMEA method evaluation procedure (reference number of a document :) 1.

2.4.8 URS data (numbering) 1.

2.4.9 rule of operation (reference number of a document :) 1.

2.4.10 maintenance code (reference number of a document :) 1.

2.4.11 technological procedure (reference number of a document :) 1.

2.4.12 deviation processing rule of management [reference number of a document: ZT-Ⅸ-00G012(03)] 1.

2.4.13 Variation control code [reference number of a document: ZT-Ⅸ-00G011(03)] 1.

2.4.14 quality standard and numbering 1.

2.4.15 sampling code and numbering 1.

2.4.16 detection code and numbering 1.

2.4.17 verification calibration code and numbering 1.

2.4.18 cleaning-sterilizing code and numbering 1.

2.4.19 verification management code and numbering 1.

2.4.20 verification operation code and numbering 1.

2.4.21 risk management code and numbering 1.

2.4.22 classification evaluation procedure and numbering 1.

2.4.23 producer's technical data 1.

Systematic influence is assessed

3.1 assessment foundations

3.1.1 systematic influence evaluation procedure (reference number of a document :) 1.

3.1.2 rule of operation (reference number of a document :) 1.

The problem design of assessment

The purpose of systematic influence assessment (SIA) is to set up the critical system having a direct impact production quality, it is simple to right It carries out key-point management.Whether assessment or the systematic influence of computerized system is assessed, and is paid close attention in evaluation process Directly focus is to bring potential risk to product quality or patient medication.If it is confirmed that existing defects, but finally will not carry Carry out patient medication safety or drug quality brings risk, the result of determination that assessment is formed can withdraw to backseat 's.

3.2.1 the problem design of computerized system assessment

3.2.1.1, system includes the parts of hardware and software the most simultaneously？

3.2.1.2 whether the parts of this software+hardware realize certain control function？

3.2.1.3 whether the parts of this software+hardware realize certain operating function？

3.2.1.4 whether the parts of this software+hardware control certain GMP related data？

3.2.1.5 whether the parts of this software+hardware control registration, pharmacopeia related data？

3.2.1.6 whether the parts of this software+hardware have data memory function？

3.2.1.7 whether the parts of this software+hardware have the warning function that exceeds standard.

Decision principle: system has hardware and software part to collectively constitute, software part complete produce control, data acquisition, Support medicine GxP management, then belong to computerized system.The most it is not judged to computerized system.

The problem design of systematic influence assessment

3.2.2.1 whether system directly affects key process parameter or Key Quality attribute；

3.2.2.2 whether system directly contacts with product, and has potential impact or carry to patient the wind comes to end product quality Danger；

3.2.2.3 whether system provides adjuvant or for producing a certain composition or solvent, and the quality of these materials (or it lacks Lose) end product quality may there be is potential impact or bring risk to patient；

3.2.2.4 whether system is for clean, sterilization or sterilizing, and the system failure may cause clean, sterilization or sterilizing Failure, thus bring risk to patient；

3.2.2.5 whether system provides a suitable environment (if nitrogen protection, the maintenance of humiture, and these parameters are for producing During product key process parameter a part of) control the risk relevant to patient；

3.2.2.6 whether system produces, processes or stores the data let pass for product or reject, key process parameter；

3.2.2.7 whether system provides container to seal or product protection, as failure will bring risk to patient or cause product Quality Down；

3.2.2.8 whether system provides product identification information (such as lot number, effect duration, anti-false sign)；

3.2.2.9 this system provides public utility or certain function for a certain system that directly affects；

3.2.2.10 a certain performance directly affecting system is had an impact by system；

3.2.2.11, in addition to stability data, whether this system provides the data declared for registration (or to support what this was declared Technical report)；

3.2.2.12 the judgement of systematic influence assessment result.In 1-8 problem in above-mentioned 11 problems, any one is asked The answer of topic is "Yes", and system is assessed as there be " directly affecting system " (or " having a direct impact ") to product.Ask for above-mentioned 11 In topic, in 9-11 problem, any one answer is "Yes", and system need to be evaluated as " remote-effects system ".If above-mentioned 11 are asked The answer of topic is no, then this system is judged to " without affecting system ".

The classification assessment of analytical tool

The impact property of analytical tool is assessed and is divided into four-stage: (1) preparatory stage, descriptive system or analytical tool；(2) GMP shadow Ring assessment；(3) instrument classification assessment；(4) calibrate and the assessment safeguarded.

3.2.3.1 the preparation of assessment.Numbering and the correlation technique data of instrument (system) is confirmed by equipment user of service. And the scope of clear and definite instrument (system) and purposes, it should be understood that relevant parameter in the description of purposes.

3.2.3.2 the assessment of GMP impact property, this assessment is made up of two problems, and its instrument answered as "Yes" needs to confirm With checking, and carry out the assessment of second stage, if "No", evaluation process can be terminated.

3.2.3.2.1 whether instrument is for GMP scope；

3.2.3.2.2 the data that instrument or instrument produce directly affect made about product itself or product quality, purity, The decision-making of titer？

3.2.3.3 the classification assessment of instrument, this assessment is made up of 5 problems, and first three question answering is "No", it is determined that for A Class；The answer of the 4th and the 5th problem is "Yes" and is judged to C class, is otherwise judged to B class.

3.2.3.3.1 whether this instrument has measurement performance；

3.2.3.3.2 whether this instrument carries out user's calibration after buying；

3.2.3.3.3 whether the use of this instrument uses observational method with the more alternate manner of external demand；

3.2.3.3.4 whether this instrument is measured numerical value or controls physical parameter；

The most whether there is a single computer in order to control instrument or to gather data；

3.2.3.3.6 the Classification Management of analytical tool: A quasi-instrument need to be followed GEP and require to be designed, install and debug；B class Instrument need to carry out installing confirmation and confirm with running；C quasi-instrument also needs Progressive symmetric erythrokeratodermia can confirm that.

3.2.3.4 calibration and the assessment of maintaining, should calibrate the instrument of parameter measurement or offer data, for The equipment having maintenance needs should formulate the work plan of preventive maintenance maintenance.

3.2.3.4.1 whether instrument is used for measuring certain technological parameter or providing one measuring or calculating data；

3.2.3.4.2 instrument carries out preventive maintenance maintenance the need of replacing spare part/consumptive material or instrument supplier suggestion；

3.3 SIA assessments

Computerized evaluation

SIA assesses

Analytical tool classification assessment

3.4 SIA Main Conclusions and management main points

SIA conclusion

4 parts criticality assessment

4.1 assessment foundations

4.1.1 parts criticality assessment code (reference number of a document :) 1.

4.1.2 FMEA method evaluation procedure (reference number of a document :) 1.

4.1.3 rule of operation (reference number of a document :) 1.

The problem design of assessment

The purpose of parts criticality assessment (CCA) is to discriminate between the parts composition situation (key feature or non-of equipment or system Key feature), provide reference for its maintaining, part replacement management.(answer of arbitrary problem is the problem of assessment "Yes" can be judged to " critical component "):

Q01 parts are for proving whether to meet the regulation of registered technique；

The normal operating of Q02 parts or control have directly impact to product quality；

Q03 component malfunction or alarm condition have directly impact to product quality or effect；

The information of these parts of Q04 is registered as batch record, batch clearance data or a part for other GMP associated documents；

Q05 parts directly contact with product or product composition；

Q06 parts are for controlling to affect the key process parameter of product quality, and to the performance of control system without independent Checking；

Q07 parts are used for creating or keep certain system core state.

Assessment (risk identification)

CCA assesses table

The FMEA assessment of 4.4 CCA assessments

Parts FMEA table

5 equipment use the risk assessment of process

5.1 assessment foundations

5.1.1 technological procedure (reference number of a document :) 1.

5.1.2 rule of operation (reference number of a document :) 1.

5.1.3 FMEA method evaluation procedure (reference number of a document :) 1.

The operating process (risk identification) that equipment uses

Purposes and parameter describe

Use state description

Technological operation assessment table

5.3 use the FMEA assessment of operation

Technological operation FMEA table

6 confirm the Cause and Effect matrix analysis with identifying object

The Cause and Effect matrix of 6.1 GMP key elements

To this evaluation item quality index in production management, quality management and implement the relevant key element of GMP: personnel (personnel To evaluation object, evaluation object is to personnel), (other relevant are set equipment by other relevant devices by evaluation object, evaluation object Standby), material (material to evaluation object, evaluation object to material), environment (environment to evaluation object, evaluation object to environment), Regulation file (management of evaluation object is required by internal file and national legislation), confirm that (confirmation of evaluation object is surveyed with detection Examination, daily monitoring) etc. each key element investigate one by one, and carry out the risk assessment being correlated with.The fishbone artwork of GMP key element assessment Formula such as Fig. 2.

Assessment foundation

6.2.1 Good Manufacturing Practice and Quality Control of Drug (revision in 2010).

6.2.2 current edition Chinese Pharmacopoeia.

6.2.3 technological procedure (reference number of a document :) 1.

6.2.4 quality standard and numbering 1.

6.2.5 FMEA method evaluation procedure (reference number of a document :) 1.

The GMP key element (risk identification) of equipment

Key element assessment table

6.4 the FMEA assessment of GMP key element

Key element FMEA table

7 quality risk control plan main points

The formulation main points of 7.1 quality risk control measure

7.1.1 the parts having Data Control or collection to require all should formulate verification calibration plan, the standard of production monitoring and monitoring Plan, the Trend Analysis Program of Monitoring Data, such as Pressure gauge, temperature probe, effusion meter.

7.1.2 have and force verification alignment requirements, perform Its Relevant Technology Standards requirement.

7.1.3 the parts directly contacted with product should have confirmation and demonstration plan, cleaning plan, sterilization or sterilizing plan.

7.1.4 production or confirmation have sampling quality Testing index requirement with checking, should be sampled adopting of index Collection, and have data statistics and Trend Analysis Program.

7.1.5 equipment specification or other technologies data have maintaining requirement, should set up clear and definite maintaining meter Draw.

7.1.6 the uninterrupted system of life-time service, should have daily monitoring plan.

The quality risk control measure main points of project

The quality risk control plan table of project

8 quality risk control measure (plan)

8.1 verification calibration requirements and plans

Verification calibration planning chart

8.2 maintaining standard and demands

Maintaining demand schedule

8.3 cleaning-sterilizings are monitored with using

Cleaning-sterilizing and detection requirement table

8.4 confirm and demonstration plan

8.4.1 confirmation (DQ) plan is designed

DQ plan of needs table

8.4.2, confirmation (IQ) plan is installed

IQ plan of needs table

8.4.3 confirmation (OQ) plan is run

OQ plan of needs table

8.4.4 confirming performance (PQ) plan

PQ plan of needs table

8.5 production and application monitoring and trend analysiss

Monitoring plan table

The conclusion of 9 risk assessment is planned with looking back assessment

9.1 risk assessment Main Conclusions

Parts criticality assessment according to this risk assessment, examination & verification revised equipment/facility/system verification calibration plan, Maintaining plan and confirmation and demonstration plan.

Use process, the risk assessment of production technology according to this risk assessment, formulate confirmation and demonstration plan, daily Monitoring plan and the plan of trend analysis (retrospective analysis before annual trend analysis and again checking).

GMP key element risk assessment according to this risk assessment, formulated confirmation and demonstration plan, daily monitoring plan and The plan of trend analysis (retrospective analysis before annual trend analysis and again checking).

The principle of risk assessment should update under conditions of deviation management, Variation control in timing, the most again initiates again Checking, again confirmation and the supplementary test of necessity.

Relevant confirmation and demonstration plan, verification calibration plan, maintaining plan, use parameter and the daily monitoring of technique The file of project documentation, the method for detection and criterion of acceptability should carry out the renewal revision of necessity according to this assessment.

Risk looks back assessment plan

When the confirmation of this evaluation item completes with checking work, should complete relevant confirmation and demonstration plan, verification calibration meter Draw, maintaining plan, use parameter, the daily monitoring of technique, the method for detection and criterion of acceptability file should be according to this assessment Carry out the renewal revision of necessity.

In year quality review work, verification verification calibration operation, maintenance work, the daily prison of technique should be checked respectively for Survey and the performance of trend analysis and the situation of investigating of deviation.

Before carrying out next time confirming and verifying, should be by all of verification calibration, maintaining, the work since risk assessment last time The daily monitoring of skill and trend analysis and the situation of investigating of deviation, Variation control and file recension are audited, and receive Enter and confirm, with the risk assessment data of checking, to carry out the renewal of necessity to next time.

The examination & verification revision of Risk Assessment Report

Deviation adjusts result to show if desired, and the revision carrying out this risk assessment procedures and assessment report should be organized perfect, it is ensured that The sustained improvement of quality management system.Without abnormal conditions, the examination & verification revision cycle of this Risk Assessment Report is raw for signature After effect 54 to 66 months.

Part III: the program part of system.

What this patent was discussed confirms that the program of the risk evaluating system with checking, with EXCEL VBA program as example, provides Programming of quality risk assessment report based on risk assessment form, the programming and this program class of other data Seemingly, the sequencing tissue of the data content of form it is mainly based upon.For the program language tissue of other data bases, with this program Similar, the concrete linguistic structure according to program is flexible or optimizes.Improvement or the optimization of these principle reality are included in Within the scope of the technical protection of this patent, improve and obtain obvious improving technology effect unless there are obvious know-why.

Claims (5)

1. the risk evaluating system for confirmation with checking, it is characterised in that: by 18 different risk assessment forms, systems Make working procedure and the working template composition of Risk Assessment Report, it is adaptable to production and the supervision of people's industrial products use, should System can be significantly reduced the confirmation of user and write workload with verifying data, and guarantees to confirm the content with checking and wind The requirement of danger assessed information is completely the same, helps user main attention to be focused among concrete quality risk management, effectively Control quality risk.

It is the most according to claim 1 a kind of for confirming and the risk evaluating system of checking, it is characterised in that: described 18 are not Same risk assessment form is respectively as follows: the basic condition table confirmed with Verification Project；It is applicable to the systematic influence of production system Assessment table；It is applicable to the classification assessment table of analytical tool；Parts criticality assessment table；The failure mode evaluation table of parts；Produce The decomposition assessment table of technique；The failure mode evaluation table of production technology；The decomposition assessment table of project GMP key element and quality index； The failure mode evaluation table of project GMP key element and quality index；Quality risk control plan summary table；The verification calibration of system unit Planning chart；The maintaining planning chart of system unit；The cleaning of project and use monitoring plan table；Design confirms (DQ) plan Table；Install and confirm (IQ) planning chart；Run and confirm (OQ) planning chart；Confirming performance (PQ) planning chart；Sampling plan and trend are divided Analysis planning chart；Confirm to assess planning chart with Verification Project.

It is the most according to claim 1 a kind of for confirming and the risk evaluating system of checking, it is characterised in that: risk assessment The working template of report, by the basic description of the risk assessment form different to 18 and collectively constituting of table position design, is Basic in the Risk Assessment Report of system describes and the position of form is to embody with the form of bookmark, template be one complete Document, after utilizing the establishment of working procedure completion report, after the catalogue in template and header, page number content are updated To complete Risk Assessment Report.

It is the most according to claim 1 a kind of for confirming and the risk evaluating system of checking, it is characterised in that: confirm and test The working procedure of the risk evaluating system of card is the working procedure being designed according to corresponding LISP program LISP, it is possible to achieve from upper State the form Data Enter to template, thus realize on the basis of working registration form, fast and accurately establishment risk assessment project Corresponding confirmation and checking material, including Risk Assessment Report, confirm with proof scheme, confirm with checking record design, confirm With checking report summaries, confirm with checking report, confirm with checking implementation record, confirm the review assessment plan with checking, really Recognize the data verification with checking, confirm to look back assessment report with checking.

It is the most according to claim 3 a kind of for confirming and the risk evaluating system of checking, it is characterised in that: risk assessment The feature composition of the working template of report includes: the content of risk assessment includes that systematic influence is assessed, and following closely Parts criticality assessment, the assessment of process operations, the assessment of GMP key element, after risk identification and risk assessment, by knowledge Each risk elements the most out carries out the overall planning of risk control, and the practical plans that assessment risk elements controls, including school Test calibration, maintaining, cleaning-sterilizing requirement and the requirement of process-monitor, confirm and checking, sampling plan and trend analysis.