Nowadays there are more and more pharmaceutical corporations producing highly active medicine, it's very normal to see that the utilization of airtight equipment in the production process of highly active productions. However many companies are still confused about the airtight performance test of this type of equipment and how to conduct the risk assessment of the test process. Therefore, this article will pay attention to the introduction of how to conduct airtight performance test and risk assessment of airtight equipment used in the production process of highly active medicine. Hoping relevant pharmaceutical corporations can be enlightened from it, and making the production and verification of highly active drugs more standardized and scientific
1. Txheej txheem cej luam
In this article, "highly active drugs" refers to the general term for drugs with high activity, high toxicity, high allergenicity, and high risk.
Tsab xov xwm 28 ntawm xyoo 2010 Suav GMP tau hais tias cov neeg ua haujlwm ntawm thaj chaw muaj kev pheej hmoo siab ua haujlwm (xws li: thaj chaw tsim khoom ntawm kev ua haujlwm siab, muaj tshuaj lom, muaj kab mob siab, cov khoom ua xua siab) yuav tsum tau txais kev cob qhia tshwj xeeb; tsab xov xwm 46 tau hais tias kev tsim cov tshuaj uas muaj cov khoom tshwj xeeb, xws li cov tshuaj ua xua (xws li penicillins) lossis cov khoom siv roj ntsha (xws li BCG lossis lwm yam tshuaj npaj nrog cov kab mob nquag), yuav tsum siv cov nroj tsuag siab thiab ywj siab, cov chaw tsim khoom thiab cov khoom siv. . Qhov no yog qhov yuav tsum tau tshwj xeeb rau cov chav kawm ntawm cov tshuaj no.
Raws li qhov yuav tsum tau muaj nyob rau hauv Tuam Tshoj GMP, lub peev xwm thiab qhov ntev ntawm kev lees paub lossis kev pov thawj yuav tsum tau txiav txim siab los ntawm kev ntsuas kev pheej hmoo. Kev ntsuas kev ua haujlwm ntawm airtight ntawm cov khoom siv airtight siv los tsim cov tshuaj muaj zog heev kuj yuav tsum muaj kev ntsuas kev pheej hmoo.
2. The elements may influence the equipment's airtight performance
2.1 Cov neeg ua haujlwm
Txawm hais tias cov neeg ua haujlwm tau raug cob qhia thiab muaj cov kev paub dhau los.Thiab ceev faj ntawm cov neeg ua haujlwm thaum lub sijhawm ua haujlwm, qhov ntau ntawm kev txav, thiab lwm yam. txhua yam yuav cuam tshuam rau cov txiaj ntsig ntawm airtight kev ua tau zoo ntawm cov khoom siv.
2.2 Cov khoom siv
It's very important for the choose of test instrument. For air sampling, the flow rate of sampling pump is usually set at 2 L/M, and the sampling pump is calibrated with a calibrated flow meter. In addition, sampling pump need to be calibrated before and after test to ensure sampling pump does not change a lot in the test process. The air flow rate is very important, and the relevant information of the pre-calibration and post-calibration should be recorded.
Rau cov qauv saum npoo, cov sampling swabs yuav tsum tsis txhob poob ntawm impurities, yuav tsum tsis txhob hnov qab txog cov tshuaj uas yuav tsum tau kuaj, yuav tsum yooj yim elute, khaws thiab siv.
2.3 Cov khoom siv
In suitable circumstance, the particle airtight performance test of the equipment can use substitute materials instead of actual materials. Test data completed with substitute materials can be used to predict similar operating conditions for actual materials. In some circumstances, using substitute materials may be necessary. For example, actual materials' chemical analysis method is not insensitive, or medicine ingredients are very expensive or medicine components are dangerous. Actual operation may have many kinds of substitute materials can be selected. However its chemical, physical properties and powder characteristics should be considered comprehensively, and should be close to the properties of the actual material.
2.4 Method
Cov qauv siv feem ntau yog cov qauv huab cua thiab qhov chaw ua piv txwv.
Air sampling of personnel usually places the sampling head in the breathing area of the personnel(mouth, nose), this can simulate the total amount of inhalable particles. When sampling in operator breathing area, sampling equipment can't disturb the normal operation of operator. Breathing area sampling is recognized as the sampling method which closest to the actual impact on the operator, because this method considers some relevant elements about operator's activities and actions.
Surface sampling(swab sampling or wipe sampling) also can be used to ensure the equipment airtight property whether meet the requirement. Surface sampling can't adopt the methods of air sampling, such as surface's particulate matter, operators' clothes, or operators' hand/glove.
Comparing with air sampling, the execution of surface sampling should use validated methods and need to consider recovery rate of substitute from specific surface to solvent. The sampling area is specific 100c㎡(10cm10cm), but for the special requirements of geometric or contaminated equipment, in this case, take a specific area.
2.5 Ib puag ncig
Airtight cov cuab yeej particle airtight kev ua tau zoo yuav tsum tau xav txog qhov kev xeem ib puag ncig cuam tshuam rau qhov kev xeem.
Thaum lub sij hawm xeem, peb yuav tsum tau sau thiab xav txog tej yam tseem ceeb ntawm kev xeem ib puag ncig, xws li huab cua zoo, kub, av noo, huab cua hloov thiab lwm yam.
2.6 Kev ntsuas
Nkag mus rau cov theem ntsuas tom qab ntsuas nrog cov ntsuas ntsuas, cov txheej txheem ntsuas yuav tsum tau txiav txim siab qhov yuam kev uas yuav tshwm sim los ntawm kev txheeb xyuas cov txheej txheem, cov ntsuas ntsuas ntsuas ntsuas ntsuas ntsuas yuav tsum ua kom nws ruaj khov thiab txhim khu kev qha. Xav tau cov txheej txheem ua haujlwm tsis raug cai los coj cov neeg ua haujlwm cuam tshuam txog kev ua haujlwm.
2.7 Kev soj ntsuam kev pheej hmoo ntawm cov cuab yeej airtight yuav tsum xav txog cov hauv qab no
● Considering any influence for the accuracy of test result of any activities now and before. For example, the presence of contamination residues may affect the results of sample analysis;
● If you want to compare the airtight performance of different sealing equipment, you should concern the change of any system related to sealing equipment, near system or support system. Because these changes may influence the airtight ability of sealing equipment, such as change of air flow in air conditioning system, change of standard operating procedure (SOP), change of equipment itself, and change of sampling equipment;
● If an activity has a potentially significant risk to the accuracy of the test results, remedial measures should be taken to reduce or eliminate the impact;
● Text details should be detailed record;
● If video or photography has no influence to the product or environment, it is a valid method to provide sit recording.
3. Cov lus xaus
The airtight environment required for highly active drugs in the pharmaceutical production process is guaranteed by sealed equipment, equipment also forms the first protective screen for staff. If the airtight performance of the equipment does not meet the requirement, not only the drug's quality will be damaged, but also the operator's health will be influence a lot. Therefor, how to ensure the airtight ability of sealing equipment is a great important question for pharmaceutical companies which produce highly active medicine. This article provides guidance or suggestions for the risk research of equipment airtight capabilities of related enterprises from the perspective of how to identify risks and possible risk points of sealing equipment, in order to bring certain help.