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. Pregled
In this article, "highly active drugs" refers to the general term for drugs with high activity, high toxicity, high allergenicity, and high risk.
U članku 28. kineskog GMP-a iz 2010. spominje se da radnik u visokorizičnom radnom području (npr.: proizvodno područje visoke aktivnosti, visoke toksičnosti, visoke infektivnosti, materijala visoke alergenosti) treba prihvatiti specijalizirani vlak; u članku 46. spominje se da se za proizvodnju lijekova s posebnim svojstvima, kao što su visokoalergeni lijekovi (kao što su penicilini) ili biološki proizvodi (kao što su BCG ili drugi lijekovi pripremljeni s aktivnim mikroorganizmima), moraju koristiti namjenska i neovisna postrojenja, proizvodna postrojenja i oprema . Ovo je poseban zahtjev za ovu klasu lijekova.
Prema zahtjevima kineskog GMP-a, opseg i opseg potvrde ili provjere treba odrediti procjenom rizika. Ispitivanje nepropusnosti za zrak nepropusne opreme koja se koristi u proizvodnji visokoaktivnih lijekova također zahtijeva procjenu rizika.
2. The elements may influence the equipment's airtight performance
2.1 Osoblje
Da li je osoblje bilo obučeno i ima li relevantno iskustvo. I oprez osoblja tijekom rada, raspon pokreta itd. sve to može utjecati na rezultate ispitivanja nepropusnosti opreme.
2.2 Oprema
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.
Za površinsko uzorkovanje, brisevi za uzorkovanje ne smiju otpadati s nečistoća, ne smiju kemijski reagirati sa tvari koja se ispituje, trebaju se lako eluirati, pohraniti i koristiti.
2.3 Materijali
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 Metoda
Metode uzorkovanja općenito su uzorkovanje zraka i površinsko uzorkovanje.
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 Okoliš
Ispitivanje hermetičke izvedbe čestica nepropusne opreme treba uzeti u obzir utjecaj ispitnog okruženja za rezultat ispitivanja.
Tijekom testa moramo zabilježiti i razmisliti o osnovnim čimbenicima testnog okruženja, uključujući kvalitetu zraka, temperaturu, vlažnost, promjene zraka i druge čimbenike.
2.6 Mjerenje
Ulaskom u faze mjerenja nakon uzorkovanja instrumentom za uzorkovanje, proces mjerenja treba uzeti u obzir pogreške koje mogu biti uzrokovane procesom analize, testni instrument za analizu uzorka treba osigurati njegovu stabilnu i pouzdanu izvedbu. Potrebni su besprijekorni instrumenti operativnih procedura za usmjeravanje rada vezan uz osoblje.
2.7 Analiza rizika nepropusne opreme također treba uzeti u obzir sljedeće čimbenike
● 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. Zaključak
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.