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.
V členu 28 kitajskega GMP iz leta 2010 je navedeno, da je treba delavce na delovnem območju z visokim tveganjem (npr.: proizvodno območje z visoko aktivnostjo, visoko toksičnostjo, visoko infektivnostjo, materiali z visoko alergenostjo) sprejeti za specializiran vlak; 46. člen je omenil, da je treba za proizvodnjo zdravil s posebnimi lastnostmi, kot so zelo alergena zdravila (kot so penicilini) ali biološki proizvodi (kot je BCG ali druga zdravila, pripravljena z aktivnimi mikroorganizmi), uporabljati namenske in neodvisne obrate, proizvodne prostore in opremo . To je posebna zahteva za to skupino zdravil.
V skladu z zahtevami kitajske GMP je treba obseg in obseg potrditve ali preverjanja določiti z oceno tveganja. Preskus neprepustnosti zrakotesne opreme, ki se uporablja pri proizvodnji visoko aktivnih zdravil, zahteva tudi oceno tveganja.
2. The elements may influence the equipment's airtight performance
2.1 Osebje
Ali je bilo osebje usposobljeno in ima ustrezne izkušnje. Pazljivost osebja med delovanjem, obseg gibov itd. lahko vpliva na rezultate preskusa neprepustnosti 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 vzorčenje tamponi za vzorčenje ne smejo padati z nečistoč, ne smejo kemično reagirati s snovjo, ki jo je treba testirati, morajo biti enostavni za eluiranje, shranjevanje in uporabo.
2.3 Materiali
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 vzorčenja so na splošno vzorčenje zraka in vzorčenje površin.
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 Okolje
Preizkus zrakotesne zmogljivosti za zrakotesne delce opreme mora upoštevati vpliv preskusnega okolja za rezultat preskusa.
Med testom moramo zabeležiti in razmišljati o osnovnih dejavnikih testnega okolja, vključno s kakovostjo zraka, temperaturo, vlago, spremembami zraka in drugimi dejavniki.
2.6 Merjenje
Pri vstopu v merilne faze po vzorčenju z instrumentom za vzorčenje mora meritveni proces upoštevati napake, ki jih lahko povzroči postopek analize, testni instrument za analizo vzorcev pa mora zagotoviti stabilno in zanesljivo delovanje. Potrebujete brezhibne postopke delovanja instrumenta za vodenje dela, povezanega z osebjem.
2.7 Analiza tveganja nepredušne opreme mora upoštevati tudi naslednje dejavnike
● 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. Zaključek
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.