1. Yevropa Ittifoqi qarorlarini qabul qilish zanjiri- talablariga muvofiq, F0 8 dan katta yoki teng boʻlgan qoldiq ehtimollik usuli, agar u 121 darajaga yeta olmasa va 15 daqiqa ichida sterilizatsiya qilmasa, tanlanishi mumkin, Savol: agar mahsulot 121 darajaga yetib, 12 daqiqada sterilizatsiya qilsa, 121 daraja va 10 daqiqani tanlamaydimi? Xuddi shunday, agar u 10 daqiqaga yetishi mumkin bo'lsa, unda 8 daqiqaga ruxsat berilmaydi, bularning barchasi F0 8 dan katta yoki tengmi?
Javob: Mikroblarni o'ldirishning matematik modelidan xuddi shunday boshlang'ich ifloslanish ostida sterilizatsiya F{0}} qiymati qanchalik baland bo'lsa, sterillik kafolati darajasi shunchalik yuqori bo'ladi. Shuning uchun mahsulotdagi qoldiq mikroorganizmlar xavfini kamaytirish uchun imkon qadar yuqori F0 qiymatini tanlash mantiqan to'g'ri kelishi aniq.
2. Barqaror mahsulot sifati sharti bilan u 121 daraja, 8 daqiqa va 115 daraja, 30 daqiqaga javob berishi mumkin. Qaysi shartga ustunlik berish kerak?
Answer: Regardless of the product's physical and chemical quality stability, theoretically the F{{0}} values reached by these two conditions are almost equal, it doesn't matter which one is preferred. However, in actual production, the heat penetration in the product in the sterilizer, the difference in F0 values actually obtained by products in different parts of the sterilizer, and the difference in F0 between products in different sterilization batches must also be considered. The sterilization process with small difference in heat distribution and small difference in product F0 value should be selected.
3. The sterilization conditions in the application materials are "121 degree , sterilization for 30 minutes". Is this standard?
Answer: "121 degree , sterilize for 30 minutes" itself is not for terminal sterilization, because it is almost impossible to calculate the F0 value in this way. The expression of sterilization conditions can refer to the Chinese Pharmacopoeia 2005 edition appendix two sterilization method 168, 121 degree 15min or 116 degree 40min.
4. Bir xil navdagi 10ml va 20ml in'ektsiya uchun bir xil sterilizatsiya usulini qo'llash to'g'rimi?
Javob: Bir xil turdagi 10ml va 20ml inyeksiyalar xuddi shu tarzda sterilizatsiya qilinishi mumkin, ammo turli hajmdagi namunalarning termal penetratsiyasi izchil yoki yo'qligini tekshirish uchun termal penetratsiya testini o'tkazish kerak va sterilizatsiya usuli sterilligini ta'minlashi kerak. katta{2}}hajmli mahsulotlar .
5. Eng yuqori sterillikdagi sterilizatsiya jarayonini tanlashda u tegishli moddalar va barqarorlik kabi mahsulot sifatiga zid kelishi mumkin., Bu qarama-qarshilikni qanday muvozanatlash kerak? Bundan tashqari, kukun in'ektsiyalari chet elda sotiladi, mahalliy ilovalar uchun ariza berishda sterilizatsiya jarayonini tanlash bo'yicha tadqiqot o'tkazish kerakmi?
Javob: Aslida, sterilizatsiya jarayonini tanlash jarayonida turli xil sterilizatsiya sharoitida namuna sifati o'zgarishini o'rganish kerak. Sterilizatsiya jarayonini tanlash jarayoni, shuningdek, sterillikni kafolatlash darajasi va (namuna sifati) fizik-kimyoviy ko'rsatkichlarini muvozanatlash jarayonidir. Klinik ehtiyojlarga ega bo'lgan mahsulotlarda sterilizatsiya jarayonini tanlash u erishish mumkin bo'lgan eng yuqori darajadagi sterillik kafolatiga asoslangan bo'lishi kerak. Chet elda sotiladigan kukunli in'ektsiya uchun, shuningdek, ichki deklaratsiya paytida kukunli in'ektsiyalardan foydalanishni o'rganish kerak. Agar asosiy dori haqiqatan ham issiqlik va namlikka nisbatan beqaror bo'lsa, chet elda bo'lgani kabi bir xil kukunli in'ektsiyadan foydalanish mumkin; agar issiqlikka qarshi bo'lmasa, Suvning beqarorligi uchun asosiy preparatning tabiatiga ko'ra sterillik kafolati yuqori bo'lgan dozalash shakli tanlanishi kerak.
6. Terminal sterilizatsiya jarayonini tanlash printsipi F0 F0 8 dan katta yoki unga teng emas, F0 Kattaroq yoki 12 ga teng; yoki F0 8 dan katta yoki unga tengmi?
Javob: Iltimos, Yevropa Ittifoqining sterilizatsiya jarayonini tanlash boʻyicha-qaror qabul qilish zanjiriga qarang.
7. Qaror qabul qilish zanjiridagi omon qolish ehtimoli usuli-121 daraja harorat holatini ham afzal ko'radimi?
Javob: Majburiy emas. Bu mahsulotning barqarorligiga qarab belgilanadi. Agar yuqori harorat va qisqaroq vaqt omon qolish ehtimoli usuliga javob bersa, past harorat va uzoqroq sterilizatsiya mahsulot uchun yaxshiroqdir. Agar mahsulot 121 daraja yuqori haroratga bardosh bera olmasa, u holda haroratni pasaytirish mumkin va mikroorganizmlarning qoldiq ehtimoli 10-6 dan kam ekanligiga ishonch hosil qiling.
8. Termik jihatdan beqaror dorilar (oqsillar, biologik mahsulotlar va boshqalar kabi) uchun aseptik ishlab chiqarish jarayoni bevosita tekshirilishi kerak.
Javob: Termik jihatdan beqaror dorilar (oqsillar, biologik mahsulotlar va boshqalar) uchun birinchi navbatda aseptik jarayonni o'rganish uchun steril filtrlash va aseptik ishlab chiqarish jarayoni yoki aseptik yig'ish jarayonini qo'llashni tekshirish kerak; Keyin jarayonni tekshiring.
9. Mahsulotni ro'yxatga olish uchun ariza berishdan oldin mahsulotning to'liq jarayon spetsifikatsiyasida ko'rsatilgan turli parametrlarni tekshirish shakllanganmi?
Answer: The drug registration management measures stipulate that after the applicant has applied for the "drug registration application form", the applicant will be notified to apply for on-site inspection to the drug certification management center if the applicant meets the requirements after the drug evaluation center reviews. The purpose of the on-site inspection is to confirm the feasibility of the production process, a batch of samples shall be taken at the same time, and the production of the samples shall meet the requirements of GMP. Thus when applying for product registration, you should have sufficient knowledge of the process used for the production of officially marketed products. This understanding is based on the entire process of product and process development, expansion, equipment and system verification, and verification batch production. The purpose of the verification batch is to prove that the process can always produce qualified products within the specified process parameters. Therefore, before proceeding with the verification batch, you should fully understand and be able to control various key variable factors in the process.
10. When verifying the sterilization process, a calibrated probe is generally placed next to the sterilizer control probe. What are the requirements for the temperature difference between the two? Should we follow the proofing standard and only allow a deviation of ±0.5 degree ?
Javob: Umuman olganda:
① The independent recording probe and monitoring probe that come with the sterilizer should complete sufficient verification data, and then correct the existing deviation;
② The accuracy of the temperature measuring probe used for verification should be better than the recording probe and monitoring probe that come with the sterilizer;
③One of the functions of the verification itself is to correct the monitoring probe and recording probe that come with the sterilizer to achieve a more accurate temperature value during normal use. At present, there is no such saying that "only allow a deviation of ±0.5 degree ".
Lens
11. Katta hajmli in'ektsiyaning bir xil ishlab chiqarish liniyasida bir nechta spesifikasiyali mahsulotlarni (masalan, 250ml, 100ml) va turli xil sterilizatsiya parametrlariga ega bo'lgan mahsulotlarni (masalan, turli xil sterilizatsiya harorati va vaqti) sterilizatsiya qilish kerak bo'lgan sterilizator mavjud bo'lsa, qanday qilib tasdiqlash va qayta tekshirish jarayonida issiqlik taqsimoti va issiqlik penetratsiyasini tekshirishni loyihalash uchun? Spetsifikatsiyalar va sterilizatsiya shartlari individual ravishda tasdiqlanganmi?
Javob: Umuman olganda, har xil spetsifikatsiyalar va turli sterilizatsiya shartlari alohida tekshirilishi kerak. Tegishli ma'lumotlarning ko'pini aniqlash mumkin bo'lmasa, turli xil texnik xususiyatlarning aralash yuklarini sterilizatsiya qilish tavsiya etilmaydi.
12. Nam issiqlik sterilizatorini tekshirish yoki qayta tekshirish jarayonida, issiqlik taqsimoti va issiqlik penetratsiyasini tekshirishda, haroratni tekshirish uchun shkafda 12 yoki 16 termojuft o'rnatilgan bo'lsa, topilgan sovuq nuqta uchta tekshirishda farq qilishi mumkin, nima? agar bu holat yuzaga kelsa, buni qilish kerakmi?
Answer: Generally speaking, the cold point of no-load heat distribution should be around a certain location, otherwise it may be caused by equipment, pressure, incomplete air replacement, steam quality and other reasons. For loading thermal penetration, the cold point of the large volume injection (LVP, >100ml) mahsulotning geometrik markazida va mahsulotning pastki qismidagi vertikal o'q bo'ylab joylashgan, ammo tekshirish talab qilinadi.Sovuq nuqtaning joylashuvi kichik hajmli inyeksiyalar uchun odatiy emas, chunki eritma deyarli bir xil tezlikda qiziydi. sterilizator sifatida.
Bundan tashqari, idishning yo'nalishi sovuq nuqtaning joylashishiga ham ta'sir qiladi va konteyner aylantirilganda yoki aylantirilganda, sezilarli sovuq nuqta bo'lmasligi mumkin.Agar yuk doimiy bo'lsa, sig'im bir xil bo'ladi, hech qanday to'siq yo'q. bug'ning kirib borishi va boshqalar va sovuq nuqta hali ham qayta paydo bo'lishi mumkin emas, uskunada, jarayonda, bosimda, bug 'sifatida va hokazolarda mumkin bo'lgan noaniqlikni tekshirish kerak.
13. Sterilizatsiya ta'siri bo'yicha to'liq yukda issiqlik taqsimoti va-yuksiz issiqlik taqsimoti o'rtasidagi farq nima?
Answer: Both tests measured the temperature distribution in the sterilization chamber, but they did not reflect the temperature and thermal benefit in the product, so they could not directly reflect the sterilization effect of the product.But what's going on in the chamber obviously affects what's going on inside the product.In the verification process, heat distribution tests of no-load, full-load and product heat penetration were carried out successively.The main purpose of such tests is to reveal as much objective information as possible with as few tests as possible.The results of the previous experiment provide information for the later experiment.
14. To'liq yuk issiqlik taqsimoti sinovi bo'sh shisha bilan yoki WFI o'z ichiga olgan infuzion shisha bilan o'tkaziladimi?
Javob: To'liq yuk issiqlik taqsimoti sinovlari simulyatsiya qilingan namunalar bilan amalga oshiriladi.
15. Agar tekshirishda yuklash rejimi yarim yuk yoki to'liq yuk bo'lsa, kelajakda ishlab chiqarishda to'liq yuk va yarim yuk o'rtasida bo'lsa, tekshirish kerakmi?
Javob: To'liq yuk va yarim yuk o'rtasidagi yuklar uchun ishlab chiqarishdagi yuklash rejimi tekshirish paytidagiga mos kelishini ta'minlash uchun to'liq yukga erishish uchun simulyatsiya qilingan mahsulotni to'ldirishdan foydalanish tavsiya etiladi.
16. Issiqlikning kirib borishini tekshirish qanday amalga oshiriladi?
Answer: The purpose of the heat penetration test is to determine the "coldest point" in the sterilization chamber loading, and to confirm that the point has obtained sufficient asepsis guarantee value in the predetermined sterilization procedure, that is, the residual amount of bacteria Less than or equal to 10-6 and the difference between the temperature of each detection point and the average temperature in the sterilization chamber Less than or equal to 2.5 degree .Verification should be done for changes in operation that may affect the sterilization effect and confirm the operation method.For example, when a stainless steel cover is added to each sterilization tray, the heating time inside the actual product (solution) is 2 minutes later than that without a cover, so add 2 minutes to the sterilization procedure setting.The placement of the thermocouple is consistent with the full load heat distribution test protocol and the standard thermocouple is placed in the center of the sterilization solution.
17, Laboratoriyada kichik partiya namunasiga ishora qilib, issiqlik penetratsiyasi testida simulyatsiya qilingan namuna tushunchasi nima?
Javob: Termal penetratsiya testidagi simulyatsiya qilingan namunalar laboratoriya kichik partiyasi namunalariga emas, balki haqiqiy namunalar bilan bir xil termal penetratsiya ko'rsatkichlariga ega bo'lgan namunalarga tegishlidir.
18, mikrobial sinov uchun biologik ko'rsatkich turini xilma-xillikka qarab tanlash kerakmi? Qanday tanlash kerak?
Javob: Mikrobial sinov uchun bioindikatorning turi va tanlovi 169-ilovaning ikkinchi qismining Xitoy farmakopeyasi 2005 yil nashri sterilizatsiya usuliga murojaat qilishi mumkin.
19, Sterilizatsiyadan oldin mikrobial ifloslanish darajasini aniqlash usuli?
Javob: Membran filtrlash eng keng tarqalgan usuldir. Ishlatishdan oldin uni tekshirish kerak.
20,Mahsulotning mikrobial chegaraviy sinov natijasi 0CFU va issiqlikka chidamli mikroorganizmlar-topilmadi. Shuning uchun, D qiymati biroz pastroq bo'lgan bacillus subtilisni tekshirish jarayonida tekshirish uchun biologik ko'rsatkich sifatida foydalanish mumkinmi?
Javob: 1). Mikrob chegarasi testi natijalari va biologik ko'rsatkich sifatida D qiymati biroz pastroq bo'lgan Bacillus subtilisni tanlash o'rtasida sababiy bog'liqlik yo'q edi.
2). According to the questioner's question, it can be considered that the method of survival probability sterilization is used.For survival probability method of sterilization process to test the survival probability can choose biological indicator, and simply because of the product or packaging itself cannot bear too much killing, and choose to compare the strict process control, and the initial bacteria amount control products, or combined with aseptic filtration process, and so on, and then select the biological indicator sensitivity test, measure the average content of bacteria N0, for not less than 4 gradient bacteria quantity, batch, quantity of the product enough before and after sterilization of microbial limit test (if necessary, also want to test with different sterilization time), to find and get greater than the decline in six logarithmic grades of state parameter, Under the condition that the value of F0 is between 8 to 12, the value of D can be calculated.