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. Gambaran keseluruhan
In this article, "highly active drugs" refers to the general term for drugs with high activity, high toxicity, high allergenicity, and high risk.
Artikel 28 GMP Cina 2010 menyebut bahawa pekerja kawasan operasi berisiko tinggi (cth: kawasan pengeluaran aktiviti tinggi, ketoksikan tinggi, jangkitan tinggi, bahan alergenik tinggi) harus diterima menggunakan kereta api khusus; Artikel 46 menyebut bahawa pengeluaran ubat-ubatan dengan sifat-sifat istimewa, seperti ubat-ubatan yang sangat alergenik (seperti penisilin) atau produk biologi (seperti BCG atau ubat-ubatan lain yang disediakan dengan mikroorganisma aktif), mesti menggunakan tumbuhan, kemudahan pengeluaran dan peralatan yang berdedikasi dan bebas. . Ini adalah keperluan khas untuk kelas ubat ini.
Mengikut keperluan dalam GMP China, skop dan takat pengesahan atau pengesahan harus ditentukan oleh penilaian risiko. Ujian prestasi kedap udara bagi peralatan kedap udara yang digunakan dalam pengeluaran ubat yang sangat aktif juga memerlukan penilaian risiko.
2. The elements may influence the equipment's airtight performance
2.1 Kakitangan
Sama ada kakitangan telah dilatih dan mempunyai pengalaman yang relevan. Dan kewaspadaan kakitangan semasa operasi, julat pergerakan, dsb. semuanya boleh menjejaskan keputusan ujian prestasi kedap udara peralatan.
2.2 Peralatan
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.
Untuk pensampelan permukaan, swab pensampelan tidak boleh jatuh dari kekotoran, tidak boleh bertindak balas secara kimia dengan bahan yang akan diuji, harus mudah dicairkan, disimpan dan digunakan.
2.3 Bahan
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 Kaedah
Kaedah persampelan secara amnya ialah pensampelan udara dan pensampelan permukaan.
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 Persekitaran
Ujian prestasi kedap udara zarah peralatan kedap udara perlu mengambil kira pengaruh persekitaran ujian untuk keputusan ujian.
Semasa ujian, kita perlu merekod dan memikirkan faktor asas persekitaran ujian, termasuk kualiti udara, suhu, kelembapan, perubahan udara dan faktor lain.
2.6 Mengukur
Memasuki fasa pengukuran selepas pensampelan dengan instrumen pensampelan, proses pengukuran perlu mempertimbangkan ralat yang mungkin disebabkan oleh proses analisis, instrumen ujian untuk analisis sampel perlu memastikan prestasinya yang stabil dan boleh dipercayai. Memerlukan prosedur operasi instrumen yang sempurna untuk membimbing kerja berkaitan kakitangan.
2.7 Analisis risiko peralatan kedap udara juga harus mengambil kira faktor berikut
● 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. Kesimpulan
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.