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. 개요
In this article, "highly active drugs" refers to the general term for drugs with high activity, high toxicity, high allergenicity, and high risk.
2010년 중국 GMP의 제28조는 고위험 작업 구역(예: 고활성, 고독성, 고감염성, 고알레르기성 물질의 생산 구역)의 작업자는 전문 열차를 수용해야 한다고 언급했습니다. 제46조는 고알레르기성 약물(예: 페니실린) 또는 생물학적 제품(예: BCG 또는 활성 미생물로 제조된 기타 약물)과 같은 특수 특성을 가진 약물의 생산은 전용 및 독립 공장, 생산 시설 및 장비를 사용해야 한다고 언급했습니다. . 이것은 이 종류의 약물에 대한 특별 요구 사항입니다.
중국 GMP의 요구사항에 따라 확인 또는 검증의 범위와 범위는 위해성 평가에 의해 결정되어야 합니다. 고활성 의약품 생산에 사용되는 기밀 장비의 기밀 성능 테스트에도 위험 평가가 필요합니다.
2. The elements may influence the equipment's airtight performance
2.1 직원
직원이 교육을 받았고 관련 경험이 있는지 여부. 그리고 작업 중 직원의 주의, 움직임 범위 등은 모두 장비의 기밀 성능 테스트 결과에 영향을 줄 수 있습니다.
2.2 장비
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.
표면 샘플링의 경우 샘플링 면봉은 불순물이 떨어지지 않아야하며 테스트 대상 물질과 화학적으로 반응하지 않아야하며 용출, 보관 및 사용이 용이해야합니다.
2.3 재료
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 방법
샘플링 방법은 일반적으로 공기 샘플링과 표면 샘플링입니다.
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 환경
기밀 장비 입자 기밀 성능 테스트는 테스트 결과에 대한 테스트 환경 영향을 고려해야 합니다.
테스트하는 동안 대기 질, 온도, 습도, 공기 변화 및 기타 요소를 포함한 테스트 환경의 기본 요소를 기록하고 생각해야 합니다.
2.6 측정
샘플링 장비로 샘플링 한 후 측정 단계에 들어가면 측정 프로세스는 분석 프로세스로 인해 발생할 수있는 오류를 고려해야하며 샘플 분석을위한 테스트 장비는 안정적이고 신뢰할 수있는 성능을 보장해야합니다. 직원 관련 작업을 안내하기 위해 완벽한 기기 작동 절차가 필요합니다.
2.7 기밀 장비의 위험 분석은 다음 요소도 고려해야 합니다.
● 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. 결론
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.