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。概要
In this article, "highly active drugs" refers to the general term for drugs with high activity, high toxicity, high allergenicity, and high risk.
2010年の中国GMPの第28条は、リスクの高い作業エリア（例：高活動、高毒性、高感染性、高アレルギー性材料の生産エリア）の労働者は専門列車として受け入れられるべきであると述べています。 第46条は、高アレルゲン薬（ペニシリンなど）や生物学的製品（BCGや活性微生物で調製された他の薬など）などの特殊な特性を持つ薬の製造には、専用の独立したプラント、製造施設、設備を使用する必要があると述べています。 。 これは、このクラスの薬剤の特別な要件です。
中国GMPの要件に従って、確認または検証の範囲と範囲は、リスク評価によって決定する必要があります。 高活性医薬品の製造に使用される気密装置の気密性能試験にも、リスク評価が必要です。
2. The elements may influence the equipment's airtight performance
2.1スタッフ
スタッフが訓練を受け、適切な経験を持っているかどうか。また、操作中のスタッフの注意、動きの範囲などはすべて、機器の気密性能テストの結果に影響を与える可能性があります。
2.2機器
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.
表面サンプリングの場合、サンプリングスワブは不純物から脱落してはならず、試験対象の物質と化学的に反応してはならず、溶出、保管、および使用が容易でなければなりません。
2.3材料
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方法
サンプリング方法は、一般的に空気サンプリングと表面サンプリングです。
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環境
気密装置粒子気密性能試験は、試験結果に対する試験環境の影響を考慮する必要があります。
テスト中は、空気の質、温度、湿度、空気の変化など、テスト環境の基本的な要素を記録して考える必要があります。
2.6測定
サンプリング機器でサンプリングした後、測定フェーズに入ると、測定プロセスでは分析プロセスによって発生する可能性のあるエラーを考慮する必要があります。サンプル分析用のテスト機器では、安定した信頼性の高いパフォーマンスを確保する必要があります。 人事関連の作業をガイドするための非の打ちどころのない機器操作手順が必要です。
2.7気密設備のリスク分析では、以下の要素も考慮する必要があります
● 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.結論
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.