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The relationship between drug quality and Legitimacy
| 작성자 | 관리자 | 카테고리 | 전문가 인사이트 |
|---|---|---|---|
| 작성일 | 2016-04-29 | 조회수 | 1,408 |
| 원문 | |||
| 출처 | |||
The relationship between drug quality and Legitimacy
- 글 Wu xiaoming
- GPKOL위원
학력사항
- 2014 Peking University / International Pharmaceutical Engineering Management (M.S)
- 2009 Anhui College of Traditional Chinese Medicine / Pharmaceuticals (M.S)
- 1995 Anhui University / Biological Chemistry (B.S)
경력사항
- 2003-2015 Anhui Pioneer Pharmaceutical Co. Ltd / Deputy general manager
- 1995-2003 Hefri dimai Pharmaceutical Co. Ltd / Quality Director
세부 전문분야 및 컨설팅 내용
- 인허가, PM
- Project manager
In pharmaceutical industry, people have been exploring the more scientific quality management concept.According to its development course, drug quality management concept has experienced three stages of development: test theory, production theory , design theory .
The first stage is the "test theory ", which is the initial stage.Due to the lack of drug quality management concept , pepole generally believed that "drug quality is controlled by the inspection",means that when drugs are inspected before release according to the specification can effectively guarantee the quality. So far, there are still some enterprises follow this concept to carry out quality management.
The second stage is the "production theory": With the continuous improvement of awareness, people gradually realized that the core of drug quality management is not only stay in the "sampling inspection" level but rely on strict process validation , key process options and process parameters.
The third stage is the "design theory": "Quality by Design (QbD)".This concept first appeared in the ICH Q8, which defined as " A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management." Information from pharmaceutical development studies can be a basis for quality risk management. It is important to recognize that quality cannot be tested into products. Those aspects of drug substances, excipients, container closure systems, and manufacturing processes that are critical to product quality should be determined and control strategies justified.
In 1990s, enterprises proposed to establish a quality management system based on drug risk assessment, should be based on knowledge and experience of drug quality risk assessment, and with the ultimate goal of protecting patients. However, although the drug has been through the formula and process research, production stage also strictly enforce the GMP management, but different batches of the same product manufactured by the same enterprise, still have different quality and clinical effect, seriously even caused the harmful event.And when we are conducting an investigation, however, it is often found that there is no violation of the production or inspection procedures
The reason is that there are still some enterprises attach great importance to the facilities , equipment and production environment, but ignore the core concept advocated by the GMP: sustainable production process ,change management and so on. Product release is usually based on its specification which generally not the most resolution method.
For example，different suppliers of drug substances will have different synthesis processes and routes, even with the same synthesis process and route, the starting materials, intermediates, reagents, production equipment, process parameters is also difficult to maintain exactly the same, so as to cause different physical and chemical properties,such as: impurity profile, crystal type, particle size, the melting point, the solubility and fluidity, wettability, specific surface area, density, isomers and chemical reaction ability. Different physical and chemical properties of drug substances will affect the properties of products, such as impurity profile and dissolution. And then affect the safety, effectiveness and quality control of drugs.
At the same time, due to insufficient sensitivity the existing testing methods may not reflect changes in the quality of products, Therefore, Even if Legitimacy, we still can not guarantee the quality of products.
Next, We can use a classic case to further elaborate: a few years ago, Roche's products Nevirapine appeared strange taste in commercial batches, so was quickly recalled. Upon examination, the products contained high levels of ethyl methane sulfonate (alkyl-based class of genotoxic impurities can be covalently bound to DNA and increase the risk of cancer). EU marketing authorization for this product had been suspended, the FDA also immediately restricted their use in children and pregnant women, until new data for risk assessment was provided.
" What exactly is the problem?" Enterprise troubled for a long time. After a lot of depth and detailed investigation, people find that: All of the materials meet their standards, the production process strictly enforced the GMP, the product was qualified by inspection. No problem! When the truth presented in front of everyone, it is incredible that the impurity is produced by the reaction between the sulfonic acid and residual ethanol which is used for cleaning the production equipment.
The incident has aroused extensive discussions on how to set the level of gene toxic impurity in the drug specification, but also caused widespread public concerns about the presence of drugs genotoxic impurities. But also it sparked another thought: What is the relationship between Legitimacy and quality?
Another serious injury event: In 2007, Some patients were severely injuried when using methotrexate made by Shanghai Hualian Pharmaceutical Co., Ltd. for intrathecal injection. Expert investigation lasted nearly two months but still could not find the reason. Until people found by chance that the patient's symptoms very like the adverse reactions of vincristine (another collinear production of anticancer drugs which can not be used for intrathecal injection). It pointed to the ultimate truth: some batches of methotrexate mixed with trace amounts of vincristine sulfate. After extended examination, another collinear products cytarabine were also included in the list of suspended use for intrathecal injection.
Several anticancer drugs of Shanghai Hualian Pharmaceutical Co., Ltd. shared the same production line, such practice is accepted in the industry, and therefore does not violate the provisions of the GMP. But in this case, the risk of methotrexate is much higher than several other products. Therefore GMP collinear risk assessment should be combined with clinical usage and adverse reactions to conduct a comprehensive assessment.
We can draw a conclusion: The Product manufactured in accordance with the provisions of GMP and inspected according to the specification, does not necessarily guarantee its quality! Therefore, the specification of product should not only according to the experimental data, but also according to the risk and benefit to patients. Specification should has sufficient resolution, so as to effectively control the quality of drugs.
Wu xiaoming
Anhui Pioneer Pharmaceutical Co., Ltd.
April 27,2016
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