The differences between the GMP and cGMP

What’s the differences between the GMP and cGMP?
The GMP standard currently implemented in China is the GMP standard formulated by the WHO for developing countries, which focuses on the requirements of production hardware such as production equipment, and the standard is relatively low. The United States, Europe and Japan and other countries to implement good manufacturing practices (cGMP), also known as dynamic drug manufacturing management practices, it focuses on the production software, such as regulating the actions of operators and how to deal with emergencies in the production process.
From the comparison of the current GMP certification specifications in the United States and China's GMP certification specifications, we can see the difference between the two and the different focus of requirements:
From the comparison of catalogs, it can be seen that for the three elements of the drug production process - hardware system, software system and personnel, the US GMP is simpler and fewer chapters than the Chinese GMP. However, there is a great difference in the internal requirements of these three elements. Chinese GMP has more requirements for hardware, and American GMP has more requirements for software and personnel. This is because the quality of drug production is fundamentally dependent on the operation of the operator, so the role of personnel in U.S. GMP management is more important than that of plant equipment.
After reading through the specific contents of Chinese and American GMPS, we can find an interesting phenomenon: in Chinese GMPS, the qualifications (educational level) of personnel are specified in detail, but there are few constraints on the duties of personnel; In the US GMP, the qualification of personnel (training level) is simple and clear, and the responsibility of personnel is strict and detailed. Such a responsibility system ensures the quality of drug production to a large extent.
Another difference that can be found from the Sino-US GMP comparison is the collection and testing of samples, especially testing. Chinese GMP only provides for the necessary inspection procedures, while in the US GMP, all inspection steps and methods are specified in great detail, which avoids the confusion and contamination of drugs at all stages, especially at the stage of raw materials, and provides protection for the improvement of drug quality from the source. Fundamentally, cGMP focuses on high standards for production software. Therefore, rather than the implementation of cGMP is to improve the level of production management, it is more accurate to change the concept of production management.
The current GMP requirements in our country are still in the "primary stage" and are only formal requirements. In order for Chinese enterprises to let their products enter the international market, they must be in line with international production management in order to obtain market recognition. Although the Chinese government has not yet mandated the implementation of cGMP in pharmaceutical companies, this does not mean that there is no urgency to implement cGMP in China. On the contrary, managing the entire production process according to cGMP specifications is an essential prerequisite for internationalization. Fortunately, at present in China, pharmaceutical companies with forward-looking development strategy vision have realized the long-term significance of this norm and have put it into practice. Canada has been writing draft regulations for nearly 30 years since 1975, and is one of the earliest countries to implement GMP.
cGMP core: The internationally accepted cGMP, whether in the United States or Europe, the cGMP compliance inspection on the production site follows the unified cGMP specification for active substances formulated by the International Coordination Conference (ICH), also known as ICH Q7A. The specification originated at the International Coordinating Conference for apis (ICH for API) held in Geneva, Switzerland, in September 1997. In March 1998, the United States FDA led the drafting of a unified "cGMP for apis", that is, ICH Q7A. In the fall of 1999, the EU and the United States reached a mutual recognition agreement on cGMP for apis, and the two sides agreed to recognize each other's cGMP certification results in the trade process of apis after the agreement came into force. For apis, the cGMP specification is actually the specific content of ICH Q7A.
The so-called dynamic drug manufacturing management practice is to emphasize Current management. When we conduct cGMP training, we find that the head of the quality department of many enterprises has a naive understanding of cGMP. After we demonstrated the cGMP on-site worker training content, we heard people say: It is so simple and need training? Yes, on the surface, the content of cGMP, especially in the field work part of the specification is not esoteric knowledge, but once the cGMP specification is implemented in the process and details of the real work, you will find that the implementation is not so simple. The main purpose of cGMP is to ensure stable product quality, drug quality is the core of cGMP, and the process (or understanding of the field) to achieve this goal is the most important.
For example, a pharmaceutical company in Europe wants to enter the US market with a good market development potential, and then submit a certified product to the US FDA. Before, in the process of raw material synthesis, there was a precision deviation in one of the two temperature gauges of the reaction tank, and although the operator was treated and asked for instructions, it was not recorded in detail on the batch record of production. After the product is produced, the quality inspector only checks the known impurities when doing chromatographic analysis, and no problems are found, and a qualified inspection report is issued. During the inspection, FDA officials found that the thermometer accuracy did not meet the requirements, but did not find the corresponding record in the production batch records, and found that the chromatographic analysis was not performed in accordance with the time required by the protocol when checking the quality inspection report. None of these cGMP violations escaped the attention of the reviewers, and the drug never made it to the U.S. market. The FDA determined that it did not enforce cGMP rules and would harm the health of U.S. consumers.
If an accuracy deviation occurs in accordance with the requirements of cGMP, further investigation should be scheduled, including an examination of the possible results of temperature deviations from the accuracy, and deviations from the process description should be recorded. All inspections of drugs are only for known impurities and known adverse substances, and unknown harmful ingredients or irrelevant ingredients cannot be fully detected by existing methods.
We evaluate the quality of a drug, often the drug through the quality inspection to determine whether the standard, or according to the effect of the product, appearance as the basis for judgment. However, in cGMP, the concept of quality is a code of conduct throughout the entire production process. A fully qualified drug may not be in compliance with cGMP requirements, because its process has the possibility of deviation, if it is not in a strict specification of the whole process, the potential danger can not be found by the quality report. This is why, as I said earlier, cGMP is not so easy to implement.
It should be said that the GMP reform of Chinese pharmaceutical enterprises is relatively smooth. If (cGMP) is implemented, there will still be difficulties. "Details" and "authenticity of the process" should be the two most difficult aspects for us to implement cGMP. China's current GMP specifications are formulated by the World Health Organization for developing countries, from the hardware point of view, as long as Chinese enterprises are passed, the gap with cGMP requirements for hardware is not very far. However, cGMP puts more emphasis on the authenticity of the process, as well as the daily implementation after certification. To implement a high standard and perfect GMP, the real challenge lies not in the certification, but in the daily control after certification. FDA's on-site inspections are "picky" about the details and implementation process, because they follow the principle of ensuring that patients' health is not compromised by potential dangers.
Most enterprises still have a substantive understanding of cGMP, and we need some time to instill the core ideas of cGMP in enterprises, which will be the key to our successful implementation of cGMP.
Specifically, to reach this norm, where are our gaps now:
In fact, the gap is mainly the adjustment and adaptation of ideas. The purpose of implementing cGMP is to detect problematic drugs before they reach the market. It is fortunate that the health of the consumer is not harmed, but from the perspective of the drug manufacturer, this outcome is unfortunate, because the product is not in accordance with the cGMP specification, which causes the manufacturer to suffer a huge financial loss. In this way, the implementation of cGMP is to pay the price, the Chinese pharmaceutical companies to bear this price is a process, need a period of time to change the concept. Chinese enterprises are willing to invest manpower, material resources and funds in technological transformation and hardware upgrading, but they do not have the heart to see the qualified drugs produced due to the non-standard process and be thrown into the cold palace, such a loss is unacceptable to manufacturers. In fact, it is time for us to redefine the concept of "conformity", and the implementation of cGMP is an opportunity.