What Is The Difference Between GMP And cGMP?

As we all know, my country is currently implementing GMP regulations, which are formulated by the WHO and are applicable to developing countries. It is also called the dynamic drug production management specification, and its focus is on the production software. So, what are the differences between these two specifications? How do we overcome these differences? Today let’s talk about the difference between GMP and cGMP?

First of all, the differences and requirements of the two are different

From the comparison of the catalogs, we can see that for the three elements in the drug production process – hardware system, software system and personnel, the American GMP is simpler than the Chinese GMP, with fewer chapters. However, the internal requirements for these three elements are very different. my country’s GMP has more requirements for hardware, while the US GMP has more requirements for software and personnel. This is because the quality of drug production depends fundamentally on the operator’s operation, therefore, the role of personnel in the US GMP management is more important than plant equipment.

After reading through the specific content of GMP in China and the United States, we can find an interesting phenomenon: in China’s GMP, there are detailed regulations on the qualifications (educational level) of personnel, but there are few restrictions on the responsibilities of the personnel; In GMP, the regulations on personnel qualifications (training level) are concise and clear, while the regulations on personnel responsibilities are strict and detailed. Such a responsibility system largely guarantees the production quality of drugs.

Secondly, the collection and inspection of samples, especially the inspection

China’s GMP only stipulates the necessary inspection procedures, while in the U.S. GMP, all inspection steps and methods are stipulated in great detail, which avoids the confusion and pollution of drugs at all stages, especially in the stage of raw materials. Provide guarantee for improving the quality of medicines from the source. Fundamentally speaking, cGMP focuses on high-standard requirements for production software. Therefore, rather than saying that the implementation of cGMP is to improve the level of production management, it is more accurate to say that it is to change the concept of production management.

Finally, how to successfully implement cGMP

my country’s current GMP requirements are still in the “initial stage”, and they are only formal requirements. However, if Chinese enterprises want their products to enter the international market, they must be in line with international standards in terms of production management in order to gain market recognition. Although the Chinese government has not mandated that pharmaceutical companies implement cGMP, 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 norms is an indispensable prerequisite for internationalization. The good news is that at present in China, pharmaceutical companies with a forward-looking development strategy have realized the long-term significance of this specification and put it into practice. Canada has a history of nearly 30 years since it was written into the country’s draft regulations in 1975, and it is one of the first countries to implement GMP.

The core of cGMP: the internationally accepted cGMP. At present, whether in the United States or Europe, the cGMP compliance inspection at the production site follows the unified cGMP specification for raw materials formulated by the International Conference on Harmonization (ICH), also known as ICH Q7A. This specification originated from the International Conference on Harmonization of Raw Materials (ICH for API) in Geneva, Switzerland in September 1997. In March 1998, led by the US FDA, a unified “cGMP for raw materials” was drafted, namely ICH Q7A. In the autumn of 1999, the European Union and the United States reached an agreement on cGMP mutual recognition of APIs. The two parties agreed that after the agreement came into force, they would mutually recognize each other’s cGMP certification results in the trade of APIs. For API companies, the cGMP specification is actually the specific content of ICH Q7A.

The so-called dynamic pharmaceutical production management standard is to emphasize on-site management (Current). When we conduct cGMP training, we find that the heads of the quality departments of many enterprises have a naive understanding of cGMP. After we demonstrated the content of cGMP on-site worker training, we heard someone say: It’s that simple and training is needed? That’s right, on the surface, the content of cGMP, especially the specification of on-site work, does not have profound 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 up. The main purpose of cGMP is to ensure stable product quality. Drug quality is the core of cGMP, and the process (or understood as the site) to achieve this goal is the most important.

For example, a pharmaceutical company in Europe wants to introduce a raw material drug with good market development potential into the US market, and then submits a certified product to the US FDA. Before, during the raw material synthesis process, there was an accuracy deviation in one of the two temperature gauges in the reaction tank. Although the operator had handled it and asked for instructions, it did not record it in detail in the production batch record. After the product was produced, the quality inspectors only checked the known impurities during chromatographic analysis, and issued a qualified inspection report if no problems were found. FDA officials found that the accuracy of the thermometer did not meet the requirements during the inspection, but no corresponding record was found in the production batch records. When checking the quality inspection report, it was found that the chromatographic analysis was not performed at the time required by the regulations. All of these cGMP violations could not escape the eyes of the inspectors, and the drug ultimately failed to enter the US market. The FDA determined that it failed to implement cGMP regulations and would harm the health of American consumers.

If it is in accordance with the requirements of cGMP, further investigation should be arranged after the precision deviation occurs, including checking the possible results after the temperature deviation from the precision, and the deviation from the process description should also be recorded. All inspections of pharmaceuticals are only for known impurities and known undesirable substances, and it is impossible to fully inspect unknown harmful or irrelevant ingredients through existing methods.

When we evaluate the quality of a drug, we often use the quality inspection to determine whether the drug is qualified, or the effect and appearance of the product as the basis for judgment. However, in cGMP, the concept of quality is a code of conduct throughout the production process. A drug with fully qualified quality may not meet cGMP requirements, because there is a possibility of deviation in its process. If there is no strict specification requirement for the whole process, potential dangers cannot be discovered by the quality report. This is what I said before, why cGMP is not so simple to implement.

It should be said that the GMP transformation of my country’s pharmaceutical companies is relatively smooth. If it is implemented (cGMP), there will still be difficulties. “Details” and “authenticity of the process” should be the two most difficult aspects for us to implement cGMP. my country’s current GMP standard is formulated by the World Health Organization for developing countries. In terms of hardware, as long as Chinese enterprises pass it, the gap with cGMP’s hardware requirements is not very far. However, cGMP emphasizes the authenticity of the process and the daily execution after certification. To implement a high-standard and perfect GMP, the real challenge lies not in the certification, but in the daily control after the certification. The US FDA’s on-site inspection is “picky” about the details and the implementation process, because the principle they follow is to ensure that the health of patients is not damaged by potential dangers.

Most companies still have a biased understanding of cGMP. We need a certain amount of time to instill the core ideas of cGMP in companies. This will also be the key to our successful implementation of cGMP.

Specifically, to achieve this specification, where is our current gap:

In fact, the gap is mainly the adjustment and adaptation of concepts. The purpose of implementing cGMP is to enable those problematic drugs to be discovered before they enter the market. Among them, it is fortunate that the health of consumers will not be damaged, but from the perspective of drug manufacturers, such results are unfortunate, because the products are produced under cGMP regulations, causing manufacturers to suffer huge economic losses. loss. From this point of view, the implementation of cGMP has to pay a price, and it will take a process for Chinese pharmaceutical companies to bear this price, and it will take a period of time to change their concepts. Chinese enterprises are willing to invest manpower, material resources and funds in technological transformation and hardware upgrading, but they can’t bear to see the qualified drugs they produce being sidelined due to irregular processes. Such losses are temporarily unacceptable to manufacturers. In fact, it is time for us to redefine the concept of “qualified”, and the implementation of cGMP is an opportunity.

The road stretches under our feet, and every step forward is one step closer to the truth. As long as we persist in catching up with the advanced pace, I believe that China’s cGMP road will not be far away.