China’s consistency evaluation standards are strict.
Q1
My country is a big country of generic drugs. Previously, my country used imitation standards when imitating drugs, that is, if the generic drugs and the imitated products implement the same quality standards, they are considered to be equivalent in quality. Generally speaking, after the patent of an original drug expires, the molecular structure, dosage, and physical and chemical properties of the active ingredient will be disclosed. In the research and development of generic drugs, the effective chemical components of the generic drugs and the original drugs should be the same. However, drug quality standards cannot contain all the content that affects the quality of drugs.
There are many reasons for this difference, such as the raw materials used in the preparation. If the purity, crystal form or related substances of the raw material drug is different from the original drug, it will directly affect the quality of the preparation. Excipients also have an impact on the quality of medicines. In addition, in terms of preparation process, generic drugs use the same raw materials as the original drug, but if the preparation process is not optimized, there will be differences in quality. The most direct impact is that after the patient takes the drug, the absorption effect of the body may not be as good as the original drug, which results in inconsistent efficacy.
Q2
my country has initiated the evaluation of the consistency of the quality and efficacy of generic drugs, which requires our generic drugs not only to be consistent in quality standards, but also in clinical efficacy. In other words, generic drug manufacturers must use reference preparations (original drugs or internationally recognized drugs) as a control to conduct comprehensive and in-depth comparison studies, including prescriptions, quality standards, crystal forms, particle sizes and related substances, Dissolution curve and other major pharmaceutical indicators prove that the generic drug is pharmacologically equivalent (PE) to the original drug. The clinical bioequivalence test proves that the bioavailability of the generic drug is consistent with that of the original drug, that is, bioequivalence (BE), so as to achieve therapeutic equivalence (TE). This is actually equivalent to re-doing the research and development of a generic drug.
Take the comparative study of pharmaceutical indicators as an example. When imitating the standard, we may only focus on the dissolution profile of the drug in one medium, but in the process of consistency evaluation, we should pay attention to the drug’s dissolution profile in the stomach, duodenum, intestine and water. Dissolution profiles in these 4 media. Of course, a few varieties can be exempted from BE if they find that their dissolution and absorption are consistent with the original drug. This is also required by the US FDA. However, there are very few varieties that can be exempt from BE in our country. In other words, the current consistency evaluation of generic drugs in my country can be said to be more stringent than foreign requirements to some extent.
Generic drugs that pass consistency evaluation can achieve import substitution
Q3
We have standards for evaluating whether a generic drug reaches the level of consistency. For example, in pharmacy, dissolution is a typical indicator. If a generic drug is pharmacologically consistent with the original drug, and clinically absorbed in the body is also consistent with the original drug, then the two must be consistent.
Now, there are voices in the market that the generic drugs that have passed the consistency evaluation are clinically inferior to the original drugs, and the adverse reactions are greater than the original drugs. Generally speaking, there are two reasons for adverse reactions: one is related substances, and the other is drug release and absorption curve. In the case of passing the consistency evaluation, the latter should not exist. Regarding the former, what I want to say is that the related substances in many domestic APIs are lower than those in foreign countries.
Q4
There are two reasons: First, in my country, the original research drug has a clinical monopoly for about 30-40 years. Both medical workers and patients have a high degree of recognition of the original research drug. The second is the existence of placebo effect factors. We all know that the placebo effect may play a 30% clinical role. “Expensive is better than cheap”, this is a common psychology of people. I personally believe that the placebo effect has greatly promoted the advancement of the original research drug in the domestic clinical status.
It has already been emphasized that for pharmaceutical companies, there is no difference between evaluating the consistency of a generic drug and re-creating a generic drug, which requires a lot of investment. From the time point of view, the consistency evaluation generally takes two years; from the capital point of view, a product needs to invest 5 million to 10 million yuan. For high-variable products with relatively large fluctuations in BE, we require that if 24 cases are not enough, 48 cases will be required, and if 48 cases are not enough, 96 cases may be required, which requires more investment. Under such strict requirements, the quality and efficacy of generic drugs that have passed the consistency evaluation should be no problem. I have said on many occasions that the quality and efficacy of products that have passed the consistency evaluation of generic drugs should be the same as the original drugs. It is for this reason that in the process of centralized procurement and use by national organizations, the passing of the consistency evaluation of generic drugs will be a prerequisite; it is also because of this that the price of original research drugs will drop significantly.
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