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52 details of the Q & A: official statement on the consistency of generic drugs 

Medical news network September 8th July 26th, the State Administration held a "generics quality consistency evaluation and effect of training in Guangzhou, based on the answering recording notes as follows. No deletion, strive for objectivity. The answering arrangement is not perfect, but has practical significance for many answer. If there is no objection to a certain content, can be provided come out, hope that we can explore together, will not the same voice into the same.
1 in the 1622 varieties, how to declare the problem again:
Answer: the production and development of clinical site verification not in the consistency evaluation of separate rules, regulations have been registered in the production site inspection, the use of research field and clinical verification inside, so the implementation of standards should be a standard, there is no new standard and old standard, the standard is the same.
Search for 2 reference preparations:
Answer: it is feasible to produce the product as a capsule, but whether it is a tablet or not
3 prescription process, packaging must be consistent with the original research:
A: there is no need to agree on any explanation. This is not a necessary condition
4 is the quality consistent and bioequivalent?
Answer: specific analysis of specific varieties. His meaning is to do the dissolution curve, but for us, the dissolution curve of the work done carefully, carefully, find out the dissolution curve of a feature, to the controllability of the production quality, and is also an important part of the evaluation of consistency.
5 if there is a change in the quality of the dissolution curve into the quality standards involved in the change, the change of the quality standards approved by where?
Answer: the quality standard for the final dissolution, the dissolution curve can be found on one or two points to make dissolution. If the quality standard now no dissolution (equal to the increase, or project) now have the dissolution, but the choice is not very appropriate, or in the solution conditions change curve in the research process, these changes are related to the quality standard, which belongs to the Pharmacopoeia Committee, if it is already on the Pharmacopoeia varieties or registration standards, should be required to contact the Pharmacopoeia Committee proposed to change the standard.
6 < < Chinese Pharmacopoeia > > standard for 30min to reach 80%, but the dissolution rate of the reference preparation is very slow, less than 80%, the consistency of the evaluation of how to pass the Pharmacopoeia?
Answer: the products are slow, what is the reason, need to do a proper analysis: 80% is reasonable 30min dissolution. USP dissolution limits are not necessarily very in place, before 30min reach 80% even dissolution, but maybe we were more severe conditions, or in the dissolution medium of adding a solvent or surfactant. I don't know the dissolution conditions of Amoxicillin Capsules, but 30min to 80% is appropriate, the reference preparation dissolution conditions and China Pharmacopoeia dissolution conditions are the same, which is more reasonable, detailed analysis of the needs analysis before you can answer.
7 the same species were collected in the Japanese orange peel, the consistency of the evaluation can be directly recognized by the method of loading?
Answer: in the end what kind of method, use where collected, what place collected in the dissolution medium, or your literature, can be used as the dissolution curve method to establish the selection of dissolution media; dissolution can be directly used, can be used after use, the key is to look at the results of the whether the breed for you.
8 reference preparations in the batch and between the big difference, the first sampling point variation coefficient is greater than 20%, the rest of the sampling point is greater than 10%, how to compare the F2?
Answer: first to confirm whether the reference preparation is really the difference between batch, or by the difference method generated by your own, whether it is because the method leads to differences between batch method. If there is no problem, is a method of discriminative moderate, the reference preparation does not batch approval uniform, then the sample is actually not as the reference preparation, should the need for reference.
9 specifications and small size of the capsule in the prescription and the process is exactly the same as the volume is different, in vitro dissolution curve can only be compared with the large size?
Answer: in fact the two specifications are to do, although the formula and technology of exactly the same, but they are not the same as the content of main drugs; drug content may be different, in vitro dissolution is inconsistent, it still need to experiment to verify.
10 in vitro dissolution, not completely related to in vitro and in vivo:
Answer: in vivo is not completely related, directly be risk must have something big, but is not necessarily equivalent, in this case, we are certainly the results of be for the final judgment, namely the in vitro dissolution and in vivo is not the same, but we also want to build a variety of the a discriminative dissolution curve, which is different from be. Then the be count? Of course or in the be test is the final judgment. So the establishment of the 4 curves are not exactly the same, but the discriminative, whether through? If be passed and consistent, and the dissolution curve has the ability to distinguish, so we think it should be through, but your dissolution curve for you after reproduction or should be with you through the be sample is exactly the same, the dissolution curve should be exactly the same, so you can ensure the product is can be bioequivalent.
 11 the impurity spectrum of the raw material was compared with that of the original preparation, and the impurity spectrum was more than two less than 1/10000:
Answer: the analysis of impurity profiling, need to compare the original research preparation in the same chromatographic conditions, if the impurity is very small, according to the provisions of SOS, as long as more than 1/1000, you need to calibrate the impurities as it is; if very small, less than 1/10000 of the impurities, if 1/10000 (1/10000 is very sensitive to below the detection limit). According to the provisions of SOS 1/10000, the need to analyze according to the doses every day. I think this is actually a comprehensive judgment: compared with the original research, you impurity what can explain, in addition, the amount is relatively large, if the amount is relatively large, more than 1/1000 or even more than 2/1000. Then you must make the impurities in the end is what, it will affect the efficacy, whether the toxic side effects; if very low or even 1/10000, so can not reproduce, generally is 1/10000 The detection limit is basic, each batch can be repeated, or it is only occasionally appeared, which according to the specific issues of specific judgment. But if 1/10000 is a known toxic impurities, according to foreign Pharmacopoeia, such as USP, EP, their control of APIs. For the known toxicity, I saw the lowest control to 0.1ppm, so we can not say 1/10000 control, the need according to the specific impurities (degradation or process), how much toxic, concrete structure, it is. So, I can't sit now say do not control the following 1/10000 with you here, or more than two can be, this is hard to say right now, you need to carry out further research.
12 use the same production line production in the United States, European Union, Japan's listing of drugs, the original application materials listed in China was reported in 2005, and recently approved the declaration materials some difference, whether this will affect the conclusion of examination and approval:
Answer: the problem is written is not too specific, I think it may be said the domestic registration information and the latest foreign registration data, there is a difference, for this point, in fact, I understand that the emphasis is now registered on the license, but also on the same production line, using the same preparation the preparation process and the same management to production, through the evaluation of consistency to prove that this is the same, this is the premise. The difference in reporting data, I do not know that you are not in Europe and the United States a new change in the process, whether the process changes affect the quality of the product, the truth is you should borrow the consistency of the evaluation data and the domestic listed foreign listed data consistent is the premise, if it comes to the supplement to apply for registration, this is to put all related with the conclusion of the evaluation, the conclusion is consistent with the premise of quality is consistent.
13 the consistency of import registration was introduced in June, foreign reference formulations are purchased before June, then these years before the purchase of the reference formulation can be used in pharmaceutical research? ()
A: I think if it meets all the requirements, just a matter of time, then you do research is not a problem, as long as you ensure that you use the quality of this thing, doing research is possible
14 is it possible to use the consistency check production inspection batch for sale?
A: if the consistency of the evaluation of the batch is safe and effective, and the products are produced under the premise of legal compliance, then it can be marketed, not to say no.
15 reference preparation specifications: orange book collection of the specifications and the production of the factory or the enterprise is different, some of the load is large, do is a small size, and some are collected is a small size, do is a large specification
Answer: this problem including forms are not consistent, unified view, that is the problem. The problem mentioned earlier, there is no clear conclusion, but also need to study, and we get less information, so we do not know your specifications for approval or approval form rationality where so, it is recommended that you record, there is a problem, I can also choose the United States, but also can choose the EU, that is not possible, I think this is the best one in order to illustrate what time record is preferred.
16 according to the Bureau number, 07 years before October 1st approved, need to complete the conformance assessment in 18 years ago, so I approved after October 1st, is not required to complete the listing declaration at the end of 18, if in 18 years is not accepted?
Answer: the document says very clearly, for approval before October 1, 2007, to be completed in 18 years. In fact, for these species, especially in the 287 catalog we mandatory requirements, of course, you are in the process of doing if there is a variety of situations, may to 2021, these special cases such as clinical test, this is the need of time. In addition, the wording of the file button, after October 1st, and did not ask you at the end of 18, this is not a problem. But in fact, as we all know, the evaluation for consistency, there are a lot of good policy, if you finished you haven't finished, whether in the market is bad, so this one though we have no mandatory requirements; in addition, the file was introduced, some people ask some varieties not in scope, that whether these varieties can not participate in the evaluation of consistency? Not really.
17 uniform import:
 Answer: consistency is in order to carry out our import administration of pharmaceutical research, including the evaluation of consistency, and the introduction of the policy, whether it is used for generic or uniformity evaluation, here I have a foreign drug, if there is a card, but if there is no license, no license in the domestic market go out and buy all the inconvenience, we pay close attention to the consistency of the evaluation documents is a great change between the draft and final release, I personally think that the major change is the restriction of this thing many bottlenecks are removed, then the surface here involves two problems: for imported drugs overseas listing control prove yourself (available in the national drug listed legal documents, imported drugs manual or the national drug regulatory department website public information as soon as possible the listing of) his problem is that three is a must Or their own choice, I personally think that the three items can be, of course, you have to get the best of the three
18 consistency of the import declaration materials submitted to the channel when to open, Guangdong province to submit information which is the 3 election of 1 or 12 election?
Answer: this question is to give us the Provincial Bureau of the very targeted, to docking with the Provincial Bureau.
 (for reference the reference preparation, but the reference preparation of the original manufacturers do not provide his manufacturers to prove that, in other words it is not with China or the origin of the promise, the promise we need these generic companies to make the original drug enterprises provide a country of origin of imported drugs and drug consistent commitment to this in fact in the process of commitment to submit the declaration of the reference preparation.)
19 I can find a lot of standards, but there is a big difference between these standards, how to choose the different media used to control the solution of how to choose the configuration method?
Answer: the selected reference or use, should be decided by the enterprise side, including such evaluation consistency, those experiments you do, whether in vivo or in vitro, your purpose is to prove your approval to the product with the original research or reference is the same, we should not set a limit, and then reach this limit can not reach this limit. Not like the degree of medium selection dissolution, different dissolution of the selected reference solution, may be a variety, but for a variety of this method is not possible so, we choose parameters for these methods or follow certain basic principles, did not say is the selection method of general.
20 American reference preparation rld are generally large specifications, with the manufacturers of small specifications can be used as a consistency assessment?
Answer: (this is not me, but I can put my understanding to tell you) first of all, we should follow the guiding principles and various documents being introduced in the selection, we do consistency evaluation of the reference preparation selection is the first choice of the original research, here, if the same agent type with the same specification, from the method it is the theory of error is minimal, so we don't need to because of his large size abroad is rld that we only choose the large size, there is a small size, have the same size. We do not choose the reference preparation choice also should grasp the principles of it, I can't say I only choose rld other specifications can not.
21 there are differences between the three batch reference, how to determine the curve? Do the three batch is the average, or how to choose?
Answer: if the reference is very different, so the choice should be suspected when the varieties could.
22 which method is used to establish the sample, is it a reference preparation or a self-made imitation?
A: in fact, just mentioned in the PPT, we carried out the pre experimental method is used to establish reference formulations
23 is the reference preparation used by the drug testing institute provided by the enterprise or the drug control agency?
A: the reference preparation prepared by the enterprise
24 what is the sex ratio in the be experiment, the original FDA report says there is no gender difference in the product, and how should the gender ratio be required in the actual trial?
Answer: I just talked about why we will be adjusted in the subjects of this is to say, there are experimental data show that the variability in the female subjects than men. The original research report in the approval of a drug in terms of gender have no significant difference, no difference refers to his AUC and Cmax female subjects? Those variations than men, so from the point of view of statistics, is the need for a certain proportion of the difference. In addition, the FDA audit report, evaluation of new drugs and generic drugs to the purpose of the evaluation is not the same, so the experimental design may have some differences. The proportion of female subjects we do not strictly limited, mainly see the indications, pharmacological action, the future for people is how, if the general population, so we set a proper proportion, there is no exact data, but now the guiding principle is just a Guidance, that is to provide a representative of the data
25 there is a specific drug, the human body absorption rate is low, the use of foreign indicators for consistency evaluation, then we can also use this?
nswer: I think abroad some guiding principles for reference we can learn from you, according to your own species, the experimental design must take the clinical evaluation index, according to the actual situation. Then the medication index you choose enough complete, is not sufficient to explain the clinical curative effect, or to according to the pharmacological effects of the drugs, what is the mechanism of clinical effect, clinical observation in which reference indicators can be. That is to say the guiding principles abroad can be used as a reference, just as the applicant of your understanding of the most varieties, his future clinical efficacy may have a guiding principle of the expected, when you you should play the subjective initiative of reference abroad.
26 the stability of the dissolution curve is to do one or more, to examine the stability of the reference preparation is a batch or batch?
Answer: this morning I said, the reason of the dissolution curve of stability for unstable physicochemical properties of the products. We will review some previous literature, there are reports that if this is not very stable, so you need to be careful, we must do some work; but if it is stable, can take a try, do a more demanding, such as acid, to see whether the change. In fact, we do not ask you the dissolution stability is a must do, for unstable physicochemical properties; but if you do not worry, you had better do, we are not required you have to know what each curve do, you can do one or more than one, this is not mandatory, because this is to check behind you based, so we do not have to do, must do one or have to do four, or More or less. If it is stable, you can not do, if you have faith letter words. In addition, the reference preparation is a batch or batch? If you can (only) to buy a batch, may not require you to do more, in addition, the purpose is to study multi group reference batch uniformity and overall stability. So there is a mandatory standard, this is our own judgment in the course of the study.
27 why do we have to evaluate the consistency of a particular species, such as an extract that has Chinese characteristics?
 Answer: Although these varieties are China in preparation, but its therapeutic effect and the quality can be guaranteed. And who, and who, this is not to say that we must have a fixed pattern. The problem that the National Bureau have published some advice or information? In fact, these special preparations should be your own enterprise is the subject of evaluation, you should be on your own products is the most understand, how to ensure the quality and efficacy, it should be you an evaluation of the proposed scheme, so we should use their brains, not you let me how do I do, in fact, each varieties are not the same and every breed has his particularity, so we can not say that this species do, such as Compound Glycyrrhizin Tablets for each species to a fixed pattern, I know it's very complicated extract and so on, then you Can't say to do the four dissolution curve, there is nothing to do, so how to evaluate? His quality is controllable, there are more than and 30 companies produced on the market at present, so the more than and 30 are not the same, some appearance is not the same. So how to make all the same. This should be the various manufacturers or associations to play a role, put forward a feasible evaluation method for this species, such as quality control, its content includes the Extractum Glycyrrhizae fingerprint, process control and so on. These can not be fixed by the conventional evaluation methods, so we hope that the enterprises of this product can first proposed a the evaluation scheme is actually through the consistency evaluation work to improve the quality of our products, we improve the curative effect. So years of product feedback in the market, in the hospital's curative effect, can be widely The feedback of Clinical Hospital collected using units, which can be used as your product quality is safe and effective in providing some basis. And then improve the quality standard, the special materials have special evaluation methods, so we need enterprise brains, each evaluation method is put forward to you can also follow the relevant work units, discuss, put forward a feasible evaluation method and convincing, and then carry out the corresponding work. Then the consistency of the evaluation group to organize the relevant experts to evaluate your program. Our teacher can give you a satisfactory answer now, said you should do this variety, this is not very realistic.
28 reference to the preparation of the record cumbersome, long time, affecting the progress of the enterprise, can simplify?
Answer: I clarify a point here, the reference preparation record does not mean that you must be prepared, be prepared, no follow-up work cannot be. This is Never mind, in other words, if the country has published the reference preparation directory, it also need to record? So it doesn't need. Is the reference preparation for the record or the recommendation, and the original research enterprise or internationally recognized generics firms to carry out independent reporting, is mainly a Duocuobingju, many different situations in different subjects, all is for faster access to the reference preparation information, I believe that if we get all the information channels is the same as the full document, then after expert review, then it is easy to reach a consensus. If you submitted something if you submitted uneven, something more, then this situation There will be more complex. In addition, as far as I know, some of the relatively large effort record business, and no other reference preparation released began to carry out related work. So the reference preparation for 60 days is also not necessarily can come down, because we are currently facing the situation is quite complicated.
29 the same species, a few companies do not recognize the Joint National Bureau?
Answer: I do not say the National Bureau accepted or not, but as far as I know, the National Bureau of industry alliance is to encourage, not necessarily to your family or family are doing, then you can engage in such exchanges, but you can't all this data set to report down, I personally think that this is possible, research, communication, communication, sharing sharing, but eventually you must be in the production line, be do their own experiment, several joint ventures can quote a number, but you can't because you are together, are the same, so a group of to number three.
30 a variety of products through the consistency of the evaluation of the work of the procurement of tenders did not pass the consistency of the evaluation of drugs, a variety of 07 years approved by the 1 new drugs?
Answer: 1 new class is 1 categories, if it is 1.1, then you are the original research, it also do consistency evaluation; if you are not 1.1, then there are a variety of situations, but the administration's announcement are written very clearly, and those who are not consistent with the original research need to do, just do the rhythm is not the same, for example, in 2018 in what we should do. In addition, with another problem, I'm injection, why didn't you want me to do? Do not let you do, is to encourage everyone to do the injection, but the specific directory introduction is carried out in stages, we do first oral, one is all the more attention, the two is known as a oral absorption process, the absorption process is generally has a great influence on the curative effect, so we do oral.
31 If the size of the be to do, then the corresponding small size of the application for exemption need not need relevant information?
Answer: the specifications do be, small size will be the dissolution curve, to prove that it is consistent with the specification. On, we have said today, you first prescription must be exactly the same, the ratio is the proportion of change, if you can. Your information will be with small size large size be test will be done, not to say that the large size made small specifications are not investigated, this is wrong. You must do the small size related to the specifications of the dissolution curve of the investigation should be done.
32 specifications have been completed do not get approval, has been listed on the low spec, now high specification for the increase of the be test has been completed, so low specifications can save?
Answer: the first is to have completed the be test with the test data, a high standard in addition to give you the approved (i.e. get approval), you need to show low specifications and high specification your prescription is completely proportional. First you have to get the approval, not only do the be test is not enough.
33 different specifications, some specifications in 50rpm paddle method can achieve platform (i.e. all the dissolution), but the 20mg of other specifications need to 75rpm, it is this two curve is inconsistent, then the two specifications in 10mg can save be test?
Answer: the first to confirm the prescription is consistent, if it is just the same size as the dissolution curve should be consistent, but now the dissolution curve of one 50rpm 75rpm can show you the dissolution process should be somewhat inconsistent. So in this case is not able to explain 10mg can apply for exemption exemption, reason should not be sufficient.
34 pre experiment is the need for the record?
A: Yes, the need for pre experiment is also the need for the approval of the Committee and the record, but also need to be publicized in the public platform for clinical trials
35 If the pretest fails, do you still need to re record it?

A. yes, every clinical trial requires the same treatment, the same record, the approval of the committee, and the public, and then the experiment

36 pre experiment be report is also submitted in accordance with the new standards, the new CDE format?

A: there are no strict rules
If the 37 has received clinical approval, whether the record is needed?
 Answer: I don't know why there are such questions, the two complement each other, a clinical document can also record, this does not affect the clinical experiment.
The 38 case for the need for consistency evaluation process to change reporting requirements after the change process, and reference preparation research, research on space before and after the change after the change of the application and supplement process change, so the consistency of the evaluation process change is related to the need for change before and after the change between the research and reference preparation three?
Answer: for consistency evaluation, any changes are intended to be studied than you after the change of the product and preparation parameters, they are the same, so before the change will no longer; but if the work is not consistency evaluation, only add to you, then you need to study on before and after the change of the product. See what you used to.
39 to carry out the dissolution of the curve is not required personnel qualification?
I just talked about, staff is a factor affecting the experimental results, then the personnel must be trained to, as for what kind of training that he can fit to carry out this work, this is determined by the enterprises themselves.
40 dissolution curve can be used F1 less than 15 of the difference factor method to evaluate?
Answer: Yes. Not only the difference factor, activity dependent law can you. What kind of approach, or out of this method with other methods, OK, but you have to say. We use the similarity factor method, because everyone is familiar with, are in use, you do not need to do too much explain, F2 is greater than 50 can be, we believe that they are similar; we are not familiar with the other, you have to explain: first you have to let the assessors understand that this method is applicable, then you can use.
41 drugs in the medium of ph1.2 instability, that is, within 1 hours of degradation may be 2%, how to study?
Answer: I just have to say, the dissolution curve of time, must be in the body of different organs, changes of dissolved in different parts, and he examines the generic preparation and reference preparation between the difference, then, if we have the degradation of the original research or reference preparation or degradation. We are not prepared to match with him, after all, this one in vitro and in vivo is different: in vivo degradation, is likely to be the dissolution of how much he is unable to absorb much degradation. So here, follow the principle of it, you can do it and reference preparation or original research preparation dissolution behavior OK.
42 there are differences in the size of the generic formulation and the reference preparation. For example, one is a circular plate, and the other is a special film
Answer: this difference in appearance, including colour differences (such as a coating without a coating), because these are not essential. We want to examine his quality and effect, Never mind differences, as long as the final consistent effect on the line.
43 how to set up a separate resolution curve?
Answer: This is not a very easy question to answer. In drug research and development including the establishment of the dissolution method, it is difficult to specify. I can only give an example: in revolutions as an example, if I chose 75rpm, 75rpm basket method is possible, then why you want to choose 75rpm clearly, I will 50,75100 the three done, 75 is the best discriminative, then 75 is the current method we investigated all the best central component, so it is reasonable to choose.
44 If the import of the original research, there must be a commitment to technology and origin, how to obtain this commitment?
Answer: may be the time I just said there is no clear, this is refers to the original research enterprise of his own declaration I want as the reference preparation, we need him to provide such a commitment, commitment to produce country and country of origin must be exactly the same. The estate of drugs also have this problem, you need to have with the original research that is exactly the same, this is the original research and original research of real estate enterprise to provide this commitment.
45 in accordance with the drug registration management approach, the imitation of the pharmaceutical declaration when the pharmaceutical phase of the reference preparations need to be prepared?
A: at present, the filing procedures for reference agents are only for consistency evaluation
46 how to do different specifications, how to change the dosage form? Or do not change the size of the small form of small dosage forms, such as ordinary tablets instead of dispersible tablets or enteric coated tablets?
Answer: is that the complexity of these problems, exactly the same, can find a different proportion, how to do, how to do it is to buy, how much to buy. Some changed formulations, such as capsules into tablets, then I take different forms of the standard, be, or this is to find the reference preparation category, because from the pharmaceutical equivalent perspective, tablet and capsule are not equivalent, although they may belong to clinical alternative, but not pharmaceutical equivalent, this is a case. In addition, we have another situation, we may have some business ideas at that time, or to the help of clinical advantages, so in the end do all kinds of changes, such as a clearly easily dissolved I want to make a non dispersible tablets, we do not need to make non enteric enteric coated tablets, this time, the consistency of the evaluation approach, large The home will be very tangled: we can not take the tablets as the reference preparation, if you can do that is not able to do be, if you can not do that is not to take the clinical effectiveness, so these are needed to study, this is the first point. Second, according to the definition of the guiding principle now. We are the original research without the original research, but it is not foreign, domestic initiative, and even some varieties also sell better, so these varieties can be regarded as the original research or reference, this is the new problem. Some varieties are generic drugs used mostly, but foreign countries have not, or have we not only abroad now has hundreds of domestic, and according to the existing resources, also do not know who when first imitation, these are to be studied. The reference preparation is too complicated, because in accordance with the classification of our new registration, or The United States 84 years after some generic bill, we have the time and they use the same generic requirements, there might not have these problems, how to solve some quality problem must be complex, these are some little changes, some are changed too much, can not find a completely foreign product comparison and there are some products, like some medicine, to a drug number, but it is a biochemical medicine, and is a group of biochemical medicine, this is not our simple synthesis or fermentation yourself out, then may also give some medicine number, is it Kayaku in the traditional sense, to review, these are a problem to the next stage of the study.
47 No. 8 Wen said, can not find the efficacy of ginseng than needed, so is the first to carry out pharmaceutical research or directly into the clinical effectiveness test?
Answer: the document said very clearly, to find the reference to carry out clinical validity test, which is divided into two situations: first, the prescription does not involve a change in the process, so the next stage can be carried out through the filing of clinical validity test, what hasn't changed, do not involve a change in the process of prescription you, what is now, the future is what it looks like, just do clinical validity test, so it does not need to carry out pharmaceutical research; two, involving the prescription process changes, then according to the administrative measures for the registration of existing as a supplementary application, supplementary applications do, need to submit approval. The clinic.
48 is the clinical efficacy trial conducted in accordance with the clinical trial of the effectiveness of the trial or the consistency of the rising quality of evaluation?
A: Mr. Li Yu has made it very clear this afternoon
49 If the top three have passed the clinical effectiveness of the test, the other companies do, can choose one when the first three home?
Answer: personally feel a little late. Three clinical trials are finished, we may give time is 2021, for our present reference preparations to push, according to current guidelines how to do clinical work, we also continue to improve, making the next stage we should also consider the state of generics the orange book, Orange Book How to develop, which can assist ratio, I believe that we will focus on the stage of consideration, that time will answer this question will be more exact.
50 to buy a reference to the preparation of the term is certainly less than his period of validity, so the stability of reference preparations need to do long time, whether in accordance with the long-term 0,3,6,9,12,24 do every month?
Answer: in fact this morning also talked about, not only the stability of the reference preparation, dissolution curve, in order to prevent you buy the reference preparation will have differences in the review process, so it is necessary to do stability (dissolution curve), after the reference preparation to buy back due to the need to do a pre experiment the dissolution curve, and in the process of pre experiment, for example, after one or two months can also make a reference preparation dissolution curve, see the reference is the dissolution curve has no difference, not to say take ginseng do stability test than in our preparation, and reporting requirements there is no study reference preparation stability, but when you changed your prescription to do a study of the stability. The reference preparation is not required to study stability, just to check on the dissolution curve of repeated test.
51 the company's production of generic drugs into the raw material is produced by the company, the raw material which needs to be related to the experiment or attention?
Answer: your own production of raw materials that you can do more in-depth study, maybe when you have some of the original reporting, but may not be enough, look in your new original research and reference literature, on his crystal type, size and other information compare your own API is more convenient, if the API to get the original research, it can according to the crystal form of the literature information and so on. In addition, the European Pharmacopoeia and other impurities like, related substances are more detailed, some products made of ten related substances of several or even more so, from the source of raw material control, whether you can achieve foreign related substance requirements, these are related to the study of you can be carried out. The more you do, the more in-depth understanding of him, then you through the grasp is bigger also.
52 a slow release variety in the selection of reference preparation, the original research has been discontinued, only the same specifications of the same dosage form but the release mechanism is not the same as the preparation, it can be used as reference preparations?
Answer: this involves the release mechanism, we see our guiding principle is given oral solid preparation, sustained-release formulations are relatively complex, the industry also often discuss this, such as the mechanism of sustained release preparations and normal preparations are not the same, that is what I want and you the same curve, or that I the curve is different but the body is the same, are very confused these problems in the early stage of our exploration, although this is correct, but if you do not go to the curve, especially controlled release preparations or other special varieties or the preparation process, curve consistent effect is very difficult to this conclusion the FDA did not say generics, especially the sustained-release preparation and release mechanism we must be the same, and not to the pharmaceutical equivalent key point, the drug release mechanism is not the same. So slow release preparations to do, then you need to do be, be do not need to do clinical trials, light from the dissolution curve angle is not enough to prove his equivalence