Biosynthic drug policy landing: can not automatically extratrot reference drug all adaptive

February 19th, February 18th, the first working day after the National Drug Administration Drug Review Center (CDE) official website issued the "Biosyspole Drug Similarity Evaluation and Adaptation Extratrophic Technical Guidelines" (hereinafter referred to as the "Guiding Principles"), for the biosynthic drug subdivision areas of product development and the use of adaptive extratrophics formally put forward clear regulatory requirements, causing industry concern.
"A comprehensive comparative study of similar drugs" to ensure quality, efficacy, safety in recent years, domestic and foreign pharmaceutical enterprises have carried out biosynthic drug research and development, existing drugs according to biosynthic drugs have been approved for market, to meet the access to clinical drugs for patients.
At present, there are more than 700 biosynthic drugs under study worldwide, entering the clinical stage in the field of product adaptation concentrated in tumor, immune and blood diseases, China has nearly 300 biosynthetic drugs in different stages of research and development, the varieties are mainly concentrated in lyxi monomath, Adamo monoanti, quartoju, Invlixi monoanti, Beva bead monoanti.
biological products have the characteristics of large molecular weight, complex structure, strong dependence on the structural integrity of biological activities, and complex production process, so it is urgent to standardize and guide the development and evaluation of biosynthic drugs and promote the healthy development of biopharmaceutical industry.
The Guiding Principles provide authoritative guiding advice and technical references for industry, researchers and regulatory agencies around the general considerations of similarity evaluation, pharmaceutical similarity, non-clinical similarity, clinical similarity, overall similarity, and general considerations of adaptive extraterrorism, adaptive extraterrorism conditions, and comprehensive evaluation.
The Guiding Principles, published this time, begin with a specific definition of the "similarity" of biosynthic drugs: candidate drugs are similar to approved reference drugs as a whole, and there are no clinically significant differences in quality, safety and ability.
industry generally agrees that "similarity" is defined as "a high degree of similarity between biosynthics and reference drugs, with no clinically significant differences in purity, safety and importance" over the Guidelines (draft for comments) issued in August last year.
", the official draft fits the actual development of the industry, and the "quality", "safety" and "effectiveness" as the standard threshold for evaluating products, more industry guidance.
In fact, new drug research is self-expedited in product effectiveness and safety through comprehensive preclinical and clinical studies, while biosypolytic drugs demonstrate their similarity to reference drugs through rigorous and detailed comparative studies, thereby bridding all safety ability data for reference drugs and considering adaptation extraterression if preconditions are met.
industry experts said that, unlike new drug research, pharmaceutical research of bio-similar drugs should not only do a full set of pharmaceutical routine research, but also with reference drugs to conduct a comprehensive comparison, the overall evidence needs to include biological products structure, function, animal toxicology, human PK/PD, clinical effectiveness, safety and immunogenicity.
can be seen that the comparison of pharmaceutical research is the basis, the study of bio-similar drugs is progressive, on the basis of pharmaceutical research, before considering non-clinical, and then clinical research.
The use of "adaptive extraterrestression conditions" should follow the principle of individualization for the industry's general concern of "adaptive extraterrestression", the Guiding Principles clearly: on the basis of the overall similarity between candidate drugs and reference drugs, when directly compared to clinical trials to prove that candidate drugs are clinically similar to reference drugs in at least one adaptation, it may be through the scientific demonstration of research data and information related to extratrophic adaptations to support its use in reference to other non-directly studied adaptations approved in China.
At the same time, the Guiding Principles require that the extraterrence of adaptation cannot be obtained directly and that the similarities and differences in pathogenesis, pathophysiology, and similarity should be considered on a case-by-case basis in terms of the characteristics of the mechanism of action of the drug, the differences and differences in pathogenesis between the studied adaptation and the proposed extratrophic adaptation, and the similarity ratio to the adquacy of the study data.
It is clear that "biosyspolor drugs cannot automatically extratrot reference drugs to all adaptations" "adaptation extraterrence should be considered on a case-by-case basis according to the characteristics of the product and target adaptation characteristics", and the "Biosyspole drug research and development and evaluation technical guidelines (trial)" issued by CDE in February 2015 require "adaptation extradulation needs to be considered on a case-by-case basis according to product characteristics".
In fact, prior to the publication of the Guiding Principles, there was a view within the industry that "adaptation extraterression" should be given "adaptation extraterression" treatment because of similarity studies, and the "Chinese Biosynthic Drug Expert Consensus" published by CSCO (China Society of Clinical Oncology) last May concluded that biosypolytic drugs could obtain all adaptations with the same mechanism of action.
The Guiding Principles, while affirming the "adaptive extraterrive individualization principle" and re-emphasizing the "inability to automatically extratrodulation of all adaptations", require companies to submit separate applications for each adaptation and submit evidence for regulatory approval, which is also the practice of overseas regulators: in addition to adaptation The push is based on the overall similarity between the candidate drug and the reference drug, and when the direct matching clinical trial can prove that the candidate drug is clinically similar to the reference drug in at least one adaptation, it may support the candidate drug directly for reference drug China approved other adaptations through the scientific demonstration of the research data and information related to the extratrophic adaptation.
Biosynthetic drugs can not automatically extratrot reference drugs of all the adaptations, should fully demonstrate whether the candidate drugs and reference drugs in the non-directly studied adaptive population, whether there is a mechanism of action, PK, PD, effectiveness, safety and immunogenicity differences.
these differences, biosypolytic drugs can be used in other unstated adaptive populations.
The Guiding Principles set out the necessary conditions for the circumstances under which biosynols can be extratroduled to other adaptations of reference drugs: adaptation extraterression requires the use of a clinical trial model that meets the following criteria1, and no clinical differences have been detected.
should be combined with the sensitivity to the study design to assess whether there are differences in impact effectiveness and safety in the proposed extratrophic population.
e.g. from one disease group to another (e.g., autoimmune diseases to cancer), the pathophysiological mechanisms of the disease vary widely, where PK and dosing regimens (dose, frequency, cycle) may be different, and additional PK/PD studies or clinical trials may be required to address uncertainty before extratrophysosis can be supported.
2 Clinically relevant mechanisms of action and/or related subjects the same drug should be as consistent as possible with the main mechanism of action of the same drug in directly compared to the study of adaptation and extratrophic adaptation, for drugs with multiple biological activities or functions (e.g. monoclonal antibodies can bind fragments via antigen (fragment antigen binding, Fab) end plays a binding or mesozoic biological activity, through the crystalline fragment (fragment crystallizable, Fc) end to play immunological function, should fully understand and evaluate the drug between the mechanism of action between different adaptations.
For different situations in which the mechanism of drug action is different in different adaptations, the similarity of their biological activity or in-body function should be fully explored, and in some cases, different target and effect cells should be used to better simulate the pathological state of the target adaptation.
additional non-clinical or clinically compared trial data are required to support adaptive extraterrence when necessary.
in-body functional tests are more sensitive to detecting differences related to adhesion.
3 has been fully evaluated for the safety and immunogenicity of the drug candidate, and there are no special or additional safety issues with the proposed extratrophic adaptation.
the sensitivity of the study to assess whether there may be a potential risk of affecting safety in the adaptive population to be extratrophic.
, if there is uncertainty that could affect safety, potentially rare adverse reactions, etc., should also be monitored after listing.
The damage to the immune system caused by different diseases can make the drug immunogenic, and usually, if the immunogenicity of the candidate drug is shown to be similar to that of the reference drug in the adaptation characterized by the complete immune system, then it can be inferred that there is similar immunogenicity in the immunosuppressed population.
attention should also be paid to the potential for differences in exposure of immunogenic characteristics (e.g., elevated or decreased ADA) in the adaptive population to be extratrophic, as well as their potential impact on effectiveness and safety.
post-market studies are needed to assess potential immunogenic-related complications when necessary.
The damage to the immune system caused by different diseases can make the drug immunogenic, and it can often be inferred that there is similar immunogenicity in immunosuppressed populations if immunogenics similar to those of reference drugs are shown in adaptations characterized by a complete immune system.
also need to be concerned about the potential for differences in exposure of immunogenic characteristics (e.g., elevated or decreased ADA) in the adaptive population of the proposed extratrophic, and their potential impact on effectiveness and safety.
post-market studies are needed to assess potential immunogenic-related complications when necessary.
Experts explain that if similar drug extratrophics and reference drug approved adaptations belong to the same disease group (e.g. cancer), clinically relevant mechanisms of action and/or subjects are the same, and in clinical matching trials, the appropriate adaptive disorders were selected, and the external extratrophics were fully evaluated, there is hope to obtain adaptation extrophics approval.