How can biosypics be approved for more allergies? CDE text guide!

Transfer from . On August 14th, China's first QutoZhudan anti-biosygenic drug from Fuhong Hanxuan was approved for sale, and all the adaptive drugs approved by hercetin, the original research product, were approved in China.
same day, the Drug Review Center (CDE) of the State Drug Administration of China publicly solicited the Guiding Principles for the Evaluation of Biosypolytic Drug Similarity and The Technical Guidelines for The Extratrophic Extratroller of Adaptation (Draft for Comments).
previously, Biotay's Adamo monobial-like drugs (Greli) and Fuhong Han-Han-lytoxi monobial-like drugs (Hanlikang) have been awarded five adaptations in China.
with the development and evaluation of biosynthic drugs, the evaluation of similarity of such products and the scientific standard of adaptation extraterrence have become the focus areas of concern in the industry.
is "similarity"? According to the draft opinion, similarity means that there is no clinically significant difference in purity, safety and ability between biosynthics and reference drugs.
biosypolytic drug similarity evaluation should be based on pharmacological, non-clinical, clinical evaluation of the results of the study to determine the overall similarity between the candidate drug and the reference drug.
opinion draft points out that similarity evaluation should be carried out at different stages of the progressive study of biosypic drugs to help guide the follow-up targeted comparing studies, and thus to evaluate similarity as a whole.
The results of the previous study showed that there was a difference between the candidate drug and the reference drug, but the effect of the difference on the safety effectiveness was uncertain, and after the follow-up targeted comparative study, no clinical significance was found, it can be considered that there is similarity between the candidate drug and the reference drug.
is an adaptive extraterrence? According to the opinion draft, the adaptation extraterroration refers to: within the scope of the reference drug approved to adapt, biosynthic drugs by direct clinical comparation of the experimental approval of the adaptive disease, through the relevant data and information to scientifically prove and obtain other non-directly studied adaptation.
the draft notes that the adaptation extraterrestress is based on all the scientific considerations of the available reference drugs and candidate drugs, and that it is important to assess and demonstrate whether there are differences in mechanisms of action, PK, PD, effective, safety and immunogenicity between candidate and reference drugs in the non-directly studied adaptive population.
Usually, extrapolation needs to meet the following conditions: 1) sensitive clinical trial models have been used to detect differences between reference and candidate drugs, 2) clinically relevant mechanisms of effect and/or associated subjects are the same, 3) the safety and immunogenicity of biosypolytic drugs have been adequately characterized, and the inferred adaptation has no special or additional safety problems.
case study Adamu monoantigen (Shumeile) is approved worldwide for the treatment of multiple adaptations by neutralizing tumor necrosis factor alpha (TNF-alpha), among which moderate to severe mandatory spina bifida, rheumatoid arthritis, plaque psoriasis, psoriasis, psoriasis, psoriasis Pathological mechanisms of pathogenic arthritis, early idiopathic arthritis, and vine membraneitis are abnormally high expression of TNF-alpha, and the main mechanism of action of adamo-monoantigens on these adaptations is mainly binding and neutraling soluble tumor necrosis factor-alpha (sTNF-alpha).
And in moderate to severe crohn's disease and ulcerative colitis, TNF-alpha as the main inflammatory factor is an important regulatory factor in the pathogenesis, and the mechanism of action of adamo monoantigen to such inflammatory bowel disease, in addition to binding to sTNF, also works by binding transfilm tumor necrosis factor-alpha (tmTNF-alpha).
opinion paper points out that when adaptive extratrophic extraterrion, it should evaluate whether sensitive models are used in PK, PD, clinical comparison studies to support clinical similarity evaluation, and pay attention to whether biological functional activity is carried out on known or potential mechanisms of adamosis in different adaptive disorders, such as sT NF alpha binding activity (ELISA), sTNF alpha binding dynamics (SPR method), TNF alpha neutralization activity, apoptosis inhibition, etc., because monoclonal antibodies have multiple biological activities, should be based on the degree of relevance to clinical effects to determine the weight of similarity, and set standards.
For example, when extraterred from psoriasis, or rheumatoid arthritis to inflammatory bowel disease, the similarity of indicators based on the biological activity or immunological properties of the Fc-end mechanism of action should be fully assessed, or consideration may be given to establishing a cell model for in-body inflammatory enteropathy IBD (e.g. inhibition of HCT-116 apoptosis and IL-8 release).
According to the clinical trial data of the original drug, among the approved adaptations, Adamo mono-anti-treatment plaque psoriasis was the most effective, with the greatest difference in efficacy at the main therapeutic endpoint compared with placebo, at 45-61%, and in other adaptations such as mandatory spinalitis at 18-37%; The difference was 18-35%, in adult staphylococcitis was 16-24%, in adult Crohn's disease-induced remission was 14-24%, and the efficacy difference was 23-26%, adult ulcerative colitis-induced remission was 7.2-9.3%, maintenance remission was 4.4%, and the difference in efficacy relative to placebo was decreasing.
where psoriasis is a separate drug, does not require a combination of immunosuppressants, and the immunogenicity of psoriasis patients is 8.4%, similar to the immunogenicity of patients with mandatory spinalitis (8.6%) and rheumatoid arthritis (12.4%), so in these adaptations, moderate to severe plaque psoriasis can be used as a more sensitive group to assess the effectiveness, safety and immunogenic similarity of candidates and reference drugs.
In addition, considering that adamosis has a clear mechanism of action in mandatory spinalitis adaptation, stable therapeutic dose, clinical use does not need to combine immunosuppressant drug characteristics, can also be used as one of the sensitive adaptors to assess the difference between candidate drugs and reference drugs.
Combined with the above multi-factor analysis, based on the purpose of similarity evaluation and adaptation extraterrence, when formulating the overall clinical research strategy of Adamo monoantigen-like drugs, we should select healthy people as far as possible for PK ratio study, and select sensitive models related to adaptive population for clinical evaluation.
If the healthy population is not selected for PK matching, it is recommended to select different sensitive models for PK and clinical studies, wherein clinical reference studies should consider selecting the most sensitive models to carry out research to fully assess the clinical similarity between candidate and reference drugs.
: a notice on public consultation on the Technical Guidelines for the Evaluation and Adaptation of Biosypole Drug Similarity and Adaptation Extratrophics (Draft for Comments). Retrieved Aug 14,2020, from Heavy! The first domestic curt bead single anti - Hanqu you ® approved for listing. Retrieved Aug 14, 2020, from ® (Adamo monoantigen injection) was approved for the fifth adaptive disorder. Retrieved Aug 11, 2020, from Blood Tumor Patient Gospel, China's first biosynthic drug Hanlikang ® two new allergens were approved. Retrieved Jul 14, 2020, from . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .