[Revised version of the statement by the DGRh on biosimilars-update 2017]. / Neufassung der Stellungnahme der DGRh zu Biosimilars ­ Update 2017.

The treatment of rheumatic diseases with bioloics has significantly improved the prognosis of patients. Currently, there are 13 preparations available in Germany for the treatment of patients with inflammatory rheumatic diseases. These original preparations generally have-depending on the individual country-15 years of patent protection. As soon as the patent has expired, approved biosimilars can be brought into use. For the approval of a biosimilar, authorities such as the European Medical Agency or the American Food and Drug Administration require proof of the best possible comparability with respect to efficacy and safety in comparison to the original or reference product. Since 2015, biosimilars of inifliximab, adalimumab, etanercept and rituximab have been granted approval in the European Union, the USA, Japan and in other countries. Further biosimilar products for these reference products are in development for treatment in rheumatology. From a societal and medical point of view, this opens up the possibility to increase the availability of biopharmaceutical products for patients through lower prices. In Germany, this possibility has already occurred-statutory health insurance physicians have introduced quotas for biosimilars, which will ultimately decrease spending and healthcare costs. This can lead to price reductions of the original products, which has already happened in Germany. Biosimilars can be prescribed for new patients or as a change from the original to the generic drug. When switching, a distinction is made between individual switching (interchangeability), which is made in individual consultation between the physician and the patient, and nonmedical switching (substitution) made at the societal or governmental level, which is made in the context of health care cost containment, and then, for example, implemented at the pharmacy level. Preliminary data from Norway and Denmark are available for substitution on the basis of results from large studies or registries in which systematic changes were made. The previous conclusion was that this does not lead to new problems for the patients. The German Society for Rheumatology recognizes the advantages of introducing biosimilars in Germany, but recommends that their use be based primarily on a joint decision by the treating physician and patient.

Similarity Evaluation of the Dissolution Curves of Generic and Original Preparation of Losartan Potassium Tablets / 中国药房

OBJECTIVE:To evaluate the dissolution curves similarity of generic and original preparation of Losartan potassium tablets,and to provide reference for improving quality evaluation of the preparation.METHODS:Using hydrochloric acid solution (pH 3.0),phosphate buffer solution(pH 4.5),phosphate buffer solution (pH 6.8) and water as medium,paddle method was adopted for dissolution test with dissolution medium volume of 900 mL and rotation speed of 50 r/min.UV-visible spectrophotometry was adopted to determine accumulative dissolution of generic and original preparation of Losartan potassium tablets with the detection wavelength of 256 um.The similarity of dissolution curves were evaluated by calculating similarity factor(f2).RESULTS:The linear range of losartan potassium was 12.11-35.96 μg/mL (r≥0.999 7).RSDs of precision,stability and reproducibility tests were all lower than 5.0％.The recoveries of 4 dissolution media were 98.66％-100.84％ (RSD=0.77％,n=9),98.91％-100.59％ (RSD=0.49％,n=9),98.33％-101.39％ (RSD=0.85％,n=9),99.46％-101.32％ (RSD=0.55％,n=9).In 4 dissolution media,f2 of the dissolution curves of 3 batches of generic and original preparation of Losartan potassium tablets were all higher than 70.CONCLUSIONS:The dissolution curves of self-made and original preparation of Losartan potassium tablets show good similarity.

Efficacy and Safety of the Generic and Original Preparation of Atorvastatin:A Systematic Review / 中国药房

OBJECTIVE:To systematically review the efficacy and safety of the generic and original preparation of atorvas-tatin,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed,EMBase,Cochrane Li-brary,CJFD,Wanfang Database,VIP and CBM,related randomized controlled trials(RCT)about generic preparation of atorvas-tatin(test group)versus original preparation of atorvastatin(control group)were collected. Meta-analysis was performed by using Rev Man 5.3 software after data extract and quality evaluation. RESULTS:Totally 16 RCTs were included,involving 2 077 pa-tients. Results of Meta-analysis showed,compared with control group,there were no significant differences in reducing total choles-terol (TC) [MD=-0.06,95%CI(-0.14,0.01),P=0.11],triglyceride (TG) [MD=-0.00,95%CI(-0.08,0.08),P=0.99], low-density lipoprotein cholesterol (LDL-C) [MD=-0.07,95%CI(-0.16,0.01),P=0.09],increasing high-density lipoprotein cholesterol(HDL-C)[MD=-0.00,95% CI(-0.03,0.03),P=0.96] and the incidence of major adverse cardiac events(MACE) [OR=1.18,95%CI(0.71,1.97),P=0.52] in test group;in terms of safety,compared with control group,there were no significant differences in the resulting in alanine aminotransferase (ALT) increased [OR=1.08,95%CI(0.51,2.30),P=0.83],the incidences of myalgia [OR=2.46,95%CI(0.70,8.65),P=0.16] and gastrointestinal adverse reactions [OR=1.11,95%CI(0.64,1.95),P=0.71]. CONCLUSIONS:Both the generic and original preparation of atorvastatin can effectively reduce blood lipid levels,with sim-ilar safety.

Consistency Evaluation of the Dissolution of Generic and Original Preparations of Dronedarone Hydrochlo-ride Tablet / 中国药房

OBJECTIVE:To establish a method for the dissolution determination of Dronedarone hydrochloride tablet,and eval-uate the quality consistency of its generic and original preparations. METHODS:UV spectrometry was performed on the column of 288 nm,dissolution media of Phosphate buffer solution (pH4.5),0.1 mol/L Hydrochloric acid solution [adding into 0.5% sodium dodecyl sulfate(SDS)],Phosphate buffer solution [pH6.8,adding into 0.5%SDS] and water,volume of dissolution medium was 1 000 ml,rotation speed was 75 r/min,the dissolution of generic and original preparations of Dronedarone hydrochloride tablet was detected,and the similarity of dissolution curve was evaluated by calculating the similarity factor (f2). RESULTS:The linear range of dronedarone hydrochloride was 2.147-25.764 μg/ml;RSDs of precision,stability and reproducibility tests were lower than 2.0%;recoveries 4 dissolution media were 99.53%-101.05%(RSD=0.48%,n=9),98.95%-100.05%(RSD=0.39%,n=9), 99.54%-100.20%(RSD=0.24%,n=9)and 98.54%-100.06%(RSD=0.44%,n=9). In the 4 dissolution media,f2 of the dissolu-tion curve of 3 batches of generic and original preparations of Dronedarone hydrochloride tablet was 56,60,63,68,68,52,59, 67,65,68,76,62,respectively. CONCLUSIONS:The method is suitable for the dissolution determination of Dronedarone hydro-chloride tablet;meanwhile,the in vitro dissolution curves of generic and original preparations of Dronedarone hydrochloride tablet show similarity,so the quality consistency is good.

Similarity Evaluation of the Dissolution Profiles of Self-made and Original Preparation of Ramelteon Tablet by f2 / 中国药房

OBJECTIVE:To evaluate the similarity of in vitro dissolution of self-made and original preparation of Ramelteon tablet. METHODS:The paddle method was adopted with rotational speed of 50 r/min,using water,pH1.2 hydrochloric acid solu-tion,pH4.0 acetate buffer solution and pH6.8 phosphate buffer solution as dissolution media,HPLC was used to determine the cu-mulative dissolution of main components of self-made and original preparation of Ramelteon tablet at different time points,dissolu-tion profile was drew,then f2 was used to evaluate its similarity. RESULTS:In the 4 dissolution media,the f2 of self-made and original preparation of Ramelteon tablet was 62.8,80.0,77.7,76.2,respectively,which indicated that the dissolution profiles showed similarity. CONCLUSIONS:The established HPLC is suitable for the dissolution determination of Ramelteon tablet;the dissolution profiles of the self-made and original preparations are similar,it preliminary indicates the prescription and technological rationality of self-made preparation.

Similarity Evaluation of Dissolution Profiles of Self-development and Original Preparation of Solifenacin Suc-cinate Tablet / 中国药房

OBJECTIVE:To explore the similarity of dissolution profiles of self-development and original preparation of Solife-nacin succinate tablet,and provide reference for the prescription and process screening of the former one and the quality similarity evaluation of the latter one. METHODS:The paddle method was adopted with rotational speed of 50 r/min,using water,pH1.2 hy-drochloric acid solution,pH4.0 acetate buffer solution and pH6.8 phosphate buffer solution as dissolution media,HPLC was used to determine the cumulative dissolution of main components of self-development and original preparation of Solifenacin succinate tablet at different time points,dissolution profile was drew,then f2 was used to evaluate its similarity. RESULTS:In the 4 dissolu-tion media,the f2 of both self-development and original preparation of Solifenacin succinate tablet was higher than 50,which indi-cated that the dissolution profiles showed similarity. CONCLUSIONS:The established HPLC is suitable for the dissolution determi-nation of Solifenacin succinate tablet;the dissolution profiles of the self-development and original preparations are basically simi-lar,which indicates the prescription and technology of self-development preparation are feasible.

Cosistency Evaluation of Dissolubility of Manidipine Hydrochloride Tablet Generic and Original Preparation / 中国药房

OBJECTIVE:To establish a method for the dissolubility determination of Manidipine Hydrochloride tablet and eval-uate the quality consistency of generic and original preparation. METHODS:HPLC was performed on the column of Waters Sym-metry C18 column with mobile phase of potassium phosphate monobasic solution (potassium phosphate monobasic 6.8 g was well-mixed with water 1 000 ml,and pH was adjusted to 4.6 by potassium hydroxide solution)-acetonitrile (49∶51,V/V) at flow rate of 1.0 ml/min,detection wavelength was 228 nm,column temperature was 25℃,and the injection volume was 20μl. The dis-solution mediums were 0.1 mol/L hydrochloric acid solution,acetic acid-sodium acetate buffer solution(pH 4.0)and phosphate buf-fer solution [pH 6.8,adding into 0.5% sodium dodecyl sulfonate(SDS)],volume of dissolution medium was 900 ml and rotating rate was 50 r/min,and the dissolubility of Manidipine hydrochloride tablet generic and original preparation was investigated and the similarity of dissolution profile was evaluated by calculating similar factor (f2). RESULTS:The linear range of manidipine hydro-chloride was 0.625-20 μg/ml;RSDs of instrument precision and stability tests were lower than 2.0%;recoveries of 3 dissolution mediums were 92.86%-102.97%(RSD=1.9%,1.8% and 2.7%,n=9),respectively. The dissolubility of 3 batches of Manidipine hydrochloride tablet generic and original preparations was higher than 85% in 0.1 mol/L hydrochloric acid solution in 15 min;f2 was >50 in acetic acid-sodium acetate buffer solution (pH 4.0) and phosphate buffer solution (pH 6.8,adding into 0.5% SDS). CONCLUSIONS:The method is suitable for the dissolubility determination of Manidipine hydrochloride tablet;meanwhile,the dis-solution profile in vitro of Manidipine hydrochloride tablet generic and original preparations has similarities,so the quality consis-tency is good.