Modern approach to the evaluation of the pharmacokinetics and pharmacodynamics of biosimilar recombinant human insulin and insulin analogues in I phase clinical study

The quality, pharmacokinetic and pharmacodynamic profiles, safety and immunogenicity must be compared to demonstrate the bio-similarities of recombinant human insulin and insulin analogues. To confirm these bio-similarities in clinical studies, it is necessary to adhere to a multi-phased approach, starting with the pharmacokinetics and pharmacodynamics of the study drugs. In this article, in accordance with modern approaches to drug research, evaluation of the pharmacokinetics and pharmacodynamics of recombinant human insulin and analogues of human insulin (biosimilar drugs) is performed in a double-blind, randomised crossover euglycaemic hyperinsulinaemic clamp study.This article describes the main approaches to the evaluation of the pharmacokinetic and pharmacodynamic parameters of recombinant human insulin preparations and insulin analogues during a euglycaemic hyperinsulinaemic clamp study. The inclusion criteria for the sample selection, design and conditions of the study, methods for the suppression of endogenous insulin, recommendations for doses of drugs, duration of the study and choice of primary and secondary pharmacokinetic and pharmacodynamic parameters for bio-similar insulin products (which depend on the duration of their effects) are described.

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Recombinant human insulin-like growth factor-I in ALS: Description of a double-blind, placebo-controlled study

Neurology ◽

10.1212/wnl.47.4_suppl_2.93s ◽

1996 ◽

Vol 47 (Issue 4, Supplement 2) ◽

pp. 93S-95S ◽

Cited By ~ 34

Author(s):

D. J. Lange ◽

K. J. Felice ◽

B. W. Festoff ◽

M. J. Gawel ◽

D. F. Gelinas ◽

...

Keyword(s):

Growth Factor ◽

Human Insulin ◽

Controlled Study ◽

Insulin Like Growth Factor ◽

Recombinant Human Insulin ◽

Double Blind ◽

Double Blind Placebo ◽

Factor I ◽

Growth Factor I

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Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs

Journal of Veterinary Pharmacology and Therapeutics ◽

10.1111/j.1365-2885.2011.01329.x ◽

2011 ◽

Vol 35 (4) ◽

pp. 342-350 ◽

Cited By ~ 5

Author(s):

M. CLARK ◽

K. THOMASETH ◽

M. HEIT ◽

M. HOENIG

Keyword(s):

Human Insulin ◽

Recombinant Human Insulin ◽

Pharmacokinetics And Pharmacodynamics ◽

Healthy Dogs

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Downstream processing of recombinant human insulin and its analogues production from E. coli inclusion bodies

Bioresources and Bioprocessing ◽

10.1186/s40643-021-00419-w ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Yin Yin Siew ◽

Wei Zhang

Keyword(s):

Inclusion Body ◽

Human Insulin ◽

Inclusion Bodies ◽

Downstream Processing ◽

Insulin Analogues ◽

World Health ◽

Recombinant Human Insulin ◽

E Coli ◽

Recombinant Insulin ◽

Health Organization

AbstractThe Global Diabetes Compact was launched by the World Health Organization in April 2021 with one of its important goals to increase the accessibility and affordability of life-saving medicine—insulin. The rising prevalence of diabetes worldwide is bound to escalate the demand for recombinant insulin therapeutics, and currently, the majority of recombinant insulin therapeutics are produced from E. coli inclusion bodies. Here, a comprehensive review of downstream processing of recombinant human insulin/analogue production from E. coli inclusion bodies is presented. All the critical aspects of downstream processing, starting from proinsulin recovery from inclusion bodies, inclusion body washing, inclusion body solubilization and oxidative sulfitolysis, cyanogen bromide cleavage, buffer exchange, purification by chromatography, pH precipitation and zinc crystallization methods, proinsulin refolding, enzymatic cleavage, and formulation, are explained in this review. Pertinent examples are summarized and the practical aspects of integrating every procedure into a multimodal purification scheme are critically discussed. In the face of increasing global demand for insulin product, there is a pressing need to develop a more efficient and economical production process. The information presented would be insightful to all the manufacturers and stakeholders for the production of human insulins, insulin analogues or biosimilars, as they strive to make further progresses in therapeutic recombinant insulin development and production.

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Does all the evidence say that insulin analogues are more effective than human insulins?

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY ◽

10.22141/2224-0721.17.7.2021.244975 ◽

2021 ◽

Vol 17 (7) ◽

pp. 581-588

Author(s):

M.V. Neborachko ◽

O.G. Phakadze

Keyword(s):

Insulin Therapy ◽

Human Insulin ◽

Insulin Analogues ◽

Recombinant Human Insulin ◽

Glucose Levels ◽

Blood Glucose Levels ◽

National Programs ◽

The Cost ◽

Use Factors

Currently, a large amount of data has been accumulated to compare recombinant human insulin with insulin analogues, including meta-analyzes of comparative efficacy and safety, as well as cost-effectiveness data and data on the possible carcinogenicity of new products. Insulin treatment is a necessity for some people with diabetes mellitus (DM) due to the need to maintain optimal blood glucose levels. The authors emphasize the need to keep in mind that new insulin drugs are much more expensive, which may limit their use. Factors such as the effectiveness of treatment, its safety, and patient satisfaction should be taken into account when deciding on the choice of therapy, but the cost of treatment cannot be ignored, given that it is usually reimbursable from the budget. In this regard, insulin therapy should be individually selected taking into account the needs of patients, treatment goals, safety, and cost. The authors propose an analysis of these data on the feasibility of using insulin analogues in comparison with recombinant human insulin for patients with type 1 diabetes and patients with type 2 diabetes and their effectiveness in both types of diabetes. A reasonable policy for the use of insulin therapy should be developed based on available clinical data based on comparative studies in different groups of diabetics and comprehensive analysis of economic data. The feasibility of a new drug should be evaluated and regularly reviewed in light of the practical results of its use in clinical practice. It is also necessary to regularly conduct a retrospective economic analysis to assess the pharmacoeconomic benefits. All of these steps should assist decision-makers and regulators in implementing effective national programs to develop new effective insulin procurement systems.

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PHARMACOKINETICS AND PHARMACODYNAMICS OF RECOMBINANT HUMAN INSULIN-LIKE GROWTH FACTOR

American Journal of Therapeutics ◽

10.1097/00045391-199505000-00005 ◽

1995 ◽

Vol 2 (5) ◽

pp. 320-331

Author(s):

John M. Morgan ◽

Anthony J. Piraino ◽

William L. Hirschhorn ◽

David M. Capuzzi

Keyword(s):

Growth Factor ◽

Human Insulin ◽

Insulin Like Growth Factor ◽

Recombinant Human Insulin ◽

Pharmacokinetics And Pharmacodynamics

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Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy

European Endocrinology ◽

10.17925/ee.2017.13.01.21 ◽

2017 ◽

Vol 13 (01) ◽

pp. 21 ◽

Cited By ~ 3

Author(s):

Jean Claude Mbanya ◽

Juergen Sandow ◽

Wolfgang Landgraf ◽

David R Owens ◽

◽

...

Keyword(s):

Insulin Therapy ◽

Human Insulin ◽

Low Income ◽

Diabetes Management ◽

Insulin Analogues ◽

Low Income Countries ◽

Recombinant Human Insulin ◽

Economic Implications ◽

Global Issue ◽

Additional Clinical Benefit

Biosynthetic human insulin and insulin analogues are the mainstay of insulin therapy for both type 1 and type 2 diabetes although access to human insulin at affordable prices remains a global issue. The world is experiencing an exponential rise in the prevalence of diabetes presenting an urgent need to establish effective diabetes therapy in countries burdened by inadequate health care budgets, malnutrition and infectious diseases. Recombinant human insulin has replaced animal insulins and animal-based semisynthetic human insulin thereby available in sufficient quantities and at affordable prices able to provide global access to insulin therapy. In many patients, analog insulins can offer additional clinical benefit, although at a considerably higher price thus severely restricting availability in low income countries. The approval process for recombinant human insulins (i.e. biosimilars) and analogue insulins is highly variable in the developing countries in contrast to Europe and in North America, where it is well established within a strict regulatory framework. This review aims to discuss the future access to human insulin therapy in a global context with an ever increasing burden of diabetes and significant economic implications.

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