Major breakthrough | Diagreat's chemiluminescence solution for the detection of macromolecules and small molecule drugs on the same platform, helping clinical precise diagnosis and treatment.

Innovation is a relay race with one baton after another, and it is also an open competition where one chase another and compete fiercely. Diagreat can stand out from this highly competitive industry, which is inseparable from Diagreat's deep research and development of raw materials for many years, and its adherence to independent innovation and innovation-driven business philosophy. With the technological breakthroughs of domestic brands and the improvement of research and development capabilities, domestic TDM (Therapeutic drug monitoring) products have obvious technical and policy advantages. Combining with the needs of customers, Diagreat has achieved a breakthrough in the detection of small molecule and macromolecule drugs on the same platform. At present, more than 30 kinds of macromolecule and small molecule drug concentration detection can be carried out.

Seek the 'key' to resolve conflicts with innovative methods

With the continuous expansion of the clinical application of macromolecular monoclonal antibody drugs, more and more clinical problems have been exposed. The most common problems are non-response to initial treatment and failing response during treatment. According to statistics, about 20-30% of patients with refractory Crohn's disease and 40% of patients with refractory ulcerative colitis do not respond to anti-TNF-α therapy, and long-term treatment of biological agents fails to respond as high as 40%. There are two reasons for unresponsiveness: the first is individual differences caused by gender, body weight, and metabolism; the second is the serum drug concentration, which is too low and may induce drug resistance due to immunogenicity Antibodies; if the blood concentration is too high, side effects will occur. Therefore, therapeutic drug monitoring is particularly important in the treatment of monoclonal antibody drugs.

Introduction to Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) was developed under the background of turning to pharmaceutical technology services to ensure patient drug safety. TDM refers to the determination of the concentration of drugs and their metabolites in the patient's blood or other body fluids through various modern testing methods, and to explore the relationship between the blood drug concentration in the patient's body and the curative effect and toxicity, so as to determine the range of effective and toxic blood drug concentrations. At present, TDM is mainly applicable to drugs with narrow safety range, long-term use, non-linear pharmacokinetics, drug combination, drug toxicity and similar symptoms, and patients with liver, kidney, heart, gastrointestinal tract and other organ diseases.

With policy support, macromolecular drug monitoring has become a new hot spot in the field of TDM

In view of the important role of TDM in individualized drug use and improving the quality of medical services, in recent years, our country's health department has included TDM in relevant evaluation or access systems. For example: accreditation standards for Grade-A tertiary hospitals and hospital pharmacy industry standards. On July 1, 2022, the pilot pharmaceutical service fee policy was officially implemented in public hospitals in Fujian Province. Guangdong and other places also encouraged the exploration of pharmaceutical service fees many times. On July 27, 2022, the 'Notice on Further Strengthening Medication Safety Management and Improving the Level of Rational Drug Use' (National Medical Letter [2022] No. 122) issued by the National Health Commission of the People’s Republic of China and the National Administration of Traditional Chinese Medicine once again mentioned that medical institutions should strengthen key monitoring of rational drug use, and identify drug risks through TDM , etc. , to formulate individualized drug regimens. TDM is conforming to national and industry policies. At the same time, TDM has the advantages of less side effects, high success rate, low treatment cost, safe and efficient medication, etc. In recent years, with the rapid development of the field of precision medicine and the continuous release of clinical needs, the TDM market has ushered in a period of vigorous development.

At present, clinical TDM mainly focuses on small molecule drugs and some macromolecular drugs. Among them, small molecule drugs mainly include: (1) cardiac glycosides: digoxin, etc.; (2) antiepileptic drugs: phenobarbital, carbamazepine, sodium valproate, etc.; (3) antipsychotic drugs : Risperidone, olanzapine, etc. (4) Asthma drugs : theophylline; (5) Anti-infective drugs: vancomycin, linezolid, voriconazole, meropenem, etc. (6) Antineoplastic drugs: methotrexate, 5-fluorouracil, paclitaxel, etc.; (7) Immunosuppressants: tacrolimus, cyclosporine A, mycophenolate mofetil , etc. In recent years, macromolecular monoclonal antibody drugs have been widely used in clinical treatment. Macromolecular antibody drug TDM is a new hot spot, especially in anti-tumor (such as solid tumors, hematological malignancies) and rheumatic immune diseases (such as rheumatoid arthritis, enteritis, asthma, etc.) areas are more prominent. For example, bevacizumab, trastuzumab, rituximab, infliximab, adalimumab, golimumab, etc., the demand for macromolecular monoclonal antibody TDM is increasing day by day.

With the development of analytical technology and the update of detection methods, it is possible to perform TDM on more and more drugs. At present, the mainstream detection methods of TDM are mainly chromatography, mass spectrometry and immunological analysis. According to the survey data on the implementation of therapeutic drug monitoring in hospitals published by China-Japan Friendship Hospital in 2018, 37% of the customers use immunological methods for detection, and the immunological methods are mainly chemiluminescent methods. Because chemiluminescence method has a series of advantages such as simple operation, less sample processing, low requirements for operators, high detection throughput, high sensitivity, accurate results, connection to hospital LIS system, and clinical macromolecular drug concentration monitoring, etc., it is becoming more and more recognized by clinicians.

Extract the 'recipe' to make hard things simple with innovative idea

To achieve precise diagnosis and treatment, the clinical importance of macromolecular drug concentration monitoring has become increasingly prominent

Many drugs require individualized medication in clinical application. Does it require routine TDM? Which method is suitable for determining its in vivo concentration? How to correctly interpret and use the measurement results? They are all the latest issues facing the majority of clinical pharmacists.

The attending doctor formulates the patient's initial medication plan and determines whether the steady-state trough concentration of the drug is within the safe and effective therapeutic concentration range. For samples that are not within the effective therapeutic concentration range, clinical pharmacists need to consider the following factors: pharmacological action characteristics and adverse drug reactions, patient physiological and pathological characteristics and liver and kidney function effects, drug interactions, patient medication compliance, drug dosage forms, route of administration, etc. In the analysis of abnormal values, it is often necessary to combine the pharmacological action characteristics, pharmacokinetic characteristics, and distribution characteristics of the drug in the body of the monitored drug, as well as the physiological and pathological conditions such as the age and gender of the patient, as well as many drug-derived factors such as the route of drug use, recent drug use, and diet, etc. A combination of factors can lead to a treatment plan that is suitable for the individual patient.

For monoclonal antibody drugs, although the initial response rate is 50-90%, many patients can benefit from monoclonal antibody therapy, but the initial response of most patients will disappear over time, leading to disease progression. The lack or loss of response to monoclonal antibody therapy is caused by a variety of reasons, including lack of understanding of epigenetic, biomolecular or pathophysiological mechanisms, and insufficient understanding of serum monoclonal antibody concentrations may be the most basic reason. Therefore, although anti-inflammatory and anti-tumor monoclonal antibodies are not yet fully understood, therapeutic drug monitoring based on individual patient serum has become an important topic for personalized targeted monoclonal antibody therapy. For example, studies have shown that when infliximab is used to treat patients with moderate vs severe ulcerative colitis (UC) and patients with Crohn's disease (CD), there are differences in the pharmacokinetics of patients. A greater proportion of patients with severe UC had undetectable serum concentrations of infliximab at the lowest level compared with patients with moderate UC and CD who were similarly treated. Undetectable morning trough concentrations of infliximab increased the risk of colectomy in patients with UC, and there was a significant correlation between the two. Undetectable or inaccurate detection of low-concentration infliximab is a problem in clinical therapeutic drug monitoring.

As the pathogenesis of more and more diseases is further clarified, precise and efficient monoclonal antibody drugs will be more and more widely used in clinical practice. However, at the same time, due to the potential risks of monoclonal antibody drugs, clinical monitoring of drugs should be actively carried out to improve the level of rational use of MAB drugs and the ability to warn adverse reactions, so as to reduce the harm to patients. 

Open the 'tips' for breakthroughs in reality with R&D innovation

Both covering --- Diagreat macromolecule and small molecule detection chemiluminescent solution on the same platform

With the technological breakthroughs of domestic brands and the improvement of research and development capabilities, domestic TDM products have obvious advantages in technology and cost. Combining with the needs of customers, Diagreat has achieved a breakthrough in the detection of small molecule and macromolecule drugs on the same platform. At present, more than 30 kinds of macromolecule and small molecule drug concentration detection can be carried out. Diagreat innovatively adopts chemiluminescence detection technology. Its drug concentration detection chemiluminescence solution realizes fully automatic high-speed detection of samples in and results out. It has the advantages of unattended, full-process quality control, and stable results, which provide comprehensive and complete professional testing services for rational drug use and precise diagnosis and treatment to protect drug safety of patients.

Detection platform

l Speed up to 120T/H

l Fully automatic, efficient detection

Superior performance, easy to operate

Small Molecule Drug TDM Detection Item list

Macromolecular drug TDM detection item