Drug consistency evaluation includes in-vitro pharmaceutical consistency and in-vivo bioequivalence between generic drugs and RLD, which aims to ensure that generic drugs have the same safety and efficacy as RLD. Pharmacokinetics is the most commonly used method to evaluate bioequivalence evaluation (BE). However, pharmacokinetic methods are not recommended for evaluation when the following conditions occur.
- There is no correlation between plasma drug concentration and clinical efficacy.
- The concentration of drugs or metabolites in plasma or urine is too low or even negligible.
- The concentration of target drugs or metabolites cannot be accurately measured by existing analytical methods.
- The measured drug concentration cannot accurately evaluate drugs' effectiveness and safety.
The above conditions can be studied for bioequivalence using validated pharmacodynamic research methods. Pharmacodynamic methods describe the relationship between the concentration of a drug at the site of action in an organism and its pharmacological effects or adverse effects.
Our Services
Our company provides a full range of one-stop bioequivalence (including pre-BE and formal BE) solutions for generic drug manufacturers, with a large number of BE success cases. We support manufacturers' use of clear, quantifiable, and objective pharmacodynamic measures comparing generic drugs with RLD to assess bioequivalence when no feasible pharmacokinetic study method is available.
Through industry-leading pharmacological and biological technologies, we systematically construct a variety of pharmacodynamic models and detection key technologies, and conduct standardized and systematic pharmacodynamic evaluation of generic drugs. With our extensive BE experience, we provide sensitive, stable, reproducible pharmacodynamic studies with low response variability.
- Drug dose-response relationships have been fully and effectively proved
- The pharmacodynamic effect corresponding to the selected dose is in the linear phase of the dose-effect relationship curve
- Sufficient measurements are selected to obtain the appropriate pharmacodynamic response-time curves
- All pharmacodynamic measurements are validated for specificity, sensitivity, accuracy, and precision
- There is sufficient statistical significance within a feasible sample size
We can help you at any stage of BE
Compared with other evaluation methods, pharmacodynamic studies need to pay special attention to the variability of end points, the measurement methods of parameters, and the formulation of evaluation criteria.
The study design of the pharmacodynamic method focused on the overall consideration of the inclusion of blinding, the use of placebo, the duration of treatment, and the dosing interval.
Preliminary experiments are helpful to explore the sample size, set the dosage, clarify the inclusion and exclusion criteria of subjects and other relevant information, so as to reduce the possible differences in the design and process requirements of formal trials.
The selection of subjects has a great influence on the results, so the number of subjects and the inclusion and exclusion criteria need to be strictly controlled. The sample size of the participants is required to have adequate statistical power, and we can conduct preliminary experiments to select appropriate pharmacodynamic end points to effectively reduce the sample size.
- Selection of pharmacodynamic end points
In pharmacodynamic methods, it is very important to select a sensitive pharmacodynamic endpoint. Single or combined pharmacodynamic endpoints with low variability should be selected for evaluation.
Our services are available in the following dosage forms
Inhaled administration is the preferred mode of administration for the treatment of respiratory diseases such as asthma. The pharmacokinetic behavior of inhaled formulations is complex, and it is difficult to evaluate the equivalence between generic drugs and RLD by pharmacokinetic studies alone. In the FDA's database of drug-specific bioequivalence guidelines, some inhaled formulations are evaluated using pharmacodynamic studies.
- Topical preparations for the gastrointestinal tract
The clinical efficacy of most drugs with local action in the gastrointestinal tract is not correlated with their pharmacokinetics, and bioequivalence cannot be accurately evaluated by pharmacokinetics.
- Topical skin preparations
In general, topical skin preparations are not absorbed into the blood after application, and body exposure is not easy to monitor and is not directly related to the efficacy of the drug. Pharmacokinetic studies are mainly used to determine the safety of topical skin preparations, and pharmacodynamic methods can be considered when evaluating drug bioequivalence.
- Injectable formulations of low molecular weight heparin
Low molecular weight heparin injection is a mixture of different polysaccharide chain molecules, which cannot be accurately separated, purified and determined by existing analytical techniques.
