General Formulation Research Articles

Analisa mutu tablet ibuprofen generik berlogo dan generik bermerek yang diproduksi industri X di Gresik

Ibuprofen tablets are one of the most widely used antipyretic analgesic drugs for self-medication in pharmacies. According to the Biopharmaceutical Classification System (BCS), Ibuprofen is included in Class II or drugs with low solubility, but high permeability. This study was carried out to determine the physical quality of branded generic and branded generic ibuprofen drugs. This research was carried out by dissolution testing on ibuprofen tablets. The results obtained from the physical quality test met the specified requirements. The dissolution test showed that Q30 had dissolved more than 70%. The conclusion is that the drug meets the requirements and there is no difference between generic drugs with the logo and branded generics.

Slab assignment to non-identical reheat furnaces running in parallel mode

This article analyses a slab assignment problem for non-identical reheat furnaces in the steelmaking industry. We tackle the problem of assigning slabs to different types of reheat furnaces, a walking beam and a pusher type furnace. Furthermore, we need to determine the feed-in as well as the residence time for each slab. The aim is to (i) reduce the energy consumption, (ii) increase the production rate and (iii) the heating quality of the slabs which depends on the assigned furnace and to what extent the slabs are overheated. Moreover, the subsequent production stage (Hot Rolling Mill), needs to be synchronized with the furnaces which is essential for a smooth production. We specify the problem as a mixed integer optimization formulation that is solved with iterative parameter adjustment. Rapid convergence leads to a novel two-phase solution method that yields furnace schedules that are optimal for the adjusted parameter values in reasonable time. The results show that our proposed method performs better than an industry benchmark by increasing the production rate and increasing the reheating quality. Furthermore, the new generic problem formulation allows using standard software and can be applied to identical or non-identical furnaces highlighting its broad applicability across steel-making companies.

Medicine Wastage in Private Clinics: Drug Suppliers’ Perspective on the Causes and Measures to Reduce It

This study examines the issue of medicine wastage in private clinics from the perspective of drug suppliers in Hong Kong. Medicine wastage refers to unused or expired medication along the supply chain, and it poses significant challenges to healthcare systems worldwide. In the private healthcare sector of Hong Kong, there is a notable issue of medicine wastage, resulting in considerable economic costs and environmental hazards. The paper explores the causes of medicine wastage, including the inefficient business model of private clinics, the frequent use of general medicines, the decline in medical tourists, disruptions in the supply chain due to the COVID-19 pandemic, and the lack of medicine recycling policy and facility. Additionally, the paper suggests implementing a centralized medicine procurement and inventory management system, separating medicine prescribing and dispensing, and developing a medicine recycling policy to reduce medicine wastage in Hong Kong.

Study of polymer component migrated in medicinal product from transportation packaging component: A systematic assessment beyond regulatory expectations

Light Density Polyethylene (LDPE) bottles with a specific resin were chosen as container closure system (CCS) to fill “Latanoprost ophthalmic solution” (a generic drug product). As an alternative packaging component, additional manufacturer of LDPE bottles with the same characteristics as the previously selected LDPE bottles was chosen. The appropriateness of both packaging components was evaluated using an extractables and leachable (E&L) study and a formal stability programme that monitored quality of latanoprost ophthalmic solution. The results of relevant quality attributes in stability samples of latanoprost ophthalmic solution packed in both LDPE bottles were compared. It noticed that an unknown impurity in latanoprost ophthalmic solution packaged in LDPE bottles manufactured by an additional manufacturer. Further study revealed that this unknown impurity is Epsilon-caprolactam, a leachable of plastic used in the transportation of LDPE bottles. The leachability was validated through an extraction analysis of a plastic bag used for transportation. Thus, in certain cases, when the source of leachable is not identifiable by an E&L examination of primary, secondary, and tertiary packaging components, the assessment could be extended to include packaging components utilized throughout the supply chain.

Role of In Vitro Tests in the Characterisation of Locally Applied, Locally Acting Drugs in the Throat: Application to Flurbiprofen.

Background/Objectives: For locally applied, locally acting generic drug products, comparison to an originator product based on systemic exposure is usually not feasible due to low plasma concentrations and inadequate reflection of local exposure at the site of action. Where a validated PD model exists, a comparative clinical study can be performed in healthy subjects; where no surrogate endpoint is available, patients with the relevant indication need to be enrolled, with all the associated factors which could result in lack of sensitivity. Even though the need for alternative in vitro approaches has been acknowledged by both industry and regulatory bodies, the complexity of in vivo drug delivery processes makes the development of guidance documents particularly difficult. Our objective was to present in vitro approaches less classically used and to address in vivo relevance of the selected tests. Methods: This article analyses current regulatory approaches in Europe and the U.S., and highlights the key advantages of in vitro tests in terms of their sensitivity, reliability, reproducibility and in vivo relevance using locally applied flurbiprofen in various formulations. Results: The in vitro esophageal retention (IVOR) model demonstrates that the first 6-10 min after application of different flurbiprofen formulations is important for their comparison and also offers the best correlation with in vivo data using the partial area under the concentration-time curves (pAUCs). Rheological evaluations further demonstrated that the mucoadhesive properties of the gel spray formulation are based on interaction with mucin. Conclusions: Designing a relevant in vitro test requires adequate evaluation of the complexity of the drug substance, drug product, dosing conditions and delivery processes.

Original drugs and generics: are there any differences from the clinician’s point of view?

The article defines the original drug (OD) and examines the history of the appearance of generic drugs (GD), as well as the evolution of views to prove their bioequivalence to OD. The question is considered to what extent pharmacokinetic equivalence can guarantee the clinical equivalence of OD and GD. The data on the rules of registration of GD in different countries are provided. A brief overview of various types of studies comparing the clinical efficacy and safety of OD and GD (meta-analyses, randomized controlled trials, observational studies, description of clinical cases) and their main results is given. The results of a number of observational studies on the replacement of OD with GD and its consequences are presented. The existing system of current quality control of GD is described, numerous cases of recall of GD due to detected violations during their production are given. It is mentioned about individual cases of clinical inefficiency of GD and their side effects identified by the practical physicians. It is concluded that a qualitatively produced GD with proven pharmacokinetic equivalence to OD is able to provide therapy of the same quality as OD. However, numerous cases of the appearance of GD on the pharmaceutical market, which does not correspond to the quality of OD, make us somewhat wary of therapy based on VP. Both the practitioner and the patient should know which of the drugs prescribed by the international nonproprietary name is OD and which is GD.

Comparative Study of Itopride Hydrochloride in-Vitro Drug Release in Various Brands of Sustained Release Capsules By RP-HPLC

Background: The World Health Organisation has advocated the use of generic medicines to make them accessible and affordable but studies have revealed that marketed products do not produce same therapeutic effects and hence are not interchangeable. Dissolution testing of generic solid dosage forms serves as a valuable tool for acquiring dissolution profiles and for assessing the similarity or dissimilarity between the formulations under examination. Objectives: To evaluate the in-vitro drug release profiles of different generic brands of Itopride Sustained release capsules that are commercially available in Indian market and compare them with the innovator product using model dependant and as well as model independent methods. To determine whether same medicine manufactured by different brands are interchangeable. Materials & Methods: In this study Eight generic brands of Itopride 150mg sustained release capsules available in the Indian market were evaluated using dissolution test with the aim to assess their bioequivalence with the innovator product (Ganaton OD). Dissolution studies were performed using USP type II apparatus at 100 rpm in 900 ml 0.1N HCl while maintaining a temperature of 37±0.5 ºC. The samples were estimated by a validated HPLC method. Dissolution test results were statistically evaluated by employing both model dependant and model independent methods. In model dependant experimental data obtained for each dissolution profile were transformed by applying the equations of different kinetic models and the best-fit model was selected whereas in model independent approach fit factors, dissolution efficiency and mean dissolution times were calculated. Results: The Weibull model best explained the release of drugs from all the brands. Upon statistical evaluation of dissolution test results its was found that while similarity factor f2 was within the limits for all generic brands, difference factor f1 of two brands was out of acceptable range thus questioning their bioequivalency with the innovator product. Also the dissolution efficiency of four out of the brands was out of acceptable limits. Keywords: bioequivalence, difference factor (f1), similarity factor (f2), dissolution profile, comparison and evaluation..

Strategic behavior and entry deterrence by branded drug firms: the case of authorized generic drugs.

Pharmaceutical firms that market brand-name drugs lose substantial market share to generic manufacturers after patent expiration. As a response to the threat of generic competition, branded manufacturers pursue defensive strategies. One such strategy is the launch of authorized generic drugs. Authorized generic drugs are produced by branded manufacturers to compete against other generic drug entrants. Such competition may lower the expected profits of generic drug manufacturers and hence deter future generic drug entry. This paper models and empirically examines whether the introduction of authorized generic drugs changes the independent generic firms' decisions on entering the market. We use an instrumental variable approach to evaluate the effect of authorized generic drugs on the responses of generic manufacturers. The results show that the entry of authorized generic drugs deters and delays the entry of generic drugs.

Validation of the Generic Version of China Health Related Outcomes Measures (CHROME-G) among individuals with type 2 diabetes in China.

The Generic Version of China Health Related Outcomes Measures (CHROME-G) was a new preference-based health-related quality of life (HRQoL) instrument designed specifically for the Chinese population. This study aimed to validate and compare measurement properties of CHROME-G with EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), Short Form-6 Dimensions version 2 (SF-6Dv2), and Diabetes-Specific Quality of Life (DSQL) scales among the elderly Chinese population with type 2 diabetes. A representative sample population was recruited across the country. Internal consistency was assessed using Cronbach's alpha. Hypotheses testing including convergent validity and known-groups validity were evaluated using Spearman's rank correlation and effect sizes, respectively. Sensitivity was examined using relative efficiency and receiver operating characteristic curve. A total of 131 individuals with type 2 diabetes (54.20% male; mean age 69.03 years) were enrolled. Cronbach's alpha was 0.94 for DSQL, 0.93 for CHROME-G, 0.87 for EQ-5D-5L, and 0.88 for SF-6Dv2. For the convergent validity of CHROME-G, 24/29 (82.76%) correlations met the predefined hypotheses, with Spearman's rank correlation coefficients ranging from 0.51 to 0.96. Among the different health subgroups, the effect sizes for CHROME-G, DSQL, EQ-5D-5L, and SF-6Dv2 were 0.19-1.26, 0.36-1.62, 0.22-1.06, and 0.49-0.87, respectively. CHROME-G, DSQL, and SF-6Dv2 had higher efficiency compared with EQ-5D-5L in detecting differences in self-reported health status, with relative efficiency of 3.18 and 1.76, 4.38 and 6.52, and 1.56 and 2.09, respectively. CHROME-G demonstrates relatively good measurement properties compared with EQ-5D-5L and SF-6Dv2 for measuring the HRQoL among the elderly Chinese population with type 2 diabetes. The sensitivity of DSQL appears to be better than that of the three generic instruments.

Cost-effectiveness analysis of direct oral anticoagulants versus low-molecular-weight heparin and no thromboprophylaxis in primary prevention of cancer-associated venous thromboembolism in China.

Cancer-associated venous thromboembolism (CAVTE) is a preventable, life-threatening complication with a considerable morbidity and mortality. Primary venous thromboembolism (VTE) prophylaxis is currently recommended; however, the health and economic benefits have not been evaluated and compared in China. This study aimed to assess and compare the cost-effectiveness of anticoagulants in primary CAVTE prevention among cancer patients in China. A Markov model with a 5-year horizon was established to evaluate the costs and effectiveness of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparins (LMWHs) and no prevention in primary prophylaxis of CAVTE in China. Key clinical outcomes were obtained from the available clinical trials, comparing DOACs (rivaroxaban and apixaban) with LMWHs or with no thromboprophylaxis. Utility and the cost inputs were all obtained from the published literature or local data with public sources. The total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated as the main endpoints of the modal for each strategy. The assessment of uncertainty was performed involving deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Impact of time horizon, generic drug price, and individual DOACs were assessed in scenario and subgroup analyses. Primary prophylaxis using DOACs were projected to yield 1.866 QALYs at a cost of $3,287.893, resulting in the ICERs of $12,895.851 (DOACs vs. no-thromboprophylaxis) and $43,613.184/QALYs (LMWHs vs. DOACs). Sensitivity analysis revealed that ICER was sensitive to the VTE and bleeding risk, drug cost of anticoagulants, self-payment ratio, and overall death rate of cancer. Probabilistic sensitivity analysis showed that DOACs and LMWHs had a 48% and 45% probability of being cost-effective at a 5-year time horizon, respectively. When the time horizon extended to 10 years, DOACs achieved a cost-effective probability of 43%. Among individual DOACs, apixaban was found to be the preferred strategy in VTE prevention due to its incremental health gain with an acceptable cost increase. Primary thromboprophylaxis with DOACs was cost-effective in cancer patients at a willing-to-pay (WTP) threshold of $37,125.24/QALY in China. Cancer death rate, risk of VTE and major bleeding, and the drug cost assumed greater relevance and importance in the decision-making process for primary thromboprophylaxis in cancer.

Mathematical Modeling of Mating Probability and Fertile Egg Production in Helminth Parasites.

In this work, we obtained a general formulation for the mating probability and fertile egg production in helminth parasites, focusing on the reproductive behavior of polygamous parasites and its implications for transmission dynamics. By exploring various reproductive variables in parasites with density-dependent fecundity, such as helminth parasites, we departed from the traditional assumptions of Poisson and negative binomial distributions to adopt an arbitrary distribution model. Our analysis considered critical factors such as mating probability, fertile egg production, and the distribution of female and male parasites among hosts, whether they are distributed together or separately. We show that the distribution of parasites within hosts significantly influences transmission dynamics, with implications for parasite persistence and, therefore, with implications in parasite control. Using statistical models and empirical data from Monte Carlo simulations, we provide insights into the complex interplay of reproductive variables in helminth parasites, enhancing our understanding of parasite dynamics and the transmission of parasitic diseases.

Estimated Savings Under the Medicare High-Value Drug List Model

This cross-sectional study describes potential reductions in out-of-pocket costs for generic medications among Medicare beneficiaries.

A generic stochastic network-based formulation for production optimization of district heating systems

AbstractDistrict heating (DH) systems are an important component in the EU strategy to reach the emission goals, since they allow an efficient supply of heat while using the advantages of sector coupling between different energy carriers such as power, heat, gas and biomass. Most DH systems use several different types of units to produce heat for hundreds or thousands of households (e.g. natural gas-fired boilers, electric boilers, biomass-fired units, waste heat from industry, solar thermal units). Furthermore, combined heat and power units units are often included to use the synergy effects of excess heat from electricity production. To address the challenge of providing optimization tools for a vast variety of different system configurations, we propose a generic mixed-integer linear programming formulation for the operational production optimization in DH systems. The model is based on a network structure that can represent different system setups while the underlying model formulation stays the same. Therefore, the model can be used for most DH systems although they might use different combinations of technologies in different system layouts. The mathematical formulation is based on stochastic programming to account for the uncertainty of energy prices and production from non-dispatchable units such as waste heat and solar heat. Furthermore, the model is easily adaptable to different application cases in DH systems such as operational planning, bidding to electricity markets and long-term evaluation. We present results from three real cases in Denmark with different requirements.

Pharmacoeconomic implications of preference toward reference- versus generic-brand antidepressants in primary care.

The prevalence of depression is gradually increasing worldwide with an increasing utilization of antidepressants. Nevertheless, despite their lower costs, generic-brand antidepressants were reported to be less prescribed. We aimed to examine the costs of reference- versus generic-brand antidepressant prescriptions in primary care practice. This cross-sectional study included electronic prescriptions for adult patients that contained antidepressants (World Health Organization's Anatomical Therapeutic Chemical (ATC)code: N06A), which were generated by a systematically selected sample of primary care doctors (n = 1431) in Istanbul in 2016. We examined the drug groups preferred, the reference- versus generic-brand status, and pharmacotherapy costs. The majority of the prescriptions were prescribed for women (71.8%), and the average age of the patients was 53.6 ± 16.2 years. In prescriptions with a depression-related indication (n = 40 497), the mean number and cost of drugs were 1.5 ± 1.0 and 22.7 ± 26.4 United States Dollar ($) per prescription, respectively. In these prescriptions, the mean number and cost of antidepressants per encounter were 1.1 ± 0.2 and $17.0 ± 13.2, respectively. Reference-brand antidepressants were preferred in 58.2% of depression-related prescriptions, where the mean cost per prescription was $18.3 ± 12.4. The mean cost per prescription of the generics, which constituted 41.8% of the antidepressants in prescriptions, was $15.1 ± 11.4. We found that if the generic version with the lowest cost was prescribed instead of the reference-brand, the mean cost per prescription would be $12.9 ± 11.2. Our study highlighted the substantial pharmacoeconomic impact of generic-brand antidepressant prescribing, whose preference over reference-brands could reduce the cost of antidepressant medication treatment by 17.5% in primary care, which could be approximately doubled if the cheapest generic antidepressant had been prescribed.

Drugs anticipated to be selected for the Medicare Drug Price Negotiation Program in 2025.

The Centers for Medicare and Medicaid Services (CMS) recently announced the Maximum Fair Price for the first 10 Medicare Part D drugs selected for price negotiation. By February 2025, CMS should announce the list of Part D drugs to be negotiated with implementation of the negotiated prices in 2027. To identify up to 15 Medicare Part D single-source drugs anticipated to be selected by CMS for price negotiation in 2025. We followed selection criteria identified in the Inflation Reduction Act and CMS guidance to identify drugs. We projected 2023 Part D gross spending using 2020-2022 data reported by CMS and linear prediction models. We ranked products according to the projected spending figure and identified those not eligible for selection because of (1) number of years since approval, (2) availability of a biosimilar or generic version, (3) approval for a single orphan indication, (4) whole human blood or plasma-derived, or (5) eligibility for the small biotech exception. We identified 13 products likely subject to Medicare drug price negotiation, including 4 anticancer therapies, 3 noninsulin antidiabetic products, 2 inhalers, 1 antifibrotic therapy, 1 gastrointestinal agent, 1 enzyme replacement therapy, and 1 product indicated for dyskinesia. These 13 products each had projected annual gross Part D spending more than $1 billion. We identified 7 additional products with uncertainty to complete the list of 15, including an insulin, an antiviral, an antibiotic, an immunologic agent, an antidiabetic, and 2 cancer drugs. These products had projected gross Part D spending between $877 million and $1.399 billion. Twenty-two products with comparable levels of spending were deemed ineligible for selection because of availability of a generic or biosimilar version (10 products), insufficient years since approval (8 products), eligibility for the small biotech exception (3 products), and expected market discontinuation (1 product). Our identification of products anticipated to be selected for negotiation in 2025 (with implementation of negotiated prices in 2027) will help inform manufacturers, payers, patients, and policymakers of the products that will likely see a decrease in Medicare drug prices as result of negotiation. We identified 22 products with levels of spending that are comparable with those anticipated to be selected for negotiation but are not eligible, primarily because of generic or biosimilar availability or insufficient time on market.

Suspected poor-quality medicines in Kenya: a retrospective descriptive study of medicine quality-related complaints reports in Kenya’s pharmacovigilance database

Poor-quality, substandard and falsified, medicines pose a significant public health threat, particularly in low-middle-income countries. A retrospective study was performed on Kenya's Pharmacovigilance Electronic Reporting System (2014–2021) to characterize medicine quality-related complaints and identify associations using disproportionality analysis. A total of 2767 individual case safety reports were identified, categorized into medicines with quality defects (52.1%), suspected therapeutic failure (41.6%), and suspected adverse drug reactions (6.3%). Predominantly reported were antineoplastic agents (28.6%), antivirals (11.7%), and antibacterial agents (10.8%) potentially linked to non-adherence to good manufacturing practices, inappropriate usage and supply chain degradation. Notably, analgesics (8.2%), and medical devices (3.5%) notified had quality defects, predominantly from government health facilities (60.0%). Antineoplastic agents (20.2%) and antivirals (3.7%) were frequently reported from suspected therapeutic failures and suspected adverse drug reactions, respectively, across both private for-profit facilities (26.5%) and not-for-profit facilities (5.4%). Underreporting occurred in unlicensed health facilities (8.1%), due to unawareness and reporting challenges. Pharmacists (46.1%), and pharmaceutical technicians (11.7%) predominantly reported quality defects, while medical doctors (28.0%) reported suspected therapeutic failures. Orally administered generic medicines (76.9%) were commonly reported, with tablets (5.8%) identified as potential sources of suspected adverse drug reactions, while quality defects were notified from oral solutions, suspensions, and syrups (7.0%) and medical devices (3.9%). The COVID-19 pandemic correlated with reduced reporting possibly due to prioritization of health surveillance. This study provides valuable evidence to supporting the use of medicine quality-related complaints for proactive, targeted regulatory control of high-risk medicines on the market. This approach can be strengthened by employing standardized terminology to prioritize monitoring of commonly reported suspected poor-quality medicines for risk-based sampling and testing within the supply chain.

Entropy Bounds for Device-Independent Quantum Key Distribution with Local Bell Test.

One of the main challenges in device-independent quantum key distribution (DIQKD) is achieving the required Bell violation over long distances, as the channel losses result in low overall detection efficiencies. Recent works have explored the concept of certifying nonlocal correlations over extended distances through the use of a local Bell test. Here, an additional quantum device is placed in close proximity to one party, using short-distance correlations to verify nonlocal behavior at long distances. However, existing works have either not resolved the question of DIQKD security against active attackers in this setup, or used methods that do not yield tight bounds on the key rates. In this work, we introduce a general formulation of the key rate computation task in this setup that can be combined with recently developed methods for analyzing standard DIQKD. Using this method, we show that if the short-distance devices exhibit sufficiently high detection efficiencies, positive key rates can be achieved in the long-distance branch with lower detection efficiencies as compared to standard DIQKD setups. This highlights the potential for improved performance of DIQKD over extended distances in scenarios where short-distance correlations are leveraged to validate quantum correlations.

Role of skin enzymes in metabolism of topical drugs

Topical drugs have gained a lot of interest with their massive market growth and are available in various dosage forms. Prodrug compounds of transdermal delivery systems can be very different and designed to convert into the form of active pharmaceutical ingredients (APIs) through enzymatic action once they enter the body. The skin, as an interfacial barrier between the body and surroundings, has demonstrated critical roles in metabolizing, filtering, and detoxifying to minimize certain side effects and improve the medication benefits of topically administered products. It is well recognized that the drug pharmacokinetics can be altered by the presence of skin enzymes driven by biotransformation reactions. To evaluate the effectiveness of a topical generic drug product, its safety, and bioequivalence with the reference one, models assessing enzyme metabolic activity are highly required for testing the amount of drugs that are metabolized or can potentially be metabolized in both healthy and compromised skin. Thus, knowledge of skin composition and enzyme expression levels is of paramount importance in mapping the relevant metabolism that may have occurred. Regulatory authorities have also been making efforts to develop efficient and harmonizable protocols to evaluate the metabolism of transdermal products. This review is a compilation of reported skin metabolizing enzymes, including their role in both drug metabolism and homeostasis regulation, along with their localization and quantification in skin equivalents (and/or membrane layers). Various aspects that potentially affect the skin enzyme metabolism study were also discussed with respect to drug development considerations.

Polyconvex inelastic constitutive artificial neural networks

AbstractThe characterization of the material behavior of inelastic materials requires a high degree of expert knowledge to identify and constitutively describe the material response. In addition, specific models are usually pre‐selected in the course of characterization and only the best parameters for these specific models are determined, but therefore not necessarily the best models. Unfortunately, a more general description of these pre‐selected models results in an increased effort during characterization, which is barely practicable by hand. This is where machine learning algorithms may help us. To get the best of both worlds, powerful machine learning and sound thermodynamic considerations, inelastic Constitutive Artificial Neural Networks (iCANNs) discover generic formulations of the Helmholtz free energy and pseudo potential. Constitutive relations guide us towards thermodynamically consistent descriptions of stresses and inelastic strains; a concept that is applicable to a wide range of inelastic phenomena from viscoelasticity, elastoplasticity, phase transformations to growth and remodeling of living tissues. Here, we equip the original iCANN framework to guarantee polyconvexity a priori, which ensures at least one minimizing deformation. We investigate the ability of our iCANN to identify the material behavior of a viscoelastic polymer at different stretch levels and strain rates. We made our source code, data, and example accessible to the public at https://doi.org/10.5281/zenodo.11084354.

A Mode Evolution Metric to Extract Reaction Coordinates for Biomolecular Conformational Transitions.

The complex, multidimensional energy landscape of biomolecules makes the extraction of suitable, nonintuitive collective variables (CVs) that describe their conformational transitions challenging. At present, dimensionality reduction approaches and machine learning (ML) schemes are employed to obtain CVs from molecular dynamics (MD)/Monte Carlo (MC) trajectories or structural databanks for biomolecules. However, minimum sampling conditions to generate reliable CVs that accurately describe the underlying energy landscape remain unclear. Here, we address this issue by developing a Mode evolution Metric (MeM) to extract CVs that can pinpoint new states and describe local transitions in the vicinity of a reference minimum from nonequilibrated MD/MC trajectories. We present a general mathematical formulation of MeM for both statistical dimensionality reduction and machine learning approaches. Application of MeM to MC trajectories of model potential energy landscapes and MD trajectories of solvated alanine dipeptide reveals that the principal components which locate new states in the vicinity of a reference minimum emerge well before the trajectories locally equilibrate between the associated states. Finally, we demonstrate a possible application of MeM in designing efficient biased sampling schemes to construct accurate energy landscape slices that link transitions between states. MeM can help speed up the search for new minima around a biomolecular conformational state and enable the accurate estimation of thermodynamics for states lying on the energy landscape and the description of associated transitions.