Summary: Forced Degradation Study as per ICH Guidelines

• Forced degradation study ICH guideline ensures pharmaceutical stability and identifies degradation pathways.
• ICH Q1A(R2) defines how to perform these studies to meet regulatory requirements.
• Helps in method development and establishing product shelf life.
• Key stress conditions: acid/base hydrolysis, oxidation, thermal, photolysis, humidity.
• Crucial for analytical method validation and impurity profiling.
• Supports regulatory submissions by proving product stability under various stressors.
• ResolveMass Laboratories offers advanced forced degradation testing as per ICH Q1A(R2).

Introduction

In pharmaceutical research, running a Forced Degradation Study ICH Guideline procedure is a must for proving a drug product’s stability, safety, and effectiveness. The ICH Q1A(R2) guideline ensures that such studies follow a globally accepted standard. At ResolveMass Laboratories Inc., our skilled team carries out these studies with great care, delivering data that can stand up to both scientific and regulatory checks.

Apart from meeting regulations, these studies help formulation scientists design products with better stability. They are particularly useful in developing complex active pharmaceutical ingredients (APIs), validating HPLC methods, and ensuring that test methods can detect even small changes in a product’s composition.

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What is a Forced Degradation Study as per ICH Guideline?

A Forced Degradation Study ICH Guideline test involves putting a drug or finished dosage form under extreme stress to:

• Identify degradation products
• Understand chemical breakdown pathways
• Prove that analytical methods are stability-indicating

The ICH Q1A(R2) guideline expects that these studies:

1. Determine the natural stability of the active ingredient
2. Use stress conditions that are scientifically justified
3. Provide data that supports method validation
4. Produce full documentation for regulatory use

By simulating tough conditions, manufacturers can address stability risks before the product reaches the market.

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Purpose of a Forced Degradation Study

These studies also prepare researchers for stability challenges during production and provide reference data for solving stability issues later in a product’s life cycle.

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ICH Q1A(R2) Expectations for Compliance

According to ICH Q1A(R2), a compliant forced degradation study should:

• Include hydrolytic (acid/base), oxidative, thermal, light, and humidity stress
• Target 5–20% degradation for reliable data
• Use analytical methods that can separate degradation products from the main drug
• Record pH, temperature, solvents, and exposure time in detail
• Support method validation for stability indication

Meeting these expectations not only ensures compliance but also strengthens product quality across the supply chain.

Stress Conditions in Forced Degradation Study ICH Guideline

The choice of stress condition should match the product’s chemistry and storage needs. Overly harsh conditions should be avoided unless backed by scientific reasoning.

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Regulatory Importance of a Forced Degradation Study

Regulatory agencies use these study results to confirm that:

• No harmful degradation products are formed
• The drug keeps its intended potency
• Product quality stays consistent until the expiry date

These tests also show that the manufacturer is applying quality-by-design (QbD) principles during development.

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Best Practices for Forced Degradation Study ICH Guideline Compliance

To meet ICH Q1A(R2) standards:

• Start degradation studies early in method development
• Aim for 5–20% degradation for useful results
• Use multiple analytical techniques to confirm findings
• Keep thorough records of all conditions and results
• Include findings in stability reports for regulatory review

Following these steps helps ensure both compliance and efficiency in development.

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The Technical Guide to Forced Degradation Studies

Execution, Validation, and Advanced Characterization According to ICH Guidelines

Section I: Foundational Concepts and Regulatory Mandate (ICH Q1A/Q1B/Q2)

1.1. Definition and Core Objectives of Forced Degradation Studies (FDS)

Forced Degradation Studies (FDS), commonly referred to as Stress Testing, constitute an essential developmental process in pharmaceutical science, involving the intentional breakdown of the Active Pharmaceutical Ingredient (API) or drug product (DP) by subjecting it to exaggerated environmental conditions. These conditions are significantly more severe than those used in formal stability testing. The core objectives of FDS, as articulated in ICH Q1A(R2), extend beyond simple stability assessment and focus on understanding the inherent chemical behavior of the molecule.  

The primary goals are threefold: first, to identify the likely degradation products (DPs) and thereby establish the intrinsic stability profile of the molecule. Second, FDS is performed to map the degradation pathways, revealing the mechanisms by which the drug breaks down under various environmental influences. Third, and crucially, FDS generates the necessary analytical samples to validate the stability-indicating power (SIP) of the analytical methods—particularly the High-Performance Liquid Chromatography (HPLC) procedures used for assay and impurity determination. The resultant data from these studies form an integral part of the information provided to regulatory authorities, demonstrating the suitability of the analytical methodology employed throughout the drug lifecycle.  

1.2. FDS vs. Formal Stability Testing: Differentiating Regulatory Roles

A key distinction must be drawn between FDS and formal stability testing. FDS is fundamentally a developmental activity, often conducted on a single batch of the Drug Substance (DS) during the pre-formulation phase. It is explicitly not considered a requirement for the formal stability program, which is used to assign shelf-life and establish storage conditions.  

Formal stability studies (long-term and accelerated), in contrast, are designed to assess longer-term chemical effects under non-accelerated conditions and to evaluate the effect of short-term excursions that might occur during shipping or temporary temperature variations. The strategic necessity of FDS lies in its ability to expose potential DPs that might not be visible during routine accelerated studies. If FDS successfully identifies a degradation pathway that leads to a potentially harmful DP, this finding creates a definitive regulatory requirement: the analytical method subsequently developed must possess the specificity (SIP) to monitor that specific impurity, even if it is only present in trace amounts during the formal stability program. The FDS thus establishes the scope of required analytical control measures, linking directly to specifications outlined in ICH Q6A.  

1.3. ICH Regulatory Context: Q1A(R2) Stress Testing Requirements

ICH Q1A(R2) mandates that stress testing of the drug substance must be comprehensive to fully characterize the molecule’s intrinsic stability. The testing must include a systematic evaluation of several critical stress conditions:

1. Thermal Stress: This involves using temperatures in 10∘C increments above the designated accelerated storage temperature (e.g., 50∘C,60∘C, etc.) to deliberately increase the rate of chemical degradation.  
2. Humidity: Where appropriate, the effect of humidity must be investigated, typically at 75%RH or greater.  
3. Oxidation and Photolysis: Susceptibility to oxidative degradation must be evaluated. Photostability testing, which assesses the drug’s stability when exposed to light, is an integral component of stress testing, governed by the specific standard conditions described in ICH Q1B.  
4. Hydrolysis: The susceptibility of the drug substance to hydrolysis must be evaluated across a wide range of pH values when the substance is in a solution or suspension.  

1.4. ICH Q2(R1) Specificity Link and the Need for FDS

Forced degradation is the necessary experimental foundation for demonstrating the specificity of an analytical method, as required by the ICH Q2(R1) guideline for method validation. Specificity is defined as the ability of the method to accurately measure the analyte in the presence of components that may be expected to be present, including impurities, degradation products, and matrix components.  

The FDS provides the complex samples necessary to prove this discrimination. ICH Q2(R1) explicitly states that specificity may be demonstrated by testing samples stored under relevant stress conditions, including light, heat, humidity, acid/base hydrolysis, and oxidation. If the developed method can successfully separate the main drug peak from all the degradants generated through these severe stress conditions, the method is confirmed to be stability-indicating, satisfying the regulatory requirement.  

Section II: Strategic Design and Execution of Stress Conditions

2.1. Philosophy of Stress Testing: Achieving Target Degradation (5–20%)

The strategic design of an FDS requires careful control over the severity and duration of the stress conditions. The objective is not maximum destruction but rather controlled, meaningful degradation. For small molecule pharmaceuticals, the generally accepted optimal degradation window is a loss of 5% to 20% of the Active Pharmaceutical Ingredient (API). This range ensures that sufficient degradation products (DPs) are formed to challenge the analytical method, while remaining relevant to the typical 10% impurity acceptance threshold used for drug products.  

There are inherent risks in deviating from this optimal window. Over-stressing a sample leads to the formation of secondary, tertiary, or even non-relevant DPs that would never be observed under formal shelf-life conditions. These artifacts significantly complicate method development and structural elucidation efforts. Conversely, under-stressing fails to reveal critical or less reactive degradation pathways, resulting in a method that lacks sufficient stability-indicating power. Given the known trial-and-error approach often adopted in FDS , incorporating sophisticated strategies such as Design of Experiments (DoE) is highly recommended. DoE allows simultaneous optimization of factors like concentration, temperature, and exposure time, reliably guiding the experimenter toward the 5–20% target range with scientific rigor, minimizing redundant experimental effort.  

2.2. Hydrolytic Stress Testing: Optimization for Acid, Base, and Neutral Conditions

Hydrolytic stress testing evaluates the drug’s susceptibility to degradation in aqueous environments across a wide pH range. Typical reagents utilized include hydrochloric acid (HCl) or sulfuric acid (H2​SO4​) for acid hydrolysis, and sodium hydroxide (NaOH) or potassium hydroxide (KOH) for base hydrolysis, generally starting in the concentration range of 0.1 M to 1 M.  

A common starting protocol involves refluxing the drug substance solution in 0.1 N acid or base for approximately eight hours. However, the selection of precise conditions must be tailored to the molecule’s known functional groups. For instance, if a drug contains an ester functionality known to be highly labile to basic hydrolysis, lower base concentrations or ambient temperatures must be employed to moderate the degradation rate. Stress testing in solution should generally be limited to a maximum exposure time of 14 days. Furthermore, modern techniques, such as the application of microwave energy, have proven effective in significantly expediting hydrolysis reactions, reducing necessary exposure times from hours to minutes while maintaining control over the reaction kinetics.  

2.3. Oxidative Stress Testing Protocol

Oxidative stress testing is performed to identify degradation pathways involving radical species or direct reaction with oxygen. The standard oxidizing agent is hydrogen peroxide (H2​O2​), typically used in concentrations ranging from 3% to 30%.  

The susceptibility of drugs to oxidation exhibits high variability. Some compounds may undergo rapid and extensive degradation when exposed to 3% H2​O2​ for a short duration at room temperature, while other, more stable compounds may resist high concentrations even under extreme conditions. Due to the rapid kinetics often involved in oxidation, stress testing using hydrogen peroxide is highly time-sensitive and is typically restricted to a maximum duration of 24 hours to prevent the over-stressing phenomena described previously.  

2.4. Matrix Effects: Drug Substance versus Drug Product Protocols

It is imperative that the protocols for forced degradation differ when applied to the Drug Substance (DS) versus the Drug Product (DP). This necessity arises from the differences in concentration and, critically, the complexity of the matrices.  

Excipients—the non-active components of the formulation—are not chemically inert; they can significantly influence the degradation profile. Excipients may act protectively, such as sugar excipients often stabilizing proteins against freeze/thaw aggregation , or they may actively induce degradation (e.g., salts promoting protein aggregation). Furthermore, excipients themselves can degrade under stress conditions, yielding peaks that might co-elute with the API or the API-derived DPs. To mitigate this matrix interference and demonstrate true method specificity, parallel stress studies on the placebo (the complete excipient mixture without the API) are mandatory. The resulting placebo chromatograms identify excipient-derived peaks, ensuring that the analytical method achieves full separation from all components in the matrix.  

Table 1 summarizes the ICH-recommended stress categories and typical conditions employed for small molecule drug substances and products.

Table 1: ICH-Recommended Stress Testing Conditions and Rationale

Section III: Development and Validation of Stability-Indicating Methods (SIM)

3.1. The Critical Requirement of Specificity (ICH Q2(R1))

The successful completion of FDS transitions the process into the analytical phase: the development and validation of the Stability-Indicating Method (SIM). The core mandate for this method, dictated by ICH Q2(R1), is specificity. The FDS-generated samples, containing a known quantity of the parent drug alongside numerous DPs and excipient components, provide the critical matrix required to demonstrate the method’s discrimination power. An SIM must accurately measure the changes in the API concentration without any interference from degradation products, impurities, or excipients. If the method fails to resolve any one of these components, it is fundamentally non-specific and unsuitable for use in stability assessment.  

3.2. Chromatographic Resolution Strategies

Demonstrating specificity involves the rigorous process of method development, where chromatographic parameters are optimized until adequate separation is achieved. This typically entails refining the choice of column stationary phase, adjusting the mobile phase composition (e.g., buffer concentration, organic modifier), and optimizing gradient elution profiles. The end goal is to ensure that the main drug peak is completely separated from all degradants generated under the various stress conditions.  

In the early stages of development, specific reference standards for all degradation products may not be available. ICH Q2(R1) addresses this practical challenge, allowing specificity to be demonstrated by comparing the test results of stressed samples against unstressed samples, focusing on achieving clear separation between the API and all resulting peaks. Advanced detectors, such as Photo Diode Array (PDA) detectors, are essential tools used in conjunction with the liquid chromatography system to verify peak purity, providing assurance that no unseen component is co-eluting with the API or any major degradation peak.  

3.3. Mitigation of Excipient Interference and Matrix Effects

A significant challenge in developing an SIM for drug products is overcoming excipient interference. Co-elution of an excipient peak or an excipient-derived degradation peak with the API or a critical DP renders the method analytically compromised. This is why the simultaneous stress testing of the placebo matrix is crucial.  

Mitigation strategies for complex matrices require aggressive chromatographic optimization. If standard adjustments fail, specific techniques might be employed, such as changing the column’s stationary phase chemistry (e.g., moving from C18 to phenyl or C8) or utilizing specialized mobile phase additives, like ion-pairing reagents, to modify retention characteristics and force resolution between active components and matrix components. The final, validated method must guarantee that all formulation components are accounted for, ensuring that the determination of the active pharmaceutical ingredient is accurate and free from interference.  

3.4. Validation Criteria for SIM using Stressed Samples

Once the method’s specificity is confirmed using the stressed samples, the method must proceed to full validation to ensure quantitative reliability, as outlined in ICH Q2(R1). The validation steps must use the stressed samples as the matrix to mimic real-world stability analysis complexity:

1. Accuracy: Recovery studies must be performed. This involves spiking known amounts of DPs into the stressed matrix, or relying on the mass balance calculation (discussed in Section IV) to confirm that the method reliably recovers the total mass.
2. Precision: Intra-day and inter-day precision experiments confirm that the method consistently and reliably quantifies both the API and the generated DPs within the complex sample matrix.  
3. Linearity and Range: The analytical method must demonstrate a linear response across the expected concentration range for the API (typically 90%−110% of label claim) and, critically, for all degradation products down to their required reporting thresholds. The method must be robust to small, intentional changes in analytical parameters, proving its reliability over long-term use.  

Section IV: Advanced Analytical Requirements: Mass Balance and RRF

4.1. The Principle of Mass Balance: Definition and Regulatory Interpretation

Mass Balance (MB) is a powerful quantitative measure of the completeness and exhaustiveness of a Stability-Indicating Method. It operates on the fundamental principle of mass conservation, requiring that the measured loss in API concentration due to degradation must be mathematically accounted for by the quantifiable accumulation of degradation products.  

The principle is quantified by the equation: $$ \text{Total Mass} (% ) = % \text{ API Remained} + % \text{ Known Degradants} + % \text{ Unknown Degradants} $$ This sum should ideally equal 100%± analytical error. Although ICH Q1A(R2) clearly defines mass balance, it intentionally avoids specifying a rigid numerical acceptance criterion, instead requiring “due consideration of the margin of analytical error”. This acknowledges that achieving a perfect 100% balance is challenging due to the inherent limitations of analytical techniques.  

4.2. Acceptable Mass Balance Tolerance Limits and Practical Interpretation

Despite the lack of a strict regulatory limit, industry practice has converged on an acceptable tolerance range for good mass balance, typically between 97% and 104%. Deviations outside this window signal specific deficiencies in the SIM:  

• Low Mass Balance (Below 97%): A low MB is a critical finding, indicating that a significant portion of the original drug mass is unaccounted for. This often suggests the formation of degradation products that are not being detected or quantified by the SIM. Potential causes include the formation of volatile species, DPs that lack a UV-active chromophore (if UV detection is used), or components that are strongly retained on the chromatographic column and never elute. When low mass balance is observed, immediate investigation, often including the evaluation and correction via Relative Response Factors, is mandated.  
• High Mass Balance (Above 104%): A high MB suggests over-quantification. Common causes include peak integration errors (e.g., accidentally including an excipient degradant in the calculation of an API degradant) or, most often, the inaccurate quantification of DPs because their detector response characteristics differ significantly from the API.  

4.3. Relative Response Factor (RRF) Methodology: Necessity and Calculation

The accurate measurement of degradation products often requires the application of a Relative Response Factor (RRF). RRF is a calculated correction factor that accounts for the differential sensitivity of the analytical detector (e.g., the difference in UV absorbance efficiency, or chromophore strength) between the API and a specific degradation product.  

If a degradation product possesses a weaker chromophore than the parent API, assuming an RRF of 1 (equal response) will lead to significant under-quantification of that DP, resulting in a low mass balance. Conversely, a DP with a stronger chromophore will be over-quantified. Establishing RRFs is crucial for accurate mass balance calculation and is frequently necessary because obtaining isolated, purified impurity standards is often difficult, costly, and time-consuming during drug development.  

4.4. Calculation of RRF using the Slope Method (Expert Level Detail)

The RRF is typically estimated using the Slope Method. This process requires established linearity data for both the API and the degradation product (or a closely related surrogate standard).  

1. A calibration curve (response versus concentration) is generated for the API standard, yielding a slope (SAPI​).
2. A calibration curve is generated for the isolated DP standard (if available), yielding a slope (SDP​).
3. The RRF is calculated as the ratio of the degradation product’s slope to the API’s slope :   RRF=SAPI​SDP​​ Once established, this RRF is used in routine quantification to convert the measured peak area count of the DP into an accurate mass percentage, effectively normalizing the measurement relative to the API and allowing for a correct mass balance calculation.  

Table 2 details the criteria for evaluating the success of mass balance and outlines the appropriate scientific responses to common deviations.

Table 2: Mass Balance Assessment Criteria and Corrective Actions

Section V: Degradation Pathway Mapping and Kinetic Analysis

5.1. Structural Elucidation of Degradation Products using LC-MS/MS

After the SIM has been validated, the stressed samples must be utilized for the structural elucidation of the generated degradation products. This clarification is critical not only for regulatory submissions but also for guiding formulation selection, informing decisions on packaging materials, and confirming safety profiles.  

Liquid Chromatography-Mass Spectrometry (LC-MS) is the definitive technique for this purpose. LC-MS offers extremely high sensitivity and selectivity, enabling the determination of the accurate mass and, subsequently, the molecular formula of unknown impurities, even those present in trace amounts. The goal is to characterize all DPs, focusing particularly on those formed under maximum stress conditions, to establish a complete chemical behavior profile of the drug.  

5.2. Detailed Mechanism of Structural Elucidation: MS/MS Fragmentation Analysis

For highly accurate structural identification, LC-MS/MS fragmentation analysis is deployed. This expert application involves isolating the precursor ion of an unknown degradation product and subjecting it to collision-induced dissociation (CID). The resulting daughter ions and neutral losses are unique fragmentation patterns that provide diagnostic information about the molecule’s skeletal structure.  

By comparing the fragmentation pathway of the unknown DP against the known fragmentation pathway of the parent API, the specific site of the chemical transformation (e.g., the exact position of oxidation, the location of a hydrolyzed bond, or a deamidation site) can be precisely determined. This comparative analysis is the intellectual keystone of FDS, as it moves beyond simply identifying the existence of a degradation product to establishing the precise chemical mechanism by which it was formed, thereby linking environmental stress directly to molecular consequence.  

5.3. Degradation Pathway Mapping: From Stress to Strategy

The culmination of the FDS and structural elucidation work is the creation of a degradation pathway map. This roadmap details the most important chemical and physical instability pathways (e.g., oxidative attack, pH-dependent hydrolysis, or aggregation for biopharmaceuticals).  

The map connects external environmental factors (light, temperature, moisture, pH) to the formation of specific degradation products. This knowledge is invaluable for quality control and formulation optimization. Knowing the pathways allows investigators to predict potential issues and select appropriate control strategies—such as incorporating specific antioxidants into the formulation, choosing moisture-barrier packaging, or modifying the manufacturing solvent system—to prevent or mitigate DP formation under long-term storage conditions.  

5.4. Chemical Kinetics in FDS: Determining Reaction Order

FDS data generated from thermal stress experiments can be utilized to calculate critical degradation kinetic parameters, including degradation rate constants (k), activation energy (Ea​), and estimated shelf life (t90​).  

The quantitative use of FDS requires establishing the reaction order of the degradation process. Drug degradation kinetics often conform to first-order reaction kinetics, where the rate of degradation is directly proportional to the concentration of the drug remaining. Establishing this reaction order is the crucial prerequisite for applying mathematical models to predict stability.  

5.5. Application of the Arrhenius Equation for Rate Constant (k) Prediction

The Arrhenius equation is used to mathematically describe the dependence of the reaction rate constant (k) on temperature (T). To apply this relationship, FDS thermal degradation studies must be performed consistently at several elevated temperatures (e.g., 60∘C,80∘C,100∘C). The degradation rate constant (k) is calculated for each temperature point.  

These results are plotted on an Arrhenius Plot, which charts the natural logarithm of the rate constant (lnk) versus the reciprocal of the absolute temperature (1/T). The resultant linear slope of this plot is directly proportional to the activation energy (Ea​), which represents the energy barrier that must be overcome for the degradation reaction to proceed.  

5.6. Extrapolation to Shelf-Life (t90​) Estimation and Stability Prediction

The linear relationship established by the Arrhenius plot provides the foundation for highly accurate stability prediction. The plot is extrapolated back to the temperature of the proposed long-term storage condition (e.g., 25∘C) to determine the predicted reaction rate constant (k) at non-accelerated conditions.  

Assuming the degradation follows first-order kinetics, this calculated k at 25∘C allows for the early-stage estimation of the shelf life (t90​), defined as the time taken for the drug potency to decrease to 90% of its initial value. This predictive capability derived from FDS provides pharmaceutical manufacturers with critical quantitative data, enabling informed decisions regarding formulation and packaging years before formal long-term stability studies reach maturity.  

Table 3 provides a comprehensive overview of the sequential stages involved in the analytical characterization and interpretation of degradation products generated during FDS.

Table 3: Stages of Degradation Product Elucidation using LC-MS/MS

Conclusion

Forced Degradation Studies are a non-negotiable scientific necessity and regulatory expectation in pharmaceutical development. While ICH guidelines, particularly Q1A(R2) and Q1B, provide the foundational framework, successful execution demands a nuanced, strategic approach that extends beyond the minimum regulatory checklist. The most critical function of FDS is generating controlled, relevant degradation samples (ideally 5%–20% loss) that serve as the foundation for validating the specificity of Stability-Indicating Methods (SIMs) as required by ICH Q2(R1).

The quantitative robustness of the SIM is definitively tested by the principle of mass balance. Maintaining mass balance within the acceptable 97%–104% range often necessitates the rigorous evaluation and application of Relative Response Factors (RRF) to correct for detector sensitivity differences between the API and its degradation products. Furthermore, the modern FDS incorporates advanced analytical technologies, primarily LC-MS/MS fragmentation, to provide atomic-level structural elucidation of degradation products. This structural information, combined with kinetic modeling using the Arrhenius equation, allows development teams to accurately map degradation pathways and gain quantitative, predictive insight into the drug’s long-term stability profile (t90​). FDS thus serves not merely as a validation requirement, but as a proactive tool that informs formulation, packaging, and ultimately, the established safety and efficacy of the drug product.

A Forced Degradation Study ICH Guideline process is more than just a regulatory requirement. It is a key scientific tool for making sure that medicines remain stable, safe, and effective. By fully following ICH Q1A(R2) standards, companies can improve product reliability, reduce risks, and speed up regulatory approval.

At ResolveMass Laboratories, our expertise in analytical method development, HPLC analysis, and forced degradation testing ensures that your stability studies meet the highest global standards.

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References

1. Blessy, M. et al. (2014). Development of forced degradation and stability indicating studies of drugs—A review. Journal of Pharmaceutical Analysis, 4(3), 159–165. https://doi.org/10.1016/j.jpha.2013.09.003
2. European Medicines Agency. (n.d.). ICH Q2(R2) validation of analytical procedures: Scientific guideline. Retrieved August 14, 2025, from https://www.ema.europa.eu/en/ich-q2r2-validation-analytical-procedures-scientific-guideline
3. ema.europa.euQ 1 A (R2) Stability Testing of new Drug Substances and Products – European Medicines Agency pmc.ncbi.nlm.nih.gov
4. Development of forced degradation and stability indicating studies of drugs—A review database.ich.orgQ1A(R2) Guideline – ICH
5. Optimization of Forced Degradation Using Experimental Design and Development of a Stability-Indicating Liquid Chromatographic Assay Method for Rebamipide in Bulk and Tablet Dosage Form https://pmc.ncbi.nlm.nih.gov/articles/PMC3097498/
6. Forced Degradation Study: An Important Tool in Drug Development https://asianjpr.com/HTML_Papers/Asian%20Journal%20of%20Pharmaceutical%20Research__PID__2013-3-4-7.html

Anusha Sinha