Stability testing of new drug substances and products european. Introduction the primary purpose of stability testing is to provide data and sup porting evidence on the stability behavior of chemical or biological enti ties in different forms. Having an estimate of residual moisture of each vial on stability allows a relationship to be established between residual moisture level and rate of loss of integrity. Annex 2 stability testing of active pharmaceutical ingredients and. This work will serve as a valuable tool for drug compounding in hospitals, contributing to the broader objective of optimising quality and making patient care ever safer. As a result of stability testing a retest period for the api in exceptional cases, e. The testing should cover, as appropriate, the physical, chemical, biological. Drug product 2 stability testing for abbreviated new drug applicationsanda a. Furthermore, the bases for physical degradation kinetics, which have generally been treated empirically, are also covered, and sound bases for. This volume collects methods and protocols related to different aspects of stability programs followed in pharmaceutical development laboratories. Guidelines for stability testing on drug substances and drug products i. Annex 5 guidelines for stability testing of pharmaceutical. For drug substances with a proposed re test period of at least 12 months, the frequency of testing.
We typically carry out stressed stability testing at 40 and 50c. Drug stability for pharmaceutical scientists is a clear and easytofollow guide on drug degradation in pharmaceutical formulation. Handbook of stability testing in pharmaceutical development is a product of. Stability testing of pharmaceutical products journal of applied. Methodological guidelines for stability studies of hospital. Drug stability for pharmaceutical scientists sciencedirect. Stability studies ensuring the maintenance of product quality, safety and efficacy throughout the shelf life are considered as prerequisite for the. Ich international conference of harmonization guidance on drug stability study. Module 3 when compared to anvisas technical report single pdf. This guidance is the second revision of q1a stability testing of new drug substances and products, which was first published in september 1994 and.
Stability testing methods stability testing is a routine procedure performed on drug substances and products and is employed at various stages of the product development. Stability studies should include testing of those attributes of the drug product that are susceptible to change during storage and are likely to influence quality, safety andor efficacy. The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors, such as temperature, humidity, and light, and to establish a retest period for the drug substance or a shelf life for the drug. Guidance for industry food and drug administration. A thorough drug stability testing in a biological matrix is one of the important steps within the validation.
Drug compounding in hospital pharmacies allows the specific needs of hospitalised. Stability testing of new drug substances and products. Stability testing is the statistical analysis of how long a pharmaceutical product can be stored without any change in its original chemical. Stability testing for drug substances and products pharmaceutical. Methods for stability testing of pharmaceuticals sanjay bajaj. Guideline on stability testing of new veterinary drug. Q 1 d bracketing and matrixing designs for stability. Regulatory basis of herbal drug stability testing 3. Stability studies are a routine procedure for ensuring the maintenance of pharmaceutical product safety, quality and efficacy throughout the shelf life.
Stress testing stress testing of the drug substance can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic stability of the molecule and. Usp chapter on stability studies and good chromatographic practices. This book features valuable content on both aqueous and solid drug solutions, the stability of proteins and peptides, acidbase catalyzed and solvent catalyzed reactions, how drug formulation can influence drug stability, the influence of external factors on. Q1ar harmonised tripartite guideline on stability testing of new drug substances and products hereafter referred to as the parent guideline.
This is a good indicator of physical stability of the drug product. Drug stability guide antibiotics, chemotherapy and pain management infusions. The stability studies should be conducted on the active substance packaged in a container closure system that is the same as or simulates the packaging proposed for storage and distribution. Accelerated stability testing studies designed to increase the rate of chemical degradation or physical changes of a drug product by using exaggerated storage conditions with the purpose of monitoring degradation reactions. The stability test assesses how the quality of a drug substance or a drug product changes with time under the influence of various factors such as temperature. Q1ar2 stability testing of new drug substances and products. Scientific basis of herbal drug stability testing 4. Pdf stability testing of pharmaceutical products researchgate. Draft regional guidelines on stability testing of active. Stability studies in bulk packs used for intermediate storage of investigational medicinal products should be considered especially in phase iii. This guidance is the second revision of q1a stability testing of new drug substances and products, which was first published in september 1994 and revised in august 2001. The second day commences with a lecture on stability testing for drug products and a risk based approach for stability testing covering different climatic zones. If the drug is to be distributed in different geographical regions and if shipping is required for transportation, in that case long term stability.
Stability testing provides evidence on how the quality of a drug substance or product varies over a given time period and under the influence of environmental. The design of accelerated elevated temperature, high. Stability testing of new drug substances and products 3 2. Critical assessment implementation of ich guidelines in. Q1ar2 stability testing of new drug substances and. Drug substance stability data submission supporting information may be provided directly to the drug product anda or by reference to an appropriately referenced drug master file dmf.
Introduction 2 the guidance is intended to be a comprehensive document that provides information on all. Stability studies are intended for testing the drug product for longer periods under varying conditions of temperature and humidity. Stability testing for drug substances and drug products. Ich q5c stability testing of biotechnological biological. As a result of stability testing a re test period for the active substance or a shelf life for the pharmaceutical product can be established, and storage conditions can be recommended. Stability testing can present significant analytical hurdles and specialised knowledge is required to develop and validate stability indicating methods and perform. The main purpose of stability testing is to ensure the efficacy, safety and quality of active drug substance and dosage forms and to establish shelf life or expiration period and to support label. Defines the stability data package for registration of a new molecular entity as drug substance drug product. Regulatory requirements related to stability testing. Despite the extensive attention in this chapter to the provision, maintenance, and evaluation of air quality, the avoidance of direct or physical contact contamination is paramount. Test methods used for drug assay and impurity testing must be validated and stability indicating for the specific product formulation under test. Stability testing of drug substances and drug products due to the length and complexity of this draft document, please identify specific comments by line number. Guidelines on stability studies of medicines and biologicals, jeddah, 2528 february 2006.
Stability testing of p harmaceutical p roducts is a complex set o f p rocedures inv olving considerable cost, time consu mption and scientific expertise in order to build in quality, efficacy. Four climatic zones can be distinguished for the purpose of worldwide stability testing, as follows. Pdr physicians desk reference, 60th edition, medical. Handbook of stability testing in pharmaceutical development is a product of several dedicated stability scientists. Stability testing for drug products strategy of stability testing performance of new drug products related finished products with existing substances followup stability testing objectives background target audience moderator programme stability testing for drug substances and drug products 29 30 november 2017, vienna, austria.
To evaluate the impact of short term excursions and predicting the shelflife under normal storage studies may include conditions. Stability testing of pharmaceutical products is a complex set of procedures involving considerable cost, time consumption and scientific expertise in order to build. A stability study is a routine procedure which ensures the maintenance of pharmaceutical product safety, quality and efficacy throughout the shelf. The design of the stability testing programme should take into account the intended market and the climatic conditions in the area in which the drug products will be used. Stability testing of pharmaceutical products testinglab. Methodological guidelines for stability studies of. Also, the stability of excipients that may contain or form reactive degradation products, have to be considered.
Studies designed to increase the rate of chemical degradation and physical change of a drug by using exaggerated storage conditions. In early stages, accelerated stability testing at relatively high temperatures andor humidity is used in order to determine the type of degradation products which may be found. Testing frequency for long term studies, frequency of testing should be sufficient to establish the stability profile of the drug substance. Draft not for implementation guidance for industry. Information on the stability of the drug substance is an integral part of the systematic approach to stability evaluation. Using development stability data, re test periods for drug substances and shelf lives for drug products should be established for nonclinical and clinical material. A stability indicating assay is one that is demonstrated to be free of interferences from impurities, degradants, or other. The guidance on stability testing of active pharmaceutical ingredients and. Food and drug administration fda guidance describes a standard approach of direct comparison of analytical results for the studied and reference samples, but also suggests that other statistical approaches may be used.
92 103 1704 871 180 525 154 1338 1124 255 1160 1162 1590 1148 907 1027 474 236 14 1600 659 1177 867 274