Fda recommendations for comparability studies to support. Guidance for industry picmc content and format of inds for phase 1 studies of drugs, including well characterized, therapeutic, biotechnologyderived products 1995 cgmp for phase 1 investigational drugs 2008 assay development for immunogenicity testing of therapeutic proteins 2009 ich q5ar1. The the working group acknowledged the difference of opinion concerning the efficacy of current. Q1ar2 stability testing of new drug substances and products. Multiple laboratory disciplines biologics safety testing stability degradation identity purity potency efficacy in vitro virus screening in vivo virus screening electron microscopy fish for genetic stability karyology histology elisa cell based assays electrochemiluminescence western blots sterility bioburden mycoplasma. Q1a is the parent guideline for stability testing of all pharmaceuticals. Stability program for pharmaceuticals and biologics ich. Ich stability requirements overcoming the challenges.
As a consultant she has assisted pharma and biotech organizations in evaluation of analytical methods and method validation for a wide range of products ranging from conventional drugs to well characterized proteins and. Analytical assays are available for quality control testing that is regulatory compliant. During such studies, however, it is not uncommon that atypical or unexpected data may arise, and given the crucial need for these studies, effective and rapid response is necessary to prevent impact on drug. Center for biologics evaluation and research this guidance is the second revision of q1a stability testing of new drug substances and products, which was first published in september 1994 and. Type ib moderate variation providing comparability, validation, testing and stability data generated in accordance with agreed protocol 7 weeks to approval major variation 28 weeks to. Maintaining the stability of biologics biopharm international. Biologics treat many conditions, for example, cancers, rheumatoid arthritis, inflammatory bowel disease, ms, psoriasis, lupus, chronic migraine, and hepatitis b. European perspectives on regulation for biologics jeanhugues trouvin afssaps demeb paris, france. Product release testing is a crucial part of ensuring drug product quality and safety.
This chapter focuses on the typical questionsambiguities encountered during the design and conduct of such. Regulatory requirements stability testing is required by a number of regulatory agencies. Photostability testing of new drug substances and products q1c stability testing for new dosage forms q1d bracketing and matrixing designs for stability testing of new drug substances and products q1e evaluation of stability data. Ich q5c stability testing of biotechnological biological. Q1c stability testing for new dosage forms q1d bracketing and matrixing designs for stability testing of new drug substances and products q1e evaluation of stability data q1f stability data package for registration applications in climatic zones iii and iv withdrawn q5c stability testing of biotechnological.
Microbial testing in support of aseptic processing. Nucleic acid characterization and genetic stability. Product stability testing stability testing demonstrates how the quality of a drug substance or drug product varies with time under the influence of a variety of different environmental factors, such as temperature, humidity, light and containerclosure interactions. This article presents three common scenarios observed during stability testing of biologics and the use of orthogonal analysis, stability experience, and troubleshooting measures to identify causes, assess risk, and define subsequent steps in the development of a biopharmaceutical. Microbiological considerations in stability programs. Abstract biological products represent a growing segment of the pharmaceutical industry. Replacing analytical methods for release and stability. The approval process for ensuring the identity, potency, purity, safety and effectiveness of a biopharmaceutical is complex, but its effective navigation is critical to the products ultimate commercial success.
Stability distributes the following groups of human tissue allografts. Biologics safety testing services with our introduction of the rcl assay, bioreliance now offers the complete range of tests needed to meet regulatory requirements see below. Sitespecific stability data for drug and biologic applications. Ich q5c stability testing of biotechnological biological products. Therefore, the objective of this article is to provide a complete, holistic view of stability studies on biologics. As a provider of stability testing, our laboratories encounter a variety of questions from drug developers relating to problems that have emerged during their stability studies. Our quality management system is designed to ensure procedural and operational excellence across the organization. Services for biologics developers and manufacturers.
Specific principles for the bracketing and matrixing in the study designs. This document covers the generation and submission of stability data for wellcharacterised proteins and polypeptides, their derivatives and products of which they are components, and which are isolated from tissues, body fluids, cell cultures, or produced using rdna technology. Stability testing of new drug substances and products fda. Therefore, the objective of this article is to provide a complete, holistic view of stability studies on biologics, with emphasis on key parts that all drug developers. It may also apply to other types of products, such as conventional. Qtpp considerations described in ich q8 r2 consider intended use clinical setting, dose, delivery, etc based on characteristics of reference product range from multiple lots target specifications ich q6b, including stability shelflife. The guidance stated in the ich harmonized tripartite guideline entitled stability testing of new drug substances and products issued by ich on october 27, 1993 applies in general to. The guidance stated in the ich harmonized tripartite guideline entitled stability testing of new drug substances and products issued by ich on.
Ich topic q 5 c quality of biotechnological products. Analytical characterisation in support of biologics. The purpose of stability testing throughout a biologicss life cycle 22. Guidelines for conducting stability studies are described in ich q1ar2 and the ich stability guidance has been adopted by the european medicines. Both stability testing for largemolecule and smallmolecule drugs are important to ensure that a product maintains specifications throughout its shelf.
Ich guideline for stability testing of biotechnologicalbiological products. The guidance stated in the ich harmonised tripartite guideline stability testing of new. Outsourcing stability testing bioprocess international. Stability testing of biotechnologicalbiological products. Her handson industrial experience covers stability and laboratory cgmp systems for both biologics and conventional drugs. Given the severity of this potential combined with the high occurrence, the hypothesis that stability testing of biologics is the more important of the two could be supported. The adequacy of the mass balance should be assessed. Supplement to the points to consider in the production and testing of new drugs and biologicals produced by recombinant dna technology. Stability studies of these complex biologics present challenges beyond those. Agc biologics is a leading global contract development and manufacturing organization cdmo, dedicated to the development and manufacture of biopharmaceuticals, from preclinical to commercial. Biologic products are typically only marginally stable, not entirely understood, may demonstrate nonarrhenius behavior, degrade by multiple pathways and possibly different pathways during different stages of shelf life. Stability studies for biologics from sgs effective stability testing of new drug substances and products for full regulatory compliance. Storage and testing services gathering pharmaceutical stability testing data on drug products or drug substances to determine an overall stability profile is a necessary step in the drug approval process. Cgmp biologics stability and release testing while mainly a contract research organization cro, kendrick labs also performs custom stability and release testing of protein biologics according to cgmp regulations.
Biologics or biologic drugs are products made from living organisms or contain components of living organisms. Our cell banks are tested for sterility and stored in a controlled environment under liquid nitrogen vapour. Stability studies of these complex biologics present challenges beyond those found for the typical smallmolecule pharmaceutical. Assay development for immunogenicity testing of therapeutic proteins 2009 ich q5ar1. Stability of biological products dr jurgen lindner principal, biopharma consulting. Documenting the stability of the biologic in different storage conditions is essential for setting specifications for expiry and shelf life. Stability testing of drug substances and drug products.
Analytical characterisation in support of biologics development. Topic background as with small molecule therapeutics, biologics require testing for stability. Pharmaceutical stability shelf life august 1, 2010 14 product shelf life nse assay 105 110 115 industry example. Lot release and comparability testing is necessary for evaluating the purity, potency, and identity of biologics. Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin 1999 container closure systems for packaging human drugs and biologics 1999. Understanding the possible pathways where degradation may occur is crucial to designing an appropriate. Regulatory guidance in regards to biotechnologybiological product is available from ich q5c and repeated in the usp chapter. Analytical procedures and methods validation for drugs and. Micah young stability testing of biopharmaceuticals must be performed according to regulatory requirements for drug development programs to establish the retestexpiry date for drugs. Ich guidelines q1a r2 stability testing of new drug substances and products q1b stability testing.
Stability testing in biopharma biopharm international. Container closure systems for packaging human drugs and biologics. The stability information should include, as appropriate, results from the physical, chemical, biological, and microbiological tests, including those related to particular attributes of the dosage form for example, dissolution rate for solid oral dosage forms. Viral safety evaluation of biotechnology products derived from. Q1c stability testing for new dosage forms may 1997 552. Stability is an fda registered and aatb accredited provider of quality products to hospitals, medical centers, and medical professionals throughout the country. Furthermore, stability storage should be operated under ichrecommended conditions with continuous maintenance, monitoring, and security in place. Typically, the first step is to perform a research feasibility test. Our commitment to your process development and cgmp manufacturing needs. Stability testing is required by a number of regulatory agencies. The current recommendation is to test 1% of the total cells or 108 whichever is less pooled vectorproducing cells by coculture with a permissive cell line. Experiments on the physical, chemical, biological, biopharmaceutical and microbiological characteristics of a drug, during. Side effects of a biologics depend upon the specific biologic drug. Ich stability testing for pharmaceuticals and biologics.
Replacing analytical methods for release and stability testing cber perspective presentation at the cmc strategy forum january 27, 2014 lokesh bhattacharyya chief, lab of analytical chemistry and blood products, div. Release and extended characterization testing realtime, accelerated, and stressed stability data release testing and 3 months real time and accelerated stability data on at least one lot of drug product all process validation data for process b 10,000l scale. Defines the stability data package for registration of a new molecular entity as drug substancedrug product. Genetic stability q5c stability testing for biological products q5b viral safety of products derived from cell lines q5a. As a biopharmaceutical company, you need to provide evidence of the stability and quality of your drug substance or drug product under a variety of conditions. Click on the link below to see individual products and descriptions. New quality vision for biologics 9these principles should now be extended to active substances and to biologics 9even if, for biologics, due to their inherent variability, the concept of space design pat or is routinely applied, 9there will be practical consequences of implementing these principles in terms of. Dedicated stability coordinators should ensure that the appropriate materials are prepared for testing when they are needed, and that testing meets andor exceeds ich guidelines from start to finish. Our quality management system is designed to ensure procedural and. Stability studies of these complex biologics present challenges beyond.
Custom biologics has prepared master and working cell banks to ensure quantity and consistency in the course of development programs, validation, stability and lot release testing. The ich harmonized tripartite guidelines on stability testing are the q1aq1e documents q1f was withdrawn in 2006 and ich q5c, which is specifically for biologics 3, 59. Ich q5c is relatively clear in terms of the logistics for a typical stability study. A typical calculated value obtained during acceler ated testing is the stability rate. Stability testing of biotechnologicalbiological products european. Biologics testing utilizing a wide variety of in vitro, in vivo, molecular and analytical methodologies, we provide a full range of services to help take your product from development to commercialization and guide you in designing testing programs for regulatory acceptance worldwide. Guidance for industry container and closure integrity testing in lieu of sterility testing as a component of the stability protocol for sterile products.
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