Dr Raj kumar Kudari, profile picture
Uploaded byDr Raj kumar Kudari
3,996 views

Ich guidelines for stability testing of biotechnological biological products (1)

This document provides guidelines for stability testing of biotechnological and biological products. It discusses selecting representative batches of drug substance and drug product for testing, establishing a stability-indicating profile including potency, purity, and other characteristics, and testing under various storage conditions like temperature, humidity, and accelerated/stress conditions. The guidelines aim to ensure biologics maintain biological activity and avoid degradation during their intended storage period.

Embed presentation

Downloaded 19 times
ICH-GUIDELINES FOR STABILITY TESTING OF BIOTECHNOLOGICAL /BIOLOGICAL PRODUCTS [Q5C] .
PREAMBLE The guidance stated in the ICH harmonised tripartite guideline “Stability Testing of New Drug Substances and Products” (27 October 1993) applies in general to biotechnological/biological products. However, biotechnological/biological products do have distinguishing characteristics to which consideration should be given in any well-defined testing program designed to confirm their stability during the intended storage period. For such products, in which the active components are typically proteins and/or polypeptides, maintenance of molecular conformation and, hence of biological activity, is dependent on non-covalent as well as covalent forces. The products are particularly sensitive to environmental factors such as temperature changes, oxidation, light, ionic content, and shear. In order to ensure maintenance of biological activity and to avoid degradation, stringent conditions for their storage are usually necessary.
PREAMBLE cont’d • The evaluation of stability may necessitate complex analytical methodologies. Assays for biological activity, where applicable, should be part of the pivotal stability studies. • Appropriate Physicochemical, Biochemical and Immunochemical methods for the analysis of the molecular entity and the quantitative detection of degradation products should also be part of the stability program whenever purity and molecular characteristics of the product permit use of these methodologies.
Scope The document covers the generation and submission of stability data for products such as cytokines (interferons, interleukins, colony- stimulating factors, tumour necrosis factors), erythropoietins, plasminogen activators,blood plasma factors, growth hormones and growth factors, insulins, monoclonal antibodies, and vaccines consisting of well-characterised proteins or polypeptides. In addition, the guidance outlined in the following sections may apply to other types of products, such as conventional vaccines, after consultation with the appropriate regulatory authorities. The document does not cover antibiotics, allergenic extracts, heparins, vitamins, whole blood, or cellular blood components.
The stability guidelines for Testing of Biological Products are monitored under the following headings. 1). SELECTION OF BATCHES A.Dug Substance (Bulk Material) B.Intermediates C. Drug Product (Final Container Product) D.Sample Selection 2). STABILITY INDICATING PROFILE A.Protocol B.Potency C.Purity and Molecular Characterization D. Other product Characteristics 3). STORAGE CONDITIONS A.Temperature B.Humidity C. Accelerated & Stress Conditions D. Light E. container Closure F. Stability after Reconstitution of Freeze Dried Products 4). TESTING FREQUENCY 5). SPECIFICATIONS 6). LABELLING
1). SELECTION OF BATCHES a) Drug Substance (Bulk Material) • Where bulk material is to be stored after manufacture but prior to formulation and final manufacturing, stability data should be provided on at least 3 batches for which manufacture and storage are representative of the manufacturing scale of production. • A minimum of 6 months stability data at the time of submission should be submitted in cases WHERE STORAGE PERIODS GREATER THAN 6 MONTHS ARE REQUESTED. • For drug substances WITH STORAGE PERIODS OF LESS THAN 6 MONTHS, the minimum amount of stability data in the initial submission should be determined on a case-by- case basis. • Data from pilot-plant scale batches of drug substance produced at a reduced scale of fermentation and purification may be provided at the time the dossier is submitted to the regulatory agencies with a commitment to place the first 3 manufacturing scale batches into the long-term stability program after approval.
1). SELECTION OF BATCHES a) Drug Substance (Bulk Material) cont’d The quality of the batches of drug substance placed into the stability program should be representative of the quality of the material used in preclinical and clinical studies and of the quality of the material to be made at manufacturing scale. In addition, the drug substance (bulk material) made at pilot-plant scale should be produced by a process and stored under conditions representative of that used for the manufacturing scale. The drug substance entered into the stability program should be stored in containers which properly represent the actual holding containers used during manufacture. Containers of reduced size may be acceptable for drug substance stability testing provided that they are constructed of the same material and use the same type of container/closure system that is intended to be used during manufacture.
1). SELECTION OF BATCHES b)Intermediates • During manufacture of biotechnological/biological products, the quality and control of certain intermediates may be critical to the production of the final product. • In general, the manufacturer should identify intermediates and generate in-house data and process limits that assure their stability within the bounds of the developed process. • While the use of pilot-plant scale data is permissible, the manufacturer should establish the suitability of such data using the manufacturing scale process.
1). SELECTION OF BATCHES c) Drug Product (Final Container Product) • Stability information should be provided on at least 3 batches of final container product representative of that which will be used at manufacturing scale. Where possible, batches of final container product included in stability testing should be derived from different batches of bulk material. • A minimum of 6 months data at the time of submission should be submitted in cases where storage periods greater than 6 months are requested. For drug products with storage periods of less than 6 months, the minimum amount of stability data in the initial submission should be determined on a case-by-case basis. • Product expiration dating will be based upon the actual data submitted in support of the application. Since dating is based upon the real-time/real- temperature data submitted for review, continuing updates of initial stability data should occur during the review and evaluation process.
1). SELECTION OF BATCHES c) Drug Product (Final Container Product) cont’d • The quality of the final container product placed on stability studies should be representative of the quality of the material used in the preclinical and clinical studies. • Data from pilot-plant scale batches of drug product may be provided at the time the dossier is submitted to the regulatory agencies with a commitment to place the first 3 manufacturing scale batches into the long term stability program after approval. • Where pilot-plant scale batches were submitted to establish the dating for a product and, in the event that product produced at manufacturing scale does not meet those long-term stability specifications throughout the dating period or is not representative of the material used in preclinical and clinical studies, the applicant should notify the appropriate regulatory authorities to determine a suitable course of action.
1). SELECTION OF BATCHES d)Sample Selection • Where one product is distributed in batches differing in fill volume (e.g., 1ml, 2 ml, or 10 ml), unitage (e.g., 10 units, 20 units, or 50 units), or mass (e.g., 1mg, 2 mg, or 5 mg) samples to be entered into the stability program may be selected on the basis of a matrix system and/or by bracketing. • Matrixing, i.e., the statistical design of a stability study in which different fractions of samples are tested at different sampling points, should only be applied when appropriate documentation is provided that confirms that the stability of the samples tested represents the stability of all samples. • The differences in the samples for the same drug product should be identified as, for example, covering different batches, different strengths, different sizes of the same closure and possibly, in some cases, different container/closure systems.
1). SELECTION OF BATCHES d)Sample Selection cont’d • [Matrixing should not be applied to samples with differences that may affect stability, such as different strengths and different containers/closures, where it cannot be confirmed that the products respond similarly under storage conditions.] • Where the same strength and exact container/closure system is used for 3 or more fill contents, the manufacturer may elect to place only the smallest and largest container size into the stability program, i.e., bracketing. • The Bracketing design assumes that the stability of the intermediate condition samples are represented by those at the extremes. In certain cases, data may be needed to demonstrate that all samples are properly represented by data collected for the extremes.
2).STABILITY-INDICATING PROFILE • On the whole, there is no single stability-indicating assay or parameter that profiles the stability characteristics of a biotechnological/biological product. Consequently, the manufacturer should propose a stability-indicating profile that provides assurance that changes in the identity, purity and potency of the product will be detected. • At the time of submission, applicants should have validated the methods that comprise the stability- indicating profile and the data should be available for review. • The determination of which tests should be included will be product-specific. The items emphasized in the following subsections are not intended to be all- inclusive, but represent product characteristics that should typically be documented to adequately demonstrate product stability.
2).STABILITY-INDICATING PROFILE a)Protocol • The dossier(Document of Reports) accompanying the application for marketing authorization should include a detailed protocol for the assessment of the stability of both drug substance and drug product in support of the proposed storage conditions and expiration dating periods. • The protocol should include all necessary information which demonstrates the stability of the biotechnological/biological product throughout the proposed expiration dating period including, for example, well-defined specifications and test intervals. • The statistical methods that should be used are described in the tripartite guideline on stability. • .
2).STABILITY-INDICATING PROFILE b)Potency • When the intended use of a product is linked to a definable and measurable biological activity, testing for potency should be part of the stability studies. For the purpose of stability testing of the products described in this guideline, potency is the specific ability or capacity of a product to achieve its intended effect. • It is based on the measurement of some attribute of the product and is determined by a suitable quantitative method. In general, potencies of biotechnological/biological products tested by different laboratories can be compared in a meaningful way only if expressed in relation to that of an appropriate reference material.
2).STABILITY-INDICATING PROFILE b)Potency cont’d • For that purpose, a reference material calibrated directly or indirectly against the corresponding national or international reference material should be included in the assay. • Potency studies should be performed at appropriate intervals as defined in the stability protocol and the results should be reported in units of biological activity calibrated, whenever possible, against nationally or internationally recognised standard. Where no national or international reference standards exist, the assay results may be reported in in-house derived units using a characterised reference material.
2).STABILITY-INDICATING PROFILE b)Potency cont’d • In some biotechnological/biological products, potency is dependent upon the conjugation of the active ingredient(s) to a second moiety or binding to an adjuvant. • Dissociation of the active ingredient(s) from the carrier used in conjugates or adjuvants should be examined in real-time/real-temperature studies (including conditions encountered during shipment). • The assessment of the stability of such products may be difficult since, in some cases, in vitro tests for biological activity and physicochemical characterisation are impractical or provide inaccurate results. • Appropriate strategies (e.g., testing the product prior to conjugation/binding, assessing the release of the active compound from the second moiety, in vivo assays) or the use of an appropriate surrogate test should be considered to overcome the inadequacies of in vitro testing.
2).STABILITY-INDICATING PROFILE c)Purity and Molecular Characterisation • For the purpose of stability testing of the products described in this guideline, purity is a relative term. Due to the effect of glycosylation, deamidation, or other heterogeneities, the absolute purity of a biotechnological/biological product is extremely difficult to determine. • Thus, the purity of a biotechnological/biological product should be typically assessed by more than one method and the purity value derived is method-dependent. For the purpose of stability testing, tests for purity should focus on methods for determination of degradation products. • The degree of purity, as well as individual and total amounts of degradation products of the biotechnological/biological product entered into the stability studies, should be reported and documented whenever possible. • Limits of acceptable degradation should be derived from the analytical profiles of batches of the drug substance and drug product used in the preclinical and clinical studies.
2).STABILITY-INDICATING PROFILE c)Purity and Molecular Characterisation cont’d • The use of relevant physicochemical, biochemical and immunochemical analytical methodologies should permit a comprehensive characterisation of the drug substance and/or drug product (e.g., molecular size, charge, hydrophobicity) and the accurate detection of degradation changes that may result from deamidation, oxidation, sulfoxidation, aggregation or fragmentation during storage. • As examples, methods that may contribute to this include electrophoresis (SDS-PAGE, immunoelectrophoresis, Western blot, isoelectrofocusing), high-resolution chromatography (e.g., reversed-phase chromatography, gel filtration, ion exchange, affinity chromatography), and peptide mapping.
2).STABILITY-INDICATING PROFILE c)Purity and Molecular Characterisation cont’d • Wherever significant qualitative or quantitative changes indicative of degradation product formation are detected during long-term, accelerated and/or stress stability studies, consideration should be given to potential hazards and to the need for characterisation and quantification of degradation products within the long-term stability program. • • Acceptable limits should be proposed and justified, taking into account the levels observed in material used in preclinical and clinical studies. • For substances that cannot be properly characterised or products for which an exact analysis of the purity cannot be determined through routine analytical methods, the applicant should propose and justify alternative testing procedures.
2).STABILITY-INDICATING PROFILE d) Other Product Characteristics • The following product characteristics, though not specifically relating to biotechnological/biological products, should be monitored and reported for the drug product in its final container: • Visual appearance of the product (colour and opacity for solutions/suspensions; colour, texture and dissolution time for powders), visible particulates in solutions or after the reconstitution of powders or lyophilised cakes, pH, and moisture level of powders and lyophilised products. • Sterility testing or alternatives (e.g., container/closure integrity testing) should be performed at a minimum initially and at the end of the proposed shelf-life. • Additives (e.g., stabilisers, preservatives) or excipients may degrade during the dating period of the drug product. If there is any indication during preliminary stability studies that reaction or degradation of such materials adversely affect the quality of the drug product, these items may need to be monitored during the stability program. • The container/closure has the potential to adversely affect the product and should be carefully evaluated.
3). STORAGE CONDITIONS a)Temperature • Since most finished biotechnological/biological products need precisely defined storage temperatures, the storage conditions for the real-time/real-temperature stability studies may be confined to the proposed storage temperature. •
3). STORAGE CONDITIONS b) Humidity • Biotechnological/biological products are generally distributed in containers protecting them against humidity. • Therefore, where it can be demonstrated that the proposed containers (and conditions of storage) afford sufficient protection against high and low humidity, stability tests at different relative humidities can usually be omitted. • Where humidity-protecting containers are not used, appropriate stability data should be provided.
3). STORAGE CONDITIONS c) Accelerated and Stress Conditions • As previously noted, the expiration dating should be based on real-time/real- temperature data. • However, it is strongly suggested that studies be conducted on the drug substance and drug product under accelerated and stress conditions. • Studies under accelerated conditions may provide useful support data for establishing the expiration date, provide product stability information for future product development (e.g., preliminary assessment of proposed manufacturing changes such as change in formulation, scale-up), assist in validation of analytical methods for the stability program, or generate information which may help elucidate the degradation profile of the drug substance or drug product.
3). STORAGE CONDITIONS c) Accelerated and Stress Conditions cont’d • Studies under stress conditions may be useful in determining whether accidental exposures to conditions other than those proposed (e.g., during transportation) are deleterious to the product and also for evaluating which specific test parameters may be the best indicators of product stability. • Studies of the exposure of the drug substance or drug product to extreme conditions may help to reveal patterns of degradation; if so, such changes should be monitored under proposed storage conditions. • While the tripartite guideline on stability describes the conditions of the accelerated and stress study, the applicant should note that those conditions may not be appropriate for biotechnological/biological products. • Conditions should be carefully selected on a case-by-case basis. • d) Light • Applicants should consult the appropriate regulatory authorities on a case-by-case basis to determine guidance for testing.
3). STORAGE CONDITIONS • e) Container/Closure • Changes in the quality of the product may occur due to the interactions between the formulated biological product and container/closure. Where the lack of interactions cannot be excluded in liquid products (other than sealed ampoules), stability studies should include samples maintained in the inverted or horizontal position (i.e., in contact with the closure), as well as in the upright position, to determine the effects of the closure on product quality. Data should be supplied for all different container/closure combinations that will be marketed. • In addition to the standard data necessary for a conventional single-use vial, the applicant should demonstrate that the closure used with a multiple-dose vial is capable of withstandingrepeated insertions and withdrawals so that the product retains its full potency, purity, and quality for the maximum periodspecified in the instructions-for-use on containers, packages, and/or package inserts. Such labelling should be in accordance with relevant national/regional requirements.
3). STORAGE CONDITIONS f) Stability after Reconstitution of Freeze-Dried Product • The stability of freeze-dried products after their reconstitution should be demonstrated for the conditions and the maximum storage period specified on containers, packages, and/or package inserts. Such labelling should be in accordance with relevant national/regional requirements.
4). TESTING FREQUENCY • The shelf-lives of biotechnological/biological products may vary from days to several years. Thus, it is difficult to draft uniform guidelines regarding the stability study duration and testing frequency that would be applicable to all types of biotechnological/biological products. • With only a few exceptions, however, the shelf- lives for existing products and potential future products will be within the range of 0.5 to 5 years. Therefore, the guidance is based upon expected shelf-lives in that range. • This takes into account the fact that degradation of biotechnological/biological products may not be governed by the same factors during different intervals of a long storage period. • When shelf-lives of 1 year or less are proposed, the real-time stability studies should be conducted monthly for the first 3 months and at 3 month intervals thereafter.
4). TESTING FREQUENCY cont’d • While the testing intervals listed above may be appropriate in the pre-approval or pre-licence stage, reduced testing may be appropriate after approval or licensure where data are available that demonstrate adequate stability. • Where data exist that indicate the stability of a product is not compromised, the applicant is encouraged to submit a protocol which supports elimination of specific test intervals (e.g., 9 month testing) for post-approval/post- licensure, long-term studies.
5). SPECIFICATIONS • Although biotechnological/biological products may be subject to significant losses of activity, physicochemical changes, or degradation during storage, international and national regulations have provided little guidance with respect to distinct release and end of shelf-life specifications. • Recommendations for maximum acceptable losses of activity, limits for physicochemical changes, or degradation during the proposed shelf- life have not been developed for individual types or groups of biotechnological/biological products but are considered on a case-by-case basis. • Each product should retain its specifications within established limits for safety, purity, and potency throughout its proposed shelf-life. • These specifications and limits should be derived from all available information using the appropriate statistical methods. The use of different specifications for release and expiration should be supported by sufficient data to demonstrate that clinical performance is not affected as discussed in the tripartite guideline on stability. •
6). LABELLING • For most biotechnological/biological drug substances and drug products, precisely defined storage temperatures are recommended. • Specific recommendations should be stated, particularly for drug substances and drug products that cannot tolerate freezing. • These conditions, and where appropriate, recommendations for protection against light and/or humidity, should appear on containers, packages, and/or package inserts. • Such labelling should be in accordance with relevant national/regional requirements.
DEFINITIONS - 1 • Conjugated Product • A conjugated product is made up of an active ingredient (for example, peptide, carbohydrate) bound covalently or non- covalently to a carrier (for example, protein, peptide, inorganic mineral) with the objective of improving the efficacy or stability of the product. • Degradation Product • A molecule resulting from a change in the drug substance (bulk material) brought about over time. For the purpose of stability testing of the products described in this guideline, such changes could occur as a result of processing or storage (e.g., by deamidation, oxidation, aggregation, proteolysis). For biotechnological/biological products some degradation products may be active. • Impurity • Any component of the drug substance (bulk material) or drug product (final container product) which is not the chemical entity defined as the drug substance, an excipient, or other additives to the drug product.
DEFINITIONS - 2 • Intermediate • For biotechnological/biological products, a material produced during a manufacturing process which is not the drug substance or the drug product but whose manufacture is critical to the successful production of the drug substance or the drug product. Generally, an intermediate will be quantifiable and specifications will be established to determine the successful completion of the manufacturing step prior to continuation of the manufacturing process. This includes material which may undergo further molecular modification or be held for an extended period of time prior to further processing. • Manufacturing Scale Production • Manufacture at the scale typically encountered in a facility intended for product production for marketing. • Pilot-Plant Scale • The production of the drug substance or drug product by a procedure fully representative of and simulating that to be applied at manufacturing scale. The methods of cell expansion, harvest, and product purification should be identical except for the scale of production.
Dr.Raj Kumar Kudari, M.Pharm, PhD. Professor Hindu College of Pharmacy Amravati Road, Guntur-522002 Andhra Pradesh. . Thank You !

More Related Content

PPTX
Stability testing of biotechnological/ biological products (Q5C )
byusha khanal
 
PPTX
Stability testing protocols
byMehulJain143
 
PPTX
Stability zones and ich guideline q5c
byKshitiz Kumar Gaund
 
PDF
ICH q5c ICH Q5C Stability testing of Biotechnological / Biological products
bysaimsoleja
 
PPTX
PHOTO STABILITY TESTING OF DRUG SUBSTANCE AND DRUG PRODUCT Q1B
byfakehanaeem1
 
PPTX
Stability Testing of Phytopharmaceuticals
byManjusha Kondepudi
 
PDF
Comparison of stability testing requirements of ich with other
byJun Brown
 
PPTX
BRACKETING AND MATRIXING DESIGNS FOR STABILITY TESTING OF NEW DRUG SUBSTANCES...
byMoremrunal
 
Stability testing of biotechnological/ biological products (Q5C )
byusha khanal
 
Stability testing protocols
byMehulJain143
 
Stability zones and ich guideline q5c
byKshitiz Kumar Gaund
 
ICH q5c ICH Q5C Stability testing of Biotechnological / Biological products
bysaimsoleja
 
PHOTO STABILITY TESTING OF DRUG SUBSTANCE AND DRUG PRODUCT Q1B
byfakehanaeem1
 
Stability Testing of Phytopharmaceuticals
byManjusha Kondepudi
 
Comparison of stability testing requirements of ich with other
byJun Brown
 
BRACKETING AND MATRIXING DESIGNS FOR STABILITY TESTING OF NEW DRUG SUBSTANCES...
byMoremrunal
 

What's hot

PDF
stability testing of phytopharmaceuticals.pdf
byKGNithyaLakshmi
 
PPTX
Rationale for the reporting control of degradation products
byManiKandan1405
 
PPTX
Impurities in residual solvents
byMehulJain143
 
PPTX
Impurity profiling and degradent characterization {presented by shameer m.pha...
byShameerAbid
 
PPTX
Residual solvents as impurities
bySanthosh Kalakar dj
 
PPTX
IMPURITIES OF NEW DRUG PRODUCTS
byprakash64742
 
PPTX
Qualification of analytical instruments
bySanathoiba Singha
 
PPTX
USFDA guidelines for bioanalytical method validation
bybhatiaji123
 
PPTX
ANALYSIS OF FERMENTATION PRODUCTS BY HIMAJA
byhimaja donthula
 
PPTX
Elemental Impurities by Shiv Kalia.pptx
byShiv Kalia
 
PPTX
Qualification of glassware
byRaghavendra institute of pharmaceutical education and research .
 
PPTX
Analysis of various milk products
byPharmacy Slides
 
PPTX
Radio Immuno Assay
byNeha Suresh
 
PPTX
Biological test and assay tetanus toxoid adsorbed
byShameerAbid
 
PPTX
Pharmaceutical validation of water system
byRaghavendra institute of pharmaceutical education and research .
 
PPTX
Assay of adsorbed diptheria vaccine and adsorbed tetanus
byRAGHAV DOGRA
 
PPT
Analytical methods validation as per ich & usp
byGANESH NIGADE
 
PPTX
BIOASSAY OF TETANUS ANTITOXIN
byDr. Koppala R.V.S. Chaitanya
 
PPTX
Qualification of instrumets
byChowdaryPavani
 
PPTX
CLEANING METHOD DEVELOPMENT
byRaghavendra institute of pharmaceutical education and research .
 
stability testing of phytopharmaceuticals.pdf
byKGNithyaLakshmi
 
Rationale for the reporting control of degradation products
byManiKandan1405
 
Impurities in residual solvents
byMehulJain143
 
Impurity profiling and degradent characterization {presented by shameer m.pha...
byShameerAbid
 
Residual solvents as impurities
bySanthosh Kalakar dj
 
IMPURITIES OF NEW DRUG PRODUCTS
byprakash64742
 
Qualification of analytical instruments
bySanathoiba Singha
 
USFDA guidelines for bioanalytical method validation
bybhatiaji123
 
ANALYSIS OF FERMENTATION PRODUCTS BY HIMAJA
byhimaja donthula
 
Elemental Impurities by Shiv Kalia.pptx
byShiv Kalia
 
Qualification of glassware
byRaghavendra institute of pharmaceutical education and research .
 
Analysis of various milk products
byPharmacy Slides
 
Radio Immuno Assay
byNeha Suresh
 
Biological test and assay tetanus toxoid adsorbed
byShameerAbid
 
Pharmaceutical validation of water system
byRaghavendra institute of pharmaceutical education and research .
 
Assay of adsorbed diptheria vaccine and adsorbed tetanus
byRAGHAV DOGRA
 
Analytical methods validation as per ich & usp
byGANESH NIGADE
 
BIOASSAY OF TETANUS ANTITOXIN
byDr. Koppala R.V.S. Chaitanya
 
Qualification of instrumets
byChowdaryPavani
 
CLEANING METHOD DEVELOPMENT
byRaghavendra institute of pharmaceutical education and research .
 

Similar to Ich guidelines for stability testing of biotechnological biological products (1)

PPT
Q5C.ppt
byKalakonda Sri Nataraj
 
PPTX
ICHQ5C
bySujeetSingh212
 
PPT
Stability study
byParth Chauhan
 
PPTX
WHO Guideline & Stability Protocols for Liquid Dosage Forms
byAnindya Jana
 
PPTX
ICH Guidelines for stability testing
byAnkitaKawtikwar
 
PPTX
stability zones and ich guideline q5c
byprakash64742
 
PPTX
QMS stability testing.pptx
byThoratPrajaktaSanjay
 
PPTX
Ich guidelines and protocols
byMalla Reddy College of Pharmacy
 
PPTX
Q1A R2 - ICH GUIDELINES OF STABILITY TESTING
byHossamKhayyal
 
PPTX
S4 KAVANA BB APA-STABILITY STUDIESs.pptx
byVenkatesan R - 6369851191
 
PPTX
ICH Guideline Stability Testing of New Drug Substances and Product Q1A(R2).pptx
byTrishala Bhatt
 
PPTX
ICH Guidelines for Stability Testing of Drug Substance and Drug Product
bysonalgupta200
 
PPTX
Ich guidelines and protocols
byceutics1315
 
PPTX
Stability study as per ich guideline
byRaKesh Rathava
 
PPTX
ICH Guidlines for stability studies
byVishnu Satpute
 
PDF
STABILITY STUDIES OF PHARMACEUTICALS.pdf
byBALASUNDARESAN M
 
PPTX
ICH
byKavitha Bitra
 
PPTX
Stability Testing_Animal Health Products
byvenkata Kumar sahu, RPh
 
PDF
Q5 c step4
byPharmaguideline
 
PPTX
ICH guidlines.pptx
bySreedhar Reddy
 
Q5C.ppt
byKalakonda Sri Nataraj
 
ICHQ5C
bySujeetSingh212
 
Stability study
byParth Chauhan
 
WHO Guideline & Stability Protocols for Liquid Dosage Forms
byAnindya Jana
 
ICH Guidelines for stability testing
byAnkitaKawtikwar
 
stability zones and ich guideline q5c
byprakash64742
 
QMS stability testing.pptx
byThoratPrajaktaSanjay
 
Ich guidelines and protocols
byMalla Reddy College of Pharmacy
 
Q1A R2 - ICH GUIDELINES OF STABILITY TESTING
byHossamKhayyal
 
S4 KAVANA BB APA-STABILITY STUDIESs.pptx
byVenkatesan R - 6369851191
 
ICH Guideline Stability Testing of New Drug Substances and Product Q1A(R2).pptx
byTrishala Bhatt
 
ICH Guidelines for Stability Testing of Drug Substance and Drug Product
bysonalgupta200
 
Ich guidelines and protocols
byceutics1315
 
Stability study as per ich guideline
byRaKesh Rathava
 
ICH Guidlines for stability studies
byVishnu Satpute
 
STABILITY STUDIES OF PHARMACEUTICALS.pdf
byBALASUNDARESAN M
 
ICH
byKavitha Bitra
 
Stability Testing_Animal Health Products
byvenkata Kumar sahu, RPh
 
Q5 c step4
byPharmaguideline
 
ICH guidlines.pptx
bySreedhar Reddy
 

Recently uploaded

PDF
Lecture 5-6, (Definition and characteristics of Auditing).pdf
byMalihaPriyoti
 
PPTX
Effect-of-Pachymic-Acid-Addition-to-AH-Plus-on-Postoperative-Pain-and-Periapi...
byharshil4576
 
PPTX
CLSI 2025 UPDATES for microbiology laboratory.pptx
bydraarthi94
 
PPT
02 Disease Surveillance finall.ppt for Nutrition
bynuramalicha
 
PDF
The-Future-of-Self-Service-Health-Assessment-Automation.pdf
byEDGreek
 
PDF
Kamada - Corporate Presentation - Each Life is Unique - November 2025
byKAMADA
 
PPT
dental diseases and systemic condition aand
byDwarika Prasad Bajgai
 
PPTX
Mgt of SAM-Therapeutic Feeding Program Report July 2005.pptx
bynuramalicha
 
PPTX
carditis.pptx carditis ppt all types and symptoms
byAaryanDuhan1
 
PPTX
UVEITIS SYMPOSIUM Uveitis types and its associations
byzwz65hkg5c
 
PDF
03/12/25 Empty Nose Syndrome (ENS) victims
bycabisew292
 
PDF
DCL.pdf (Distubed conscious level how to approach)
byOmarEssa13
 
PPTX
Palliative Care Home-Based Support in Coimbatore
byanbusrisaihomenursin
 
PPTX
ANEMIA IN PREGNANCY -a detailed ses.pptx
bysimpleshilpasharma
 
PPTX
The Role of Technology in Transforming Healthcare Services in Varanasi.pptx
byGangoshri Hospital
 
PPTX
Role of a nurse in preventive psychiatry
bySharley3
 
PPTX
Ankura - Ten Tips for Viral Fever..pptx
byIAPTCB
 
PPT
14778AIDS presentation..ppt for sutdents
bygamah0506
 
PPTX
Compartment_Syndrome_in_traumaticleg.pptx
byjiniaiservice14
 
DOCX
What Is Meditation in the Bible? A Complete Guide to Modern Readers
byYOGASADHANA
 
Lecture 5-6, (Definition and characteristics of Auditing).pdf
byMalihaPriyoti
 
Effect-of-Pachymic-Acid-Addition-to-AH-Plus-on-Postoperative-Pain-and-Periapi...
byharshil4576
 
CLSI 2025 UPDATES for microbiology laboratory.pptx
bydraarthi94
 
02 Disease Surveillance finall.ppt for Nutrition
bynuramalicha
 
The-Future-of-Self-Service-Health-Assessment-Automation.pdf
byEDGreek
 
Kamada - Corporate Presentation - Each Life is Unique - November 2025
byKAMADA
 
dental diseases and systemic condition aand
byDwarika Prasad Bajgai
 
Mgt of SAM-Therapeutic Feeding Program Report July 2005.pptx
bynuramalicha
 
carditis.pptx carditis ppt all types and symptoms
byAaryanDuhan1
 
UVEITIS SYMPOSIUM Uveitis types and its associations
byzwz65hkg5c
 
03/12/25 Empty Nose Syndrome (ENS) victims
bycabisew292
 
DCL.pdf (Distubed conscious level how to approach)
byOmarEssa13
 
Palliative Care Home-Based Support in Coimbatore
byanbusrisaihomenursin
 
ANEMIA IN PREGNANCY -a detailed ses.pptx
bysimpleshilpasharma
 
The Role of Technology in Transforming Healthcare Services in Varanasi.pptx
byGangoshri Hospital
 
Role of a nurse in preventive psychiatry
bySharley3
 
Ankura - Ten Tips for Viral Fever..pptx
byIAPTCB
 
14778AIDS presentation..ppt for sutdents
bygamah0506
 
Compartment_Syndrome_in_traumaticleg.pptx
byjiniaiservice14
 
What Is Meditation in the Bible? A Complete Guide to Modern Readers
byYOGASADHANA
 
In this document
Powered by AI

Introduction to ICH guidelines for stability testing of biotech/biological products and their unique storage needs.

Covers stability data submission for various biological products like cytokines, vaccines, and monoclonal antibodies.

Details testing framework including batch selection, stability profile, and sample selection protocols.

Establishes the need for a profile indicating product stability, including potency, purity, and product characteristics.

Defines essential storage conditions: temperature, humidity, container interactions, and post-reconstitution stability.

Discusses variations in testing frequency based on product shelf-lives between days and years.

Outlines specifications for biological products, focusing on safety, purity, and potency during shelf life.

Guidelines for labelling including required storage conditions and protection against environmental factors.

Definitions related to biotechnological products crucial for understanding stability testing processes.

Ich guidelines for stability testing of biotechnological biological products (1)

  • 1.
  • 2.
    PREAMBLE The guidance statedin the ICH harmonised tripartite guideline “Stability Testing of New Drug Substances and Products” (27 October 1993) applies in general to biotechnological/biological products. However, biotechnological/biological products do have distinguishing characteristics to which consideration should be given in any well-defined testing program designed to confirm their stability during the intended storage period. For such products, in which the active components are typically proteins and/or polypeptides, maintenance of molecular conformation and, hence of biological activity, is dependent on non-covalent as well as covalent forces. The products are particularly sensitive to environmental factors such as temperature changes, oxidation, light, ionic content, and shear. In order to ensure maintenance of biological activity and to avoid degradation, stringent conditions for their storage are usually necessary.
  • 3.
    PREAMBLE cont’d • Theevaluation of stability may necessitate complex analytical methodologies. Assays for biological activity, where applicable, should be part of the pivotal stability studies. • Appropriate Physicochemical, Biochemical and Immunochemical methods for the analysis of the molecular entity and the quantitative detection of degradation products should also be part of the stability program whenever purity and molecular characteristics of the product permit use of these methodologies.
  • 4.
    Scope The document coversthe generation and submission of stability data for products such as cytokines (interferons, interleukins, colony- stimulating factors, tumour necrosis factors), erythropoietins, plasminogen activators,blood plasma factors, growth hormones and growth factors, insulins, monoclonal antibodies, and vaccines consisting of well-characterised proteins or polypeptides. In addition, the guidance outlined in the following sections may apply to other types of products, such as conventional vaccines, after consultation with the appropriate regulatory authorities. The document does not cover antibiotics, allergenic extracts, heparins, vitamins, whole blood, or cellular blood components.
  • 5.
    The stability guidelinesfor Testing of Biological Products are monitored under the following headings. 1). SELECTION OF BATCHES A.Dug Substance (Bulk Material) B.Intermediates C. Drug Product (Final Container Product) D.Sample Selection 2). STABILITY INDICATING PROFILE A.Protocol B.Potency C.Purity and Molecular Characterization D. Other product Characteristics 3). STORAGE CONDITIONS A.Temperature B.Humidity C. Accelerated & Stress Conditions D. Light E. container Closure F. Stability after Reconstitution of Freeze Dried Products 4). TESTING FREQUENCY 5). SPECIFICATIONS 6). LABELLING
  • 6.
    1). SELECTION OFBATCHES a) Drug Substance (Bulk Material) • Where bulk material is to be stored after manufacture but prior to formulation and final manufacturing, stability data should be provided on at least 3 batches for which manufacture and storage are representative of the manufacturing scale of production. • A minimum of 6 months stability data at the time of submission should be submitted in cases WHERE STORAGE PERIODS GREATER THAN 6 MONTHS ARE REQUESTED. • For drug substances WITH STORAGE PERIODS OF LESS THAN 6 MONTHS, the minimum amount of stability data in the initial submission should be determined on a case-by- case basis. • Data from pilot-plant scale batches of drug substance produced at a reduced scale of fermentation and purification may be provided at the time the dossier is submitted to the regulatory agencies with a commitment to place the first 3 manufacturing scale batches into the long-term stability program after approval.
  • 7.
    1). SELECTION OFBATCHES a) Drug Substance (Bulk Material) cont’d The quality of the batches of drug substance placed into the stability program should be representative of the quality of the material used in preclinical and clinical studies and of the quality of the material to be made at manufacturing scale. In addition, the drug substance (bulk material) made at pilot-plant scale should be produced by a process and stored under conditions representative of that used for the manufacturing scale. The drug substance entered into the stability program should be stored in containers which properly represent the actual holding containers used during manufacture. Containers of reduced size may be acceptable for drug substance stability testing provided that they are constructed of the same material and use the same type of container/closure system that is intended to be used during manufacture.
  • 8.
    1). SELECTION OFBATCHES b)Intermediates • During manufacture of biotechnological/biological products, the quality and control of certain intermediates may be critical to the production of the final product. • In general, the manufacturer should identify intermediates and generate in-house data and process limits that assure their stability within the bounds of the developed process. • While the use of pilot-plant scale data is permissible, the manufacturer should establish the suitability of such data using the manufacturing scale process.
  • 9.
    1). SELECTION OFBATCHES c) Drug Product (Final Container Product) • Stability information should be provided on at least 3 batches of final container product representative of that which will be used at manufacturing scale. Where possible, batches of final container product included in stability testing should be derived from different batches of bulk material. • A minimum of 6 months data at the time of submission should be submitted in cases where storage periods greater than 6 months are requested. For drug products with storage periods of less than 6 months, the minimum amount of stability data in the initial submission should be determined on a case-by-case basis. • Product expiration dating will be based upon the actual data submitted in support of the application. Since dating is based upon the real-time/real- temperature data submitted for review, continuing updates of initial stability data should occur during the review and evaluation process.
  • 10.
    1). SELECTION OFBATCHES c) Drug Product (Final Container Product) cont’d • The quality of the final container product placed on stability studies should be representative of the quality of the material used in the preclinical and clinical studies. • Data from pilot-plant scale batches of drug product may be provided at the time the dossier is submitted to the regulatory agencies with a commitment to place the first 3 manufacturing scale batches into the long term stability program after approval. • Where pilot-plant scale batches were submitted to establish the dating for a product and, in the event that product produced at manufacturing scale does not meet those long-term stability specifications throughout the dating period or is not representative of the material used in preclinical and clinical studies, the applicant should notify the appropriate regulatory authorities to determine a suitable course of action.
  • 11.
    1). SELECTION OFBATCHES d)Sample Selection • Where one product is distributed in batches differing in fill volume (e.g., 1ml, 2 ml, or 10 ml), unitage (e.g., 10 units, 20 units, or 50 units), or mass (e.g., 1mg, 2 mg, or 5 mg) samples to be entered into the stability program may be selected on the basis of a matrix system and/or by bracketing. • Matrixing, i.e., the statistical design of a stability study in which different fractions of samples are tested at different sampling points, should only be applied when appropriate documentation is provided that confirms that the stability of the samples tested represents the stability of all samples. • The differences in the samples for the same drug product should be identified as, for example, covering different batches, different strengths, different sizes of the same closure and possibly, in some cases, different container/closure systems.
  • 12.
    1). SELECTION OFBATCHES d)Sample Selection cont’d • [Matrixing should not be applied to samples with differences that may affect stability, such as different strengths and different containers/closures, where it cannot be confirmed that the products respond similarly under storage conditions.] • Where the same strength and exact container/closure system is used for 3 or more fill contents, the manufacturer may elect to place only the smallest and largest container size into the stability program, i.e., bracketing. • The Bracketing design assumes that the stability of the intermediate condition samples are represented by those at the extremes. In certain cases, data may be needed to demonstrate that all samples are properly represented by data collected for the extremes.
  • 13.
    2).STABILITY-INDICATING PROFILE • Onthe whole, there is no single stability-indicating assay or parameter that profiles the stability characteristics of a biotechnological/biological product. Consequently, the manufacturer should propose a stability-indicating profile that provides assurance that changes in the identity, purity and potency of the product will be detected. • At the time of submission, applicants should have validated the methods that comprise the stability- indicating profile and the data should be available for review. • The determination of which tests should be included will be product-specific. The items emphasized in the following subsections are not intended to be all- inclusive, but represent product characteristics that should typically be documented to adequately demonstrate product stability.
  • 14.
    2).STABILITY-INDICATING PROFILE a)Protocol • Thedossier(Document of Reports) accompanying the application for marketing authorization should include a detailed protocol for the assessment of the stability of both drug substance and drug product in support of the proposed storage conditions and expiration dating periods. • The protocol should include all necessary information which demonstrates the stability of the biotechnological/biological product throughout the proposed expiration dating period including, for example, well-defined specifications and test intervals. • The statistical methods that should be used are described in the tripartite guideline on stability. • .
  • 15.
    2).STABILITY-INDICATING PROFILE b)Potency • Whenthe intended use of a product is linked to a definable and measurable biological activity, testing for potency should be part of the stability studies. For the purpose of stability testing of the products described in this guideline, potency is the specific ability or capacity of a product to achieve its intended effect. • It is based on the measurement of some attribute of the product and is determined by a suitable quantitative method. In general, potencies of biotechnological/biological products tested by different laboratories can be compared in a meaningful way only if expressed in relation to that of an appropriate reference material.
  • 16.
    2).STABILITY-INDICATING PROFILE b)Potency cont’d •For that purpose, a reference material calibrated directly or indirectly against the corresponding national or international reference material should be included in the assay. • Potency studies should be performed at appropriate intervals as defined in the stability protocol and the results should be reported in units of biological activity calibrated, whenever possible, against nationally or internationally recognised standard. Where no national or international reference standards exist, the assay results may be reported in in-house derived units using a characterised reference material.
  • 17.
    2).STABILITY-INDICATING PROFILE b)Potency cont’d •In some biotechnological/biological products, potency is dependent upon the conjugation of the active ingredient(s) to a second moiety or binding to an adjuvant. • Dissociation of the active ingredient(s) from the carrier used in conjugates or adjuvants should be examined in real-time/real-temperature studies (including conditions encountered during shipment). • The assessment of the stability of such products may be difficult since, in some cases, in vitro tests for biological activity and physicochemical characterisation are impractical or provide inaccurate results. • Appropriate strategies (e.g., testing the product prior to conjugation/binding, assessing the release of the active compound from the second moiety, in vivo assays) or the use of an appropriate surrogate test should be considered to overcome the inadequacies of in vitro testing.
  • 18.
    2).STABILITY-INDICATING PROFILE c)Purity andMolecular Characterisation • For the purpose of stability testing of the products described in this guideline, purity is a relative term. Due to the effect of glycosylation, deamidation, or other heterogeneities, the absolute purity of a biotechnological/biological product is extremely difficult to determine. • Thus, the purity of a biotechnological/biological product should be typically assessed by more than one method and the purity value derived is method-dependent. For the purpose of stability testing, tests for purity should focus on methods for determination of degradation products. • The degree of purity, as well as individual and total amounts of degradation products of the biotechnological/biological product entered into the stability studies, should be reported and documented whenever possible. • Limits of acceptable degradation should be derived from the analytical profiles of batches of the drug substance and drug product used in the preclinical and clinical studies.
  • 19.
    2).STABILITY-INDICATING PROFILE c)Purity andMolecular Characterisation cont’d • The use of relevant physicochemical, biochemical and immunochemical analytical methodologies should permit a comprehensive characterisation of the drug substance and/or drug product (e.g., molecular size, charge, hydrophobicity) and the accurate detection of degradation changes that may result from deamidation, oxidation, sulfoxidation, aggregation or fragmentation during storage. • As examples, methods that may contribute to this include electrophoresis (SDS-PAGE, immunoelectrophoresis, Western blot, isoelectrofocusing), high-resolution chromatography (e.g., reversed-phase chromatography, gel filtration, ion exchange, affinity chromatography), and peptide mapping.
  • 20.
    2).STABILITY-INDICATING PROFILE c)Purity andMolecular Characterisation cont’d • Wherever significant qualitative or quantitative changes indicative of degradation product formation are detected during long-term, accelerated and/or stress stability studies, consideration should be given to potential hazards and to the need for characterisation and quantification of degradation products within the long-term stability program. • • Acceptable limits should be proposed and justified, taking into account the levels observed in material used in preclinical and clinical studies. • For substances that cannot be properly characterised or products for which an exact analysis of the purity cannot be determined through routine analytical methods, the applicant should propose and justify alternative testing procedures.
  • 21.
    2).STABILITY-INDICATING PROFILE d) OtherProduct Characteristics • The following product characteristics, though not specifically relating to biotechnological/biological products, should be monitored and reported for the drug product in its final container: • Visual appearance of the product (colour and opacity for solutions/suspensions; colour, texture and dissolution time for powders), visible particulates in solutions or after the reconstitution of powders or lyophilised cakes, pH, and moisture level of powders and lyophilised products. • Sterility testing or alternatives (e.g., container/closure integrity testing) should be performed at a minimum initially and at the end of the proposed shelf-life. • Additives (e.g., stabilisers, preservatives) or excipients may degrade during the dating period of the drug product. If there is any indication during preliminary stability studies that reaction or degradation of such materials adversely affect the quality of the drug product, these items may need to be monitored during the stability program. • The container/closure has the potential to adversely affect the product and should be carefully evaluated.
  • 22.
    3). STORAGE CONDITIONS a)Temperature •Since most finished biotechnological/biological products need precisely defined storage temperatures, the storage conditions for the real-time/real-temperature stability studies may be confined to the proposed storage temperature. •
  • 23.
    3). STORAGE CONDITIONS b)Humidity • Biotechnological/biological products are generally distributed in containers protecting them against humidity. • Therefore, where it can be demonstrated that the proposed containers (and conditions of storage) afford sufficient protection against high and low humidity, stability tests at different relative humidities can usually be omitted. • Where humidity-protecting containers are not used, appropriate stability data should be provided.
  • 24.
    3). STORAGE CONDITIONS c)Accelerated and Stress Conditions • As previously noted, the expiration dating should be based on real-time/real- temperature data. • However, it is strongly suggested that studies be conducted on the drug substance and drug product under accelerated and stress conditions. • Studies under accelerated conditions may provide useful support data for establishing the expiration date, provide product stability information for future product development (e.g., preliminary assessment of proposed manufacturing changes such as change in formulation, scale-up), assist in validation of analytical methods for the stability program, or generate information which may help elucidate the degradation profile of the drug substance or drug product.
  • 25.
    3). STORAGE CONDITIONS c)Accelerated and Stress Conditions cont’d • Studies under stress conditions may be useful in determining whether accidental exposures to conditions other than those proposed (e.g., during transportation) are deleterious to the product and also for evaluating which specific test parameters may be the best indicators of product stability. • Studies of the exposure of the drug substance or drug product to extreme conditions may help to reveal patterns of degradation; if so, such changes should be monitored under proposed storage conditions. • While the tripartite guideline on stability describes the conditions of the accelerated and stress study, the applicant should note that those conditions may not be appropriate for biotechnological/biological products. • Conditions should be carefully selected on a case-by-case basis. • d) Light • Applicants should consult the appropriate regulatory authorities on a case-by-case basis to determine guidance for testing.
  • 26.
    3). STORAGE CONDITIONS •e) Container/Closure • Changes in the quality of the product may occur due to the interactions between the formulated biological product and container/closure. Where the lack of interactions cannot be excluded in liquid products (other than sealed ampoules), stability studies should include samples maintained in the inverted or horizontal position (i.e., in contact with the closure), as well as in the upright position, to determine the effects of the closure on product quality. Data should be supplied for all different container/closure combinations that will be marketed. • In addition to the standard data necessary for a conventional single-use vial, the applicant should demonstrate that the closure used with a multiple-dose vial is capable of withstandingrepeated insertions and withdrawals so that the product retains its full potency, purity, and quality for the maximum periodspecified in the instructions-for-use on containers, packages, and/or package inserts. Such labelling should be in accordance with relevant national/regional requirements.
  • 27.
    3). STORAGE CONDITIONS f)Stability after Reconstitution of Freeze-Dried Product • The stability of freeze-dried products after their reconstitution should be demonstrated for the conditions and the maximum storage period specified on containers, packages, and/or package inserts. Such labelling should be in accordance with relevant national/regional requirements.
  • 28.
    4). TESTING FREQUENCY •The shelf-lives of biotechnological/biological products may vary from days to several years. Thus, it is difficult to draft uniform guidelines regarding the stability study duration and testing frequency that would be applicable to all types of biotechnological/biological products. • With only a few exceptions, however, the shelf- lives for existing products and potential future products will be within the range of 0.5 to 5 years. Therefore, the guidance is based upon expected shelf-lives in that range. • This takes into account the fact that degradation of biotechnological/biological products may not be governed by the same factors during different intervals of a long storage period. • When shelf-lives of 1 year or less are proposed, the real-time stability studies should be conducted monthly for the first 3 months and at 3 month intervals thereafter.
  • 29.
    4). TESTING FREQUENCYcont’d • While the testing intervals listed above may be appropriate in the pre-approval or pre-licence stage, reduced testing may be appropriate after approval or licensure where data are available that demonstrate adequate stability. • Where data exist that indicate the stability of a product is not compromised, the applicant is encouraged to submit a protocol which supports elimination of specific test intervals (e.g., 9 month testing) for post-approval/post- licensure, long-term studies.
  • 30.
    5). SPECIFICATIONS • Althoughbiotechnological/biological products may be subject to significant losses of activity, physicochemical changes, or degradation during storage, international and national regulations have provided little guidance with respect to distinct release and end of shelf-life specifications. • Recommendations for maximum acceptable losses of activity, limits for physicochemical changes, or degradation during the proposed shelf- life have not been developed for individual types or groups of biotechnological/biological products but are considered on a case-by-case basis. • Each product should retain its specifications within established limits for safety, purity, and potency throughout its proposed shelf-life. • These specifications and limits should be derived from all available information using the appropriate statistical methods. The use of different specifications for release and expiration should be supported by sufficient data to demonstrate that clinical performance is not affected as discussed in the tripartite guideline on stability. •
  • 31.
    6). LABELLING • Formost biotechnological/biological drug substances and drug products, precisely defined storage temperatures are recommended. • Specific recommendations should be stated, particularly for drug substances and drug products that cannot tolerate freezing. • These conditions, and where appropriate, recommendations for protection against light and/or humidity, should appear on containers, packages, and/or package inserts. • Such labelling should be in accordance with relevant national/regional requirements.
  • 32.
    DEFINITIONS - 1 •Conjugated Product • A conjugated product is made up of an active ingredient (for example, peptide, carbohydrate) bound covalently or non- covalently to a carrier (for example, protein, peptide, inorganic mineral) with the objective of improving the efficacy or stability of the product. • Degradation Product • A molecule resulting from a change in the drug substance (bulk material) brought about over time. For the purpose of stability testing of the products described in this guideline, such changes could occur as a result of processing or storage (e.g., by deamidation, oxidation, aggregation, proteolysis). For biotechnological/biological products some degradation products may be active. • Impurity • Any component of the drug substance (bulk material) or drug product (final container product) which is not the chemical entity defined as the drug substance, an excipient, or other additives to the drug product.
  • 33.
    DEFINITIONS - 2 •Intermediate • For biotechnological/biological products, a material produced during a manufacturing process which is not the drug substance or the drug product but whose manufacture is critical to the successful production of the drug substance or the drug product. Generally, an intermediate will be quantifiable and specifications will be established to determine the successful completion of the manufacturing step prior to continuation of the manufacturing process. This includes material which may undergo further molecular modification or be held for an extended period of time prior to further processing. • Manufacturing Scale Production • Manufacture at the scale typically encountered in a facility intended for product production for marketing. • Pilot-Plant Scale • The production of the drug substance or drug product by a procedure fully representative of and simulating that to be applied at manufacturing scale. The methods of cell expansion, harvest, and product purification should be identical except for the scale of production.
  • 34.
    Dr.Raj Kumar Kudari,M.Pharm, PhD. Professor Hindu College of Pharmacy Amravati Road, Guntur-522002 Andhra Pradesh. . Thank You !