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Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products

FinalCenter for Drug Evaluation and Research Center for Biologics Evaluation and Research08/18/1999
Good Manufacturing PracticesProcess ValidationCharacterizationLot Release

Description

This guidance document provides guidance on general principles for the setting and justification, to the extent possible, of a uniform set of international specifications for biotechnological and biological products to support new marketing applications.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

5
Biotechnological Products

Example of a control strategy summary for biological drug substances

Biological Products

Requires analytical comparability per ICH Q5E

Biotechnological/Biological Products

Covered by GFI #99

Drug Substance

RTRT and CTD sections apply to drug substances

Drug Product

RTRT and CTD sections apply to drug products

Stakeholders

1
Manufacturer

Entity responsible for submitting NDINs

Regulatory Context

Regulatory Activities

4
Marketing Applications

Submissions for product approval.; Submission of raw data supporting study endpoints; Additional Data Files for Marketing Applications for MDS Drugs

Conditions of approval

Specifications are approved by regulatory authorities

Marketing Authorization

Risks relating to products that have a marketing authorization

Submission

Submission of PBRERs when reporting intervals differ

Document Types

3
Drug Substance Specification

Section III.A of the guidance.

Marketing Application

Submissions standardized by ICH guidelines

Drug Product Specification

List of tests and acceptance criteria for the drug product; Tests and acceptance criteria considered applicable to all drug products

Attributes

7
Physicochemical Properties

Factor for consideration in analytical assessment.

Isoform Pattern

Physicochemical property determined by isoelectric focusing

Extinction Coefficient

Molar absorptivity determined at specific wavelengths

Purity

specifications for the purity, strength, and composition of dietary supplements

Biological Activity

Term used for materials instead of potency.

Potency

Measurement of potency for biological products

Heterogeneity

Variations in patient preferences even within the same disease state

Technical Details

Substances

10
Proteins

Products composed of well-characterized proteins

Glycoproteins

Carbohydrate content and structure analysis

Excipient

Component used in human and animal drugs

Raw Materials

Components necessary to manufacture a device

Excipients

Differences in excipients may affect product stability

Drug Product

Finished dosage form undergoing stability testing

Drug Substance

Postapproval changes to drug substances; the active pharmaceutical ingredient being modified; Evaluation of physical properties for drug substance; Active ingredient intended to furnish pharmacological activity; The molecule or ion responsible for the physiological or pharmacological action.; The active pharmaceutical ingredient subject to postapproval changes

Polypeptides

Products composed of well-characterized polypeptides

In-house reference material

Well-qualified material used as a calibration point in comparability exercises.

Host cell proteins

Process-related impurity arising from cell substrates

Testing Methods

10
Analytical Procedures

Used to examine samples for physical, chemical or biological changes

Immunoassay

Used for correlations between factor activity and antigen levels

Nuclear Magnetic Resonance

Used for analysis of characteristic structures like uronic acid

Circular Dichroism

Used to examine higher-order structure

Capillary Electrophoresis

Used in series with mass spectrometry

UV/Visible Spectrophotometry

Used to determine extinction coefficient

Isoelectric Focusing

Used for determining isoform pattern

SDS-Polyacrylamide Gel Electrophoresis

Specific electrophoresis method in the Japanese Pharmacopoeia.

Size Exclusion Chromatography

Used to characterize molecular weight distribution

Peptide Mapping

Complementary analytical technique

Processes

8
Affinity Chromatography

Procedures employing monoclonal antibodies for purification

Clearance Studies

Used to demonstrate removal of cell substrate-derived impurities

Lyophilization

Physical modification that does not result in chemical alteration.; A process that does not typically chemically alter an ingredient

Characterization

Determination of the properties of a cell substrate or cell bank.

Stability Testing

Primary process described in the guideline; Core activity described in the guidance; General process for evaluating product quality over time; Formal stability studies to assess adjuvant stability; Evaluation of attributes at all storage conditions; The process of evaluating product quality over time under specified conditions.; Evaluation of product quality over time

Post-translational modification

Biosynthetic process producing glycoforms

Downstream processing

Source of impurities such as processing reagents or column leachables.

Manufacturing Process

Changes to this process may affect the identity and NDI status of an ingredient.; Changes to this process may create an NDI; you should describe the manufacturing process and provide detailed information; includes fermentation as an intrinsic part of identity

Identified Hazards

Hazards

5
Contaminants

identity and level of any impurities and contaminants

Adventitious Viruses

Viruses introduced during production; Contamination risk in production batches

Product-Related Impurities

Molecular variants of the desired product formed during manufacture or storage; Molecular variants of the desired product including degradation products

Process-Related Impurities

Measurement of stereoisomers as impurities

Adventitious Agents

Transmission of adventitious agents is a key issue in human- and animal-derived materials.; Human- and animal-derived materials increase the risk of introducing adventitious agents

Standards & References

External Standards

2
Pharmacopoeia

recognized standard reference for analytical methods

Pharmacopoeial Standards

Basis for inorganic impurity acceptance criteria.

Specifications

4
Acceptance Criteria

limits for solid state form and particle size; Tightening acceptance criteria; Numerical limits or ranges for tests

Shelf-life Limits

Limits applied throughout the storage period of the product

Release Limits

Limits applied at the time of batch release

Action Limits

Limits for total microbial counts and endotoxins

ICH References (6)

ICH Q6B

Specifications for biotechnological/biological products; Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products

ICH Q5A

Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin

ICH Q5D

Recommendations for cell bank stability

ICH Q2A

Text on Validation of Analytical Procedures

ICH Q2B

Validation of Analytical Procedures: Methodology

ICH Q5C

Quality of Biotechnological Products: Stability Testing

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products | Guideline Explorer | BioRegHub