N:
Spectroscopy technique using chemometrics statistics for identification and qualification of Biopharmaceuticals and verification of physicochemical properties.
EMA Guideline on the use of Near Infrared Spectroscopy (NIRS) by the pharmaceutical industry and the data requirements for new submissions and variations, 20. January 2012, http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/02/WC500122769.pdf
A deficiency in a characteristic, product specification, process parameter, record, or procedure that renders the quality of a product unacceptable, indeterminate, or noncompliant with specified requirements.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry: Quality Systems Approach to Phramaceutical CGMP Regulations, September 2006, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070337.pdf
See noncritical process parameters.
All input process parameters that fall outside the definition for critical process parameters (CPPs) are noncritical. These are divided into key and nonkey process parameters.
C. Julien and W. Whitford in BioProcess International "Hitchhikers"s Guide" to Bioprocess Design, March 2008, http://www.bioprocessintl.com/multimedia/archive/00078/BPI_A_080603SUPAR07__78643a.pdf
See nonkey process parameters.
C. Julien and W. Whitford in BioProcess International "Hitchhikers"s Guide" to Bioprocess Design, March 2008, http://www.bioprocessintl.com/multimedia/archive/00078/BPI_A_080603SUPAR07__78643a.pdf
An input process parameter that has been demonstrated to be easily controlled or that has a wide acceptable limit. Nonkey process parameters may have an impact on drug substance quality or process performance if acceptable limits are exceeded.
C. Julien and W. Whitford in BioProcess International "Hitchhikers"s Guide" to Bioprocess Design, March 2008, http://www.bioprocessintl.com/multimedia/archive/00078/BPI_A_080603SUPAR07__78643a.pdf
A defined range, within the proven acceptable range, specified in the manufacturing instructions as the target and range at which a process parameter is controlled, while producing unit operation material or final product meeting release criteria CQAs.
O:
Measurement where the sample is removed, isolated from, and analyzed in an area remote from the manufacturing process.
ASTM International, U.S., West Conshohocken, PA E2363-06a Standard Terminology Relating to Process Analytical Technology in the pharmaceutical Industry., 1. July 2006, http://www.astm.org/Standards/E2363.htm
Measurement where the sample is diverted from the manufacturing process, and may be returned to the process stream.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, September 2004, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070305.pdf
See process parameter
American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012, http://asq.org/glossary/
Activities conducted by a contract acceptor under a written agreement with a contract giver.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceutical Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
P:
Any material intended to protect an intermediate or API during storage and transport.
A measurable or quantifiable characteristic of a system or process.
ASTM International, U.S., West Conshohocken, PA E2363-06a Standard Terminology Relating to Process Analytical Technology in the pharmaceutical Industry., 1. July 2006, http://www.astm.org/Standards/E2363.htm
A system of release that gives assurance that the product is of the intended quality based on the information collected during the manufacturing process.
ASTM International, U.S., West Conshohocken, PA E2363-06a Standard Terminology Relating to Process Analytical Technology in the pharmaceutical Industry., 1. July 2006, http://www.astm.org/Standards/E2363.htm
Partial Least Squares Regression is a bilinear modeling method where information in the original X-data is projected onto a small number of underlying (“latent”) variables called PLS components. The Y-data are actively used in estimating the “latent” variables to ensure that the first components are those that are most relevant for predicting the Y-variables. Interpretation of the relationship between X-data and Y-data is then simplified as this relationship in concentrated on the smallest possible number of components.
CAMO Software, Norway, Oslo Glossary for Multivariate Statistical Methods, viewed: March 2012, http://www.camo.com/downloads/Glossary_of_terms.pdf
See performance parameter.
Measureable values used to quantify quality objectives to reflect the performance of an organization, process, or system, also known as "performance metrics" in some regions.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceuticalo Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
An output variable or outcome that cannot be directly controlled but is an indicator that the process performed as expected.
C. Julien and W. Whitford in BioProcess International "Hitchhikers"s Guide" to Bioprocess Design, March 2008, http://www.bioprocessintl.com/multimedia/archive/00078/BPI_A_080603SUPAR07__78643a.pdf
Mangagement system to direct and control a pharmaceutical company with regard to quality.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceuticalo Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
See Quality Target Product Profile, ISPEs definition of FDAs Quality Target Product Profile.
T. Garcia et al. in the Journal of Pharmaceutical Innovation vol. 3 PQLI Key Topics - Criticality, Design Space, and Control Strategy, May 2008, http://www.springerlink.com/content/08664220x00622v6/fulltext.pdf
The production of a recombinant protein by a procedure fully representative of and simulating that to be applied on a full commercial manufacturing scale. The methods of cell expansion, harvest, and product purification should be identical except for the scale production.
US Food and Drug Administration, U.S., Rockville, MD Guideline for Industry, Q5B, Quality of Biotechnological Products: Analysis of the Expression Construct in Cells Used for Production of r_DNA Derived Proetein Products, Februar 1996, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073459.pdf
Potency is the measure of the biological activity using a suitably quantitative biological assay, based on the attribute of the product which is linked to the relevant biological properties.
US Food and Drug Administration, U.S., Rockville, MD Guideline for Industry, Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, August 1999, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073488.pdf
The POS is the region between the maximum and minimum value of interest to the sponsor for each process parameter. The POS can also be considered as the extent of the sponsor’s quality system with respect to these parameters.
R. A. Lionberger et al. Iin AAPS Journal, Vol. 10 Quality by Design: Concepts for ANDAs, June 2008, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751376/pdf/12248_2008_Article_9026.pdf
The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision and reproducibility. It is usually expressed as the variance, standard deviation or coefficient of variation of a series of measurements.
ICH, Switzerland, Geneva ICH Harmonised Tripartite Guideline, Validation of Analytical Procedures: Text and Methodology Q2(R1), November 2005, http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf
Preliminary Hazard Analysis is an inductive method of analysis whose objective is to identify the hazards, hazardous situations and events that can cause harm for a given activity, facility or system.
S2S - A Gateway for Plant and Process Safety, viewed: March 2012, http://www.safety-s2s.eu/modules.php?name=s2s_wp4&idpart=4&idp=50
Action to eliminate the cause of a potential nonconformity or other undesirable potential situation. NOTE: Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceutical Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
PCA is a bilinear modeling method which gives an interpretable overview of the main information in a multidimensional data table. The information carried by the original variables is projected onto a smaller number of underlying (“latent”) variables called principal components. The first principal component covers as much of the variation in the data as possible. The second principal component is orthogonal to the first and covers as much of the remaining variation as possible, and so on. By plotting the principal components, one can view interrelationships between different variables, and detect and interpret sample patterns, groupings, similarities or differences.
The accumulated laboratory, nonclinical, and clinical, experience for a specific product quality attribute. This knowledge may also include relevant data from other similar molecules or from the scientific literature.
CMC-Biotech Working Group A-Mab: a Case Study in Bioprocess Development, Version 2.1, 30. October 2009, http://www.ispe.org/pqli/a-mab-case-study-version-2.1
A documented description of the operations to be performed, the precautions to be taken, and measures to be applied directly or indirectly related to the manufacture of an intermediate or API.
Materials, excluding solvents, used as an aid in the API that do not themselves participate in a chemical or biological reaction (e.g., filter aid, activated manufacture of an intermediate or carbon).
System for designing, analyzing, and controlling manufacturing through timely measurements of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, September 2004, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070305.pdf
A statistical measure of the inherent process variability of a given characteristic. The most widely accepted formula for process capability is six sigma.
American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012, http://asq.org/glossary/
The value of the tolerance specified for the characteristic divided by the process capability. The several types of process capability indexes include the widely used cPk and cP.
American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012, http://asq.org/glossary/
See characterization study
An attribute of the manufacturing system.
ASTM International, U.S., West Conshohocken, PA E2363-06a Standard Terminology Relating to Process Analytical Technology in the pharmaceutical Industry., 1. July 2006, http://www.astm.org/Standards/E2363.htm
Ability of a process to tolerate variability of materials and changes of the process and equipment without negative impact on quality.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, Q8(R2) Pharmaceutical Development, November 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073507.pdf
See unit operation
The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, Process Validation: General Principles and Practices, January 2011, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070336.pdf
Molecular variants of the desired product arising from processing or during storage which do not have properties comparable to those of the desired product with respect to activity, efficiacy, and safety.
US Food and Drug Administration, U.S., Rockville, MD Guideline for Industry, Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, August 1999, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073488.pdf
The intended results of activities or processes; products can be tangible or intangible.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry: Quality Systems Approach to Phramaceutical CGMP Regulations, September 2006, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070337.pdf
PQLI is intended by the ISPE to work with industry and regulatory agencies worldwide to facilitate a common understanding of quality by design, and introduce pragmatic and practical means for the implementation of ICH guidance"s, based on sound scientific, engineering and business principles.
T. Garcia et al. in the Journal of Pharmaceutical Innovation vol. 3 PQLI Key Topics - Criticality, Design Space, and Control Strategy, May 2008, http://www.springerlink.com/content/08664220x00622v6/fulltext.pdf
The Product Quality Research Institute (PQRI) is a collaborative process involving FDA’s Center for Drug Evaluation and Research (CDER), Industry, and Academia. The mission of PQRI is to conduct research to generate specific scientific information that should be submitted in a regulatory filing to CDER. PQRI has been in development since January of 1996, guided by a Steering Committee composed of representatives from its sponsoring organizations.
Achievement of a product with the quality attributes appropriate to meet the needs of patients, health care professionals, and regulatory authorities (including compliance with marketing authorization) and internal customers requirements.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceutical Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
Molecular variants of the desired product arising from processing or during storage which do not have properties comparable to those of the desired product with respect to activity, efficiacy, and safety.
US Food and Drug Administration, U.S., Rockville, MD Guideline for Industry, Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, August 1999, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073488.pdf
Molecular variants of the desired product which are active and have no deleterious effect on the safety and efficacy of the drug product. These variants possess properties comparable to the desired product and are not considered impurities.
US Food and Drug Administration, U.S., Rockville, MD Guideline for Industry, Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, August 1999, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073488.pdf
All operations involved in the preparation of an API from receipt of materials through processing and packaging of the API.
A characterized range of a process parameter for which operation within this range, while keeping other parameters constant, will result in producing a material meeting relevant quality criteria.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, Q8(R2) Pharmaceutical Development, November 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073507.pdf
Q:
Action of proving and documenting that equipment or ancillary systems are properly installed, work correctly, and actually lead to the expected results. Qualification is part of validation, but the individual qualification steps alone do not constitute process validation.
See conformance lots
The degree to which a set of inherent properties of a product, system or process fulfills requierements.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, Q9 Quality Risk Management, June 2006, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073511.pdf
The total sum of the organized arrangements made with the object of ensuring that all APIs are of the quality required for their intended use and that quality systems are maintained.
A molecular or product characteristic that is selected for its ability to help indicate the quality of the product. Collectively, those attributes define identity, purity, potency, and stability of the product, as well as safety with respect to adventitious agents. Specifications measure a selected subset of the quality attributes.
ICH, Switzerland, Geneva ICH Harmonised Tripartite Guideline, Comparability of Biotechnological/Biological Products Sybject to Changes in their Manufacturing Process Q5E, November 2004, http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5E/Step4/Q5E_Guideline.pdf
A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and risk mangement.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, Q8(R2) Pharmaceutical Development, November 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073507.pdf
Checking or testing, that specifications are met.
Document specifying the quality management system of an organization.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceutical Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
A means to translate the quality policy and strategies into measurable activities.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceutical Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
Part of quality management focused on setting quality objectives and specifying necessary operational processes and related resources to fulfill the quality objectives.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceutical Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
Overall intentions and direction of an organization related to quality as formally expressed by senior management.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry , Q10 Pharmaceutical Quality System, April 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073517.pdf
A systematic process for the assessment, control, communication, and review of risks to the quality of the drug product across the product lifecycle.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, Q9 Quality Risk Management, June 2006, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073511.pdf
The sum of all aspects of a system that implements quality policy and ensures that quality objectives are met.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, Q9 Quality Risk Management, June 2006, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073511.pdf
A prospective summary of the quality characteristics of a drug product that ideally will be achived to ensure the desired quality, taking into account safety and efficacy of the drug product.
US Food and Drug Administration, U.S., Rockville, MD Guidance for Industry, Q8(R2) Pharmaceutical Development, November 2009, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073507.pdf
An organizational unit independent of production that fulfills both quality assurance and quality control responsibilities. This can be in the form of separate QA and QC units or a single individual or group, depending upon the size and structure of the organization.
The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. The quantitation limit is a parameter of quantitative assays for low levels of compounds in sample matrices, and is used particularly for the determination of impurities and/or degradation products.
ICH, Switzerland, Geneva ICH Harmonised Tripartite Guideline, Validation of Analytical Procedures: Text and Methodology Q2(R1), November 2005, http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf
The status of materials isolated physically or by other effective means pending a decision on their subsequent approval or rejection.
