s

A:

An ANDA contains data which when submitted to FDA"s Center for Drug Evaluation and Research, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product to provide a safe, effective, low cost alternative to the American puplic.

US Food and Drug Administration, U.S., Rockville, MD, viewed: March 2012, http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/abbreviatednewdrugapplicationandagenerics/default.htm

Limits, ranges, or process signatures for making a decision to accept or reject the result of a process, in-process variable, a product or any other convenient subgroups of manufactured units.

The accuracy of an analytical procedure expresses the closeness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found.

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

A substance intended to be used in the manufacture of Biopharmaceuticals becomes a pharmacological active ingredient of the drug product.

A statistical procedure for troubleshooting industrial processes and analyzing the results of experimental designs with factors at fixed levels. It provides a graphical display of data. Ellis R. Ott developed the procedure in 1967 because he observed that nonstatisticians had difficulty understanding analysis of variance. Analysis of means is easier for quality practitioners to use because it is an extension of the control chart. In 1973, Edward G. Schilling further extended the concept, enabling analysis of means to be used with non-normal distributions and attributes data in which the normal approximation to the binomial distribution does not apply. This is referred to as analysis of means for treatment effects.

American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012, http://asq.org/glossary/

A basic statistical technique for determining the proportion of influence a factor or set of factors has on total variation. It subdivides the total variation of a data set into meaningful component parts associated with specific sources of variation to test a hypothesis on the parameters of the model or to estimate variance components. There are three models: fixed, random and mixed.

American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012,
http://asq.org/glossary/

The analytical procedure refers to the way of performing the analysis. It should describe in detail the steps necessary to perform each analytical test. This may include but is not limited to: the sample, the reference standard and the reagents preparations, use of the apparatus, generation of the calibration curve, use of the formulae for the calculation, etc..

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

An instrument designed to measure and report a property of the process, material, or environmental condition.

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 removed, isolated from, and analyzed in close proximity 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

Characteristics or inherent property or feature.

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

B:

A specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture.

A noncontinous operation in which discrete quantities of material are transformed using individual or sequential steps.

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

Level and type of microorganisms that can be present in raw materials, API starting material, intermediates or APIs.

The specific ability or capacity of the product to achieve a defined biological effect. Potency is the quantitative measure of the biological activity.

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

See drug substance

C:

Demonstration that an instrument results within specified limits by comparison with results refer to a standard over a range of measurements.

Ability of a process to realize a product that will fulfill the requirements of that product. The concept of process capability can also be defined in statistical terms.

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 tool for analyzing process dispersion. It is also referred to as the “Ishikawa diagram”, because Kaoru Ishikawa developed it, and the “fishbone diagram”, because the complete diagram resembles a fish skeleton. The diagram illustrates the main causes and subcauses leading to an effect (symptom).

American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012, 
http://asq.org/glossary/

A systematic approach to proposing, evaluating, approving, implementing, and reviewing changes.

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

The factors, elements or measures that define and differentiate a process, function, product, service or other entity.

American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012, http://asq.org/glossary/

A late-stage study that evaluates a process to increase process knowledge and examines proposed operational ranges and their individual and/or combined impact on target protein quality.

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

Charge-coupled devices are sensors used in digital cameras and video cameras to record still and moving images. The CCD captures light and converts it to digital data that is recorded by the camera. For this reason, a CCD is often considered the digital version of film.

Tech Terms Computer Dictionary, viewed: March 2012, http://www.techterms.com/definition/ccd

Mathematical multivariate methods to analyse or compare data.

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

The CFR is the codifiction of the general and permanent rules published in the Federal Registry by the departments and agencies of the U.S. Government. It is divided into 50 titles where title 21 - chapter 1 is issued by the FDA.

US Food and Drug Administration, U.S., Rockville, MD, viewed: March 2012, http://www.fda.gov/medicaldevices/deviceregulationandguidance/databases/ucm135680.htm

Random error or bias in a performance measure due to endemic deviation from the expected value in the process of its measurement. This type of variability is inherent in a system as it exists, and it is both predictable (probabilistically) and definable. Causes of variation that are inherent in a process over time. They affect every outcome of the process and everyone working in the process.

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 conclusion that products have highly similar quality attributes before and after manufacturing process changes and that no adverse impact on safety or efficacy, including immunogenicity, of a drug product occurred. This conclusion can be based on an analysis of product quality attributes. In some cases, nonclinical data might contribute to the conclusion.

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 predetermined number of production lots, typically three, that represent the licensed process and evaluated to demonstrate consistency.

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 conformance lots

Any adventitiously introduced materials in the drug substance not intended to be part of the manufacturing process.

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 undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API during production, sampling, packing, or repackaging, storage or transport.

Recurring activity to increase the ability to fulfill 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

An ongoing effort to improve products, services, and processes. These efforts can seek incremental improvement over time or breakthrough improvement all at once. Optimizing the characteristics and parameters to a target value and reducing variation around that value.

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 alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated.

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

A manufacturer who performs some aspect of manufacturing on behalf of the original manufacturer.

Region within the design space that defines the operational limits (for process parameters and input variables) used in routine manufacturing. Control space can be a multidimensional space or a combination of univariate process ranges.

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 planned set of controls, derived from current product and process understanding, that assures process performance and product quality. The controls can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control.

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

Action to eliminate the cause of a detected nonconformity or other undesirable situation. NOTE: Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent occurrence.

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

The CAPA method is a systematic approach to correct, prevent, and eliminate the cause of potential nonconforming product and other quality problems. Corrective refers to a reaction or an activity meant to correct a nonconformance that has already occured. Preventive refers to an action or activity meant to prevent recurrence of a nonconformance.

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

The ratio of tolerance to six sigma, or the upper specification limit (USL) minus the lower specification limit (LSL) divided by six sigma. It is sometimes referred to as the engineering tolerance divided by the natural tolerance and is only a measure of dispersion.

American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012, http://asq.org/glossary/

Equals the lesser of the USL minus the mean divided by three sigma (or the mean) minus the LSL divided by three sigma. The greater the cPk value, the better.

American Society for Quality - ASQ, U.S., Milwaukee, WI, viewed: March 2012, http://asq.org/glossary/

Describes a process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined criteria to ensure that the API meets its specification.

A physical, chemical, biological or microbiological property or characteristic of a material that should be within an appropiate limit, range, or distribution to ensure the desired product quality.

A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired 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

A physical, chemical, biological characteristic that should be within an appropiate limit, range, or distribution to ensure the desired product 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

D:

The process of combining data from different sources and providing users with a unified view of those data.

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

Person(s) with the competence and authority to make appropiate and timely quality risk management decisions.

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

Molecular variants resulting from changes brought about over time and/or by the action of, e.g., light, temperature, pH, water, or by reaction with an excipient and/or the immediate container/closure system. Degradation products may be either product-related substances or product-related 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

A structured, organized method for determining the relationship between factors affecting a process and the output of that process.

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

The multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered to be a change and would normally initiate a regulatory postapproval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval.

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

(1) The protein that has the expected structure, or (2) the protein that is expected from the DNA sequence and anticipated post-translational modification (including glycoforms), and from the intended downstream modification to produce an active biological molecule.

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 sources of variation are defined and controlled, and end product variation is minimal.

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

The ability to discover or determine the existence, presence, or fact of a hazard.

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 detection limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value.

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

Departure from an approved instruction or established standard.

Data or result outside of an expected range; an unfulfilled requirement; may be called nonconformity, defect, deviation, out-of-specification, out-of-limit, or out-of-trend.

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

A pharmaceutical product type that contains a drug substance, generally in association with excipients.

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 Material that is subsequently formulated with excipients to produce the drug product. It can be composed of the desired product, product-related substances, and product- and process-related impurities. It may also contain excipients including other components, such as buffers.

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

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