Acceptance Criteria:  The acceptable limits of a GMP Critical Parameter to ensure product SISPQ (Strength,

Identity, Safety, Purity, or Quality). The criteria a product must meet to successfully complete a test phase or to achieve delivery requirements. This is usually associated with a performance qualification. It may require an exact result (such as the ability of a bar code system to identify correct or incorrect codes) or it may state an acceptable range (such as an incubator demonstrating the ability to maintain a temperature set point plus or minus a given tolerance).

 

Airlock:A room or space designed to act as a means of segregating areas of different air classification or quality. It may contain a method to remove particulate contamination from clean room garments as personnel pass through, and usually includes HEPA filtered air supply and interlocking doors. Airlocks pressure will "float" between those of the spaces being protected. With all doors closed, the airlock pressure will be somewhere between that of the highest adjoining room and that of the lowest adjoining room as air flows through it from room to room. "Ventilated airlocks" are in neutral ducted air balance (supply CFM = return CFM).

 

Alert Level:  An established level outside of the normal operating range that requires an adjustment or evaluation but does not necessarily indicate a process or product failure.

 

API (Active Pharmaceutical Ingredient):  Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body.

 

API Starting Material: A raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API Starting Material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house. API Starting Materials are normally of defined chemical properties and structure.

 

Batch (or Lot): A specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits. In the case of continuous production, a batch may correspond to a defined fraction of the production. The batch size can be defined either by a fixed quantity or by the amount produced in a fixed time interval.

 

Batch Number (or Lot Number): A unique combination of numbers, letters, and/or symbols that identifies a batch (or lot) and from which the production and distribution history can be determined.

 

Bioburden: The level and type (e.g. objectionable or not) of micro-organisms that can be present in raw materials, API starting materials, intermediates or APIs. Bioburden should not be considered contamination unless the levels have been exceeded or defined objectionable organisms have been detected.

 

Calibration:  The documentation that a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurement.

Challenge Condition:  An extreme in the anticipated process parameters intentionally generated to demonstrate the ability of the process to meet the predetermined specifications throughout the operating range.

 

Change Control:  A formal system by which qualified individuals of appropriate disciplines review and document proposed changes to assure that a validated state is maintained.

 

CIP (Clean In Place):Internally cleaning a piece of equipment without relocation or disassembly. The

equipment is cleaned but not necessarily sterilized. The cleaning is normally done by acid, caustic, or a combination of both, with WFI rinse. The design of a CIP system should considered the operating volume design for the water consumption, chemical and biowaste effluent, and energy required to clean a given circuit or piece of equipment.

 

cGMP ( Current GMP) :Current accepted standards of design, operation, practice, and sanitization. The FDA

is empowered to inspect drug-manufacturing plants in which drugs are processed, manufactured, packaged, and stored for compliance with these standards. ( see also GMP)

 

Commissioning: “A well planned, documented, and managed engineering approach to the start-up and turnover of facilities, systems, and equipment to the End-User that results in a safe and functional environment that meets established design requirements and stakeholder expectations.”  The documented process, verifying that equipment and systems are installed and wired according to specifications, placing the equipment and systems into active service and verifying its proper operation.  It is documentation process that verifies that equipment and systems are installed and operate according to specifications, and is therefore ready for qualification/validation.

 

Computer System: A group of hardware components and associated software, designed and assembled to perform a specific function or group of functions.

 

Computerized System: A process or operation integrated with a computer system.

 

Contamination: 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, packaging or repackaging, storage or transport.

 

Contract Manufacturer: A manufacturer performing some aspect of manufacturing on behalf of the original manufacturer.

 

Controlled Area:An area constructed and operated in such a manner that some attempt is made to

control the introduction of potential contamination, and the consequences of accidental release of living organisms. The level of control exercised should reflect the nature of the organism employed in the process. At a minimum, the area should be maintained at a pressure positive to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants.

 

Critical: 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.

 

Critical Instruments:  Equipment used to measure, monitor, and record a parameter that may have a direct impact on product quality.

 

Critical Process Parameters (CPPs):  A measured variable that has a known effect upon a product quality attribute.  A process parameter that must be controlled within a specified range to assure product quality

 

Cross-Contamination: Contamination of a material or product with another material or product.

 

Design Qualification:  Documented verification that the proposed design of equipment/systems is suitable for the intended purpose.

 

Deviation: A failure to meet acceptance criteria. Departure from an approved instruction or established standard.

 

Drug (Medicinal) Product:

The dosage form in the final immediate packaging intended for marketing.

 

Drug Substance:

See Active Pharmaceutical Ingredient

 

Equipment Train: The summation of all major pieces of equipment within a specific process.

 

Equipment Qualification: Documented evidence by which a piece of equipment is certified to perform as per manufacturer specifications under controlled predetermined conditions.

 

Exception: A departure for the Process Model or Study Plan as approved in the Protocol, Amendment or Addendum

 

Good Engineering Practices (GEP):  “Established engineering methods and standards that are applied throughout the project lifecycle”.  A combination of standards, specifications, codes, regulatory and industrial guidelines as well as accepted engineering and design methods intended to design, construct, operate, and maintain pharmaceutical facilities taking into account not only regulatory compliance but also safety, environmental protection and operability.

 

Good Manufacturing Practices (GMP):GMP refers to the Good Manufacturing Practice Regulations promulgated by the US Food and Drug Administration under the authority of the Federal Food, Drug, and Cosmetic Act. These regulations, which have the force of law, require that manufacturers, processors, and packagers of drugs, medical devices, some food, and blood take proactive steps to ensure that their products are safe, pure, and effective. GMP regulations require a quality approach to manufacturing, enabling companies to minimize or eliminate instances of contamination, mix-ups, and errors.  This in turn, protects the consumer from purchasing a product which is not effective or even dangerous. Failure of firms to comply with GMP regulations can result in very serious consequences including recall, seizure, fines, and jail time.

 

GMP regulations address issues including recordkeeping, personnel qualifications, sanitation, cleanliness, equipment verification, process validation, and complaint handling. Most GMP requirements are very general and open-ended, allowing each manufacturer to decide individually how to best implement the necessary controls. This provides much flexibility, but also requires that the manufacturer interpret the requirements in a manner which makes sense for each individual business.

 

GMP is also sometimes referred to as "cGMP". The "c" stands for "current," reminding manufacturers that they must employ technologies and systems which are up-to-date in order to comply with the regulation. Systems and equipment used to prevent contamination, mix-ups, and errors, which may have been "top-of-the-line" 20 years ago, may be less than adequate by today's standards

 

GMP Critical Parameter:A parameter that has a direct effect on product quality.

 

GMP Facility:A production facility or clinical trial materials pilot plant for the manufacture of pharmaceutical products. It includes the manufacturing space, the storage warehouse for raw and finished product, and support lab areas. A GMP facility operates under the guidelines established by the CFR (Code of Federal Regulations) Title 21, Parts 225 (Current Good Manufacturing for Medicated Feeds - Subpart B), and Part 226 (Current Good Manufacturing Practice for Type A Medicated Articles - Subpart B).

 

Installation Qualification (IQ): Documented evidence by which equipment/systems are installed as per design specifications and manufacturer recommendations.

 

ISO 14644:A worldwide federation of national standards bodies (ISO member bodies). International Cleanroom Standard ISO 14644 consists of the following parts:

Part 1: Classification of Air Cleanliness. ISO 14644-1:1999

Part 2: Cleanroom Testing for Compliance. ISO 14644-2:2000

Part 3: Biocontamination Control of Surfaces 4.

Part 4: Cleanroom Design & Construction 5.

Part 5: Cleanroom Operations 6.

Part 6: Terms, Definitions & Units 7.

Part 7: Minienvironments & Isolators

 

Key Component:  A component that may impact the critical functionality of the equipment.

 

Must: Auxiliary verb indicating an obligation to comply with the main verb that follows.

 

Non-Critical Parameter: Operating parameter that has been shown not to have an impact on the product and can be adjusted within an acceptable range while product is being manufactured.

 

Non-Process Related Error: One that is independent of the manufacturing process and where the cause is known.

 

Operational Qualification (OQ): Documented evidence by which equipment/systems are functioning and operating at the intended operational parameters at which it will be used in production and/or manufacturer recommendations.

 

Operating Range: A set of conditions encompassing upper and lower values actually permitted in the operation.

 

Packaging Material:Any material intended to protect an intermediate or API during storage and transport.

 

Parenteral Drug (LVP, SVP):A parenteral drug is defined as one intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal, so that active substances they contain are administered, using gravity or force, directly into a blood vessel, organ, tissue, or lesion. They are infused when administered intravenously (IV),

or injected when administered intramuscularly (IM), or subcutaneously into the human body. A large volume parenteral (LVP) is a unit dose container of greater than 100ml that is terminally sterilized by heat. Small volume parenteral (SVP) is a "catch-all" for all non-LVP parenterals products except biologicals.

 

Procedure :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.

Procedures usually are referred to as Standard Operating Procedures (SOP).

 

Process Assessment:  Assessment of a newly introduced process subsequent to technology transfer and prior to process validation for the purpose of demonstrating successful operation in the production environment with all normal production factors in place.

 

Process Flow Diagram (PFD):  A diagram that shows key process steps and equipment.

 

Process system: The combination of equipment, support systems and procedures used to execute a process.

 

Protocol:  A written plan stating how the qualification/validation will be conducted.  The protocol is formally reviewed and approved prior to execution.  Upon successful execution, the protocol is intended to produce documented evidence that the process does what it purports to do.

 

Prospective Validation:  Study where the adequacy of the process is determined by specific testing performed on critical steps in that manufacturing process prior to commercial manufacture of the product.  Validation carried out before routine production of products intended for sale.

 

Purified Water, U.S.P.:Water rendered suitable for pharmaceutical purposes by processes such as distillation, ion-exchange treatment (deionization or demineralization), or reverse osmosis. It meets rigid specifications for chemical purity, the requirements of the Federal Environmental Protection Agency (EPA) with respect to drinking water, and it contains no added substances. Cannot be used as raw material for parenterals. Common uses

are: a rinse for equipment, vials, and ampoules, and as make up for cosmetics, bulk chemicals, and oral products.

 

QA (Quality Assurance):The sum total of the organized arrangements made to ensure that all APIs (Active Pharmaceutical Ingredients) are of the quality required for their intended use and that quality systems are maintained.

 

QC (Quality Control):Checking or testing, that specifications are met, or the regulatory process through which the industry measures actual quality performance, compares it with standards, and acts on the difference.

 

Qualification:Action of providing 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.

 

Retrospective Validation: Validation of a process for a product which has been marketed based upon accumulated manufacturing, testing and control batch data.

 

Re-Validation: A repeat of the process validation to provide an assurance that changes in the process/

equipment introduced in accordance with change control procedures do not ad-ersely affect process characteristics and product quality.

 

Risk analysis: Method to assess and characterise the critical parameters in the functionality of an equipment or process.

 

Should: Auxiliary verb indicating a lesser obligation to comply with the main verb that follows.  Used when there is recognition that although bound by duty, there may be circumstances that warrant not proceeding as stated.

 

SIP (Steam In Place):The introduction of steam to sanitize or sterilize a piece of equipment without

relocating the equipment.

 

Specification:A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described.  It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use.  “Conformance to specification” means that the material, when tested according to the listed analytical procedures, will meet the listed acceptance criteria.

 

Standard Operating Procedure ( SOP ) : See Procedures.

 

System: Interconnected or related pieces of equipment that function collectively as one unit (e.g., kettle, agitator, and associated piping).

 

System Life Cycle: The methodology that defines the phases through which a system passes from its conception to the termination of its use; e.g., the phases and activities.

 

Technical Specification (TSP): The technical specifications defines all the engineering requirements needed to integrate the information contained in the P&ID’s, in order to clearly define the functional, mechanicals, and operational issues of the systems’ components.

 

Unit Operation or Unit Process: A single, discrete step that is typically a subdivision of the entire process and evaluated on its own merit.

 

User Requirement Specifications (URS): The URS document defines “what” are the business and system requirements. General User Requirements are prepared in advance of the purchase of the equipment, and they define the requirements as needed by all of the user departments, which typically include Safety, Engineering, Production, Quality Control, and Validation.  They are a description of what the equipment or system is supposed to do, and as such is normally written by the user. 

 

Validation:A documented project that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria. Establishing documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.

 

Validation Protocol :A written plan stating how validation will be conducted and defining acceptance criteria.  For example, the protocol for a manufacturing process identifies processing equipment, critical process parameters/operating ranges, product characteristics, sampling, test data to be collected, number of validation runs, and acceptable test results.

 

Variance: A failure to meetan acceptance criteria) or an Exception (departures form the Process Model or Study Plan included in the approved Protocol, Amendment or Addendum).

 

WFI (Water For injection), U.S.P.: WFI is water purified by distillation or by reverse osmosis, it contains no added substance. WFI meets the purity requirements under Purified Water. Although not intended to be sterile, it meets a test for a limit of bacterial endotoxin. It must be produced, stored, and distributed under Sterile Water for Injection.

 

Worst Case: A condition or a set of conditions encompassing upper and lower processing or operating limits and circumstances, that should not necessarily result in product or process failure. The highest or lowest value of a given control parameter actually evaluated in a validation exercise.

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