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Qualification
Kenneth W. Sigvardson,* Joseph A. Manalo, Robert W. Roller, Fatieh Saless, and David Wasserman
what is appropriate.
T
he concept of Acceptable Analyti- Results: How to Conduct Laboratory In-
cal Practices (AAPs) was developed vestigations; Forced Degradation Studies:
by the Analytical Research and De- Issues and Controversies; and Analytical
velopment Steering Committee of Methods Transfer. This article presents the
the Pharmaceutical Research and Manu- first of these presentations. The three re-
facturers of America to share information maining topics will be covered in future
about how the pharmaceutical industry issues of this magazine.
has implemented the CMC and Quality Regulations regarding the qualification
Kenneth W. Sigvardson is Guidances of the International Confer- of laboratory equipment often are vague
a director and Joseph A. ence on Harmonization and worldwide and subject to interpretation. The good
Manalo is a quality scientist
at The DuPont Pharmaceuticals
regulatory authorities. AAPs were designed manufacturing practice requirements state
Company, Experimental to provide a process by which one could that “the calibration of instruments, appa-
Station, PO Box 80353, learn from the experience of experts in ratus, gauges, and recording devices at suit-
Wilmington, DE 19880-0353. pharmaceutical research and development able intervals in accordance with an estab-
Robert W. Roller is an and enhance the understanding of ana- lished written program containing specific
associate senior analytical
chemist at Eli Lilly and
lytical practices that reflect good science directions, schedules, limits for accuracy
Company (Indianapolis, IN). and sound regulatory compliance. The and precision, and provisions for remedial
Fatieh Saless is vice- process of discussing and publishing AAPs action in the event accuracy and/or preci-
president and senior consultant also is intended to identify and address sion limits are not met” (1). The good labo-
at JMS Biopharmaceuticals critical issues in which guidance is lack- ratory practice regulations impose similar
Consulting (Calabasas, CA).
David Wasserman is an
ing, ambiguous, or contradictory. requirements, stating that “equipment used
operations coordinator at Pfizer Initially, the process adopted for the de- for the generation, measurement, or as-
Global Research & velopment of the first four AAPs involved sessment of data shall be adequately tested,
Development (Eastern Point a two-and-a-half-day workshop held 19–21 calibrated, and/or standardized” (2).
Road, MS). September 2000. The four topics discussed
*To whom all correspondence
should be addressed.
were Laboratory Equipment and Instru- Terminology and definitions
ment Qualification; Out-of-Specification In this industry, considerable variation ex-
102 Pharmaceutical Technology OCTOBER 2001 www.phar mtech.com
Equipment qualification definitions
Calibration collects measurement data from the equipment. Packaged system
The set of operations that establish,under specified A device or collection of components that perform A computerized system in which the computer
conditions,the relationship between values a process to produce a result (9). system and the controlled-function equipment are
indicated by a measuring instrument or measuring Equipment qualification designed and constructed as an integrated assembly
system,or values represented by material measure The action of proving that any equipment works (3).
and the corresponding values of the measurand (5). correctly and actually leads to accurate and reliable Performance qualification
Used by regulatory agencies to refer to the process results (10). The process of demonstrating that an instrument
of checking or adjusting instruments. Includes IQ,calibration,and OQ. consistently performs according to a specification
Change control Some include DQ and/or PQ. appropriate for its routine use (8).
A formal monitoring system by which qualified Installation qualification Documented verification that the integrated
representatives of appropriate disciplines review Establishes that the instrument is delivered as computerized system performs as intended in its
proposed or actual changes that might affect a designed and specified,that it is properly installed in normal operating environment,i.e.,the computer-
validated status to determine the need for corrective the selected environment,and that this environment related system performs as intended (3).
action that would assure that the system retains its is suitable for the operation and use of the Process performance qualification
validated state (3). instrument (8). Establishing confidence that the process is effective
A formalized program by which qualified Documented verification that all key aspects of and reproducible (11).
representatives review proposed and actual changes hardware installation adhere to appropriate codes
to products,processes,equipment,or software to Process validation
and the computer system specification (3). Establishing documented evidence that provides a
determine their potential effect on the validation Establishing confidence that process equipment
status (6). high degree of assurance that a specific process will
and ancillary systems are capable of consistently consistently produce a product meeting its
Started after IQ. operating within established limits and tolerances predetermined specifications and quality attributes
Computerized system (11). (11).
A system that has a computer as a major,integral Instrument
part.The system is dependent on the computer Product performance qualification
A device (chemical,electrical,hydraulic,magnetic, Establishing confidence through appropriate testing
software to function (7). mechanical,optical,pneumatic) used to test,
Computer hardware components assembled to that the finished product produced by a specified
observe,measure,monitor,alter,generate,record, process meets all release requirements for
perform in conjunction with a set of software calibrate,manage,or control physical properties,
programs,which are collectively designed to perform functionality and safety (11).
movements,or other characteristics (12).
a specific function or group of functions (3). A device that takes a physical measurement and Requalification and revalidation
Design qualification displays a value or has no control or analytical Requalification is the repetition of the qualification
Defines the functional and operational specifications function,e.g.,stopwatches,timers,and effort or a selected portion of it (6).
of the instrument and details the conscious decisions thermometers (9). Revalidation is the repetition of the validation
of the selection of the supplier (8). effort or a selected portion of it.Requalification is a
Operation qualification revalidation activity (6).
Includes functional requirements and The process of demonstrating that equipment will
specifications as well as the design specifications. function according to its operational specifications in Standardization
Equipment the selected environment (8). The assignment of a compositional value to one
The collective analytical measurement instruments, Documented verification that the system or standard on the basis of another standard (13).
in conjunction with firmware,assembled to perform subsystem operates as specified in the computerized Verification
a mechanical process. system specifications throughout representative or Confirmation by examination and provision of
In a computerized system,the equipment is anticipated operating ranges (3). evidence that specified requirements have been met
controlled by the computer system.The computer (14).
ists in the terminology used in the quali- General requirements Individual procedures, specific to the
fication of equipment. The “Equipment The equipment qualification program equipment used, also must be docu-
qualification definitions” sidebar lists must be defined and documented. The mented. Specific procedures for equip-
commonly used terms with their defini- program must contain provisions for the ment qualification can be documented in
tions. Throughout this document the term qualification, maintenance, and docu- one of two ways: First, separate SOPs can
equipment is used to represent both in- mentation of failures of all equipment be written that contain the procedures
struments and equipment as they are de- used to collect data for regulatory sub- used for qualifying and maintaining each
fined in the sidebar. missions. This is usually accomplished by type of equipment. Alternatively, master
using a standard operating procedure SOPs can be used to describe the com-
(SOP) that describes the overall program. pliance requirements for a variety of
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108 Pharmaceutical Technology OCTOBER 2001 www.phar mtech.com