Audits and regulatory warning letters are increasing in the pharmaceutical industry. The biggest area of noncompliance in
pharmaceutical development and production is laboratory quality control1 (Figure 1). Yet, laboratory quality control is one of the most critical components of drug development.
The cGMP regulations are designed to ensure that products meet safety, efficacy, purity, and stability standards. Compliance
with cGMP regulations is verified by reviewing a company's documented adherence. Because random regulatory inspections of
commercial laboratories can be conducted anytime—without prior notification—experts suggest that all commercial laboratories
conduct routine comprehensive cGMP self-evaluations.
This article identifies key components of a laboratory control system and discusses current cGMP practices and challenges.
The Laboratory Facility
Facility personnel designate cGMP areas on the building's floor plans. To carry out all cGMP operations consistently, facilities
must be of adequate size and design; the general condition of the airflow, temperature, and humidity systems must be monitored
to ensure that all laboratory operations are carried out in a controlled environment. Work areas must be kept clean and uncluttered,
cleanliness maintained and assessed continuously. Separation of test articles must be maintained to ensure that the samples
are not exposed to contamination or stress, and prevented from mixing or handling errors.2
A lack of adequate space for new equipment is a common problem because laboratories are usually designed to hold existing
equipment, which deteriorates slowly. When a new piece of equipment is needed, it must be properly qualified for its intended
use. Then, regular maintenance and calibration must be performed to ensure that the results generated are valid.
Figure 1. Common cGMP deficiencies for 2004–2005.1
Maintenance and operation should be based on standard operating procedures (SOPs) or operating manuals. Equipment logs, a
vital source of information to demonstrate overall compliance, are maintained to document adherence to SOPs, calibrations,
and to report adverse events. All equipment must be categorized by cGMP status and by cGMP critical or noncritical use. Equipment
with critical status requires preventive maintenance and calibration and must undergo full qualification and validation. Other
categories of equipment may require qualification or validation, based on the specific equipment use. Automatic, mechanical,
and electronic equipment all require validation.
All laboratory processes, including facilities, equipment, analytical methods, and computer programs used in the analytical
testing of pharmaceutical products must be validated.2 Following an initial evaluation, every supplier is audited and qualified. Validation includes several different qualification
activities: a validation master plan outlines the overall approach to be taken for validation. User requirement specifications
(URS) and functional requirement specifications (FRS) are defined for design qualification (DQ) or for subsequent validation
testing. URS specifies the users' needs, as well as any regulatory requirements. FRS are statements that specify what the
system must be able to do to meet the users' needs. These act as key reference points of validation.
Qualification ensures that a specific process has met its pre-determined acceptance criteria. Qualification involves installation
qualification (IQ), operational qualification (OQ), and performance qualification (PQ). IQ verifies and documents that the
installation and any modification of the facility or equipment comply with the manufacturer's approved design and recommendations;
OQ verifies and documents correct operation of the system under working conditions during which individual tests with defined
acceptance criteria are performed; and PQ verifies and documents that the facility or equipment performs specific testing
for its routine use within the assigned acceptance criteria.