The GMPs specify that the quality control unit must have organizational independence from manufacturing — with sole authority
to release or reject product, raw materials, key procedures, specifications, and reports. Why go to such great lengths, and
surely add to the cost of medicines, in this way? The answer, again, lies in human nature and experience. Production personnel
are focused on delivering product on time. If asked to judge the quality of the product they have just produced, they face
a conflict of interest. To assure safety for the consumer, an internal group must be insulated from supply chain pressures
and given a different priority: quality. The quality unit provides systems, interprets regulations, and sets the philosophy
within the firm. It is the judge when GMP decisions must be made and is held responsible, along with executive management,
for product quality. The regulations make it clear that QC oversees production and assures that procedures are being followed.
The ability of quality assurance to reject or recall bad product is the last safety check that keeps the consumer from harm.
Other GMP Requirements
Table I lists the key stipulations of the GMP regulations. The regulations specify basic, minimum requirements for the buildings
and facilities in which pharmaceuticals are manufactured, stored, or handled. These emphasize prevention of contamination
or cross-contamination, adequate labeling, and building design to prevent mix-ups. These also cover standards for the quality
of the air, production surfaces, and gowning in controlled areas to maintain a clean safe environment.
Subpart F of 21 CFR 211 discusses production and process controls, defining the systems required to maintain a "state of control."
A large section is devoted to control of raw materials and components, perhaps because so many tragic events resulted from
the use of improper or contaminated materials.
You may wonder why the packaging and labeling section is so detailed. Even today, with the benefit of over a century of regulation
in the industry, mix-ups and labeling errors still remain the number one sources of adverse events in hospitals as well as
homes. The risk of mis-labeling a drug product is reduced by having dedicated, segregated areas; by controlling the labels;
by instituting multiple line checks; and by performing reconciliation. Reconciliation is the process of comparing counts of
labels or other items before and after a process step, in order to check for strays. The process of reconciliation has prevented
numerous potential medical accidents from occurring. The discovery that 25 kgs have been removed from a 10 kg container can
greatly aid in discovering that a mix-up has occurred.
Do GMPs Work?
Today, more people than ever are taking pharmaceuticals. Adverse events do happen, and some lots of product that have met
specifications are released to the public, and are later recalled due to quality concerns. However, the incidence of safety
problems is quite low as a result of GMP systems, talented people, and the use of advanced technologies.
As with democracy, the GMPs work quite well but not perfectly. The quality of a medicine depends on every individual person,
instrument, and material in the production chain following defined systems and processes. Quality systems are the back-up
that help to assure that errors will be detected and impact assessed before the product is released to the public. Most adverse
events can be traced to a violation of one or more of the GMP rules, suggesting that GMP is a powerful way to assure quality.
Until someone comes up with a better way, GMPs are likely to remain with us.
1. FDA. 21 CFR 210, 211, 800. Available at:
2. FDA. Milestones in US food and drug law history. Available at
3. Young JH. Sulfanilamide and diethylene glycol. In Parascandola and Whorton, editors. Chemistry and modern society: historical
essays in honor of Aaron J. Ihde. Washington, DC: ACS; 1983.
Paula J. Shadle, Ph.D., is the principal consultant at Shadle Consulting, 501 McBride Drive, Lafayette, CA 94549, 925.878.5130,
fax 925.962.0862, Shad1357@aol.com