The US Food and Drug Administration recognizes more than 20 standard-setting organizations. There are also several organizations
recognized by the medical device industry as producing standards easily referenced in 510(k) filings and whose procedures
are equally beneficial and applicable to the pharmaceutical industry. Take, for example, the International Organization for
Standardization (ISO), which publishes sterility and air-quality standards, and the American Society for Testing and Materials
(ASTM), which publishes packaging material standards.
The Code of Federal Regulations, specifically 21 CFR 211.194(a)(2) on laboratory records, requires companies to indicate the procedures they use to release their product to the
market. The regulation also asks companies to document the "location of data that establish that the methods used in the testing
of the sample meet proper standards of accuracy and reliability as applied to the product tested." This concept seems straightforward
enough. But additional text in the regulation in parenthesis is more intriguing: "(If the method employed is in the current
revision of the United States Pharmacopeia [USP], National Formulary [NF], AOAC International, Book of Methods, or in other recognized standard references, or is detailed in an approved new drug
application and the referenced method is not modified, a statement indicating the method and reference will suffice)."
Many people in the pharmaceutical industry are familiar with USP–NF, and have heard of AOAC, but how many of us know the names of the organizations that collectively make up the "other recognized
standard references" category? FDA's Center for Devices and Radiological Health (CDRH) website provides some insight. CDRH
runs a Standards Program through which companies can access the Center's FDA-Recognized Consensus Standards Database. This
database allows individuals to search by the name of the standards organization, the type of standard, or the standards category.
This database is important to those outside the device industry because the information contained in CDRH's database applies
to products regulated by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research
(CBER). To exemplify, I did a test search in the database for USP sterility standards and got nine results meeting the defined
criteria. Of these results, four standards were for evaluating drug products, all commonly used in CDER and CBER registrations.
However, when clicking on the title of the standard in the database, the resulting information only pertains to medical devices.
Other searches yield similar results.
I went on to test the simple search feature for the term "air classification." As expected, ISO 14644-1 on Cleanrooms and
Associated Controlled Environments displayed. Many pharmaceutical companies use this standard to determine air quality when
manufacturing injectable products. There was no mention, however, of this standard applying to anything other than "...medical
devices where processing in controlled environments is a component of the development and manufacture of the product."
Many standards included in the database are considered "recognized consensus standards," which CDRH defines as one that "...FDA
has evaluated and recognized for use in satisfying a regulatory requirement and for which FDA has published a notice in the
Federal Register." Organizations developing consensus standards for FDA recognition must follow a process in which "the standard development
is transparent (i.e., open to public scrutiny), where the participation is balanced, where an appeals process is included,
where the standard is not in conflict with any statute, regulation, or policy under which FDA operates, and where the standard
is national or international in scope."
Going back to 21 CFR 211.194(a)(2) on laboratory records, which allows for use of recognized standards beyond those included in USP–NF, the Office of New Drug Quality Assessment has begun to recognize other standards through its Manual of Policies and Procedures (MAPP). The manual states that it may sometimes be appropriate to reference monographs contained in these publications in
investigational new drug and new drug applications. CBER and CDER seem to be moving in the direction of CDRH with respect
to recognizing consensus standards and this direction is definitely positive for industry. It will be exciting to watch their