Download How USP Standards Apply

Workshop on Suitability and Compatability for Packaging
and Delivery Systems – Cosponsored by USP and PQRI
How USP Standards Apply
Under USP Rules and in Federal Law
Matthew B. Van Hook
Assistant General Counsel
Version 2.4, June 10, 2013
Overview – How USP Develops Standards
 Standards
for articles recognized in USP-NF are expressed in the
article’s monograph, applicable general chapters, and Gen Notices.
 Articles
are recognized in USP when a Monograph is published; it
sets forth the article’s name, specification and other requirements.

The name (i.e. title) specified in a monograph is the official title for such article
(GN 2.20). The identity test in a monograph is used to establish whether it is
the article named in the USP-NF monograph (GN 5.40). Failure of an article to
meet all of the requirements of a prescribed identity test indicates that the article
is mislabeled and/or adulterated.
 USP-NF
standards apply at all times in the life of the article from
production to expiration.

USP does not specify any particular time, place or frequency for testing (GN
3.10). But articles expected to meet USP standards if tested; any actually
tested must meet USP-NF standards to demonstrate conformance.

Enforcement of USP standards is the responsibility of FDA and other govt
authorities in US and elsewhere; USP has no enforcement role (GN 2.30).
2
USP Role Under Federal Law – DRUGS & BIOLOGICS
• 1906 Food & Drugs ‘Wiley’ Act
– U.S. Government can act if adulterated or misbranded
– USP strength, quality & purity used to define adulteration
• 1938 Federal Food, Drug, and Cosmetic Act
– FDA application – safety – but no preapproval
– USP naming & Identity (drug named in official compendium)
USP packaging & labeling (FDCA 502(g))
• 1962 FD&C Drug Amendments
– FDA pre-market approval authority; safety & efficacy
– FDA authority to require GMPs to assure safety, strength purity
– FDA authority to change USP official/nonproprietary names
• 1997 FDA Modernization Act Amendments
– Ratify FDA policy that all FDCA requirements (e.g. adulteration,
misbranding, GMPs) apply to PHS Biologics. PHService Act §351(j)
• 2010 Biologics Price Competition and Innovation Act
– 351(k) biosimilars subject to same regulatory requirements as 351(a)
How USP Standards are Recognized In Law

Drug deemed misbranded unless its label bears the
“official title” recognized in USP-NF. FDCA 502(e)(3)

FDCA & PHS Act drugs recognized in USP are deemed
adulterated or misbranded if they fail to meet USP
standards for identity, strength, quality or purity (FDCA
501(b); 21 CFR 299.5) packaging & labeling (FDCA 502(g))
• FDA-approved names in NDAs and BLAs are
considered by FDA to be “interim established names,”
that exist only unless and until USP designates a name.
See, e.g. Novartis v. Leavitt, 435 F.3d 344 (D.C.Cir. 2006)
– FDA name may have to change: “The USP Nomenclature
Committee acts under its own schedule, so that its designation of
a name qualifying under §352(e)(3)(B) need not coincide with the
FDA’s approval of a drug.”
Novartis v. Leavitt, 435 F.3d 344, 352 (D.C. Cir. 2006).
Adulterated Drugs – 501(b); USP Strength, Quality, Purity
• “Such determination as to strength, quality, or
purity shall be made in accordance with the tests
or methods of assay set forth in such
compendium….”
– If FDA finds the tests or assays to be insufficient for
determining compliance with USP standards, and USP
doesn’t timely revise, FDA may set appropriate tests
and assays by rulemaking.
• Exception: if drug strength, quality or purity differ
from compendial standards, and the difference “is
plainly stated on its label.”
5
Overview re Legal Role of USP Standards –
FDA-Enforceable, if drug recognized in USP-NF?
• Identity – YES, Always
• Strength – YES
Unless Any Difference
Is Plainly Stated
• Quality – YES
On The Label
• Purity – YES
• Compendial Packaging/Labeling - YES
Law and compliance a complex fabric of dual and
sometimes overlapping roles
– USP standards, 501(b) – since 1906, 1938
– FDA GMPs, 501(a) – since 1962
apply upon approval, regardless of USP/NF
– FDA product approval specs – very detailed, including re
manufacturing and drug quality, since 1962
Or FDA OTC Monograph System – provides for marketing
of GRASE drugs; see 21 CFR Part 330
What Testing Does USP Require re: USP-NF Standards?
• Compliance with USP standards is required at any and all
times in the life of an article. Any official article is expected to
meet USP standards if tested, and any article actually tested
as directed in the monograph must meet USP standards to
demonstrate compliance.
• Frequency of testing, whether and when to test if at all, is
left to the preferences and direction of those performing
compliance tests, and other users of USP-NF
(manufacturers, buyers, regulatory authorities).
• FDA and manufacturers help ensure compliance with
applicable USP compendial standards, with e.g. FDA specs,
GMPs, Quality by Design initiatives.
See USP General Notices, §3.10
USP Packing & Labeling Standards, §502(g)
• The FDCA Section 502 Misbranding provision deems
a drug mislabeled “If it purports to be a drug
[recognized in USP or NF], unless it is packaged and
labeled as prescribed therein.”
– Note, the USP method of packing, but not the USP
required labeling, “may be modified with the consent of
the Secretary [FDA].”
• Example – Labeling Limits on Cap & Ferrule
Overseals (See General Chapter <1> Injections; soon
to be moved to new <7> )
• Note re 503(b)(2) – dispensed Rx drugs are exempt
from most 502 labeling requirements, however “the
packaging requirements” of paragraph 502(g) are
excepted, i.e. continue to apply to dispensed drugs.
Thank You; Questions and Feedback
 QUESTIONS?
 For
further information on this presentation, please contact
 Matt
Van Hook, [email protected], 301.230.6357