The
quality and safety of the U.S. (and international) drug supply has garnered
much attention over the past year. Whether it is quality control problems in
popular medications, heists resulting in stolen pharmaceuticals, substandard,
adulterated, or counterfeit drugs being sold in developing countries (and even
in developed nations), the industry has faced a barrage of negative headlines.
Of course, ensuring high quality and safe medications is a complex task,
particularly as the industry has grown into a global one. It takes many
components, including vigilant regulatory bodies, ethical manufacturers, and
ever-evolving standards-setting bodies. The role of the latter tends to be the
most unfamiliar to the general public, but also to some who work in the
pharmaceutical industry. Yet quality standards remain an essential element of
maintaining a well-functioning system—and are becoming even more vital as
contamination and adulteration issues increase. Quality standards as set by the
U.S. Pharmacopeial Convention (USP) play an important role, and include
standards for finished drug products (for both small molecules and biologics),
active and inactive pharmaceutical ingredients, and packaging and distribution
standards, as well as storage standards, labeling standards, practice standards
for pharmacists, nomenclature standards, and others.
The Role of USP
Quality
standards for pharmaceuticals have historically been a critical—yet largely
behind-the-scenes—component of the safety nets that protect the quality of
medicines. In the United States, USP, a private nonprofit organization,
develops standards that help ensure the identity, quality, purity, strength,
and consistency of finished medicines and their active and inactive
ingredients. Pharmaceutical products and their ingredients are required by U.S.
law to comply with USP’s standards, or risk being deemed adulterated or
misbranded.
In the
last several years, we’ve seen a number of instances in which contaminated or
adulterated products or ingredients have presented threats to public health.
One of the most well-known examples is the adulteration of the blood thinner
heparin, which resulted in patient deaths and adverse reactions in the United
States and around the world. Responding
to these threats, USP revised standards that have been—or are at heightened
risk of being—adulterated based on economic motivations. This was the case with
heparin, as well as with the excipient glycerin (with specific incidents of
adulteration involving cough syrup and toothpaste incorporating the sweetener)
and others. USP has also addressed contamination issues, which include revising
its standards for elemental impurities (heavy metals).
Focus on Packaging and Distribution
Along with
modifying product and ingredient standards, another critical area of focus for
USP in the coming years will be that of packaging standards. While consumers,
legislators, regulators, and advocacy groups are concerned with lead and other
impurities in drug products and other consumer products, there has also been a
great deal of attention regarding such components in drug product packaging.
We’ve also seen increasing exploration and utilization of new packaging
technologies to address counterfeit medications as this problem has grown.
Beyond packaging, USP is looking at the distribution of medicines as a whole as
supply chains grow increasingly complex, providing new opportunities and
avenues for counterfeiters. USP is currently prioritizing its work for its new
2010–2015 cycle (the organization renews its focus every five years following
its USP Convention meeting, electing experts to serve on its scientific
committees and creating new work plans on standards activities) in these and
other areas. We hope to engage the pharmaceutical industry as we consider these
modifications, as they will certainly affect domestic and worldwide operations.
Some of these changes will be voluntary (guidance chapters), while others will
be mandatory for manufacturers marketing products in the United States.
Supply Chain Complexity, Security
Of course,
it is not breaking news that supply chains have grown longer and more
complex—and are continuing to do so. Recognizing the global
nature of today’s pharmaceutical operations and the long, multi-step journey a
drug product can travel through the supply chain to the end-user, USP has
undertaken a major revision of its guidelines detailing best practices for the
storage and transportation of drug products (contained in the USP–NF General Chapter Good Storage and Shipping Practices for Drug Products <1079>). The new approach takes into account
global issues that can arise, not only with regard to items such as keeping
medicines at their proper temperature during transport, but going far beyond
its original contents by discussing the importance of having a systems-wide
approach to securing supply chains. It covers topics such as the role of
quality agreements to ensure clarity and transparency regarding the
responsibilities of each party in the supply chain, along with a host of other
issues. USP will be looking to expand on many of the areas in the chapter in
much more detail, with possible spinoff chapters on temperature mapping and
supply chain security, among other topics. As dangers such as hijacked pharmaceuticals
during transportation continue to grow, these chapters can help set forth
important guidance.
Exposure Issues—Elemental Impurities and
Extractables/Leachables
In
addition to revising its elemental impurities standards for drug products and
dietary supplements, USP is looking at elemental impurities in packaging
materials. Metals are of concern in product packaging, just as they are in
finished drug products. When considering limits for metals in packaging
materials, this will require a completely different set of specifications and
limits (allowable levels). One of the biggest USP efforts in the packaging area
will be a new guidance chapter on extractables and leachables. Because
packaging containers are not inert, by-products from plastics, glass, and
rubber materials could migrate into a drug product. Chemicals used in the
manufacturing of packaging components are increasingly controversial—not just in
the pharmaceuticals industry but across the board. Indeed, extractables and
leachables may alter a medicine and thus impact a patient. Some medicines, such
as parenteral products injected directly into a patient, may be particularly
vulnerable. USP plans to develop an informational chapter on this topic, but
also will likely be incorporating some required updates into its chapters
focusing on Elastomeric Closures for
Injections <381>, Containers—Plastics
<661>, and Containers—Glass <660>.
Proposals for these changes, as with all USP standards, will be published in
the Pharmacopeial Forum—the vehicle
through which USP proposes revisions and new standards and accepts comments on
them.
Anticounterfeiting
An area of
constant innovation is anticounterfeiting technologies in packaging. There are
of course significant economic concerns for pharmaceutical manufacturers, and
public health concerns for all when medications are tampered with, or when fake
medications are produced and packaged under a false name—using a company name
and similar packaging to trick patients. What chapters can be developed, and
how USP can provide helpful guidance to industry as it considers and
incorporates a host of new technologies, is something the organization is
looking into as its Packaging, Storage, and Distribution Expert Committee
begins its work.
Advancing Public Health through Quality
Standards
With the
function of standards evolving to meet current threats, USP has embarked on a
public awareness campaign to highlight the role that these standards play in
securing the U.S. and international drug supply, supplementing other essential
efforts of regulators and manufacturers. USP has developed an online resource
center containing videos of public health experts articulating the need for
standards, as well as a host of other resources explaining how FDA and USP
collaborate and showcasing “standards in action.” These materials are available
at www.usp.org/aboutUSP/impactVision/valueOfStandards/. We invite all
interested parties to visit the site to learn more about our role, and to
monitor www.usp.org to stay up-to-date as USP advances work
on its packaging, distribution, and product-specific standards.