The Medical Industry’s Move Toward Quality, Part
Six
The first article in this series discussed recent
FDA initiatives designed to speed up the introduction of
drug and biologic products into the marketplace while improving
their quality and safety (Quality Digest, Feb. 2004). These
initiatives introduced risk management and process analytical
technology into the pharmaceutical review process, paralleling
some medical device initiatives already underway both in
the United States and the rest of the world.
Succeeding articles discussed related efforts in the medical
devices sector, including the introduction of ISO 13485:2003
and ISO 14971:2000, as well as international harmonization
of both medical device and pharmaceutical review processes.
This article looks at the FDA’s latest initiatives
in risk management for pharmaceuticals.
Early in 2003, the FDA issued risk-management concept
papers outlining its intended approach. Now, the agency’s
Center for Drug Evaluation and Research, as well as its
Center for Biologics Evaluation and Research, have released
three draft guidance documents to help manufacturers achieve
greater benefits from drugs and biologics while minimizing
their risks. Collectively, the documents describe safety
issues that can arise throughout a product’s life
cycle, including development, review, approval and market
availability.
The documents are designed to bring more attention to
what the agency is already doing, states Steven Galson,
acting director of the CDER. According to Galson, voluntary
recommendations wouldn’t lengthen the drug development
process. So far, pharmaceutical R&D laboratories and
manufacturing companies are welcoming the FDA’s guidances
on risk management strategies, saying the documents will
help them better understand the agency’s expectations
in an increasingly important area for the pharmaceutical
industry.
On June 12, 2002, Congress authorized the Prescription
Drug User Fee Act for the third time. Under PDUFA III, drug
manufacturers pay a fee for FDA inspections, while the FDA
is charged with improving both the speed and efficacy of
the new drug review process. One of the FDA’s goals
in response to PDUFA III is to produce industry guidance
on risk management for drug and biological products. As
an initial step, the FDA sought public comment on risk management
by issuing three concept papers last year. Each one focused
on a separate aspect of risk management--premarketing risk
assessment, risk minimization tools and postmarketing pharmacovigilance
and pharmacoepidemiologic assessments.
The FDA solicited written comments on the three papers
and held a public workshop in April 2003 to discuss them.
The agency then considered the comments received while it
produced three draft guidance documents on risk management
activities. The following documents have now been issued
and are available online (www.fda.gov/cder/meeting/riskManageI.htm):
Premarketing Risk Assessment (Premarketing Guidance)
Development and Use of Risk Minimization Action Plans (RiskMAP
Guidance)
Good Pharmacovigilance Practices and Pharmacoepidemiologic
Assessment (Pharmacovigilance Guidance)
Each draft guidance document focuses on one aspect of risk
management. The premarketing and pharmacovigilance documents
focus on premarketing and postmarketing risk assessment,
respectively, while the Risk MAP document focuses on risk
minimization. Under the FDA’s terminology, risk assessment
and risk minimization are the components of risk management.
Note that this definition is similar to the one found in
ISO 14971:2000, which refers to risk assessment and risk
control as the two components of risk management.
The FDA views risk management as a four-part iterative
process:
1. Assessing a product’s benefit-risk balance
2. Developing and implementing tools to minimize risks
while preserving benefits
3. Evaluating each tool’s effectiveness and reassessing
the benefit-risk balance
4. Adjusting the tools to further improve the benefit-risk
balance
This process continues throughout a product’s life
cycle, and the results of ongoing risk assessment continually
influence the manufacturer’s decisions regarding risk
minimization. It is an integral part of the intensive and
continual improvement process that must be applied to every
product that involves human health and safety.
Note, too, that these FDA guidance documents don’t
establish legally enforceable responsibilities. They’re
primarily designed to provide industry guidance on good
risk assessment practices during the development of prescription
drug products, including biologics. They describe the agency’s
current thinking on the topic and are only recommendations--unless
specific regulatory or statutory requirements are cited.
The topics covered in the documents are also being discussed
in a variety of international forums, such as the International
Conference for Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use. The FDA actively
participates in these discussions to ensure that the recommendations
in the guidance documents reflect current international
thinking on related issues.
In the past, the FDA’s oversight of new drug quality
involved reviewing technical information submitted by the
manufacturer as well as inspecting facilities for conformance
to the Code of Federal Regulations’ requirements regarding
current good manufacturing practices for pharmaceuticals.
These two approaches combine to help ensure the quality
of medical products available in the United States.
The FDA is evaluating these programs’ currency as
we approach the 25th anniversary of the last major revision
to the pharmaceutical cGMP. New drug products, the increased
use of drugs in treating illness and the medical industry’s
globalization are straining the FDA’s resources. To
meet these challenges, the agency has announced an initiative
known as Pharmaceutical cGMPs for the 21st Century: A Risk-Based
Approach. It’s hoped that these three guidance documents
will help contribute to a new era in oversight of the pharmaceutical
industry.
Stanley A. Marash, Ph.D., is chairman and CEO of The
SAM Group, which includes STAT-A-MATRIX Inc. and Oriel Inc.
He is the author of the recently published Fusion Management
(QSU Publishing Co., 2003). Fusion Management is a trademark
of STAT-A-MATRIX Inc. ©2004 STAT-A-MATRIX Inc. All
rights reserved.
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