Longer supply chains and growing imports raise questions about the ability of drug manufacturers to ensure the quality and
safety of all of their drug products. At the same time, FDA cannot feasibly check the thousands of products and ingredients
coming into the US. As a result, the agency expects manufacturers to do more to ensure that contractors and suppliers have
a commitment to quality and that they are routinely monitored and inspected. The aim is to prevent future adulteration crises
such as those involving heparin, melamine, and diethylene glycol (DEG)-contaminated glycerin in medical products.
Along these lines, FDA's Center for Drug Evaluation and Research (CDER) continues to emphasize the importance of manufacturer
quality-by-design (QbD) and risk-management systems to ensure drug quality. CDER officials are evaluating a QbD review pilot
and launching a similar initiative for biotech therapies. Additional efforts to harmonize quality standards, possibly for
excipients and pharmacopeial standards, are under discussion. An electronic drug registration and listing system was fully
implemented this past year, replacing paper submissions, which should make it easier for FDA to identify and track products
and manufacturing facilities.
Manufacturers also could benefit from a long-awaited FDA guidance on reducing the volume of manufacturing supplements that
require preapproval. The aim is to permit companies to report certain changes in annual reports, instead of filing supplements,
an approach that will provide more predictability to companies contemplating improvements and scale-up of production processes.
Drug safety and risk assessment
FDA is involved in multiple initiatives to ensure the appropriate use of approved medicines. It will be interesting to see
whether the added tools for ensuring drug safety through the product life-cycle encourages agency approval of new medicines
that raise safety concerns. The FDA Amendments Act of 2007 (FDAAA) authorizes postapproval label changes when new safety issues
arise and penalizes manufacturers that fail to conduct agreed-on postmarketing studies. The Act mandates for a more extensive
listing of clinical trials and study results on the ClinicalTrials.gov public website and for the use of Risk Evaluation and Mitigation Strategies (REMS) to govern postmarket prescribing and surveillance.
Manufacturers—along with regulatory authorities, health professionals and patient groups—will be watching to see how well
these programs detect and prevent drug safety problems. FDA has approved REMS for more than 90 products, including drugs and
medical products already on the market as well as new treatments. A high-profile initiative is to develop a REMS for the entire
class of extended-relief opioid medicines. The goal is to ensure continued access to these medications for patients suffering
from chronic pain, while also curbing inappropriate prescribing, unintentional overdosing, and intentional abuse through a
more coordinated risk- management strategy.
Internally, FDA is bolstering its safety assessment efforts. CDER's Safety First program integrates oversight of drug-safety
issues by clarifying responsibility for pre- and postapproval drug safety assessment and by strengthening safety-related policies
and procedures. The agency's Sentinel Initiative includes the development of an electronic system for monitoring medical-product
safety. After a few pilot projects, the system eventually should be able to identify emerging safety problems and patient
subgroups experiencing adverse events through links to healthcare-system databases.
FDA's Safe Use initiative, which Hamburg announced in November, aims to build partnerships with other components of the healthcare
system to ensure that medicines are used safely and appropriately. The agency plans to partner with other government agencies
and with healthcare providers to address situations that lead to medication errors and inappropriate prescribing.
The Sentinel System for monitoring drug safety requires access to electronic health information systems, a prominent goal
of health-reform efforts. The HITECH (health information technology) portion of economic stimulus legislation jumpstarted
this effort by providing $19 billion to support the use of electronic health records by doctors and hospitals and to develop
standards and systems supporting electronic health information exchange. Electronic databases promise to accelerate detection
of drug adverse events and to streamline data collection from clinical trials and population studies.
At the same time, broader access to personal health information has generated demands for stronger protections against unauthorized
disclosure of personal patient records. The concern for the biomedical research community is that privacy issues could limit
access to patient information needed for pre-clinical and postapproval studies.
An expert panel organized by the Institute of Medicine recommends simplified approaches to clinical research that use a distributed
model for health surveillance and assessment, based on the data-sharing capabilities of electronic information systems.