FDA also is urging manufacturers to assume greater responsibility for ensuring the quality and safety of their products at
all points on the supply chain. At the PDA workshop, CDER Director Janet Woodcock called on industry to "up the ante on vigilance"
and to devise real solutions to supply-chain problems. Modern track-and-trace technology can help manage far-flung supply
chains, but should be linked to programs for qualifying suppliers and for monitoring global conditions. Also important are
robust security measures able to deal with overt criminal activity and networks for communicating within industry and with
FDA about these issues.
Although increased outsourcing by manufacturers may appear to reduce production costs, Woodcock noted that such approaches
actually may generate hidden expenditures. Suppliers with less of a track record may require more extensive due diligence
and monitoring. And doing business in countries with weaker regulatory systems may open the door to counterfeiting. It's the
manufacturer's responsibility to ensure the reliability of suppliers, she emphasized, especially in times of ingredient shortages
or political upheavals that can disrupt imports and product distribution.
A company's supply-chain security should be regarded as part of a manufacturer's broader quality system for managing known
and emerging risks, Woodcock added. A quality risk-management system should include strategies to prevent quality problems
and to better detect risks, including those related to incoming raw materials. This approach parallels quality by design in
manufacturing, which involves controlling the physical attributes of raw materials such as particle size or state of hydration,
to ensure quality throughout the production process. Pharmaceutical companies should establish quality agreements with suppliers
to clarify where ingredients come from and to stipulate the importance of rapid notification about supply disruptions.
Conversely, continued industry difficulties in managing supply-chain issues may lead to stricter oversight and regulation
by FDA, possibly including mandatory supplier audits. The agency is contemplating revisions in good manufacturing practices
(GMPs) for starting materials, for example, and Congress may legislate added tracking requirements and other safeguards.
Identification and tracking
Efforts to identify illegal imports and stolen products stand to gain from the development of standards and validated technologies
that can better secure the nation's supply chain against counterfeit, substandard, adulterated, or expired drugs, as required
by one provision in the FDA Amendments Act of 2007. FDA took an important step toward fulfilling this mandate by issuing guidance
in March that establishes a standardized numerical identifier (SNI) for prescription drug packages. The standard is based
on a serialized National Drug Code, combined with a unique serial number of 8 to 20 characters that can identify individual
drug packages. Despite pressure for additional information on the identifier, FDA does not require expiration date or lot
and batch numbers for fear of making the SNI too long and complex. The aim is to be compatible with international identifier
standards and to set the stage for additional numerical identifiers for cases and pallets.
FDA also launched a campaign to heighten public awareness about the dangers of drug theft and diversion and to spur manufacturers
to improve warehouse and supply-chain security. The agency has established a Cargo Theft mini website on
http://www.fda.gov/ that now cites some 20 theft incidents in the past year involving insulin, inhalers, infant formula, and contact lenses in
addition to prescription drugs.
In an April letter to trade associations for manufacturers, wholesalers, pharmacists, and makers of medical devices and infant
formula, FDA advised companies to establish action plans for responding quickly to thefts. Companies need to report thefts
quickly to local and federal agencies, including FDA's Office of Criminal Investigations, so that public-health risks can
be assessed and communicated. FDA said its overarching goal is to ensure consumer safety, citing the case of diabetes patients
becoming ill following treatment with stolen insulin that had lost effectiveness due to poor storage. In investigating such
cases, FDA wants manufacturers to provide detailed descriptions of stolen products, including lot and NDC numbers, storage
requirements, antitampering protections, and how much of each lot is missing.
The standard identifier for drug packages is expected to facilitate development of a uniform system for tracking and tracing
pharmaceuticals through the product life cycle. European drug companies recently conducted a successful pilot test of a drug-scanning
system that identified fakes, counterfeits, and expired goods, despite some coding problems. Technology vendors are announcing
almost daily new tracking and authentication methods that can verify product movement through the supply chain, monitor transport
conditions, test for impurities, and prevent tampering. Manufacturers seeking to distinguish authentic from counterfeit products
are producing photo libraries that display pictures of authentic packing, labels, serial numbers, tamper-resistant seals,
and paper pedigrees.
Companies also are developing tools and best practices for dealing with suppliers such as scorecards with standardized data
and nomenclature, as well as templates for supplier quality agreements. Experts advise more personal meetings and information-sharing
with key vendors to address manufacturers' and suppliers' concerns and to emphasize the importance of ensuring product quality.
Parallel to these initiatives is a deliberate effort by companies to clarify policies and terms for disqualifying suppliers
who fail to adopt quality practices or to maintain secure supply chains. Manufacturers increasingly recognize that it may
be wiser to sever ties with a troublesome supplier than to run the risk of obtaining poor-quality ingredients or packaging
that can compromise product safety and efficacy. Such an approach requires clear records on supplier performance and compliance
with standards and specific actions that would signal the need to end a supplier relationship. Exit plans for terminating
supplier relationships are becoming part of supply-chain management programs. Of note, in April, International Pharmaceutical
Excipients Auditing, a subsidiary of the International Pharmaceutical Excipients Council, received ANSI accreditation of its
excipient supplier GMP certification qualification program, which was encouraged by FDA.
Unfortunately, FDA policy governing manufacturing changes can make it difficult to switch suppliers. Engaging a new source
for active ingredients or components for licensed drugs and biologics requires prior approval by the agency, which can take
months. Generic-drug makers, in particular, complain that the agency often takes two years to approve a manufacturing supplement.
Under the prescription drug user fee program, FDA is supposed to approve supplements for branded drugs within four months,
but the process can take longer if applications are complex or raise questions. In the past, manufacturers often preferred
to continue working with problem suppliers, rather than to go through the supplement process, but that appears to be changing
with increased focus on product quality and supplier performance. FDA is looking to streamline its manufacturing supplement
oversight procedures, but is unlikely to drop the prior-approval requirement for changes in ingredient suppliers.