Many publications have described the drug shortage issue and its causes and potential remediation.  The GAO recently published a report titled “Drug Shortages, FDA’s Ability to Respond Should be Strengthened.”  The data provided in this report do not appear to be substantially different from those of other publications, including an earlier one from FDA.  The GAO recommends that Congress consider establishing a requirement for manufacturers to notify FDA of any changes that could impact the supply of drugs they manufacture. This recommendation seems to be addressed in the interim final rule amending the existing post-marketing reporting requirements of 21 CFR314.81(b)(3)(iii) (see the Rx-360 Summary of this rule).  Further, the GAO encourages FDA to develop information systems that will permit tracking and management of drug shortages.

To view or download the US GAO Report, click here

To view or download the Rx-360 Summary, click here 

FDA Notifications:

News reports have announced that an interim final rule has been published regarding amending the postmarketing reporting requirements, specifically those in 21 CFR 314.81.(b)(3)(iii) published as final on October 18, 2007. This addressses the need to notify FDA in advance when a sole manufacturer plans to discontinue manufacture of a “life supporting,life sustaining, or intended for use in the preventino of a debilitating disearse or condition”. 

This interim final rule supports the Executive Order 13588 from October 31, 2011 that directs FDA to “take steps that will help to prevent and reduce current and future disruptions in the supply of lifesaving medicines…one important step is ensuring that the FDA and the public receive adequate advance notice of shortages whenever possible”.  The changes put forth in this document add two definitions to the existing rule, one for “discontinuance” and one for “sole manufacturer”.  The intent of these changes is to provide FDA assistance in the management of the dramatic increase in drug shortages.  The definition of “discontinuance” has been expanded to include “…both temporary and permanent interruptions in manufacturing, if the interruption could lead to a disruption in supply of the product”.  The FR announcement includes examples of situations that would trigger such a notification as well as those instances where no notification would be necessary. The definition of “sole manufacturer” is clarified to mean “…the only applicant currently supplying the U.S. market with the drug products.”  It does not mean the sole NDA/ANDA holder. 

To view or download Federal Register Notice, click here

To view or download Final Rule, click here

There has been significant national news coverage in the USA of drug shortages, especially related to drugs used to treat cancer. 

Rx-360 has previously presented and publicized that during shortages, opportunities are presented for noncompliant companies, unethical players and even criminals to enter the supply chain and introduce substandard, contaminated, adulterated and even counterfeit materials, often with tragic consequences.   In fact, shortage of raw material in China was one of the contributing factors in the economically motivated adulteration of Heparin which led to numerous deaths in the USA and Europe.

With the current shortages of drugs in the USA, the Institute for Safe Medication Practices has issued a safety alert based on their survey of 549 hospitals, indicating widespread accounts of frustration, outrage, and serious compromises to patient care.

According to the press release from ISMP: "When critical medications become scarce and are no longer available through a hospital’s usual channels of distribution, unscrupulous gray market distributors have been quick to jump in with inexplicably obtained supplies of these drugs that they are more than willing to sell to healthcare providers at exorbitant costs. Capitalizing on the desperation of pharmacy directors and buyers, these distributors have been unrelenting in their quest to make huge profits by supplying hospitals with lifesaving medications that are otherwise unavailable."

The survey generated hundreds of comments from respondents "who feel unsupported by regulatory agencies that have not stepped in to control the gray market, betrayed by some pharmaceutical manufacturers or wholesalers who they presume may have sold medications in short supply to gray market vendors, perplexed regarding how gray market vendors know about pending drug shortages before hospitals do, outraged by the price gouging that accompanies the sale of these vital medications, and frustrated by the wasted time spent on unsolicited communications (telephone calls, emails, faxes) from gray market vendors."

The follow findings also come from the ISMP Survey:

About half (52%) of all respondents reported purchasing one or more pharmaceutical products from gray market vendors during the past 2 years. Most (80%) of these respondents told us that their purchases had increased in the past 2 years as drug shortages began hitting record highs.

Numerous respondents reported feeling pressured by physicians and hospital administrators to purchase medications from the gray market. Any resistance to the purchase, despite expressed risks, pegs the pharmacist as the “bad guy.” While some states have enacted regulations that require documentation of authenticity (pedigree) of any purchased pharmaceutical products, half (50%) of respondents in these states with pedigree laws still reported purchasing medications from the gray market during the past 2 years. Of these, only 35% reported always receiving the required documentation of authenticity.

In general, the most common reasons respondents did not purchase medications (48%) from gray market vendors during the past 2 years were: concerns with authenticity (74%), ethical concerns (66%), cost (69%), and concerns about the storage conditions prior to purchase (58%).

Among all respondents, only 23% told us they require documentation of authenticity from the gray market vendor before purchase.

Up to 12% of respondents reported awareness of a product authenticity issue, medication error, or adverse drug reactions associated with the use of gray market products in the past 2 years. 

Numerous respondents made recommendations for improvement but until these actions are implemented, ISMP recommendations are summarized in Table 1 (below), which includes a series of actions developed by Premier to help organizations ensure a safe, reliable medication purchase. Readers are also referred to our October 7, 2010, newsletter article, "Weathering the storm: Managing the drug shortage crisis" www.ismp.org/Newsletters/acutecare/articles/20101007.asp for suggested actions, including a template of a failure mode and effects analysis to promote safe use of alternative drugs used during a drug shortage.

Table 1. Actions to Ensure A Safe, Reliable Medication Purchase
1	Understand the risks associated with purchases from the gray market, including the possibility that the drugs may be counterfeit, stolen, diverted, mishandled, and/or adulterated.
2	Develop a policy on how your pharmacy will deal with gray market vendors, including details regarding any exceptions that may be allowed.
3	Purchase supplies only from distributors that are an authorized distributor of record for the drug manufacturer (which are listed on the manufacturer’s website) or an otherwise appropriately licensed and Verified-Accredited Wholesale Distributor (VAWD) (which are listed on the National Association of Boards of Pharmacy [NABP] website).
4	Require any non-authorized distributors of record to provide a pedigree prior to or upon purchase of a product (which they are required to keep), and authenticate and track each transaction back to the manufacturer’s authorized distributors of record.
5	Keep a list of suspect distributors as a resource to check prior to making purchases.
6	Compare the package, label, and contents of products from a non-authorized distributors of record with the manufacturer’s original product. If differences are identified, question its authenticity.
7	Report any suspect suppliers and violations to pedigree laws to your State Board of Pharmacy, the FDA, the Federal Trade Commission, and other applicable law enforcement authorities.

Rx-360 also published an editorial calling for stricter criminal penalties for economically motivated adulteration, counterfeiting and other nefarious activities.  The editorial stated "Looking at events over the past several years, it is clear - unethical individuals and criminals are present in the pharmaceutical supply chain. The reason for this growing phenomenon is simple “greed”. Unethical individuals and criminals have learned that selling substandard, adulterated or counterfeit medicines is highly profitable and involves very little if any personal risks." The entire editorial can be read at: http://www.rx-360.org/News/Rx360Newsletters/Rx360NewsNovember2010/EditorialStricterCriminalPenaltiesRequired/tabid/215/Default.aspx