Presentation by

Anita T. Ducca
Senior Director, Regulatory Affairs
Healthcare Distribution Management Association (HDMA)

Wholesale Distributor Perspectives on the
Proposed Class-Wide REMS for Opioids
At the FDA Public Meeting on Risk Evaluation and Mitigation Strategies for Certain Opioid Drugs; May 27 & 28, 2009

74 Fed. Reg. 17,967 (April 20, 2009) [Docket No. FDA-2009-N-0143

May 27, 2009

Good morning and thank you for allowing me this opportunity to speak.  I am Anita Ducca, Senior Director for Regulatory Affairs for the Healthcare Distribution Management Association (HDMA).

HDMA represents primary, full-service healthcare distributors.  Each business day, HDMA member companies deliver more than eight million prescription medicines and healthcare products to pharmacies, hospitals, nursing homes, clinics, physician offices, government and other providers in all 50 states.  This essential public health function is provided with tremendous efficiency, saving the nation’s healthcare system nearly $32 billion each year.  For more information, visit www.HealthcareDistribution.org.

I’m going to focus on question #2 under “Systems Issues” in the Federal Register notice for this meeting.  This question asks if the contemplated class-wide Risk Evaluation and Mitigation Strategy (REMS) for certain opioids should include controls on distributors and, if so, how those controls could be implemented without being unduly burdensome.1 

Distributors have a unique position at the center of a sophisticated pharmaceutical supply chain and play a vital role in supporting the healthcare system.  Further, we are able to do so while realizing multi-billion-dollar savings.  In addition to providing vitally needed healthcare products, distributors also provide numerous additional and important services, including supporting management of the pharmaceutical product inventory in the supply channel.

HDMA understands the concerns underlying FDA’s decision to move forward with an opioid REMS, and is supportive of the overall objective to seek to reduce patient risks associated with these important products.   Since FDA announced the potential class-wide REMS for opioids, distributors have been examining their capabilities and services with an eye towards determining how they may be able to provide support to those who will be implementing the REMS.  Based on these evaluations, we feel compelled to urge FDA to proceed with caution when considering potential “controls” on distributors given their important role within the healthcare system. 

It is unclear what “controls” on distributors the Agency has in mind that would resolve the safety concerns FDA cites as the impetus for this REMS, given that distributors have no contact with patients.  Moreover, any changes in the well established and smoothly functioning distribution system are likely to present many challenges that may disrupt availability of these products.  Given that the Federal Register notice for this meeting cited an iPLEDGE program-type approach as a possible model for the opioid REMS, we believe FDA may be considering two types of controls.  One is to require distributors to verify that their customers meet certain REMS criteria before distributing opioids to them, similar to the current restricted distribution under iPLEDGE.  The other may be to require after-the-fact reports containing data on what products have been distributed and to whom.  Our greatest concern is that such controls on distributors would simultaneously fail to advance the goals of the class-wide REMS for certain opioids while potentially disrupting the flow of these products to the marketplace.  I will address each of the two potential controls on distributors in turn.

First, regarding potential restrictions on distribution, FDA has made clear that the class-wide REMS for opioids is necessitated by an increase in adverse events.2  Patients may be receiving inappropriately prescribed opioids, may not sufficiently understand their proper use, and may potentially be obtaining multiple prescriptions that may be filled at multiple pharmacies. 

Distributors are not in a position to remedy any of these abuse problems.  Distributors do not see patients, do not write or review prescriptions and have no expertise nor involvement in the practice of medicine or pharmacy.  Therefore, they cannot do anything with regard to physicians’ prescribing or patient-education practices nor address patient behavior to curb the abuses of concern to FDA.

Further, a REMS that requires a distributor to confirm a dispenser/customer before distributing certain opioids to that customer would substantially duplicate existing controls.  State and federal laws require that distributors confirm that customers are licensed by the state and registered with the Drug Enforcement Administration (DEA) to handle controlled substances.  DEA also requires that distributors monitor “suspicious orders” and report to the DEA if it appears a pharmacy’s controlled substances volume or pattern of ordering might signal diversion or other concern about the controlled substances’ movement within the supply chain.3  Thus, additional distribution restrictions would duplicate existing requirements and fail to have any effect whatsoever upon the patient abuse the REMS is attempting to mitigate. 

More importantly, such restrictions are very likely to have profound, highly disruptive effects upon access to these and all the other pharmaceuticals that we distribute.  This disruption is likely because of the enormous volume that distributors handle.  The healthcare system relies heavily on HDMA member distributors to ship more than 8 million pharmaceutical and related products to customers every day in a rapid, efficient, cost-effective manner.  To achieve this kind of efficiency, distribution systems are highly automated.  A typical distribution center delivers to more than 1,000 dispensing sites.  They also distribute over 64,000 product packages daily.  Further, distributors provide many multi-million dosage units of the products potentially covered by the opioid REMS in any given month.  If there is a change in what and how we distribute, or in the software used to maintain product and customer information, it must be constructed so that it does not affect or delay ordering and delivery for either the opioid products or any of the other hundreds of thousands of products stored in the same warehouse and tracked by the same systems.

We have noted errors in the much smaller iPLEDGE system which complicate matching approved pharmacies to distributors’ customer lists.  iPLEDGE involves a fraction of the number of the products and customers (about 44,000 – 45,000 pharmacies) that would be subject to the class-wide opioid REMS, where we estimate that there could be from 150,000 to over 1.3 million healthcare entities.4  The potential for delays in shipments to customers in a class-wide opioid REMS will be many-fold greater than in iPLEDGE, depending on how many participate.  Further, if distributors must separate out and restrict distribution of opioid drugs from the other 8 million or more products distributed daily, the potential for adverse impacts on distribution of the non-opioid drugs must be noted. 

We are also concerned that, as FDA evaluates and structures additional REMS, there will be new criteria for pharmacies and/or prescribers that are different for each REMS and the additional, multiple REMS will be layered over and over on top of each other, with differing restriction criteria, even for the same customers.  The resulting massive, continuous Information Technology (IT) structuring and restructuring as practitioners and dispensers become “certified,” renew participation, or leave these multiple REMS programs, will potentially create a system that will not be sustainable, if it is even feasible to begin with. 

Turning to the second control that FDA may be contemplating, we also do not believe it is appropriate to require distributors to provide after-the-fact reports regarding what products have been distributed and to which customers.  Distributors already report three forms of information concerning controlled substance distribution to the DEA.

1. DEA’s regulations require that every order for a Schedule II product be placed on DEA Form 222 and DEA must receive a copy of that completed form.5  Form 222 includes the name, address, and DEA registration number of both the supplier and the customer, the product name, dosage form, and strength.  
2. DEA’s ARCOSregulations require distributors to report, on at least a quarterly basis, their inventories, acquisitions, and dispositions of all substances in Schedules I and II, as well as all narcotic and Gamma-Hydroxybutyric Acid (GHB) substances in Schedule III.6 
3. As mentioned earlier, distributors must even report to DEA if they detect that a customer’s controlled substances volume or pattern of ordering might constitute a “suspicious order.”7

Thus, any additional reporting requirements for distributors would be highly duplicative and would not advance the goals of the class-wide REMS for certain opioids.

Moreover, additional reporting on sales data is not an appropriate step for distributors because it cannot be accomplished without substantial IT challenges (which would exact an enormous cost on the healthcare system), and will potentially disrupt the provision of these products to pharmacies, hospitals, and other healthcare entities.  To set up a system that could electronically separate out, and accurately communicate, the vast number of records for the opioid products from the even more massive number of records for all the other products that distributors ship will be an enormous challenge.

The difficulty of reporting will be compounded if the REMS will require records that differ in any way from those distributors are already sending to DEA.  Additionally, smaller distributors often have more limited IT capabilities.  Smaller distributors tend to service independent pharmacies, and rural and other difficult-to-reach areas, and if significant reporting requirements jeopardize their ability to participate in the REMS, such requirements could potentially disrupt the efficient flow of these and other healthcare products to such areas and inadvertently limit patient access.

There are a host of additional technical, policy and legal questions, not the least of which include: how to ensure confidentiality of a massive amount of data; standardizing data currently stored in a variety of formats among distributors; potentially diverting resources from existing safety initiatives (such as track-and-trace technology) to work on the REMS reporting; and more.  It likely will require years of cross-industry technical expertise to identify, much less resolve, these issues. 

We are also very concerned that as FDA considers additional, multiple REMS for different products, such reporting requirements will involve even more massive and complex IT systems revisions that will, if unchecked, risk our members’ ability to supply such data and even the products themselves. 

Again, none of the data that distributors could provide will yield any direct information about patients or prescriptions.  So, we cannot even speculate how such data will advance FDA’s stated goals for the opioid REMS.  We believe that the REMS sponsors will not have much more use for such data than simply to say that it is “nice to know.”  

In closing, I would like to leave you with our recommendations: 

• We agree with other organizations that are encouraging FDA to establish the REMS in a step-wise fashion.  To us, it makes sense to address the main concerns that FDA feels necessitates the REMS – such as provisions most likely to directly help avoid patient misuse.  If manufacturers and FDA find that they are not effective, FDA may then consider adopting additional requirements.  The additional time and expense for controls on others in the supply chain may not even be necessary if the primary causes are directly addressed.  

• Second, if despite our views, FDA and the sponsors still believe that restricting distribution and/or after-the-fact reporting by distributors is necessary, then the REMS should not specify any restrictions on the fees that distributors are allowed to charge for these services.   It will cost significant sums to implement such a program and the marketplace will have to determine how those costs are allocated.

• Finally, regardless of the elements that FDA may determine are to be included in a REMS, we urge the agency to allow, and even encourage, pre-testing of the REMS elements to help ensure their efficacy and operational feasibility. 

Thank you and I’ll be happy to take any questions.