Attachment A

1. During a recent meeting with both majority and minority staffs on the drug reimportation proposals, your staff provided a three-page budget document that illustrated the likely costs of these proposals for the FDA. Staff asked for the supporting work papers used to arrive at the many assumptions put together in the three-page document. Staff was told that no work papers exist, and that most of this was done by a "working group." It is curious that an agency embracing legislation that will dramatically increase its workload does not have a detailed set of work papers or other supporting documents to support such analysis. Please provide us with all documentation used to arrive at the budgetary predictions made on the three-page document you provided to the Committee.

2. It is my understanding that the FDA has still not developed a specific frequency target for agency inspections of foreign firms that ship to the U.S. for Good Manufacturing Practices (GMPs). Please explain whether this is the case, and if so, why the FDA has not done so. If it is not the case, please describe the present frequency target FDA uses to inspect foreign firms that make drug products shipped to the U.S.

3. It is my understanding that many foreign firms that ship drug products to the U.S. have not received a GMP inspection from the FDA in as many as six to eight years, and maybe longer. Because FDA’s information technology system(s) still remains in disarray (and has been that way for years), your agency still cannot generate an accurate assessment of precisely (a) what firms currently are shipping to the U.S., (b) when they should have been last inspected, and (c) when they actually were last inspected. Please explain why this is still the case, and describe any public health implications that may result for failure to inspect these manufacturers on regular two-year intervals.

4. As accurately as possible, please provide your present backlog of foreign inspections today as measured against FDA’s effort to conduct such inspections on a two-year basis. Please also describe the factors that led to FDA’s current backlog.

5. Please state what resources are needed for FDA to know the internal GMP conditions of all plants shipping drug products to the U.S. Please provide this in both dollar amounts and FTEs, if possible.

6. One of the most significant problems facing FDA’s foreign inspection program is that the OASIS system still cannot adequately keep pace with FDA’s present workload. It is my understanding that FDA is attempting to upgrade and/or replace much of that system, and has hired an outside contractor for this effort. Please provide (a) the cost of the outside contractor; (b) what this upgrade is expected to cost; and (c) how long the system upgrade/replacement will take. Also, I understand that the contractor has already issued cost and other analyses to the FDA. Please provide all such reports.

7. In previous correspondence with this Subcommittee, FDA disclosed that a number of foreign firms were exporting (or have exported) drug-related materials to the U.S., yet have never been inspected by FDA authorities. Now, your testimony states that there are as many as 242 drug manufacturers in 36 countries that appear to have exported to the U.S. in 1999, but have not been inspected. Please provide a list of these firms to the Subcommittee, and what products each has shipped. Also, please provide an analysis of what the potential implications of this finding are on the safety of the Nation’s drug supply. Finally, please state specifically what the FDA is now doing about these firms.

8. Please provide an explanation of whether the FDA now believes that the threat of drug counterfeiting is less today than before the Prescription Drug Marketing Act went into effect.

9. On a recent trip to China to investigate issues relating to both FDA foreign inspections and pharmaceutical counterfeiting, Commerce Committee staff were told by several security officials that counterfeit material is often mixed into shipments of legitimate products, as an additional tactic to elude regulators. Thus, rather than entire shipments being counterfeit, in some cases only a part of a total shipment may be illegitimate.

(a) Does FDA believe that such a tactic might be used by counterfeiters today? Has the agency ever seen evidence of this method? If so, please describe the details.

(b) Is batch testing, which the proposed legislation has as the primary test of authenticity, a reliable method for protecting the U.S. consumers from potentially rogue and dangerous counterfeit drugs?

(c) If a batch test were only to test the legitimate product contained in a mixed shipment, how, under this legislation, will counterfeit material be detected? Is there a methodology for doing this?

(d) FDA has long told this Committee that quality assurance cannot be "tested" into a system (hence, the purpose behind the current foreign inspection program), which is why the agency has rejected batch testing as a final test for finished product and bulk materials sent to the U.S. Do you believe that batch testing is suitable to meet the same stringent safety requirements long relied upon by the agency?

10. Why doesn’t the FDA simply batch test raw ingredients as they come into the U.S. instead of relying on expensive GMP inspections?

11. The PDMA and its implementing regulations established standards for storage and handling of medicines as they move from a manufacturer to a retail pharmacy. These provisions were enacted because pharmaceuticals are very sensitive to various environmental factors, and therefore drugs are packaged under controlled conditions. Storage of pharmaceuticals under extreme environments can, as you know, lead to premature deterioration of the drug. The new legislation’s testing requirements for product degradation will provide information on drug potency at the point a test is conducted (and not across the shelf life of the drug). This means there is no guarantee that a product imported from another country will arrive with roughly the same shelf life as envisioned by the manufacturer. If drug products have been subjected to temperature extremes while being shipped or stored, or are improperly repackaged, the medicines could not be guaranteed to meet its specifications up to the expiration date. Moreover, imported drugs will require repackaging and relabeling so that the imported product conforms with an FDA-approved and required dosage form, packaging, and product labeling for the American market. This means there is a very real chance that an American patient will unknowingly receive pharmaceuticals that are not fully efficacious because of premature loss of potency. Do you agree with this assessment, and if so, how can these very real and potentially dangerous possibilities be dealt with in the implementation of the new legislation?

12. As you know, in the United States, pharmaceutical recalls are initiated by manufacturers because a manufacturer can quickly and efficiently locate its products through its wholesale distribution system. Under the new legislation, imported drug manufacturers may not have a systematic way of knowing where a drug originated, or even if a product has been transshipped to multiple countries before entering the United States. It not only allows a drug to be shipped through multiple foreign locations, but also for a drug to be transferred among any number of intermediaries. Because of the likelihood of repackaging, it is not even certain that the product will be labeled with the original manufacturers lot number. How can a manufacturer’s recall be administered efficiently and effectively under these new conditions?

13. If in the future we see many new repackaging facilities play a role in bringing products to the U.S. market, do you have any concerns regarding these facilities?

14. It appears that certain products are inherently difficult to repackage or re-label, such as sterile injection solutions, auto injectors, ointments, and pre-filled syringes. What are the issues relating to repackaging such products, and what are FDA’s concerns regarding any new legislation that allows for relabeling and repackaging?

15. What percentage of the bulk raw material used to manufacture drugs globally is considered substandard or even adulterated?

16. Which countries are the most problematic when it comes to selling substandard or counterfeit bulk ingredients, or does FDA even have such an assessment?

17. Which countries are the most problematic when it comes to selling substandard or counterfeit finished products? Does FDA have such an assessment?