THE DOD/FDA SHELF LIFE EXTENSION PROGRAM TO EXTEND THE SHELF LIFE OF CRITICAL STOCKPILES OF MEDICAL MATERIEL FOR THE FEDERAL GOVERNMENT

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1 THE DOD/FDA SHELF LIFE EXTENSION PROGRAM TO EXTEND THE SHELF LIFE OF CRITICAL STOCKPILES OF MEDICAL MATERIEL FOR THE FEDERAL GOVERNMENT Introduction To assure preparedness for war or other contingencies, the Federal government maintains significant pre-positioned stocks of critical medical materiel, to include pharmaceuticals. These pharmaceuticals possess finite, labeled expiration dates. Routinely replacing this stock is costly for the Federal Government and the taxpayers. To reduce overall costs, while maintaining the same capability, the Federal Government participates in a cooperative product evaluation program with the U.S. Food and Drug Administration (FDA). This program is known as the DoD/FDA Shelf-Life Extension Program (SLEP). The FDA evaluates selected materiel for shelf life extension by testing samples submitted from SLEP participants. If the testing results warrant, the FDA authorizes extended product dating. The Defense Medical Standardization Board s (DMSB) Staff Office coordinates the program and acts as the single interface between SLEP participants and the FDA. SLEP participants fund the program, manage their inventories, and receive the benefit of deferred materiel replacement costs for items they possess. SLEP assures the safety and effectiveness of those products that are enrolled in the program. The DoD/FDA Shelf Life Extension Program is an internal component of the Medical Readiness Strategic Plan (MRSP). The Office of the Secretary of Defense developed it for Health Affairs and the Military Medical Departments. This interagency program originated in response to Congressional concern over the conservation of strategically important military medical resources. This is the only program of its kind that is authorized by the FDA. Participation is limited to Federal-level organizations with stockpiled pharmaceuticals that are currently in the program or meet the criteria for inclusion. History Prior to the introduction of the program, the Services were investing significant funds in replacement costs for potency dated pharmaceutical products (pre-positioned stocks, war reserves and depot-stocked pharmaceuticals). One of the methods suggested to limit expenditures and defer drug replacement costs for this materiel was to test the expiring inventory to verify that it was still within the specifications of the product s official monograph. In July of 1985, representatives from the Air Force Surgeon General s Office and the FDA met to determine the feasibility of testing drugs for possible extension. An agreement resulted from this meeting to establish a pilot project. Although the FDA was conservative in 1

2 their estimates, some of the tested items were granted extensions of up to 3 years beyond their initial expiration date. In January of 1986, a signed interagency agreement created the DoD/FDA Shelf Life Extension Program (SLEP). The DMSB staff office was tasked as the Quad-Service, DoD focal point for the program. Testing of items submitted by the Services and by DSCP began during fiscal year Over the next 3 years, the program grew considerably and the FDA dedicated program resources (facilities and personnel) to support requirements for new testing as well as retesting projects. The program has changed significantly, as pharmaceutical industry practices and knowledge about product safety and stability have evolved. After September 11, 2001, the program was expanded beyond DoD to include other selected Federal Agencies. Currently, the following organizations participate in the program: the FDA, the DMSB, Army, Navy, Air Force, Marine Corps, Coast Guard, Defense Logistics Agency, the Department of Health and Human Service s Strategic National Stockpile (SNS), the Veterans Administration Emergency Preparedness Program, the Department of Agriculture and the National Guard Bureau. SLEP is oriented towards the testing of military significant products, those that are either militaryunique, possessing no commercial (non-dod) market, or drugs the Federal Government procures in such large quantities, for pre-positioned stocks, that vendors are unwilling to accept them for credit upon expiration. FDA Testing The FDA is the independent evaluator and proponent for quality control of medical materiel, performing all required testing of items entered into the DoD/FDA SLEP. The FDA uses the U.S. Pharmacopoeia or the original manufacturer s test data on each item to establish a protocol for testing. Accelerated testing (also called stress testing) is the method used most often to predict the extension period. The accelerated testing protocols increases the rate of chemical or physical degradation of the drug substance by using exaggerated storage conditions. Each item is "stressed" (placed in chamber which maintains a temperature of 50 degrees centigrade and 75% humidity) for 60 days. The potency of the stressed samples is compared with the standard for each item and, using the comparison, the FDA estimates the extendable life of the product. The FDA testing process, from the time the DMSB presents the project s candidate list until the DMSB receives results, typically takes six months. The FDA will not test all items presented to them as program candidates. The FDA s Center for Biologics Research (CBER) has never authorized the testing of any biological products (vaccines, toxoids, serums, blood products, etc.) by SLEP. In addition, nutritional products and products with a history of poor performance in the SLEP testing process (e.g. water purification tablets and Mefloquine ) are not accepted for testing, nor are items where the testing is time and/or cost prohibitive. The testing conducted by the FDA is comprehensive and scientifically sound. The FDA bases their expiration date extensions on conservative estimates of the useful life of the product as substantiated by the test results. Statistical methods are employed to predict when each 2

3 product would be expected to breach the acceptable potency specification, and a date is selected that is less than the expected breach timeframe. The FDA will grant extensions to all SLEP participants whose materiel, specified by lot number, expiration date, and manufacturer, and stored under appropriate conditions, has been tested and approved. Testing SLEP products is an ongoing process. Materiel is retested to confirm extended dating (or to permit further extension) on an annual or biannual basis. This is a mandatory requirement for all materiel remaining in the SLEP. If products fail testing at any time, they are identified for immediate destruction, regardless of their labeled expiration date. Products that are not tested or products that do not receive additional extensions are destroyed upon reaching their final expiration date. The Current SLEP Process All pre-positioned stocks should rotate when possible; however, quantities often exceed normal requirements. In June 2005, DoD/FDA SLEP database was modified from desktop application that was only accessible at Fort Detrick to a Web-Based, Oracle application that is accessed via the internet by all users of the SLEP system. The system requires users to enter their on-hand inventory of stockpiled medical materiel as soon as the materiel is received and users must continue to update their inventory at least once per quarter. Efforts are currently underway to update those inventory quantities with DMLSS-AM data provided by the Joint Medical Asset Repository. Participant Points of Contact (POC) now use this data for budgeting, reporting and management of stockpiled materiel Once a quarter, a list is generated of all materiel due to expire in the next 180 days. This list, compared against the total on-hand quantities and the original expiration date of the item, identifies testable materiel. The FDA will not currently extend any materiel beyond 10 years from the original manufacturer s expiration date. The FDA testing procedures determine the length of extension and some items fail testing prior to the 10-year endpoint,( e.g. silver sulfadiazine cream, which turns brown after 5 years of testing and diazepam, which builds up impurities after seven years). The FDA generally requires a cumulative value (per lot) of at least $10,000 between all SLEP participants, prior to testing a specific lot number. Otherwise, it is not cost-effective to test. The SLEP user at a stockpile location is critical to the program. Each user must correctly identify all stock in the SLEP application to ensure testing decisions are based on the most accurate data. As lots are identified as potential test candidates, they are marked in the SLEP application with a Lot Status: Add to Test. When sufficient number of test samples have accumulated or when the FDA is ready to begin planning for a new test project, the DMSB staff office sends a list of potential test candidates for the next 180 days and requests remaining samples be sent to the FDA. The SLEP application sends an automated sample request to participating SLEP POC s with the specific lot numbers. The POCs task one of their activities to provide a designated quantity of materiel, by lot and NSN, to the FDA. The activity ships the materiel to one of two FDA sites. However, in some cases the FDA may only request a copy of the product label and not the actual product. This occurs when the manufacturer produced 3

4 several lots from one batch where the testing history for one lot will serve as the reference for the entire batch extension. When a sample is required for testing, the FDA will usually request enough materiel for a total of three extension tests, the first test plus two subsequent tests. This is because most items are usually tested three times before they fail or the on-hand quantity falls below the testing threshold. The FDA requires sample receipt within 30 days of the request. Item samples not received within 30 days are dropped from the test project. Timely submission of samples is critical to successful completion of a project. Once the FDA has received all the new test samples or it has been 30 days from the samples request date, the FDA assigns a project number. This project number represents a list of products, by lot number, to be tested. The FDA sends the project number and a list of lot numbers that will not be tested to the DMSB staff office. The DMSB staff office enters this information into the SLEP application and sends an message listing the lots for that project to all SLEP participants. A message is also sent through the Defense Messaging System to identified Commands. Upon completion of testing, the FDA forwards the test results to the DMSB staff office. The DMSB staff enters the information into the SLEP application and sends a notification message to all SLEP participants. SLEP participating activities with those items (by lot number) may extend that materiel to the new expiration date, but only if that materiel has been properly stored in accordance with the manufacturer s specifications. All products tested initially will be re-tested biannually or annually until the product fails testing, or it reaches the 10-year maximum, or stocks are depleted. The program s direction has changed since its inception. The switch from a large, DoD depot supply system to predominantly prime vendor suppliers and just-in-time deliveries for dayto-day requirements, has refocused the program to pre-positioned stockpiles of Chemical Biological Radiological Nuclear (CBRN), Pandemic and anti-malaria materiel. The prime vendor system reduced the need for centrally controlled warehousing of drugs and therefore reduced the eligibility pool of testable products. Additionally, all DoD medical facilities may participate in a Return Goods Program to receive credit or replacements for expired items. The Return Goods Program provides replacement of expiring products at little or no cost to the facility. The DoD continues to have tremendous success with the SLEP program because only products with a high probability extension are included in test projects unless there are compelling reasons for testing. Labeling Requirements and Guidance The FDA requires products be labeled and relabeled in accordance with the Food, Drug and Cosmetic Act of 1938 (or subsequent amendments) or the Food and Drug Modernization Act of Products not relabeled in accordance with these laws or CFR are considered misbranded if they are sold, distributed, or dispensed and are in violation of these Acts. The FDA Center for Drugs (CDER) compliance office requires that products extended under SLEP be relabeled with the lot number, new expiration date and FDA project number. 4

5 The new label does not have to be the same font and color as the old label. However, the new label must not obscure the writing on the original label and the new label must be legible. In addition, the sticker must adhere to the old label in such a way that if it were peeled off, the label underneath would also peel off. It is not necessary nor is it advised to remove the original label and apply a new label. The FDA does not want the original product label removed. Applying a new label on the product would require approval by the FDA compliance office. The intent of this guidance is to instill user confidence that the products they receive are of high quality, completely safe and will work effectively, as expected. For DoD-owned inventory, the FDA has authorized a deferral of the requirement to relabel every individual unit of issue but it only applies while the materiel is maintained under centralized SLEP Participants control. The deferral was granted to reduce the cost of multiple relabeling efforts, since SLEP products may be extended multiple times prior to being issued. The FDA permits DoD SLEP participants to label only the outer cartons of products with the updated information so long as they remain in centralized storage, control, and management. Prior to being distributed and issued to activities or individuals, the materiel must be relabeled completely, to individual units of issue. Due to the requirements for immediate readiness of all SNS drugs, they have opted to relabel all SLEP items immediately after the FDA grants extensions. The ability to print and distribute the extension label is being developed as an automated process in the SLEP. This feature should be fully operationally by the fall of Each SLEP participant can make the decision to defer or completely relabel items, based on the urgency of need and timeline for a contingency situation. Non-DoD participants are referred to USC Title 21 for guidance on relabeling or are advised to contact a licensed repackager. Sampling of Data from Items Tested under SLEP It is important to note that products tested under this program have tightly managed, controlled conditions at a limited number of locations. It is inappropriate to extrapolate this data to drugs stored outside of these conditions. Storage conditions vary widely across the enterprise and SLEP is not used unless storage conditions are verifiable and are based on the same reference standard. Even within SLEP, products known to have been stored under adverse conditions (i.e., high temperature or low temperatures) are excluded from the program, unless marked and tested separately from normal stocks. Medications previously issued to individuals or removed from the centralized stockpile locations cannot be tested for extension under the SLEP Program. Items issued to individuals, units, or activities are dispensed and never permitted back into the supply chain, regardless of SLEP testing results since storage conditions and security of these items cannot be assured. Dispensed products turned-in after completion of an operation are destroyed. Similar practices are executed in routine peacetime care for both DoD facilities and civilian medical practice. The number of drugs tested each year has fallen to an average of 13, but the size and number of lots of each drug has increased drastically. 5

6 This SLEP is a tremendous value to participants but it is only cost effective for large stockpiles of medical materiel or for medical materiel with limited commercial use (i.e., antidotes for chemical agents). POCs: MAJ Kevin Wright or Ms Ellen Kavanagh /4179 Updated: Oct 2007 DoD/FDA SLEP Air Force Army Navy Activities Update/Validate onhand inventory Annual Reports/ FDA Testing Internet Marine Corps Internet SLEP DB Update/Validate View/Generate Reports DLA SLEP Servers Service Reps JPEO- CBD-CBD/OSD PMs, FDA, DMSB SNS/VA 6