Prescript Pharmaceuticals, Inc. 22-Dec-03

VIA FEDERAL EXPRESS

December 22, 2003

Mr. William J. Hartig, President
Prescript Pharmaceuticals, Inc.
39 California Street, Suite 1010
Pleasanton, CA 94566

WARNING Letter

Dear Mr. Hartig:

During an inspection of your facility located at 39 California Street, Suite 101, Pleasanton, CA, on July 1 through August 11, 2003, we determined that your company, Prescript Pharmaceuticals, Inc., repackages various drug products,which are human drugs within the meaning of section 201(g)(1)(B) of the Federal Food, Drug and Cosmetic Act (the Act).

The inspection revealed that the drugs repackaged by your firm are adulterated within the meaning of section 5a1(a)(2)(B) of the Act in that they are human drugs and the methods used in, or the facilities or controls used for, their processing, packing or holding do not conform with current good manufacturing practice (cGMP) regulation for drugs specified in Title 21, Part 211 of the Code of Federal Regulations (21 CFR211), as follows,

1. Failure to conduct repackaging of penicillin and non-penicillin drug products in separate facilities. [21 CFR 211.42 (d), 211.46 (d) and 211.176]

The cGMP regulations explicitly require that penicillin drug products be processed in a separate facility from all other drug products. These regulations require that the separate facility be equipped with an air-handling system that is separate from the air-handling system used for other drug products. They also require that if the possibility exists that a non-penicillin drug is exposed to penicillin, that the non-penicillin drug be tested for the presence of penicillin.

Your firm is in violation of the above cGMP regulations in that there are no containment procedures to ensure that individuals who are engaged in the repackaging of penicillin drug products do not cross-contaminate non- penicillin drug products with penicillin. Our inspection observed that immediately after repackaging penicillin drug products, employees could enter non-penicillin areas and handle non-penicillin drugs without exercising any decontamination procedures. Our inspection observed an employee repackage a penicillin drug then a non-penicillin drug product during the same day without exercising any decontamination procedure such as washing and changing clothing. The employee was observed wearing the same street clothing with no protective garment during the repackaging operations for both penicillin and non-penicillin products.

Our inspection found that repackaged penicillin drug products are being sealed, labeled and held in the area of your facility that is also used for packaging non-penicillin drugs. This practice also violates the above CGMP regulations; which require complete separation of operations for penicillin and non-penicillin drugs.

Your firm also is in violation of the above cGMP regulations because there is not a separate air-handling system in the room used to repackage penicillin drug products. The inspection found that the same air-handling system services both the penicillin and non-penicillin areas. Further, it was noted that the penicillin room has no air vents, and it opens directly into the non-penicillin packaging area, thereby increasing the potential for cross-contamination. Your firm's noncompliance with these cGMP regulations means that you must not distribute any products that may have been exposed to penicillin as a result of your lack of penicillin containment control.

Additionally, considering the lack of penicillin containment, your firm is also required by 21 CFR 211.176 to test samples of all non-penicillin drug products, including any cephalosporin drugs, that could have been exposed to penicillin in your facility, for the presence of penicillin. Such testing must be conducted using suitable, sensitive analytical methods. Under the additional authority of this regulation, should the testing detect the presence of penicillin, the products must not be distributed. (Please note, however, that even if testing does not detect the presence of penicillin, this does not assure that penicillin contamination does not exist and under section 501(a){2)(B) of the Act, your firm still must not distribute any products that may have been exposed to penicillin as a result of your lack of penicillin containment control, as discussed above.) The absence of penicillin contamination in test results should not be construed as evidence that your firm has adequate containment procedures given the limitations of testing only a random sampling of products.

Considering that non-penicillin products contaminated with even trace amounts of penicillin pose a serious health hazard to patients who have sensitivity to penicillin, your firm should assess what actions to take with regard to non-penicillin drug products previously distributed by your firm which have not yet reached their expiration date. Please immediately apprise us as to what actions you intend to take regarding previously marketed drug products.

Further, we wish to point out that in order to reach the goal of no cross-contamination, a system-based approach towards separation should be taken. This entails a complete separation of every aspect of the repackaging operations conducted by your. firm. Adequate separation should include physical barriers, air-handling systems, personnel, and equipment with well established written procedures and controls. The separation should be verified by testing, auditing, and if necessary, continuous monitoring.

2. Failure to conduct repackaging of cephaldsporin drug products in separate facilities from those used for penicillin and non beta-lactam drug products.[21 CFR 211.42(c)]

Our inspection found that your firm has no procedures to ensure that operations relating to the repackaging of cephalosporin drug products are conducted in a separate facility from the repackaging of other drug products repackaged by your firm. The inspection found that the same facility, work areas and equipment are used to repackage cephalexin, (which is a cephalosporin), non-cephalosporin, and non-penicillin drug products.

Cephalosporin drug products, like penicillin drugs, are beta-lactam drugs and pose a serious health hazard to patients who are sensitive to such compounds. Like penicillin, intolerance of beta-lactam ingredients can trigger reactions that range from a rash to life-threatening anaphylaxis. Additionally, there is evidence that patients tolerant of penicillin may be in tolerant of cephalosporins, and non-penicillin beta-lactams also have the potential to sensitize individuals and cause severe allergic reactions. Consequently, the same procedures outlined above for containment of penicillin drugs also applies to cephaiosporins.

The repackaging of cephalosporins must be conducted in separate facilities with separate air-handling systems from those used for non beta-lactam and for peniciilirn drug products. Due to the lack of cephalosporin containment in your facility, non-cephalosporin drug products that could have been exposed to cephalosporins in your facility should be tested for the presence of cephalosporins. We also request that you apprise us of what actions you intend to take concerning previously marketed drug products that may have been exposed to cephatosporins in your facility.

3. Failure to assign expiration dates to repackaged drug products that are determined by appropriate stability testing, and failure to assure that liquid drugs are not altered during repackaging operations. [21 CFR 211.137 and 211.166]

Your firm assigns the expiration dating on the manufacturer's original container, but not exceeding 24-months from the date of repackaging, to the solid and liquid dosage form drug products that are repackaged by your firm. Our inspection found that stability testing has not been conducted on drug products repackaged by your firm to justify the use of up to 24-months expiration dating. Additionally, your firm does not have test data demonstrating that drug products are being repackaged into equivalent container-closure systems that are at least as protective or more protective than the manufacturers' bulk container-closures from which the drugs are being repackaged. Consequently, there is no basis for assigning the original manufacturer's expiration dating or up to 24 months expiration dating to the drug products that are repackaged by your firm.

Your firm's continuing practice of repackaging prescription oral-liquid drug products without any basis for the expiration dating assigned to these products, and without any data demonstrating compatibility of liquid drugs with their container-closures, are serious deviations from the cGMP regulations. Similarly, the failure to demonstrate through appropriate testing,that the repackaging process does not alter the chemical; physical and microbiological properties of the liquid drug products, is a serious deviation from the cGMP regulations.

4. Failure to have written procedures requiring that expired drug products and rejected bulk and repackaged drug products are held in quarantine and discarded in a timely fashion to prevent their use in repackaging operations. [21 CFR211.10U (a)]

Our inspection observed many expired and rejected prescription drug products stored in quarantine racks and in the same refrigerator used for holding unexpired drugs. For example, several containers of [redacted] found in the expired drugs storage bin in your refrigerator had expired on November 1, 2000. You informed the investigator that you forgot about these expired drugs in your refrigerator. You also informed our investigator that expired drugs are held in quarantine until they can be returned to your supplier for credit. However, the inspection observed many expired drugs in your inventory for several months to over a year beyond their expiration date. It is unclear to us why these drugs are being held in inventory for such lengthy periods. There were no written procedures for identification or segregation of quarantined drugs, or for discarding rejected drugs in a reasonable period of time. We are very concerned about your lack of procedures to ensure that rejected and expired drugs are not being distributed.

5. Failure to retain appropriately identified reserve samples that are representative of each lot of each drug product repackaged by your firm. Your firm has failed to retain any reserve samples of drug products that are repackaged. [21 CFR 211.170(b)]

Repackagers are not exempt from the cGMP requirements to retain reserve samples of each lot or batch of drug product. Your firm must retain a reserve sample of the repackaged drug product from each shipment of each lot of bulk drug product received by your firm. Additional reserve samples are required for each separate repackaging operation, if the bulk drug product is not completely repackaged in one operation.

The reserve samples must be of a sufficient quantity to conduct any required testing pursuant to investigations, and to perform the minimum yearly visual examination for evidence of any drug product deterioration. However,considering the limited examination and testing that are normally required in association with repackaging operations, the size of the samples to be retained would usually be smaller than the size of samples retained by the original drug product manufacturer.

Reserve samples must be stored in the same immediate container-closure system in which the drug product is marketed or in one that has essentially the same characteristics. Since the cGMP regulations do permit the use of an immediate container-closure system having essentially the same characteristics, one size container may represent several sizes from the same lot or batch.

Reserve samples must be examined visually at least once a year for evidence of deterioration unless visual examination would affect the integrity of the reserve sample. The results of the examination, or justification for not conducting an examination of reserve samples, must be recorded and retained.

6. Failure to have adequate written procedures for the sampling, examination and testing of drug product containers and closures, and labeling, used for the repackaging and relabeling of drug products by your firm. [21 CFR 211.80(a) and 211.122 (a)]

Your procedures lack acceptance criteria for containers and closures, and for labeling. Additionally; they fall to include sampling criteria to ensure that a representative sampling of each shipment of each lot of containers and closures, and labeling is examined and, or, tested to ensure conformance with all appropriate specifications.

The above identification of violations is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to assure adherence with each requirement of the Current Good Manufacturing Practice Regulations. Federal agencies are advised of the issuance of all warning letters about drugs so that they may take this information into account when considering the award of contracts. Additionally, pending NOA, ANDA, or export approval requests may not be approved until the above violations are convicted.

We are extremely concerned about your firm's history of non-compliance with the cGMP regulations. Some of the same significant cGMP deviations found during the most recent inspection were previously cited in a July 6, 1995, warning letter, and in the FDA inspections that followed the warning letter. You should take prompt action to correct the violations observed during FDA's most recent inspection. Failure to promptly correct these violations may result in regulatory action without further notice, such as seizure and/or injunction.

Please respond in writing within fifteen {15} days from your receipt of this letter. Your response should describe each step that has been taken to completely correct the current violations and to prevent the recurrence of similar violations and any documentation necessary to show that correction has been achieved. If you cannot complete all corrections before you respond, please explain the reason for your delay and the date by which each such item will be corrected and documented.

Please send your reply to Russell A. Campbell, Compliance Officer, U.S. Food and Drug Administration, San Francisco District, 1431 Harbor Bay Parkway, Alameda, CA 94502. If you have any questions, Mr. Campbell may be reached at 510-837-6861.

Sincerely,

/S/

Dennis K. Linsley
District Director