Inspections, Compliance, Enforcement, and Criminal Investigations
Patient First Corporation 15-Mar-05
Department of Health and Human Services
Public Health Service
Baltimore District Office
Refer to FEI:1122528
March 15, 2005
VIA HAND DELIVERY
RETURN RECEIPT REQUESTED
George H. Morison, President
Patient First Corporation
5000 Cox Road, Suite 100
Glen Allen, Virginia 23060-9263
Dear Mr. Morison:
During an inspection of your facility located at above referenced address on November 23 and 24 and December 1 and 9, 2004, we determined that you repack 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 repacked by your firm are adulterated within the meaning of section 501 (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 CFR 211) as follows:
1. Failure to have operations performed within specifically defined areas of adequate size as necessary to prevent contamination and to have operations relating to the manufacture, processing, and packing of penicillin and cephalosporin performed in facilities separate from those used for other drug products for human use [21 CFR 211.42(c) and (d)].
For example, penicillin products (amoxicillin and penicillin VK) and a cephalosporin product (cephalexin) were repacked using the same equipment and/or in the same production area of your facility as other non-penicillin products.
Cephalosporin products, like penicillin products, are categorized as beta-lactam drugs and present a health hazard to consumers with sensitivities to these compounds. Consequently, under 21 CFR 211.42(c) and (d), the Agency requires that the manufacture, processing. and packaging of beta-lactam drugs (e.g., penicillin and cephalosporin) be separate from non-beta-lactam drugs (e.g., ibuprofen). Pursuant to 21 CFR 211.42(d), penicillin and non-penicillin beta-lactam drugs must also be separate from each other. In this case, there is neither separation of the cephalosporin and penicillin drug products repackaging processes, nor separation between the beta-lactam and non-beta-lactam products.
The agency has taken the position that all three of those drug products should be separated from each other. 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 manufacturing operation. 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 continuous monitoring if necessary.
2. Failure to have a completely separate air-handling system for the manufacture, processing, and packing of penicillin from those for other drug products for human use and to have an adequate air filtration system [21 CFR 211.46(c) and (d)].
For example, a single HVAC air handling system fitted with one [redacted] filter at the air intake unit located on the roof top is used to process the air supplied to the area of your facility where penicillin products (amoxicillin and penicillin VK), a cephalosporin product (cephalexin), and non-penicillin products (including but not limited to Methocarbomol, Ibuprofen, Levaquin, Macrobid) are repacked. In addition, the inspection disclosed that you have not established measures to control recirculation of contaminants (i.e. dust observed on ducts) through the HVAC air handling system
3. Failure to follow written procedures for the cleaning of equipment and utensils used in the drug repacking operation [21 CFR 211.67(b)].
For example, the investigator observed white residue on the inside surface and on the outside surface of several tablet/capsule holding cassettes, yellow residue in‘the interior surface of another cassette, white powdery residues on a product-counter machine and white powdery residue on the counter top on a product-counter machine after cleaning operations had been performed.
4. Failure to conduct stability studies or to have such studies conducted for you to justify the expiration dates that you use on solid oral dosage forms repacked into unit-of-use containers (21 CFR 211.166(a)].
For example, your firm did not have any stability data for solid oral dosage forms repacked in container and closure systems that are different from the original container and closure systems [e.g., use of a desiccant) to support the use of the manufacturers’ expiration dates on the repackaged drug products.
We acknowledge receipt of Mr. Warren Bridges’ correspondence and supporting documentation faxed to Investigator [redacted] December 14, 2004 in response to the Form FDA-483 of December 9, 2004. The written response reports that certain changes have been carried out that would help eliminate any chance of cross contamination among drug products repacked by your firm. The response is inadequate because repacking of penicillin, non-penicillin beta-lactam products, and non-beta-lactam products remain in the physical barriers separation and by using the same equipment [redacted] machine.
The written response claims that the ]redacted] machine, by design, and as stated in [redacted] sales brochure (“The accuracy and speed of automated dispensing with the convenience of on-site calibration”) would not lend itself to the cross-contamination of drug products. Further, the written response contends that the [redacted] machine has been designed specifically for the type of repacking that your firm does. As indicated, 21 CFR 211.42(c) and (d) requires the packing of penicillin and cephalosporin products to be performed in facilities separate from those used for other non-beta-lactam drug products for human use.
The violations identified in this letter are not intended to be an all inclusive list of deficiencies at your facility. It is your responsibility to ensure that your operations and products conform to each requirement of the Act and regulations. You should take prompt action to correct these deviations. You should notify this office in writing as soon as possible but in any event no more than 5 days after receipt of this letter, of the specific steps you have taken to correct the noted violations. Please send your response to Jose R. Hernandez, Compliance Officer, US Food and Drug Administration, 2810 North Parham Road, Suite 160, Richmond, Virginia 23294. If you have questions regarding any issue in this letter, please contact Mr. Hernandez at (804) 747-0124, extension 103.
Director, Baltimore District