Inspections, Compliance, Enforcement, and Criminal Investigations
Pallimed Solutions, Inc. 2/19/14
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| New England District Office|
One Montvale Avenue, 4th floor
Stoneham, MA 02180
VIA UPS OVERNIGHT
February 19, 2014
Mr. James Nahill, Owner
Pallimed Solutions, Inc.
400 West Cummings Park, Suite 1050
Woburn, MA 01801
Dear Mr. Nahill:
Between March 20, 2013 and March 29, 2013, a U.S. Food and Drug Administration (FDA) investigator conducted an inspection of your facility, Pallimed Solutions, Inc., located at 400 West Cummings Park, Suite 1050, Woburn, MA 01801. During the inspection, the investigator noted that your firm produced sterile drug products for a variety of intended uses including erectile dysfunction and hormone replacement. The investigator observed insanitary conditions for producing sterile drug products, which put patients at risk. For example, your firm did not determine the source or implement permanent corrective actions after visual particulates were observed in several lots of drug products purported to be sterile. In addition, we observed aseptic breaches such as technicians with exposed skin, and poor aseptic practices such as a technician leaning forward inside the aseptic hood during production. These observations and others were noted on a FDA Form 483 issued on April 9, 2013.
A. Violations of the FDCA
Under section 501(a)(2)(A) of the FDCA [21 U.S.C. § 351(a)(2)(A)], a drug is adulterated if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth or rendered injurious to health. Numerous subvisible microorganisms and other contaminants are ubiquitous in an ordinary environment. A firm producing sterile drugs must take certain steps in order to ensure removal of contaminants through various controls that focus on safeguarding drug sterility by assuring the quality of the processing environment (e.g., surfaces, personnel, air) and the materials that go into a drug product. Otherwise, drugs that are intended or expected to be sterile may become contaminated during preparation and, when administered to a patient, may result in infections and/or pyrogenic responses that pose a life-threatening health risk to a patient. Failure to take these steps when producing drugs that are intended or expected to be sterile causes the drugs to be prepared, packed, or held under insanitary conditions.
FDA investigators noted that drug products intended or expected to be sterile that were produced by your firm were prepared, packed, or held without taking necessary steps to ensure removal of contaminants present in the ordinary environment. Therefore, all of your drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA [21 U.S.C. § 351(a)(2)(A)]. Examples of the insanitary conditions observed at your firm include:
1. The conditions within your facility are such that they allowed for the introduction of filamentous and brown floating particles observed in several lots of sterile drug products produced by your firm. During the inspection, our investigator performed a visual inspection of several sterile drug product lots produced and held at your firm intended for patient use. As a result of that visual inspection, approximately 56 vials were observed to contain what appeared to be visible particulates (e.g., white filamentous material and black floaters) in 9 sterile drug product lots.
2. During the inspection, a (b)(4) to produce sterile drug products was observed. Additionally, cracks and chipped paint were observed in the ceiling of the compounding room, as well as discoloration in the metal grid in front of the HEPA filters in the laminar flow hood used in the compounding of sterile drug products.
3. Your firm failed to adequately clean, maintain and sanitize equipment used in the preparation of sterile drug products. The laminar flow hood was observed to contain a yellow/brownish discoloration in the metal grid in front of the HEPA filters. Also, the clear plastic curtains used to divide the gowning area from the rest of the compounding room were observed to have an unknown residue covering them.
4. The (b)(4) processes used to render your products sterile do not ensure sterility is achieved while maintaining appropriate strength, purity, and quality. Your firm did not use a (b)(4) to sterilize product. The manufacturer of the (b)(4) stated that the (b)(4) was recommended for research use only and not intended for in-vitro diagnostic or for parenteral use. Furthermore, your firm did not perform (b)(4) testing on the (b)(4) after use to show that they were (b)(4) (that is, to ensure that the (b)(4) would prevent the drug products from becoming contaminated).
5. Your container-closure systems were not depyrogenated (a process needed to remove or reduce pyrogens. Pyrogens can result in a serious and sometimes deadly immune response including fever, hypotension, and/or shock in a patient.).
6. Your firm does not perform fingertip sampling and gowning assessments as part of either an initial competency evaluation or a routine monitoring program to assess compounding personnel aseptic practices. Additionally, we observed technicians with exposed skin and a technician leaning forward inside the aseptic hood during production.
7. Your facility design allows for equipment (e.g., the lyopholizer) used in the preparation of sterile products to be placed in unclassified areas. Therefore, once filled in the ISO 5 area, partially stoppered vials are required to be transferred to the unclassified area to complete the processing. Additionally, there is a lack of continuous monitoring of differential pressure between controlled and uncontrolled areas. Your (b)(4) sink is a potential microbiological contamination risk because there is inadequate separation between this water source and the area where product is being aseptically manipulated. Furthermore, you have not conducted unidirectional airflow studies under dynamic conditions in the ISO 5 area.
These production processes do not ensure removal of contaminants and, when producing drugs that are intended or expected to be sterile, result in drug products that may have become contaminated with filth or rendered injurious to health
B. Corrective Actions
We acknowledge your action on March 26, 2013, to recall all sterile products within expiry dispensed after January 1, 2013, after visual particulates (filaments) were seen in several sterile drug products. We also understand that you are under a Cease and Desist and Quarantine Notice issued on March 22, 2013, by the Commonwealth of Massachusetts Board of Registration in Pharmacy. Furthermore, on June 13, 2013, we witnessed the loading of drugs for off-site destruction, and confirmed verbally that your firm was not in operation and was selling off equipment. FDA strongly recommends that if you decide in the future to resume production of sterile drugs, your management first undertake a comprehensive assessment of your operations, including facility design, procedures, personnel, processes, materials, and systems. In particular, this review should assess your aseptic processing operations and design.
Please note that the violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations. It is your responsibility to assure that your firm complies with all requirements of federal law and FDA regulations.
If you decide to resume operations, you should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction. FDA may re-inspect to verify corrective actions have been completed.
Within fifteen working days of receipt of this letter, please notify this office in writing if you have taken any specific steps to correct violations or if you do not intend to resume production of sterile drugs. If you intend to resume production of sterile drugs in the future, please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you do not believe that the products discussed above are in violation of the FDCA, include your reasoning and any supporting information for our consideration.
In addition to taking appropriate corrective actions, you should notify this office prior to resuming production of any sterile drugs in the future. Your notification should be addressed to Karen N. Archdeacon, Compliance Officer New England District: One Montvale Ave, Stoneham, MA 02180. If you have questions regarding any issues in this letter, please contact our office at 781-587-7491.
Acting District Director
New England District
Food and Drug Administration
John J. Commisso
Mr. Nahill’s Legal Representative
c/o Jackson Lewis, LLP
75 Park Plaza
Boston, MA 02116
 Although sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act (FDCA or the Act) provide exemptions from certain provisions of the Act when certain conditions are met, the exemptions do not extend to the FDCA provisions that are discussed in this letter [21 U.S.C. §§ 353a, 353b]. As a result, this letter does not address whether your firm’s operations meet the conditions set forth in section 503A or section 503B of the Act.