- Delivery Method:
- VIA Electronic Mail
Recipient NameKevin P. Hogan
Recipient TitlePresident & Owner
- Innoveix Pharmaceuticals Inc
3790 Arapaho Road
Addison, TX 75001-4311
- Issuing Office:
- Office of Pharmaceutical Quality Operations, Division II
January 26, 2022
Dear Mr. Hogan:
From May 11, 2021, to May 27, 2021, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Innoveix Pharmaceuticals, Inc., located at 3790 Arapaho Road, Addison, Texas 75001. During the inspection, the investigator noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.
FDA issued a Form FDA 483 to your firm on May 27, 2021. FDA acknowledges receipt of your facility’s response, dated June 14, 2021. Additionally, FDA acknowledges that on July 9, 2021, your firm voluntarily recalled compounded (b)(4) Semorelin/Ipamorelin 3 mg for subcutaneous or intramuscular injection and compounded (b)(4) AOD-9604, 3 mg for subcutaneous or intramuscular injection due to a lack of sterility assurance. Based on this inspection, it appears that you produced drug products that violate the Federal Food, Drug, and Cosmetic Act (FDCA).
A. Compounded Drug Products Under the FDCA
Section 503A of the FDCA describes the conditions under which human drug products compounded by a licensed pharmacist in a State licensed pharmacy or a Federal facility, or a licensed physician, qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) (section 501(a)(2)(B)); labeling with adequate directions for use (section 502(f)(1)); and FDA approval prior to marketing (section 505) [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)].
B. Violations of the FDCA
Adulterated Drug Products
The FDA investigator noted that 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. For example,
1. Your firm used an unsuitable (b)(4) unit to sterilize bulk drug solutions. The label on the (b)(4) unit states: “This product is not intended for use in direct patient care or diagnostic procedures.” In addition, your firm failed to perform post-use (b)(4) testing on the (b)(4) used to sterilize drug products. Therefore, you do not have assurance that the (b)(4) was integral throughout use.
2. Your firm exposed (b)(4) vials that were used to produce drug products intended to be sterile to less than ISO 5 classified aseptic processing quality air. Specifically, trays of (b)(4) vials were improperly wrapped with foil and transferred from the ISO 8 area to the ISO 7 area without being disinfected. Therefore, sterile vials were exposed to less than ISO 5 quality air.
3. The investigator observed that an operator blocked first air by placing gloved hands directly over open sterile containers that were used to fill drug products intended to be sterile.
4. Your firm used a (b)(4) that is not part of a sanitation or sterilization process. The (b)(4) is not routinely cleaned and disinfected prior to use. The (b)(4) is not protected from contamination by (b)(4) on (b)(4).
5. Your media fills were not performed under the most challenging or stressful conditions and do not simulate your production process. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility.
6. Your firm used household dish detergent to clean and sanitize glassware used in the production of sterile injectable drug products.
7. Your firm used a non-sterile disinfectant within the ISO 5 aseptic processing area.
Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.
C. Corrective Actions
We have reviewed your firm’s response to the Form FDA 483.
We acknowledge that on July 9, 2021, your firm voluntarily recalled compounded (b)(4) Semorelin/Ipamorelin 3 mg for subcutaneous or intramuscular injection and compounded (b)(4) AOD-9604, 3 mg for subcutaneous or intramuscular injection due to a lack of sterility assurance.
Regarding your responses related to the insanitary conditions, some of your corrective actions appear adequate; however, we cannot fully evaluate the adequacy of the following corrective actions described in your response because you did not include sufficient information or supporting documentation:
You stated that you will cease using the (b)(4) and return to using (b)(4) to (b)(4) sterilize your drug products that are intended to be sterile, but you did not provide any documentation to show which (b)(4) will be used in the future to (b)(4) your drug products that are intended to be sterile. In your response, you did not state whether post-use (b)(4) testing will be performed.
Regarding your responses related to the insanitary conditions, the following corrective actions appear deficient:
1. Your firm acknowledged the Pharmacist in Charge (PIC) briefly blocked first air by placing their gloves over sterile vials and stated less than five vials were impacted. These vials were not discarded and were used to prepare Sermorelin/Ipamorelin 3mg Injectable lot SIP225. Your firm stated the PIC is familiar with proper aseptic technique and reverted to correct aseptic technique after being notified during the inspection. No additional corrective actions were provided to prevent future lapses of aseptic technique from occurring.
2. Your firm stated that the (b)(4) cycle is self-cleaning as it is designed to eliminate any microbes that may exist therefore sterilizing itself. The Agency is not aware of any evidence to support that (b)(4) cycles is equivalent to a sterilization cycle inside the (b)(4) chamber.
Your firm stated that once the (b)(4) cycle is complete, the PIC cleans the interior of the (b)(4) chamber with sterile (b)(4) wipes under ISO 5 conditions while wearing sterile garb. Your firm also stated that moving forward, a detergent and sporicidal agent will be used to clean the interior of the (b)(4). However, there is no documentation or evidence to support that the (b)(4) chamber and its parts are cleaned and disinfected immediately prior to use.
Your response also stated that you have not failed a sterility test in five years. However, a passing sterility test does not prove the sterility of each unit of each lot you produce and should not be solely relied upon as an indication of product sterility.
3. Your response stated that USP <797> does not specify the number of media filled units required to verify an employee’s aseptic technique and requested guidance on how many vials should be filled. You also stated that the kit vials are not designed to be (b)(4), but that you will (b)(4) the media filled vials going forward. Our expectation is that the media fill is used to evaluate the aseptic process in addition to operator technique. Media fills should simulate the most challenging operating conditions, including the number of units filled during routine production and (b)(4) to simulate the (b)(4) process. Units should not be frozen as this may adversely impact the media and potentially inhibit growth of microorganisms.
Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A.
FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug processing expertise should assist you in conducting this comprehensive evaluation.
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 ensure that your firm complies with all requirements of federal law, including FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to adequately address this matter may result in legal action without further notice, including, without limitation, seizure and injunction.
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of any violations, as well as copies of related documentation. If you believe that your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.
Your written notification should refer to the Warning Letter Number above (Case # 624782). Please electronically submit your signed reply on your firm’s letterhead to CDR John W. Diehl, M.S., Director, Compliance Branch, at firstname.lastname@example.org and email@example.com.
If you have questions regarding the contents of this letter, you may contact Mr. Thao Ta, Compliance Officer, via phone at 214-253-5217 or e-mail at firstname.lastname@example.org.
Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations, Division II
cc: Via Electronic Mail
Dan Lype, Attorney
Leichter Law Firm
1602 East 7th Street
Austin, Texas 78702