Selected passages from the FDA letter
Quoted FDA text from the published dataset. These selected excerpts are not the complete letter.
Passage 1Your 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.
Passage 2Your 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.
Passage 3The 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.
Passage 4Your 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).
Passage 5Your 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.
Passage 6Your firm used household dish detergent to clean and sanitize glassware used in the production of sterile injectable drug products.
Passage 7Your firm used a non-sterile disinfectant within the ISO 5 aseptic processing area.
Passage 8You 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.
Passage 9Your 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.
Passage 10Your 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.
Passage 11Your 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.
Passage 12Your 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.
Passage 13Your 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.