FDA warning letter linked network, involving the world's top 500 enterprise subsidiaries!

On October 29, the FDA sent a warning letter about PETNET solutions, a subsidiary of Siemens, according to the website The company received a warning letter from FDA on October 17, in which it mentioned that during the period from March 19 to April 5, 2019, when FDA inspected the factory, it found that the factory was in disrepair for a long time, and microorganism was detected in the sterile area, and asked the company to rectify as soon as possible PETNET solutions Inc is a health services company owned by Siemens, which operates more than 50 pet drug pharmacies around the world PETNET solutions has a global network of manufacturing operations and pet drug stores The warning letter posted on the FDA website is as follows: warning letter CMS October 17, 2019 Dear Mr Scott: the U.S Food and Drug Administration (FDA) inspected your drug manufacturing facility, PETNET solutions Inc., Fei 3006577728, at 350 Washington Street, unit 268, Woburn, Massachusetts, from March 19 to April 5, 2019 The U.S Food and Drug Administration (FDA) inspected PETNET solutions Inc.'s drug manufacturing facilities from March 19 to April 5, 2019 This warning letter summarizes significant violations of current good manufacturing practice (CGMP) Regulations for positron emission tomography (PET) drugs See 21 CFR, Part 212 See 21, 212 CFR Because your methods, facilities, or controls for compounding, processing, packing, or holding do not conform to CGMP, your PET drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C 351 (a) (2) (b) Because your methods, facilities, manufacturing processes, packaging or storage methods do not comply with CGMP regulations, your pet drug is considered a violation under section 501 (a) (2) (b) of the federal food, drug, and Cosmetic Act (FD & C), 21 U.S.C 351 (a) (2) (b) We reviewed your April 26, 2019, response to our form FDA 483 in detail and acknowledge receipt of your subsequence response During our inspection, our investigators observed specific violations including, but not limited to, During the inspection, our inspectors found specific violations including but not limited to the following: 1 Your firm's facilities are not adequate to ensure the prevention of contract of equipment or product by environmental conditions that could reasonably be expected to have an adverse effect on product quality (21 CFR 212.30 (a)) Your company's facilities are not sufficient to ensure that the pollution of environmental conditions may have adverse effects on the quality of equipment or products Facility suitability during the inspection, our investigator observed a state of repair and lay of cleanliness in your facility that commercial manufactures stile injectable pet drugs For example, rusted screws were observed holding up a light fixture in the ISO 5 area of the (b)(4) where you aseptically fill PET drug products Furthermore, our investigator observed a hole in the top of your (b)(4) enclosure, approximately three inches in diameter, open to the surrounding room The top of the (b)(4) surrounding the open hole was visibly dirty Also, Our investigator observed filter and damaged floor tiles in the immediate surrounding area of the room directly in front of the (b) (4) For example, in the ISO 5 area of (b) (4) of aseptically filled pet drugs, rusty screws were observed holding a lamp In addition, our researchers observed a hole, about three inches in diameter, in the top of your (b) (4) shell, opening through the surrounding room It's obviously dirty around the hole In addition, our investigators observed dirty and damaged floor tiles in the surrounding area directly in front of the room Your response stated that the (b)(4) is negatively pressured to protect the operator and draws air from the surrounding environment The presence of a negatively pressured area adjacent to an ISO 5 area requires careful facility and equipment design, as well as attentiveness to ongoing control, maintenance, cleaning, and disinfection activities To ensure appropriate air quality for your acoustic filling environment The presence of negative pressure areas adjacent to ISO 5 areas requires careful facility and equipment design and attention to continuous control, maintenance, cleaning and disinfection activities to ensure proper air quality in a sterile filling environment Environmental conditions between March 2016 and March 2019, alternative trends were identified in environmental and personal monitoring samples taken from the ISO 5 areas where you conduct informal simulations Isolates from these samples frequently included bacillus, spp., and related biological spacing specifications Also, during the (b)(4) certifications conducted by a third party between July 2017 and January 2019, During the period from March 2016 to March 2019, adverse factors were found in the environmental and personnel monitoring samples collected from the ISO 5 area where you conducted aseptic operation The isolates in these samples include bacillus and related bacterial sporogens In addition, during the (b) (4) inspection conducted by a third party between July 2017 and January 2019, spore forming fungi were repeatedly detected in the (b) (4) ISO 8 region immediately adjacent to the (b) (4) ISO 5 region In 2017, your firm also had a sterility test failure for a batch of fludoxyglucose (FDG) F18 injection You identified the micro contaminant as the sporeforming bacteria, Brevibacillus limnophilus It is confirmed that the microbial pollutant is sporogen, i.e Brevibacterium Sporeforming organisms can pose a significant challenge to disinfection processes We note you implemented a (b)(4) disinfection regimen However, significant trends of sporeforming organisms continue in your facility For example, in January and February 2019, your environmental monitoring identified Bacillus species in multiple surface samples for the ISO 5 Biological Safety Cabinet (BSC) you use to aseptically prepare final product vial assemblies Over approximately three years, you failed to adequately respond to data indicating insufficient microbial control in the areas where you conduct aseptic Spore forming bacteria may be the key cleaning objects in the disinfection process We have noticed that you have implemented a disinfection program However, in your facility, spore forming bacteria still exist For example, in January and February 2019, your environmental monitoring monitored bacillus in multiple surface samples of the ISO 5 biosafety cabinet (BSC) for aseptic preparation For about three years, you didn't fully respond to the data in the area where you conducted aseptic operation, as well as the adjacent area The data showed that the microbial control in the area was not strict Exceptions and trends in environmental monitoring results should be monitored and prompt reviewed Advance trends should trigger a comprehensive evaluation of the state of control of your manufacturing operation An adverse trend should lead to a comprehensive assessment of the control status of your production operations In your response, you stated that your facility is being remodeled However, your risk assessment for facility remediation lacked sufficient details Your response also did not include a plan for ensuring that your facility is adequately maintained, and environmental conditions are appropriate, In your reply, it is said that the facilities are under reconstruction However, the risk assessment of facility rehabilitation lacks sufficient details The response also did not include plans to ensure that your facilities are adequately maintained, as well as appropriate environmental conditions to ensure product quality In response to this letter, provide: for this letter, please provide:, But is not limited to: conduct a comprehensive risk assessment of all pollution hazards related to aseptic processes, equipment and facilities Provide independent evaluation, including but not limited to: all human interactions within the ISO 5 area equipment placement and ergonomics air quality in the ISO 5 area and surrounding room facility layout personal flows and material flows (through all rooms used to conduct and support rigid operations) equality of procedures to ensure ongoing maintenance And control of the layout and efficiency of all personnel activities and equipment in your facility ISO5 area and air quality facilities layout in surrounding rooms in ISO5 area personnel flow and material flow (all rooms used to carry out and support aseptic operation) ensure the adequacy of continuous maintenance and control procedures of facilities monitoring conducted from April 2019 to present Describe each interim measure implemented to ensure risk mitigation and provide all testing and all monitoring results obtained during remodeling Also include facility monitoring trends and any excursions (e.g., differential pressure, humidity, non-viable particles, During this period List the date of production, name of product, lot number, and equipment used Describe in detail when the overall remoting work became and ended, and what construction was performed each day and the location Describe each interim measure implemented to ensure risk mitigation and provide all tests and all monitoring results obtained during rectification It also includes facility monitoring results and any offsets (e.g., differential pressure, humidity, inactive particles, active particles) during this period List production date, product name, batch number and equipment used Describe in detail when the whole reconstruction project starts and ends, as well as the construction and location carried out every day • your planned variance (pv00000182) document and enhanced environmental monitoring protocols (d0013699 and d0013698) referred in your risk assessment