1.Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality (21 CFR 211.84(d)(1) and 211.84(d)(2)).
2.Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).
Your firm failed to maintain the buildings used in the manufacture, processing, packing, or holding of a drug product in a clean and sanitary condition and to keep them free of infestation by rodents, birds, insects, and other vermin. Trash and organic waste matter shall be held and disposed of in a timely and sanitary manner. [21 CFR 211.56(a)]. Specifically, on July 14, 2023, your Quality Assurance team observed a box of food from June 16, 2023, covered in scuttle fly pupae in the mechanical room which houses the air handling units and failed to remove the box of food until July 31, 2023. After this event, scuttle fly larvae were found in ten environmental and personnel monitoring samples collected in the cleanrooms in July 2023. Additionally, on July 26, 2023, in Suite (b)(4) Clean Room (b)(4) (Grade (b)(4)) a living scuttle fly was observed on the tube rack. Adequate control of insect infestation is needed to ensure product quality and safety.
1.Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).
2.Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).
You failed to ensure that the investigation was conducted according to the investigational plan [21 CFR 312.60].
未能确保按照研究计划进行研究[21 CFR 312.60]。
As a clinical investigator, you are required to ensure that your clinical studies are conducted in accordance with the investigational plan. The investigational plan for Protocol (b)(4) required the investigational drug (b)(4) to be administered to subjects according to their weight and in accordance with the protocol's titration schedule for the 20-week Titration Phase. During the 20-week Titration Phase, the protocol required a daily dose of (b)(4), with the dose of (b)(4) to increase according to the titration schedule at each study visit, which occurred every two weeks. According to the protocol's titration schedule, subjects at Visit 2 who were 12 to <18 years old were to receive an (b)(4) of (b)(4) at a daily dose of 0.2 mg/kg, not to exceed 12.5 mg per day.
1.Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
2.Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
3.Your firm failed to establish adequate written procedures for production and process control designed to assure that drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and to follow all of your written production and process control procedures (21 CFR 211.100 (a) and 211.100 (b).
1.Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).
2.Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
Information on the label and labeling of your "Hard Steel" and "Gold Hard Steel Plus" products demonstrate that these products are marketed as dietary supplements. However, under section 201(ff)(3)(B)(i) of the FD&C Act, 21 U.S.C. 321(ff)(3)(B)(i), a dietary supplement may not include an article that is approved as a new drug under section 505 of the FD&C Act unless that article was marketed as a dietary supplement or food before its approval as a drug. FDA approved Viagra (containing sildenafil as the active ingredient) as a new drug on March 27, 1998. Given that sildenafil was not marketed as a dietary supplement or as food before Viagra was approved, your "Hard Steel" and "Gold Hard Steel Plus" products are excluded from the definition of dietary supplement under section 201(ff)(3)(B)(i) of the FD&C Act, 21 U.S.C. 321(ff)(3)(B)(i).
“Hard Steel”和“Gold Hard Steel Plus”产品标签和说明书上的信息表明，这些产品作为膳食补充剂上市销售。但是，根据FD＆C法案第201(ff)(3)(B)(i)节[21 U.S.C. 321(ff)(3)(B)(i)]，膳食补充剂不得包括根据FD＆C法案第505节被批准为新药的物品，除非该物品被批准为药物之前作为膳食补充剂或食品上市销售。FDA于1998年3月27日批准万艾可（含有西地那非作为活性成分）为新药。鉴于西地那非在万艾可获批之前并未作为膳食补充剂或食品上市销售，企业的“Hard Steel”和“Gold Hard Steel Plus”产品不符合FD＆C法案第201(ff)(3)(B)(i)节[21 U.S.C. 321(ff)(3)(B)(i)]节的膳食补充剂定义。
1.The IRB failed to conduct continuing review of research at intervals of not less than once per year [21 CFR 56.109(f)]
1.IRB未能按照至少每年一次的间隔对研究进行持续审查[21 CFR 56.109(f)]。
2.The IRB failed to prepare, maintain, and follow required written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and [the] Food and Drug Administration (FDA) [21 CFR 56.115(a)(6) and 56.108(b)(3)].
1.Your firm failed to establish and follow required laboratory control mechanisms, and to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(a) and 211.160(b)).
2.Your firm's quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).
