No person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed…
(1) The Secretary shall promulgate regulations for exempting from the operation of the foregoing subsections of this section drugs intended solely for investigational … [Sponsor’s IND] contain[s] such information about the drug … including… (B) adequate information on the chemistry and manufacturing of the drug, controls available for the drug
The following acts and the causing thereof are prohibited:
(a) The introduction or delivery for introduction into interstate commerce of any food, drug, device, tobacco product, or cosmetic that is adulterated or misbranded.
[(a)(2)(B]) A drug…shall be deemed to be adulterated…if it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess…
…For purposes of paragraph (a)(2)(B), the term ‘current good manufacturing practice’ includes the implementation of oversight and controls over the manufacture of drugs to ensure quality, including managing the risk of and establishing the safety of raw materials, materials used in the manufacturing of drugs, and finished drug products.
…(b) The Food and Drug Administration is aware that many manufacturers of pharmaceutical products utilize extramural independent contract facilities, such as testing laboratories, contract packers or labelers, and custom grinders, and regards extramural facilities as an extension of the manufacturer's own facility.
…(b) If a person engages in only some operations subject to the regulations… and not in others, that person need only comply with those regulations applicable to the operations in which he or she is engaged.
(c) An investigational drug for use in a Phase 1 study, as described in 312.21(a) of this chapter, is subject to the statutory requirements set forth in 21 U.S.C. 351(a)(2)(B). The production of such drug is exempt from compliance with the regulations in part 211 of this chapter…
“Sponsors are responsible for … maintaining an effective IND with respect to the investigations, … in each phase of the investigation sufficient information is required to be submitted to assure the proper identification, quality, purity, and strength of the investigational drug…
Examples of information requiring an [IND] information amendment include: (1) New toxicology, chemistry, or other technical information…”
“Manufacturers of APIs should implement CGMP appropriate to the stage of clinical development and consider the recommendations described in this guidance for the manufacture of APIs used in Phase 1 investigational drugs.”
“CGMP consists of steps that a manufacturer takes to ensure the safety and quality of the investigational drug. This information is submitted to FDA in the IND. Through FDA’s IND authority, FDA has the ability to take appropriate actions to address manufacturing issues if there is a safety risk to subjects…”
“Therefore, a financially strapped company may choose to use a less expensive approach other than the one recommended in a guidance, but the alternative approach must comply with the relevant statutes and regulations in assuring patient safety, and the company would be prudent to consult FDA before using the alternative approach.”
“…release of material by an untrained person violates United States CGMP…[the Ph1 Guidance] indicates that, under very limited circumstances and where justified, only a person trained in CGMP and quality control functions should be given the dual responsibility of manufacture and release.”
