Targeted radiopharmaceutical conjugates intended for therapeutic use often are made of three key components, a decaying radionuclide, a chemical chelator/linker, and a targeted molecular entity. The National Cancer Institute (NCI) Experimental Therapeutics Program has accepted four radiopharmaceutical drug products so far that fit the targeted radiopharmaceutical conjugate class. As the NCI sharpens its thinking about its role as an investigational new drug sponsor for radiopharmaceuticals in clinical development, it has considered the relative merits of modular radiopharmaceutical drug master files. Here, the NCI provides its perspective on modular radiopharmaceutical drug master files as it initiates a clinical development program for such agents and further organizes its radiopharmaceutical Small Business Innovation Research portfolio.

To ensure comparable grafts for autologous hematopoietic cell transplantation (HCT) in the National Institute of Allergy and Infectious Diseases-sponsored Investigational New Drug protocols for multiple sclerosis (HALT-MS) and systemic sclerosis (SCOT), a Drug Master File approach to control manufacture was implemented, including a common Master Production Batch Record and site-specific standard operating procedures with \"Critical Elements.\" We assessed comparability of flow cytometry and controlled rate cryopreservation among sites and stability of cryopreserved grafts using hematopoietic progenitor cells (HPCs) from healthy donors. Hematopoietic Progenitor Cells, Apheresis-CD34+ Enriched, for Autologous Use (Auto-CD34+HPC) graft specifications included ≥70% viable CD34+ cells before cryopreservation. For the 2 protocols, 110 apheresis collections were performed; 121 lots of Auto-CD34+HPC were cryopreserved, and 107 of these (88.4%) met release criteria. Grafts were infused at a median of 25 days (range, 17 to 68) post-apheresis for HALT-MS (n = 24), and 25 days (range, 14 to 78) for SCOT (n = 33). Subjects received precryopreservation doses of a median 5.1 × 106 viable CD34+ cells/kg (range, 3.9 to 12.8)  for HALT-MS and 5.6 × 106 viable CD34+ cells/kg (range, 2.6 to 10.2) for SCOT. Recovery of granulocytes occurred at a median of 11 days (range, 9 to 15) post-HCT for HALT-MS and 10 days (range, 8 to 12) for SCOT, independent of CD34+ cell dose. Subjects received their last platelet transfusion at a median of 9 days (range, 6 to 16) for HALT-MS and 8 days (range, 6 to 23) for SCOT; higher CD34+/kg doses were associated with faster platelet recovery. Stability testing of cryopreserved healthy donor CD34+ HPCs over 6 months of vapor phase liquid nitrogen storage demonstrated consistent 69% to 73% recovery of viable CD34+ cells. Manufacturing of Auto-CD34+HPC for the HALT-MS and SCOT protocols was comparable across all sites and supportive for timely recovery of granulocytes and platelets.

In Taiwan, the quality of active pharmaceutical ingredients is recorded in a drug master file (DMF), the applications for which can be submitted in two dossier types, either full (complete technical information) or abbreviated (partially complete technical information with an approved document issued by developed countries). However, the advantages of the abbreviated approach remain unknown. This study compared full and abbreviated dossier profiles and reviewed their outcomes in acceptance rates and deficiencies leading to rejection. Data were collected from new submissions of both dossier types that were completed in 2014 by the Center for Drug Evaluation, Taiwan. The results revealed that the abbreviated applications took shorter review time and had a higher acceptance rate. Among the eligible types of document for abbreviated applications, Certification of Suitability to the Monographs of the European Pharmacopeia (CEP) was the most frequently used. For categorical deficiencies, both dossier types presented the deficiencies in similar sections leading to rejection, namely Manufacture (3.2.S.2), Control of drug substance (3.2.S.4), and Stability (3.2.S.7). In summary, CEP serves a favorable document for the abbreviated DMF application in which it shortens the review time, increases the acceptance rate, and its deficiencies are similar to those of the full DMF application.

Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance. Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential. An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be \"generally recognized as safe\" (GRAS).