FDA/M-CERSI Co-Processed API Workshop Proceedings.

These proceedings contain presentation summaries and discussion highlights from the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) Workshop on Co-processed API, held on July 13 and 14, 2022. This workshop examined recent advances in the use of co-processed active pharmaceutical ingredients as a technology to improve drug substance physicochemical properties and drug product manufacturing process robustness, and explored proposals for enabling commercialization of these transformative technologies. Regulatory considerations were discussed with a focus on the classification, CMC strategies, and CMC documentation supporting the use of this class of materials from clinical studies through commercialization. The workshop format was split between presentations from industry, academia and the FDA, followed by breakout sessions structured to facilitate discussion. Given co-processed API is a relatively new concept, the authors felt it prudent to compile these proceedings to gain further visibility to topics discussed and perspectives raised during the workshop, particularly during breakout discussions. Disclaimer: This paper reflects discussions that occurred among stakeholder groups, including FDA, on various topics. The topics covered in the paper, including recommendations, therefore, are intended to capture key discussion points. The paper should not be interpreted to reflect alignment on the different topics by the participants, and the recommendations provided should not be used in lieu of FDA published guidance or direct conversations with the Agency about a specific development program. This paper should not be construed to represent FDA's views or policies.

The effect of continuous positive airway pressure therapy on nasal patency.

BACKGROUND: Nasal congestion and obstruction are reported in the majority of continuous positive airway pressure (CPAP) users and are frequently cited as reasons for noncompliance. To our knowledge, no study has demonstrated a change in objective or subjective nasal patency in patients with obstructive sleep apnea (OSA) after a therapeutic trial of CPAP therapy. METHODS: This prospective nonrandomized trial tested the hypothesis that CPAP therapy would result in both objective and subjective improvements in nasal patency in patients with OSA. Prior to initiation of CPAP, acoustic rhinometry (AR) was used to determine nasal volume and minimum cross-sectional area in the upright and reclined positions. Subjective nasal patency was assessed with the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire. Both assessments were repeated at follow-up visits. RESULTS: AR data demonstrated a statistically significant increase in total nasal volume (TV) in the reclined position (p = 0.002) and minimum cross-sectional area (MCA) in both the sitting and reclined positions (p = 0.006, p = 0.021) in OSA patients after >30 days of CPAP therapy and with >70% compliance. NOSE scores decreased significantly (p = 0.038) representing an improvement in nasal patency. CONCLUSION: Objective and subjective measurements of TV and MCA increased after initiation of CPAP therapy in this prospective study.

Effectiveness of alimemazine in controlling retching after Nissen fundoplication.

BACKGROUND: Retching, an early component of the emetic reflex, is a common and distressing symptom in children after Nissen fundoplication. Alimemazine (trimeprazine, Vallergan; Castlemead, Herts, UK) is a phenothiazine derivative histamine(1) antagonist, which anecdotally relieves the retching symptoms. MATERIAL AND METHODS: A prospective, double-blind, randomized, crossover, placebo-controlled study of 15 neurologically impaired children with retching after Nissen fundoplication over a period of 1 year (December 2002-December 2003). Patients were randomly allocated to receive 1 week each of alimemazine and placebo with crossover. A diary was maintained of retching episodes 1 week before, during, and 1 week after the trial. Dosage of alimemazine used was 0.25 mg/kg 3 times a day (maximum, 2.5 mg per dose). Statistical analysis was done using a paired Student's t test, where P value of less than .05 was considered significant. Results are presented as mean +/- SD. RESULTS: Twelve parents completed the diaries (9 open, 3 laparoscopic Nissen fundoplication). Median age of the child was 36 months (8-180 months), median duration of retching was 4.5 months (1-52 months), and mean number of retching episodes per week was 60 +/- 29.40. Mean number of retching episodes with alimemazine was 10.42 +/- 9.48 vs 47.67 +/- 27.79 with a placebo (P < .0001). No adverse effects were reported in those cases that completed the study. CONCLUSION: At low dose, alimemazine (Vallergan) is a safe and effective drug in the management of retching after Nissen fundoplication.