QuestionsQuestions (FDA Circular No. 2015-007)
Medical gases recognized in different pharmacopeias have therapeutic/diagnostic/prophylactic indications; the circular states they are classified as drugs under FDA regulatory jurisdiction.
All government and private hospitals and other health facilities engaged in the manufacture of medical gases.
Medical gases are any gas or mixture of gases intended for administration to patients for anesthetic, therapeutic, diagnostic, or prophylactic purposes, which may be manufactured in liquefied, non-liquefied, or cryogenic state and administered as a gas, stored in cylinders, pressurized tanks, or low pressure collecting tanks.
All covered establishments engaged in the manufacture of medical gases must secure an LTO as drug manufacturer, regardless of manufacturing method, scale, delivery mode, end users, or ownership type.
No. The circular explicitly states that LTO is required regardless of method (concentrator, chemical synthesis, purifier), scale, mode of delivery (cylinders or pipelines), end users, or ownership.
An establishment engaged in operations involved in the production of drug products, including preparatory processing, compounding, formulating, filling, packaging, repackaging, altering, ornamenting, finishing, and labeling for the end in view of storage, sale, or distribution. It does not apply to compounding and filling of prescriptions in drugstores and hospital pharmacies.
They include: (1) a completely filled-out and notarized application form signed by the pharmacist and owner/authorized representative; (2) proof of business name registration (DTI for single proprietorship; SEC/Articles for corporations/partnerships; CDA for cooperatives with approved by-laws; law creating government-owned/controlled corporations); (3) credentials of pharmacist-in-charge (PRC ID, FDA licensing seminar attendance certificate, and resignation letter if previously employed); (4) a general Risk Management Plan (RMP); (5) a location plan with sketch and GPS coordinates in decimal degrees; (6) Site Master File (per latest PIC/S GMP); (7) proof of payment; and (8) Self-Assessment Toolkit (SATK).
The establishment must provide GPS coordinates in decimal degrees (latitude and longitude) and clear directions with identifiable landmarks for inspection.
The pharmacist-in-charge signs the application (with the owner/authorized representative), must have specific credentials (PRC ID and FDA licensing seminar attendance), and is part of the compliance framework. Other qualified personnel are also identified and may be verified during inspection.
A general RMP must detail how the establishment identifies, characterizes, prevents or minimizes risks relating to the medical gases it engages in, including pharmacovigilance activities and interventions to manage those risks.
The SMF must be submitted in accordance with the latest edition of the Pharmaceutical Inspection Cooperation Scheme (PIC/S) Good Manufacturing Practice (GMP) requirements.
First is a pre-opening inspection after desktop evaluation to determine compliance with PlC/S-GMP, with additional documents verified on manufacturing (e.g., QMS, quality manual/SOPs, contract agreements, qualification/validation documents, master/batch production records, specifications, personnel credentials, and other GMP-related records). Second is post-licensing routine inspection for ongoing GMP and other applicable practice compliance, with possible additional inspection for major variations or regulatory triggers.
Examples listed include: Quality Management System (incorporating the manufacturing facility), Quality Manual and SOPs, contract agreement with supplier/installer of the manufacturing machine, qualification/validation documents, master/batch production records, specifications, credentials of other qualified personnel, relevant reference materials, and other protocols, records, and reports as required by PIC/S-GMP.
Major variation includes change of ownership and transfer of location. Minor variation (prior approval) includes expansion of establishment, change of business name, and zonal change in address. Minor variation (notification) includes change of pharmacist-in-charge or other qualified personnel; however, FDA should be informed of any changes regardless of classification.
Hospitals and other health facilities applying for minor variations may continue business operations provided that the application for such variation has already been filed.
Hospitals and other health facilities were given until 30 June 2015 to file their LTO application following the circular’s documentary requirements. Those that continue engaging in the covered activities without filing are grounds for administrative charges. Facilities that already filed before the deadline may continue operations until issuance of LTO, subject to risk-based intensive inspection transition phasing.
It must secure an LTO prior to operations; FDA will inspect these establishments once transition phasing for previously submitted applications has been completed.
LGUs are enjoined to monitor licensed hospitals and other health facilities in their localities for compliance with existing laws and their respective rules and regulations, and any violation inconsistent with FDA rules and regulations must be reported to FDA for regulatory action.