QuestionsQuestions (FDA CIRCULAR NO. 2014-016)
It implements Administrative Order (A.O.) No. 2013-0022 dated 13 August 2013, which provides guidelines for CGMP clearance and inspection of foreign drug manufacturers.
It applies to all establishments importing drugs, foreign drug manufacturers, and concerned FDA offices.
Prior to registration, all importers must obtain GMP clearance from FDA for each of their foreign drug manufacturer(s) involved in any operations in production. GMP clearance is declared a requirement for product registration.
To ensure foreign drug manufacturers comply with current Good Manufacturing Practices (cGMP) and to establish systems (including databases/coding) to track compliant foreign manufacturing sites and related applications.
The Center for Drug Regulation and Research (CDRR) and the Field Regulatory Operations Office (FROO), specifically those in charge of GMP. CDRR evaluates GMP evidence and issues clearance/denial, while FROO processes inspections and conducts foreign GMP inspection.
They assess GMP clearance applications; recommend inspection for non-satisfactory evidence; maintain databases of compliant/noncompliant manufacturers and imported products with GMP clearance; maintain records of foreign inspection reports; refer inspection triggers to FROO; and issue GMP Clearance/Letter of Denial.
They process foreign GMP inspection applications; coordinate logistics with local establishment; schedule inspections; conduct foreign GMP inspections; and forward results with recommendations to CDRR for issuance of GMP clearance or denial.
Application for GMP Clearance via GMP Evidence Evaluation and application for Product Registration of the earliest affected product must be submitted simultaneously, following the current FDA submission process.
CDRR shall disapprove the application outright pursuant to Section 4, Article I, Book II of the IRR of RA 9711. CDRR may also recommend legal actions to the LSSC.
CDRR issues a Notice requiring the foreign manufacturing site inspection. The applicant must comply within ninety (90) working days upon receipt by filing an application for foreign GMP inspection and paying applicable fees.
Visa application (when needed), plane ticket booking, other transportation requirements and expenses, and hotel accommodations.
The inspection schedule must be implemented within ninety (90) days from the date of decision, unless extended for justifiable reason but not later than thirty (30) days. If not implemented for reasons imputable to the applicant, the inspection is deemed abandoned and FROO recommends disapproval of the registration covering the importer’s drug product.
FROO forwards the inspection results and recommendation to CDRR, which then issues GMP Clearance.
Re-application is allowed six (6) months after receipt of the Letter of Denial by the importer.
Three (3) months before expiration of the GMP Clearance, drug importers must re-apply and submit renewal requirements with an attached copy of the latest GMP clearance letter.
CDRR shall take regulatory actions as provided under the Circular, including possible actions such as cancellation of clearance and disapproval of renewal applications of covered CPRs, and other measures to protect public health.
Situations where quality, safety, or efficacy of a product has been compromised, such as cancellation by the originating country’s regulatory authority, withdrawal due to safety/efficacy/quality issues.
Cancellation of an issued GMP Clearance, disapproval of applications for renewal of covered CPRs, product recall, and initiation of action for suspension or revocation of CPR.
Full implementation is on 28 September 2014. All initial and renewal applications for product registration (including existing products) after that date require valid GMP Clearance; failure to comply means denial of the product application and subsequent revocation of the CPR.