Philippines: Drug Establishment Regulation

Administrative Order Overview

• Issued in 2014, it concerns the licensing and regulation of drug establishments in the Philippines.
• Covers entities involved in manufacturing, clinical trials, distribution, and importation/exportation of drug products.

Rationale

• Aligns with the 1987 Constitution, emphasizing the right to health and affordable healthcare.
• Aims to ensure safe and effective medicines by regulating drug establishments.

Key Objectives

• Establish licensing rules for drug establishments, in line with current laws.
• Ensure compliance with FDA (Food and Drug Administration) and international regulatory standards like Good Manufacturing Practice (GMP)
• Encourage the use of electronic innovations in FDA processes.

Scope

• Applies to local and government entities involved in drug product handling.
• Includes Contract Research Organizations (CROs).
• Entities involved in drug donations, promotion or advertising require proper authorization.

Definition of Terms

• Clinical Trial: Investigations on human subjects to evaluate drug effects, safety, and efficacy.
• Contracting: Documented activities by a contract acceptor to its contract giver.
• Drug Establishment: Any entity involved in the manufacturing, distribution, or handling of drug products.
• Good Clinical Practice (GCP): Standards for clinical trials that ensure data credibility, accuracy, and protection of trial subjects.
• Institutional Pharmacy: Non-government entities that procure drugs for dispensing to employees or dependents.
• Investigational New Drug (IND): A pharmaceutical form or placebo for testing in a clinical trial.
• License to Operate (LTO): Authorization granted by FDA for entities in the manufacture and handling of drug products.
• Pharmacy Compounding: Practice of a pharmacist combining ingredients based on a prescription.
• Special Permit: Authorization for entities procuring drugs for specific purposes.
• Testing: Analysis to determine the safety, efficacy, and/or quality of drug products.

General Guidelines

• An LTO or appropriate authorization is needed for any activity regarding drug products.
• CRO and/or sponsors need a license from the FDA before conducting a clinical trial
• Drug establishments are accountable for the safety and quality of drug products.
• A risk management plan is needed for LTO issuance.
• Distributors cannot sell directly to the public unless they have an LTO as a drugstore.
• Continuous compliance with existing rules is required for licensed establishments.
• Violations will result in LTO suspension/revocation.
• Drug products banned in the manufacturing country cannot be imported or sold.
• Recalls for unsafe products should be immediately done.
• Entities procuring drugs for distribution require a drug distributor license.
• Institutional pharmacies must secure an LTO.
• Retail establishments must have a registered pharmacist.
• Compliance with cold chain management is required for temperature-sensitive drugs.
• Promoting drug use materials should be displayed visibly.
• The FDA can enter establishments for inspection or verification and may conduct inspections for either compliance or verifying submitted documents.
• Establishments must comply with FDA's electronic submission guidelines.
• CROs and sponsors must adhere to safety, efficacy and ethical practice standards.
• Hospital pharmacies must adhere to Administrative Order No. 2012-0012.

Specific Guidelines for CROs and Sponsors

• A 90-day transition period for CROs and sponsors, and 1-year for government offices, to comply.
• The Administrative Order will be reviewed 2 years after issuance.

Classification of Establishments

• Drug Manufacturer: Involved in the production of drug products with the end in view of distribution or sale.
• Drug Manufacturer-Repacker: Repacks finished drug products into smaller quantities with the end in view of distribution or sale.
• Drug Manufacturer-Packer: Packages a bulk drug product into its immediate container with the end in view of distribution or sale.
• Drug Manufacturer-Trader: Owns a drug product and the formulation, procures materials, but subcontracts manufacture of the product.
• Drug Distributor-Exporter: Exports raw materials, active ingredients and finished products for distribution to other drug establishments outside the country.
• Drug Distributor-Importer: Imports raw materials, active ingredients and finished products for wholesale distribution to other local FDA-licensed drug establishment.
• Drug Distributor-Wholesaler: Procures and distributes in wholesale basis.
• Drugstore/Pharmacy/Botica: Where registered drugs, chemical products, dental, medicinal and household remedies are dispensed directly to the general public on a retail basis.
• Retail Outlet for Non-Prescription Drugs (RONPD): Sells OTC and household remedy products directly to the general public on a retail basis.
• Sponsor: Entity which takes responsibility for the initiation, management, and/or financing of a clinical trial.
• Contract Research Organization (CRO): A person or organization contracted by the sponsor to perform one or more of the sponsor's trial-related duties and functions.

LTO and Authorizations: Process

• Applications are filed upon submission of complete requirements and payment.
• Evaluation is based on compliance with requirements and standards.
• Fraudulent applications will be disapproved, with penalties.
• Notifications will be issued for clarifications on the application.
• Pre-opening inspection for drugstores, RONPDs, sponsors, and CROs is waivable if requirements are met.
• Drug manufacturers and distributors require pre-opening inspection.
• Post-licensing inspections are done for all establishments after LTO issuance.

Decision on Application

• Approval is granted if the establishment complies with all requirements.
• Disapproval occurs if there is no satisfactory evidence of compliance, with clear grounds stated.
• Disapproval does not prevent re-application, but the payment is forfeited.

Validity of LTO

• Initial LTO is valid for two years.
• Renewal of LTO is valid for three years.
• LTO is valid only in the address indicated.

Renewal of LTO

• Application must be filed within 6 months before LTO expiration.
• Late applications are subject to surcharges.
• Applications beyond 120 days after expiration incur higher fees and are subject to initial filing fees.
• Applications undergo initial filing and evaluation procedures.
• Requirements are waived unless there are changes in the establishment.
• Automatic renewal applies if the application is filed before expiration, fees are paid, and there are no changes reported.

Application for Variation (Post-Approval)

• Variations are changes to implement from the previously approved and issued LTO.
• Major variations significantly affect safety, efficacy, or quality of drug products and affecting the particulars of the issued LTO and requires notification, documents, and FDA approval.
• Minor variations have minimal impact.

Other LTO Considerations

• A lost LTO can be re-issued after filing requirements and payment.
• Automatic cancellation occurs if renewal is not filed within 120 days after expiration.
• Voluntary cancellation requires formal notification and must not defraud the government.

Regulatory Action

• The FDA can execute regulatory actions for public health and safety.
• Actions include re-inspection, suspension, or revocation which require a formal notice stating the grounds.
• Suspension lifting requires compliance with deficiencies.
• Those with revoked LTOs can re-apply after three years and fees and other charges follow existing regulations.

Clauses

• If any provision is found void, it does not affect the remaining provisions.
• Administrative Order No. 56 s. 1989, and any inconsistent orders, are withdrawn and repealed.

Effectivity

• The order takes effect 15 working days after publication in a national newspaper and submission to the University of the Philippines Law Center.