Guidelines for Manufacturers and Traders

1 OBJECTIVES To provide stakeholders engaged in the manufacturing processes for ENDS/ENNDS products a general overview of FDA s regulation for Manufacturers and Traders To ensure that all concerned stakeholders understand the process for the application of a license to operate and the regulatory requirements during operations MANUFACTURER means an establishment engaged in any and all operations involved in the production of health products including preparation, processing, compounding, formulating, filling, packing, repacking, altering, ornamenting, finishing and labeling with the end in view of its storage, sale or distribution. A trader shall be categorized a manufacturer. trader means any establishment which is a registered owner of a health product and procures the raw materials and packing components and provides the production monographs, quality control standards and procedures, but subcontract the manufacture of such product to a licensed manufacturer.

2 In addition, a trader may also engage in the distribution and/or marketing of its products. Manufacturing Process Manufacturer Formulation Procurement and preparation of raw materials Production Process Testing and Inspection Storage / Warehousing Delivery / Distribution The same process can apply for Traders , with the exemption of the production process that is subcontracted to a manufacturer. The coverage of the contract between a trader and a manufacturer vary, depending on the agreement between the two establishments. Operational Requirements Quality System Documentation Personnel Premise Equipment Sanitation and Hygiene Production Quality Control These are the key areas that a manufacturer needs to establish and maintain for its operation. The FDA shall be issuing a detailed guideline for all areas and shall be discussed during the QPIRA Seminar QUALITY SYSTEM A comprehensively designed and correctly implemented system to ensure the attainment of the company s objectives A company s quality system must be appropriate for its current activity Quality Manual Quality Procedures Work Instructions Records The company must at least establish its quality manual, organizational structure, procedures, controls, work instructions, forms, and other records.

3 DOCUMENTATION Site Master File A document providing a general overview of the structure and activities of the manufacturer. Raw Material Specifications Describe in detail the requirements with which the materials used or obtained during manufacture have to conform. They serve as a basis for quality evaluation. Master Formula, Procedures, and Standards This contains all information about the manufacturing process for the product and the expected output. This document is kept and controlled by the QA personnel. Standard Operating Procedures Written instructions of the performance of specific activities. Records Provide evidence of various actions taken to demonstrate compliance with instructions, activities, events, investigations, and in the case of manufactured batches a history of each batch of product, including its distribution. Records include the raw data which is used to generate other records. For electronic records regulated users should define which data are to be used as raw data.

4 At least, all data on which quality decisions are based should be defined as raw data. DOCUMENTATION SITE MASTER FILE I. Table of Contents II. Company Overview General Information Site Overview Products Produced III. Personnel Organizational Chart Employees with Job Description Training Requirements Health and Hygiene Requirements IV. Premise and Equipment General Location of Site Detailed Site Layout (with dimensions) Personnel, Material, and Product Flow List of Manufacturing Equipment Maintenance and Calibration V. Documentation SOPs and Forms VI. Contract Manufacturing and Analysis Toll Manufactured Products Analysis Contracted Out VII. Internal Quality Audit and FDA Reporting and Inspection Inspections Conducted Compliance History Standard Operating Procedures Training of personnel Handling of Raw Materials Acceptance of Incoming Dispensing Disposal of Expired & Reject Handling of Raw Materials Acceptance of Incoming Dispensing Expired & Reject Production Procedure Pre-production preparation Dispensing Mixing Packaging & Labelling Checking Storage Batch Numbering System Handling of Finished Products Approval and Release Returned, Expired & Reject Storage Raw Materials Finished Products Distribution of Finished Products Handling of Complaints Product Recall Laboratory Analysis of Finished Products Records Keeping PERSONNEL General Requirements.

5 Chart showing the hierarchy of responsibilities General Manager / President Production Manager Head of Admin and Sales Quality Assurance Manager Quality Control Warehouse Processing Admin Sales PERSONNEL General Requirements: 2. Personnel File Qualifications and background Job description Duties and responsibilities Training records Medical records KEY PERSONNEL PRODUCTION MANAGER Develop and establish SOPs in production Ensure proper implementation of SOPs within the production area at all times Ensure production personnel are capacitated prior to deployment in the production area Ensure all areas of the production facility are well maintained KEY PERSONNEL QUALITY ASSUARANCE MANAGER Must be an Allied Health Science Professional ( PRC registered pharmacist, chemist, chemical engineer, nurse, med tech, etc.) Establish standard operating procedures for inspection, testing and clearance of starting materials, packaging materials, intermediate, bulk and finished products; Ensure all starting materials, packaging materials, intermediate, and finished products are of quality and within current standards Ensure all critical processes of the company are followed accordingly based on written procedures and policies Keep and maintain all documents and records of the company Approve and monitor 3rd party testing laboratories Lead the conduct of internal quality audits and investigations.

6 KEY PERSONNEL QUALIFIED PERSON Ensure that all operations of the company are in accordance with current national standards and regulations Ensure that all the necessary marketing authorizations are secured and up-to-date prior to operation and/or distribution of products Shall act as the point person of the company in relation to FDA-related processes Note: The Quality Assurance Manager can also serve as the Qualified Person SAMPLE PREMISE SAMPLE PREMISE PRODUCTION PROCESS FLOWCHART Quarantined Storage Raw Material QC Check Approved Storage Raw Material Return to Supplier or Disposal Passed Failed Production Dept. QA Master Formula Customer Order Weighing Bulk Processing / Mixing QC Check Filling and Packaging Passed Failed Can be reworked? Yes Reject / Dispose Warehouse No Reconciliation Quarantine Storage Finished Product QC Check Approved Storage Finished Product Passed Distribution Reject / Disposal Warehouse Failed Can be reworked?

7 Yes BATCH MANUFACTURING RECORD BATCH MANUFACTURING RECORD PRODUCT PACKAGING AND LABELING Primary Packaging Secondary Packaging shall mean any material, including printed material, employed in the packaging of product, excluding any outer packaging used for transportation or shipment, that is in direct contact with the electronic cigarette refill solution shall mean any material, including printed material, employed in the packaging of product, excluding any outer packaging used for transportation or shipment, that is not in direct contact with the electronic cigarette refill solution ( product inserts, tags, etc.) LABELING REQUIREMENTS Restrictions Samples of Restricted Content All Health Claims Smoking Cessation Claims Harm Reduction Claims Potentially Misleading Content Terms such as: 1. Light; Lites; Ultra lite 2. Supreme 3. 4. Leading 5. Most 6. Finest Explicit/Implicit Conveyance of FDA Endorsement Terms such as: mention of FDA or mention of Philippine FDA imitation of such words and initials FDA Logo Any imitation of the FDA Logo PRIMARY LABELING REQUIREMENTS Article Required 1.

8 The declared commercial name of the product (transliterated into the English alphabet) a. Brand name b. Name of Product Variant 2. The term ENDS/ENNDS solution OR single-use electronic cigarette, as applicable, to describe the product. 3. The exact statement, Keep out of the reach of children. 4. Electronic cigarette liquid solution volume in mL, rounded to the nearest ( mL) 5. Nicotine concentration expressed in mg/mL nicotine or the words nicotine-free, as applicable, rounded to the nearest one mg/mL. 6. Batch/Lot number(s) 7. Expiry date 8. FDA Electronic Registration Number SECONDARY LABELING REQUIREMENTS 1. The declared commercial name of the product (transliterated into the English alphabet) a)Brand name b)Name of Product Variant 2. The term ENDS/ENNDS solution OR single-use electronic cigarette, as applicable, to describe the product. 3. Nicotine concentration expressed in mg/mL or the words nicotine-free, as applicable 4.

9 Electronic cigarette liquid solution volume in mL, rounded to the nearest 5. Marketing Authorization Holder Information a)Company Name b)Company Address c)Company Contact Details d)LTO Number 6. Country of Origin SECONDARY LABELING REQUIREMENTS of ingredients contained in the product, in descending order of concentration, with potential allergens emphasized in bold characters. The declaration should follow the succeeding format, inclusive of the Chemical Abstracts Service Registry Number [CAS No.]: 8. FDA Electronic Registration Number 9. Instructions on the handling, use, and storage of the ENDS/ENNDS solutions 10. Usage cases to be avoided (in the context of current medications, health conditions, and interactions with other drugs and other substances) 11. Instructions for the disposal of the ENDS/ENNDS solutions and container Chemical/Ingredient CAS No. Propylene glycol 57-55-6 Vegetable Glycerin 56-81-5 Nicotine 56-81-5 [potential allergen] [as appropriate] SECONDARY LABELING REQUIREMENTS 12.

10 Directions in case of ingestion or skin contact 13. GHS Pictogram, Signal Word, and Hazard Statement 14. Undesirable adverse health effects 15. Warning statements: a)Do not swallow b)Keep out of the reach of children c)Avoid prolonged contact with the skin d)Nicotine is an addictive substance. e)Not suitable for pregnant women, nursing mothers, children, persons with respiratory or cardiovascular diseases. f)Call the poison center or the hospital near you in case of accidents, injury, or illness arising from the use of this product. 16. The updated contact information of University of the Philippines, National Poison Control and Information Service, as of the time of manufacture 17. The exact statement: For any complaints or reports on product quality and safety, please contact the Food and Drug Administration by email: LICENSING PROCEDURE for a user account by going to this link and accomplishing the online form: LICENSING PROCEDURE Authorization Letter or Proof of Ownership LICENSING PROCEDURE trader and Distributors Manufacturer Accomplished online application form for Traders /Distributors Accomplished application form for Manufacturers Proof of Business Name Registration Proof of Business Name Registration Business Permit/Barangay Permit Business Permit/Barangay Permit FDA QPIRA (Qualified Personnel in Regulatory Affairs) Certificate for ENDS/ENNDS Attendance FDA QPIRA (Qualified Personnel in Regulatory Affairs) Seminar for ENDS/ENNDS Government Issued ID of authorized person and qualified personnel Government Issued ID of authorized person and qualified personnel (Allied Health Science Professional) Payment (PhP 10, + LRF) Site Master File Payment (PhP 15, + LRF) Note: A notarized commitment letter shall be submitted in lieu of the QPIRA Certificate LICENSING PROCEDURE 2.