April 10, 2015

FDA CIRCULAR NO. 007-15

I. Background/Rationale

Section 15, Article II of the 1987 Philippine Constitution declares it a policy of the State to protect and promote the right to health of the people and instill health consciousness among them. Further, Section 11 of Article XIII mandates the State to adopt an integrated and comprehensive approach to health development which shall endeavor to make essential goods, health and other social services available to all the people at affordable cost.

In

Oxygen, Nitrous Oxide, Carbon Dioxide, and other medical gases recognized in different pharmacopeias have diverse indications for use and are therefore classified as drugs under the regulatory jurisdiction of FDA.

Presently, manufacturers of medical oxygen in cylinder tanks are required to be licensed as drug manufacturers. Their products are also required to be registered with FDA.

With the recent increase in the number of hospitals and other health facilities setting-up their own medical gas generating machines and subsequent engagement in the manufacture of medical gas both for inpatient use and other consumers, FDA, as the drug regulatory authority of the Philippines responsible for ensuring the safety, efficacy, and quality of drug products, hereby promulgates the following rules and regulations on the licensing of these establishments. This Circular is issued following the provisions of

II. Objectives

The objective of this Circular is to promulgate the rules and regulations on the licensing of hospitals and other health facilities involved in the manufacture of medical gases as drug manufacturers.

III. Scope

These

IV. Implementing Details

A. Establishment Required Licensing

All government and private hospitals and other health facilities engaged in the manufacture of medical gases are required to secure a License to Operate (LTO) as drug manufacturer. For the purpose of this Circular, a "manufacturer" refers to any establishment engaged in any or all operations involved in the production of drug products, including preparatory processing, compounding, formulating, filling, packaging, repackaging, altering, ornamenting, finishing, and labeling with the end in view of its storage, sale or distribution; provided, that the term shall not apply to the compounding and filling of prescriptions in drugstores and hospital pharmacies.

An LTO is required for abovementioned establishments regardless of the following:

1) Method of medical gas manufacturing (e.g.,concentrator, chemical synthesis, purifier)

2) Scale of manufacturing (e.g.,small, medium, large)

3) Mode of gas delivery (e.g.,from cylinders, from a medical gas pipeline system)

4) End users of the manufactured medical gas (e.g.,inpatients of hospitals and other health facilities, other consumers)

5) Type of ownership [e.g.,Department of Health (DOH)-retained, Local Government Unit (LGU)-owned, privately-owned]

B. Documentary Requirements

1) Application Form

A completely filled-out and notarized application form signed by the pharmacist and owner/authorized representative must be submitted.

2) Proof of Business Name Registration

A valid proof of business name registration must be submitted:

(a) For single proprietorship Certificate of Business Registration issued by the Department of Trade and Industry (DTI)

(b) For corporation, partnership and other juridical person Certificate of Registration issued by the Securities and Exchange Commission (SEC) and Articles of Incorporation

(c) For cooperative Certificate of Registration issued by the Cooperative Development Authority and the approved by-laws

(d) For government-owned or controlled corporation the law highlighting the provision creating such establishment

The proof of business name registration must specify the exact and complete address, e.g.,unit number, floor, building, lot, block, phase, street, barangay,city/municipality, province, where applicable.

3) Credentials of the Pharmacist-in-Charge

The credentials of the identified pharmacist-in-charge must be submitted, which include:

(a) Valid Professional Regulation Commission (PRC) ID

(b) Certificate of Attendance to appropriate FDA Licensing Seminar

(c) Resignation letter of the pharmacist from previous employer (if previously employed)

The other qualified personnel shall be listed, which include the (1) hospital engineer or equally qualified person responsible for overseeing the operations of the manufacturing facility and (2) personnel responsible for maintenance. The credentials will not be submitted during application but may be verified during inspection.

4) Risk Management Plan

A general Risk Management Plan (RMP) for the establishment must be submitted. The RMP shall contain details on how to identify, characterize, prevent or minimize risks relating to the medical gas they engage in. These shall include pharmacovigilance activities and interventions of the establishment to manage the risks.

5) Location Plan

A sketch of the location of the establishment must be submitted which shall be used for inspection purposes. This sketch must indicate clear directions with identified landmarks to locate the establishment.

In addition, the Global Positioning System (GPS) Coordinates in decimal degrees (D) Latitude and Longitude must be indicated in the submission.

6) Site Master File

The Site Master File (SMF) must be submitted, in accordance with the latest edition of the Pharmaceutical Inspection Cooperation Scheme (PIC/S)-Good Manufacturing Practice (GMP).

7) Proof of Payment

Proof of payment (e.g.,official receipt or authorized bank payment slip) must be included as proof of filing of application.

8) Self-Assessment Toolkit

To guide and facilitate the submission, a Self-Assessment Toolkit (SATK) must be submitted, which shall also serve as the worksheet during evaluation of FDA.

The list of documentary requirements for initial and renewal applications of LTO, reissuance of lost or destroyed LTO, as well as voluntary cancellation of LTO is attached as Annex A.

C. Evaluation of Application

1) Desktop Evaluation

All applications shall be initially reviewed by the respective FDA Regional Field Offices to determine compliance with the administrative and technical requirements.

The FDA, in the course of its evaluation may require additional or supplemental documents as proof of compliance to the existing regulations.

2) Pre-opening Inspection

After evaluation of the LTO application, the establishment shall be subjected to pro-opening inspection to determine compliance with the existing guidelines on PIC/S-GMP.

In addition to the documentary requirements submitted during application (Section IV, B of this Circular),the following documents related to the manufacturing of medical gas shall be verified during inspection:

Quality Management System of the establishment, incorporating the medical gas manufacturing facility;

Quality Manual and Standard Operating Procedures of the medical gas manufacturing facility;

Contract Agreement between the supplier/installer of the medical gas manufacturing machine and the establishment

Qualification and Validation Documents

Master and/or Batch Production Records

Specifications

Credentials of other qualified personnel

Relevant reference materials (e.g.,Republic Acts, PIC/S-GMP Guide, standard practice guidelines)

Other procedures, protocols, records, and reports as required by PIC/S-GMP

The abovementioned additional documents will serve as proof of compliance by the establishment with the existing regulations on licensing.

A report shall be issued to the drug establishment after inspection, which shall be the basis for further decision/action of FDA, (e.g.,approval/disapproval of an application for LTO, and/or for such other purposes).

3) Post-licensing Inspection

All establishments with approved LTO shall be subjected to routine inspection for their compliance to GMP and other relevant and applicable practices. In addition, major variation applications may require post-licensing inspection prior to the approval of such variation. Establishments which are subject to regulatory action due to different triggers (e.g.,violation of any of the provisions of FDA laws, rules and regulations, and any other laws related thereto, occurrence of adverse drug reactions, as well as other quality, safety, and/or efficacy issues) shall also be inspected.

D. Application for Variation

The following are the applicable variations to an approved LTO:

1) Major Variation

(a) Change of Ownership

(b) Transfer of Location

2) Minor Variation Prior Approval

(a) Expansion of Establishment

(b) Change of Business Name

(c) Zonal Change in Address

3) Minor Variation Notification

(a) Change of Pharmacist-in-Charge or Other Qualified Personnel

FDA should be duly informed of any changes to the approved LTO, whether or not these are classified as variations described above. Other changes may also be added to the variations mentioned, which shall be subject of an appropriate regulation.

The list of documentary requirements for the abovementioned variations is attached as Annex B.

All variations are subject to the existing variation/amendment fee except for transfer of location which is subject to initial payment for two (2) years validity of LTO.

Hospitals and other health facilities applying for minor variations may continue business operations provided that an application for such variation has already been filed.

E. Accessibility

All electronic fillable forms shall be made accessible at the FDA Website.

V. Responsibilities of Other Implementing Offices

Consistent with the regulatory powers provided under (3), c, Sec. 2, Article III, Book I of the

In addition, Local Government Units (LGUs) are enjoined in monitoring licensed hospitals and other health facilities in their localities for their compliance to the existing laws and their respective rules and regulations. Any violation found by the LGU inconsistent with the FDA rules and regulations shall be reported to FDA for regulatory action.

VI. Transitory Provisions

Hospitals and other health facilities are given until 30 June 2015 to file their application for LTO following the existing documentary requirements. Hospitals and other health facilities that continue to engage in the activities described herein without any application shall be a ground for the filing of administrative charges pursuant to the existing rules and regulations of FDA and the Health Facilities and Services Regulatory Bureau.

Hospitals and other health facilities with existing medical gas manufacturing facilities which have filed the LTO application before the aforementioned deadline may continue operations until issuance of LTO. An intensive inspection transition phasing shall be employed by FDA using a risk based approach.

Table 1. Inspection Transition Phasing

Incoming applications after 30 June 2015 shall need to secure an LTO prior to operations; FDA will inspect these establishments once all the transition phasing for previously submitted applications have been completed.

VII. Repealing Clause/Separability Clause

Provisions of previous FDA circulars and memoranda that are inconsistent with this issuance are hereby withdrawn, repealed, and/or revoked accordingly. In case any part, term or provision of this FDA Circular is declared contrary to law or unconstitutional, other provisions which are not affected remain in force and effect.

VIII. Effectivity

This Circular shall take effect immediately upon approval and signature by the FDA Director General.

(SGD.) ATTY. NICOLAS B. LUTERO III, CESO III
OIC-Director IV
Food and Drug Administration

ANNEX A

List of Documentary Requirements for Hospitals and Other Health Facilities as Manufacturers of Medical Gases LTO Applications

A. Initial LTO Application

1) Application Form

2) Proof of Business Name Registration

3) Credentials of the Pharmacist-in-Charge

4) Risk Management Plan

5) Location Plan

6) Site Master File

7) Proof of Payment

8) Site Assessment Toolkit

B. Renewal LTO Application

1) Application Form

2) Copy of Certifications issued as a result of LTO Variation

3) Proof of Payment (e.g.,official receipt or authorized bank payment slip)

4) Self-Assessment Toolkit

C. Reissuance of Lost or Destroyed LTO

1) Letter of Request

2) Affidavit of Loss or Destruction

3) Proof of Payment (e.g.,official receipt or authorized bank payment slip)

D. Voluntary Cancellation of LTO

1) Letter of Request

2) Original LTO

ANNEX B

List of Requirements for Variation Applications for Hospitals and Other Health Facilities as Manufacturers of Medical Gases

A. Major Variations

B. Minor Variations Prior Approval

C. Minor Variations Notification