Drug Approval System of The Philippines PDF

Drug Approval System of
the Philippines
Drafted Version
(Expected to be revised)
May 2016
APEC Harmonization Center

Abbreviation
ACTD: ASEAN Common Technical Dossier

AO: Administrative Order
CDRR: Center for Drug Regulation and Research
CPR: Certificate of Product Registration
CSP: Compassionate Special Permit
DOH: Department of Health
DTN: Document Tracking Number
EO: Executive Order
ICH: International Council on Harmonisation
LOD: Letter of Disapproval
LTO: License to Operate
NOD: Notice of Deficiency
PAIR: Public Assistance, Information, and Receiving
RA: Republic Act
Notice
1. Due to the purpose of this document, most of the information was
quoted directly from the website or related guidelines of each
country’s drug regulatory agencies, and reviewed by the agencies.
2. This document is limited only to pharmaceutical products, not

applicable to biological and herbal products.
3. When referring to the contents of this document, check the up-to-

date information including related laws and regulations, and
revision of guidelines.
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Table of Contents
I. Drug Regulatory Agency ···························································· 5

1. Food and Drug Administration···················································· 5
1.1 Organization·································································· 5
1.2 Tasks··········································································· 6
1.3 Contact Information························································· 8
II. Related Laws and Regulations······················································ 9
1. Republic Acts ······································································· 9
2. Related Regulations ································································ 9
III. Pharmaceutical Products and its Classification································ 10

1. New Drug··········································································· 11
2. Generic Drug······································································· 11
3. Orphan Drug········································································ 11
IV. Drug Approval System······························································ 12

1. Clinical Trial Application························································ 12
1.1 Establishments Authorized to Conduct Clinical Trial················· 12
1.2 Clinical Trial Application Requirements································ 13
1.3 Clinical Trial Approval Process·········································· 14
1.4 Amendment·································································· 14
1.5 Review Period······························································· 14
2. Drug Application and Registration·············································· 15
2.1 Overview····································································· 15
3. New Drug Application···························································· 16
3.1 Application Dossier························································ 17
3.2 Processing Timelines······················································· 19
4. Generic Drug Application························································ 20
4.1 Application Dossier························································ 20
4.2 Processing Timelines······················································· 21
5. Orphan drugs······································································· 21
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6. Facilitated Applications··························································· 22
V. Others ·················································································· 23
1. Good Manufacturing Practice···················································· 23
1.1 GMP Inspection of Local Manufacturers······························· 23
1.2 GMP Clearance/Certificate of Foreign Manufacturers················ 23
2. Product Interchangeability························································ 23
2.1 Products Covered··························································· 26
2.2 BE Studies Conducted Abroad··········································· 26
2.3 Enforcement of Requirement············································· 26
3. Labeling Materials································································· 27
4. Certificate of Pharmaceutical Product ········································· 28
5. Renewal of Drug Registration··················································· 28
6. Post-Approval Changes ·························································· 29
6.1 Major Variation····························································· 29
6.2 Minor Variation – Prior Approval (MiV-PA) and Minor Variation –
Notification (MiV-N)······················································ 29
7. Fees ················································································· 30
VI. References·············································································· 32
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List of Figures
Figure 1. Organization of the Food and Drug Administration
Figure 2. Overview of Drug Registration Process
List of Tables
Table 1. Comparison of ACTD and ICH CTD Documentation
Table 2. Documents Required for GMP Evidence Dossier
Table 3. Fees and Charges for LTO, CPR, Clinical Trials, Foreign GMP, and other
Certifications
List of Appendixes
Appendix 1. Organization of ACTD
Appendix 2. List of Molecules Requiring Proof of Interchangeablity
Appendix 3. Details on the Minimum Labeling Information
Appendix 4. List of Information Required per Labeling Material
Appendix 5. List of Post Approval Changes
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I. Drug Regulatory Agency
1. Food and Drug Administration
As a regulatory agency under the Department of Health (DOH), the Food and Drug
Administration (FDA), created in 1963, is mandated to ensure the safety, efficacy or quality
of health products, which include food, drugs, cosmetics, devices, biologics, vaccines, in-
vitro diagnostic reagents, and household/urban hazardous substances and/or a combination of
and/or a derivative thereof. Also included are products that may have an effect on health,
which require regulations as determined by the FDA.
1.1 Organization
The FDA is comprised mainly by the following: the Internal Management Office, the
Field Regulatory Operations Office (FROO), four (4) centers according to product
jurisdiction, and the common services laboratory. Other main offices include the Policy and
Planning Service (PPS) and the Legal Service (LS).
Figure 1. Organization of the Food and Drug Administration1
1
As provided under Department Circular No. 2011-0101, “Implementing Rules and Regulations of R.A. No.
9711”, but with minor adjustments as recommended by the Department of Budget and Management (DBM)
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1.2 Tasks
The tasks of the abovementioned offices are as follows:
1) Internal Management Office

 develops plans and programs relative to finance and administrative management
 determines and evaluates administration and finance risk management in
coordination with other offices within the FDA
 coordinates with the Field Regulatory Operations Office (FROO) on matters
related to administration and finance
 implements systems and procedures that will further enhance administration and
financial management
2) Field Regulatory Operations Office

 supervision of all Regional Field Offices (RFOs), Laboratories and the Regulatory
Enforcement Units (REU);
 recommend other government and private testing laboratories in the regions
qualified and properly equipped to conduct testing, calibration, assay, and
examination of samples and health products
 implements systems and procedures that will further enhance field operations
management
3) The RFOs have the following functions:

 implement laws, policies, plans, programs, rules and regulations of the FDA in the
regional area
 administratively support the REU assigned in their respective region;
 implement the postmarketing surveillance system in monitoring health products
and incidents of adverse events involving such products in coordination with the
PRSDD of each Center;
 operate field and/or satellite laboratories in their respective regions;
 inspect and evaluate establishments and issue appropriate renewal licenses, and
other appropriate authorizations as may be delegated and undertake compliance
monitoring;
 evaluate health products and issue appropriate authorizations, as may be delegated
(except product registration) and undertake compliance monitoring;
 coordinate with regional offices of other departments, bureaus and agencies in the
area;
 coordinate with local government units in the area;
4) Policy and Planning Service

 provides services on policy formulation, project development and evaluation,
research development and analysis, and coordination and monitoring
 formulates, updates and conducts advocacy campaigns for appropriate legislation
on any matter relating to health products. PPS (i) coordinates with the executive
and legislative branches of the national government and other stakeholders on
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matters and issues pertaining to regulation of health products and health product
establishments; (ii) manages the legislative, executive and other intergovernmental
liaison service support to the FDA and its different units or offices; and (iii)
monitors and reviews legislative and executive proposals on legislation of all
health products and health product establishments' regulation. PPS also coordinates
with the Legal Service (LS) and other Centers on technical matters pertaining to
legislation and regulation of health products and health product establishments
 initiates, coordinates and implements the conduct of all relevant policy research
and development work, including maintenance of database of statistics related to
health products and supervises the collection, monitoring and publication thereof;
 formulates and conducts advocacy, training and communication programs in
coordination with other government agencies, nongovernment and private entities
and sectors in furtherance of the mandate of the FDA
 conducts integrated and performance-based planning and budgeting in consultation
with other offices
5) Legal Service
 provides legal services to the entire FDA in the implementation of its mandate and
objectives
 assists in the promulgation of rules governing the activities relating to the
operations of the FDA
 coordinates with PPS in providing technical assistance and advisory services on
existing and proposed legislation and regulation on health products and health
products establishment
6) Common Services Laboratory

 analyzes and inspects health products
 establishes analytical data to serve as basis for the preparation of health products
standards, and to recommend standards of identity, purity, safety, efficacy, quality
and fill of container
 conducts appropriate tests on all applicable health products prior to the issuance of
appropriate authorizations
 audits centers conducting bioavailability and bioequivalence tests, as may be
delegated
 accredits private testing laboratories
7) Centers
 regulate the manufacture, importation, exportation, distribution, sale, offer for sale,
transfer, promotion, advertisement, sponsorship of, and/or, where appropriate, the
use and testing of health products
 conduct research on the safety, efficacy, and quality of health products
 institute standards for the safety, efficacy, and quality of health products
 inspect and evaluate establishments covered by the particular Center and issue
appropriate licenses;
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 evaluate and issue appropriate authorizations for all health products and health
product establishments regulated by each Center
 conduct PMS on health products;
 employ a consultative risk management approach to decision-making across all
product classes;
 provide technical assistance, consultative and advisory services to stakeholders and
other government agencies in the implementation of laws, rules and regulations
pertaining to health products
1.3 Contact Information
 Website: www.fda.gov.ph
 Email: info@fda.gov.ph, report@fda.gov.ph
 Phone: +63 2 857 1900
 Social Media: www.facebook.com/FDAPhilippines
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II. Related Laws and Regulations
1. Republic Acts2
In the regulation of drug products, the FDA is guided mainly by under Republic Act (RA)
3720, series of 1963, as amended by EO 175, series of 1987, otherwise known as the “Food,
Drugs and Devices, and Cosmetics Act”, and subsequently RA 9711 otherwise known as
“The Food and Drug Administration Act of 2009:.
The FDA is also guided by the following RA:

 RA 3720, Food, Drugs and Devices, and Cosmetics Act
 RA 9711, Food and Drug Administration (FDA) Act of 2009
 RA 5921, Pharmacy Law
 RA 6675, The Generics Act of 1988
 RA 7394, Consumer Act of the Philippines
 RA 8203, Special Law on Counterfeit Drugs
 RA 9165, Comprehensive Dangerous Drugs Act of 2002
 RA 9502, Universally Accessible Cheaper Quality Medicines Act of 2008
 RA 10352, Philippine National Health Research System Act of 2013
 RA 10354, The Responsible Parenthood and Reproductive Health Act of 2013
 RA 10747, Rare Diseases Act of the Philippines
2. Related Regulations
As a policy and standard setting body, regulatory requirements are provided in the
following issuances:
 Executive Orders3
 Administrative Orders4
 FDA Circulars5
 FDA Memorandum Circulars6
2
http://www.fda.gov.ph/issuances-2/pharml-1/pharml-republic-act
3
http://www.fda.gov.ph/issuances-2/pharml-1/pharml-executive-order
4
http://www.fda.gov.ph/issuances-2/pharml-1/pharml-administrative-order
5
http://www.fda.gov.ph/issuances-2/pharml-1/pharml-fda-circular
6
http://www.fda.gov.ph/issuances-2/pharml-1/pharml-memorandum-circular
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III. Pharmaceutical Products and its Classification
Pharmaceutical product, drug, drug product or finished pharmaceutical product refers to:
1) any article recognized in the official United States Pharmacopoeia-National
Formulary (USP-NF), official Homeopathic Pharmacopoeia of the United States,
Philippine Pharmacopoeia, Philippine National Drug Formulary, British
Pharmacopoeia, European Pharmacopoeia, Japanese Pharmacopoeia, Indian
Pharmacopoeia, any national compendium or any supplement to any of them;
2) any article intended for use in the diagnosis, cure, mitigation, treatment or prevention
of disease in humans or animals;
3) any article other than food intended to affect the structure or any function of the
human body or animals;
4) any article intended for use as a component of any articles specified in clauses (1), (2)
and (3) not including devices or their components, parts or accessories;
5) herbal and/or traditional drugs which are articles of plant or animal origin used in folk
medicine which are:
(a) recognized in the Philippine National Drug Formulary
(b) intended for use in the treatment or cure or mitigation of disease symptoms,
injury or body defects in humans
(c) other than food, intended to affect the structure or any function of the human
body
(d) in finished or ready-to-use dosage form; and
(e) intended for use as a component of any of the articles specified in clauses (a), (b),
(c) and (d).
In the Philippines, drug products are classified into the following:

1) New Drugs or New Chemical Entities
2) Biological Products
3) Generic Drugs
4) Traditionally-Used Herbal Products
5) Herbal Medicines
6) Household Remedies
7) Over-the-Counter Preparations
8) Veterinary Drugs
9) Medical Gases
10) Stem Cell Products
For Purposes of this paper, the following shall be covered:
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1. New Drugs7
New drug or new chemical entity (NCE) refers to a product previously authorized for
marketing in any pharmaceutical use in the Philippines. It may refer to:
1) Any drug the composition of which is such that said drug is not generally recognized
among experts qualified by scientific training and experience to evaluate the safety,
efficacy, and quality of drugs as safe, efficacious and of good quality for use under the
conditions prescribed, recommended, or suggested in the labelling thereof.
2) Any drug the composition of which is such that said drug, as a result of previous
investigations to determine its safety, efficacy and good quality for use under certain
conditions, has become so recognized but which has not, otherwise than in such
investigations, been used to a material extent or for a material time under new
conditions.
3) "New drugs" shall include drugs:
(a) containing a newly discovered active ingredient
(b) containing a new fixed combination of drugs, either by molecular or physical
combination
(c) intended for new indications
(d) in an additional new mode of administration;
(e) in an additional dosage of strength of the dosage form, which meets the conditions
as defined under the new drug.
New drugs are registered under monitored-release status.
2. Generic drugs8
Generic drug is a product considered to be essentially similar or bioequivalent to a

reference drug. These are drugs that are pharmaceutically equivalent but may or may not be
therapeutically equivalent, and are not covered by patent protection and which are labeled
solely by their international non-proprietary name or generic name.
3. Orphan drugs9
Orphan drug refers to any drug or medicine used to treat or alleviate the symptoms of
persons afflicted with a rare disease and declared as such by the DOH upon recommendation
of the National Institutes of Health (NIH).
7
Executive Order No. 175, “Further Amending Republic Act No. 3720, Entitled “An Act to Ensure the Safety
and Purity of Foods, Drugs, and Cosmetics Being Made Available to the Public by Creating the Food and Drug
Administration which shall Administer and Enforce the Laws Pertaining thereto”, as Amended, and for Other
Purposes”
8
Definition from the following: Republic Act No. 6675, “Generics Act of 1988”, and ACTD Glossary, as
adopted by Administrative Order No. 2013-00021
9
Republic Act No. 10747, “Rare Disease Act of the Philippines”
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IV. Drug Approval System
1. Clinical Trial Application
The FDA is mandated to conduct, supervise, monitor and audit research studies on health
and safety issues of health products undertaken by duly authorized by the FDA10. All clinical
trials to be conducted in the Philippines need to secure approval of their protocol prior to the
conduct, which is required per phase of the trial.11
Clinical trial is defined by the FDA as any investigation in human subjects intended to
discover or verify the clinical, pharmacological and/or other pharmacodynamics effects of an
investigational product(s) (IP), and/or to identify any adverse reactions to an investigational
product(s), and/or to study absorption, distribution, metabolism, and excretion of an
investigational product(s) with the object of ascertaining its safety and/or efficacy. The terms
clinical trial and clinical study are synonymous 12 . Investigational new drug (IND) or
investigational product refers to a pharmaceutical form of an active ingredient or placebo
being tested or used as a reference in a clinical trial, including a product with a marketing
authorization when used or assembled (formulated or packaged) in a way different from the
approved form, or when used for an unapproved indication, or when used to gain further
information about an approved use. The definitions were adopted from the International
Council for Harmonisation (ICH) (previously International Conference on Harmonisation)
guideline on Good Clinical Practice (GCP)13.
In the conduct of clinical trial, strict adherence to GCP, good laboratory practice, and other
best practices is required, including full disclosure of all pertinent documentation during
application and inspection.14
1.1 Establishments Authorized to Conduct Clinical Trial
Establishments authorized by the FDA include Sponsors and Clinical Research

Organizations (CROs) 15 . The FDA issues a License to Operate (LTO) as proof of
authorization for these establishments.
Sponsor is defined as an individual, company, institution, organization or an entity which
takes the responsibility for the initiation, management, and/or financing of a clinical trial.
CRO, on the other hand, is defined as a person or an organization (commercial, academic,
or other) contracted by the sponsor to perform one or more of the sponsor’s trial-related
duties and functions. As long as the CRO engages in any of the following activities as
delegated by the sponsor, LTO is required:
10
Section 5 (n) of RA 9711
11
Administrative Order No. 47-a s. 2001, Rules and Regulations on the Registration, including Approval and
Conduct of Clinical Trials, and Lot or Batch Release Certification of Vaccines and Biologic Products
12
Administrative Order No. 2014-0034, Rules and Regulations on the Licensing of Establishments Engaged in
the Manufacture, Conduct of Clinical Trial, Distribution, Importation, Exportation, and Retailing of Drug
Products, and Issuance of Other Related Authorizations
13
ICH Harmonised Tripartite Guideline, Guideline for Good Clinical Practice E6(R1)
14
FDA conducts postlicensing inspection
15
FDA Circular No. 2015-003, Guidelines on the Implementation of New Rules and Regulations on the
Licensing of Sponsors and Contract Research Organizations (CROs) following Administrative Order No. 2014-
0034, dated 13 October, 2014
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1) Oversight (e.g. ensuring quality assurance and/or quality control systems are in place
to ensure clinical trials are conducted, data is gathered, and subsequently reported)
2) Management of clinical trials
 development of protocols and/or trial design;
 selection of investigator(s) and/or site(s);
 screening and/or recruitment of subjects;
 data handling (e.g. collection, analysis/evaluation, and record keeping)
Entities involved in the procurement/importation, storage, and/or distribution of

investigational product(s) are not required to secure an LTO as CRO, unless they are
involved in other activities mentioned above. These entities must follow other existing
licensing requirements.
1.2 Clinical Trial Application Requirements
A clinical trial dossier is required, consisting of the following documents:
Part A: Clinical Trial Protocol and other documents

1) Name and dosage form of product
2) Title and aim of the trial; Description of the trial design
3) Treatment profile; Operational aspects
4) Adverse events
5) Evaluation of results
6) Informed consent form, case report form and patient information sheet
7) Resumes of principal and other investigators
8) For multicentre studies, a list of principal investigators with contact details (and CVs)
including trial sites
Part B: Pharmaceutical Data

1) GMP statement from manufacturing/Certificate from Regulatory Body
2) Certificate of Analysis
3) Stability Data (storage conditions)
4) Manufacturing Data and Formulation
5) Product labelling (coded and labelled: blinding)
Part C: Investigator’s brochure (Efficacy and Safety data)

1) Safety data:
a. Non-clinical studies; Toxicology studies
b. Pharmacology: PK/PD studies
c. Marketing experience, Periodic Safety Update Reports (PSUR), product status if
marketed abroad
d. Risks and ADR anticipated
2) Efficacy data:
a. PK/PD data in human subjects;
b. In-house preliminary data
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c. Summaries of clinical trial studies conducted (Phase I,II,III)
d. Published clinical data
1.3 Clinical Trial Approval Process
Application begins upon submission of the clinical trial dossier through the of an
electronic copy application at the Public Assistance, Information, and Receiving (PAIR)
without the need for appointment16.
Once an applicant submits the dossier, CDRR evaluates the documents and determines if:
 Study has scientific value and worth pursuing/conducting
 Conducted by duly licensed establishments
 Compliant with GCP, and other applicable best practices
 Compliance to safety and efficacy standards of ICH17
If the protocol is found to be acceptable, a Clinical Trial Protocol Approval is issued by

the FDA and gives instructions to the applicant to apply for Import Permit for Clinical Trials
to access imported INDs, including ancillary supplies such as laboratory kits, reagents, and
other materials to be used for the clinical trial18.
1.4 Amendment
If, during the conduct of the clinical trial, changes in the protocol are necessary,
appropriate amendments should be submitted to the FDA seeking approval.
1.5 Review Period
A maximum of 90 calendar days is given by the FDA in the processing of clinical trial
approval applications; for amendment, 60 calendar days; and for import permit, 30 calendar
days.
16
FDA Circular No. 2014-009, Filing and Submission of Applications for the Approval of Clinical Trial
Protocol, Compassionate Special Permit (CSP), Import Permit for Investigational Drug Products,
Pharmacovigilance, Adverse Events/Adverse Reaction Reports, and other related documents
17
FDA Circular No. 2013-019, Adoption of the International Conference on Harmonisation (ICH) Safety and
Efficacy Guidelines
18
FDA Circular No. 2012-007, Recognition of Ethical Review Board/Committee (ERB/ERC) for Purposes of
the Conduct of Clinical Trials on Investigational Medicinal Products in the Philippines and for Other Purposes
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2. Drug Application and Registration
2.1 Overview
For a company to be able to market a drug product in the Philippines, securing a

marketing authorization in the form of a Certificate of Product Registration (CPR) is
necessary. A CPR covering a particular drug product shall be a prima facie evidence of the
registrant's marketing authority for the said drug product in connection with the activities
permitted pursuant to the issuance of a LTO. The figure below generally describes the process
of registration.
Submission
Evaluation
No With Yes
deficiencies?
Issuance of CPR NOD/LOD
Releasing
Figure 2. Overview of Drug Registration Process
The process above generally describes the process of registration. The process begins with
the submission of an electronic copy application using the Integrated Application Form at the
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PAIR, by appointment schedule 19 of an applicant company (which may be a licensed
manufacturer, trader, or distributor).
Once an applicant submits the dossier, CDRR evaluates the documents and determines if
the product meets the standards of safety, efficacy, and quality. If the product meets these
standards, a CPR is issued valid for five (5) years. Should deficiencies be noted, depending
on the criticality, a Notice of Deficiency (NOD) or Letter of Disapproval (LOD) may be
issued.
The FDA disapproves products based on the following grounds20:
 The application requirements submitted show that the drug product does not meet the
required technical requirements or appropriate standards;
 The applicant made misrepresentations, false entries, or withheld any relevant data;
 Major inconsistencies in the information provided in the registration dossier;
 Major queries that were not clarified or addressed satisfactorily by the applicant
company in the compliance for NOD; and
 Major inconsistencies in the compliance for NOD and the registration dossier.
3. New Drug Application
In 1 July 2013, the FDA adopted the Association of Southeast Asian Nations (ASEAN)
Common Technical Dossier (ACTD) and Common Technical Requirements (ACTR) for the
registration of pharmaceutical products for human use21. The ACTD is a product of the
tireless efforts of the ten ASEAN Member States’ (AMS) drug regulatory authorities (DRAs)
conducting consultative meetings through the ASEAN Consultative Committee for Standards
and Quality (ACCSQ) – Pharmaceutical Product Working Group (ACCSQ-PPWG). The
objective of the ACCSQ-PPWG is to develop harmonized schemes in pharmaceutical product
regulation acceptable to ASEAN DRAs.
The ACTD, which is defined as the part of marketing authorization application dossier
common to all AMS, covered (1) new drugs or NCEs, (2) prescription generic drug products,
and biological products. ACTR, a set of written materials intended to guide applicants to
prepare application dossiers in a way that is consistent with the expectations of all ASEAN
DRAs, consists of the following guidelines:
 ASEAN Guidelines on Stability Study of Drug Product
 ASEAN Guidelines on Submission of Manufacturing Process Validation Data for
Drug Registration
 ASEAN Guidelines for Validation of Analytical Procedures
 ASEAN Guidelines for the Conduct of Bioavailability and Bioequivalence Studies
 ASEAN Guidelines on Nonclinical (Safety) Document
 ASEAN Guidelines on Clinical (Efficacy) Document
 ASEAN Variation Guidelines for Pharmaceutical Products
19
FDA Circular No. 2014-00, “Filing and Receiving of Registration, Licensing and Other Application Using
the Integrated Application Form”
20
As provided under the IRR of RA 9711
21
Administrative Order No. 2013-0021, “Association of Southeast Asian Nations (ASEAN) Common
Technical Dossier (ACTD) and Common Technical Requirements (ACTR) for the registration of pharmaceutical
products for human use”
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The FDA also allows flexibilities of submission for products following the ICH Common
Technical Document (ICH CTD) format, but following specific requirements acceptable to
ASEAN (e.g. Stability requirements)22. The table below describes the flexibilities between
ACTD and ICH CTD.
Documents Location
ACTD ICH CTD
Administrative Documents Part I Module 1
and Product Information
Common Technical Incorporated in Parts II, III, Module 2
Document Overview and and IV
Summaries
Quality Documents Part II Module 3
Non-Clinical Documents Part III Module 4
Clinical Documents Part IV Module 5
Table 1. Comparison of ACTD and ICH CTD Documentation
3.1 Application Dossier
As new drugs are covered by ACTD, the required documents23 are as follows:
Part I: Administrative Data and Product Information

1) Section A: Introduction
2) Section B: Table of Contents
3) Section C: Guidance on the Administrative Data and Product Information
a. Integrated Application Form
b. Letter of Authorization (where applicable)
c. Certifications
d. Labeling
e. Product Information
Part II: Quality

1) Section A: Table of Contents
2) Section B: Quality Overall Summary
3) Section C: Body of Data
Drug Substance
a. General Information
b. Manufacture
c. Characterization
d. Control of Drug Substance
e. Reference Standards or Materials
22
FDA Circular No. 2013-019, “Organization of the ASEAN Common Technical Dossier (ACTD) for the
Registration of Pharmaceutical Products for Human Use”
23
Guidance for each document is provided under the ACTD Guidance Document available at
http://www.fda.gov.ph/industry-corner/downloadables/217-requirements-for-drug-registration
- 17 -
f. Container Closure System
g. Stability
Drug Product
a. Description and Composition
b. Pharmaceutical Development
c. Manufacture
d. Control of Excipients
e. Control of Finished Product
f. Reference Standards or Materials
g. Container Closure System
h. Product Stability
Part III: Nonclinical Document

2) Section B: Nonclinical Overview
3) Section C: Nonclinical Written and Tabulated Summaries
a. Nonclinical Written Summaries
b. Content of Nonclinical Written and Tabulated Summaries
c. Nonclinical Tabulated Summaries
4) Section D: Nonclinical Study Reports
a. Table of Contents
b. Pharmacology
c. Pharmacokinetics
d. Toxicology
5) Section E: List of Key Literature References
Part IV: Clinical Document

2) Section B: Clinical Overview
3) Section C: Clinical Summary
a. Summary of Biopharmaceutic Studies and Associated Analytical Method
b. Summary of Clinical Pharmacology Studies
c. Summary of Clinical Efficacy
d. Summary of Clinical Safety
e. Synopses of Individual Studies
4) Section D: Tabular Listing of All Clinical Studies
5) Section E: Clinical Study Reports (if applicable)
a. Reports of Biopharmaceutic Studies
b. Reports of Studies Pertinent to Pharmacokinetics Using Human Biomaterials
c. Reports of Human Pharmacokinetic (PK) Studies
d. Reports of Human Pharmacodynamic (PD) Studies
e. Reports of Efficacy and Safety Studies
f. Reports of Post-Marketing Experience
g. Case Report Forms and Individual Patient Listing
- 18 -
6) Section F: List of Key Literature References
Country specific requirement include submission of foreign GMP Clearance 24 for

imported products.
The organization of ACTD including its subsections is attached as Appendix 1.
3.2 Processing Timelines
A maximum of 254 calendar days is given by the FDA in the processing of initial
applications for new drugs, excluding stop-clocks due to noted deficiencies.25
24
Administrative Order No. 2013-0022, “Guidelines for Current Good Manufacturing Practice (cGMP)
Clearance and Inspection of Foreign Drug Manufacturers”
25
CDRR’s Citizen Charter for the processing of initial applications as provided at
http://www.fda.gov.ph/issuances-2/cosmetic-laws-and-regulations-pertaining-to-all-regulated-cosmetic-
products/cosmetic-memorandum-circular/226409-fda-citizen-s-charter-cdrr-2
- 19 -
4. Generic drug approval application
4.1 Application Dossier
The requirements for generic drug registration depend on the dispensing category of the
products. For prescription products, application dossier is based on ACTD:

1) Section A: Introduction
2) Section B: Table of Contents
3) Section C: Guidance on the Administrative Data and Product Information
a. Integrated Application Form
b. Letter of Authorization (where applicable)
c. Certifications
d. Labeling
e. Product Information
Part II: Quality

2) Section B: Quality Overall Summary
3) Section C: Body of Data
Drug Substance
a. General Information
b. Manufacture
c. Characterization
d. Control of Drug Substance
e. Reference Standards or Materials
f. Stability
Drug Product
a. Description and Composition
b. Pharmaceutical Development
c. Manufacture
d. Control of Excipients
e. Control of Finished Product
f. Reference Standards or Materials
g. Container Closure System
h. Product Stability
i. Product Interchangeability
For over-the-counter (OTC) preparations and household remedy (HR) products,

application dossier is based on national guidelines:
 Integrated Application Form
 Valid agreements between the manufacturer, trader, importer, distributor, where
applicable
- 20 -
 Unit Dose and Batch Formulation
 Technical Specifications of all Raw Materials
 Certificate of Analysis of active Raw Material(s)
- From supplier of API
- From manufacturer of finished product
 Technical Specifications of Finished Product
 Certificate of Analysis (CA) of Finished Product (from the same batch of
representative sample)
 Manufacturing Procedure, Production Equipment, Sampling, In-process controls, and
Master Packaging Procedure (including specification for container closure system)
 Assay and Other Test Procedures including Identity, Purity Tests, with Data Analysis,
where applicable
 Stability Studies
 Labeling Materials (facsimile labels)
 Product Interchangeability
Country specific requirement for both include submission of foreign GMP Clearance for
imported products.
4.2 Processing Timelines
A maximum of 254 calendar days is given by the FDA in the processing of initial
applications for generic drug products, excluding stop-clocks due to noted deficiencies.
5. Orphan drugs
Orphan drugs are registered following a facilitated registration process and may fall either
through the abovementioned categories (or as biological preparations), or may be accessed by
patients using a Compassionate Special Permit (CSP). A CSP is a special permit signed by
the FDA Director granting a Specialized Institution (SI) and Specialty Society (SS) the
privilege to avail of an unregistered drug and device product through a certain licensed
establishment for certain kind/type of patients, specific volume and period. Patients having
the following conditions are allowed to use CSP:
1) Acquired Immune Deficiency Syndrome (AIDS)
2) Cancer
3) Life-threatening conditions
The requirements for securing a CSP are the following:

1) Letter of Application
2) Name and contact details of Specialist of the patient
3) Prescription
4) Medical Abstract of Patient
A maximum of 15 calendar days is given by the FDA in the processing of CSP.
- 21 -
6. Facilitated Applications26
The FDA provides a facilitated registration of applications following certain categories:

1) Products to be manufactured exclusively for export
2) New drug products considered to be a major therapeutic advance
3) The first 5 products of newly licensed establishments without any registered drug
product yet to its name
4) Products for government programs and projects
5) Imported prequalified vaccines
A maximum of 90 calendar days is given by the FDA for facilitated applications,

excluding stop-clocks due to noted deficiencies.
26
CDRR Memorandum No.: 0003, Series 2013, Facilitation of Applications for Product Registration
- 22 -
V. Others
1. Good Manufacturing Practice

In the Philippines, the standard of Good Manufacturing Practice (GMP) is the
Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme
(PIC/S-GMP)27.
Once an application for GMP clearance/certificate is received by the FDA, whether (1)
part of securing a License to Operate (LTO) of a local manufacturer, or (2) prior to
registration of a product from a foreign manufacturer, CDRR and FROO assesses the GMP
compliance of a manufacturer through desktop review and, where applicable, inspection.
PIC/S-GMP consists of the following elements:
 Quality Management
 Personnel
 Premises and Equipment
 Documentation
 Production
 Quality Control
 Contract Manufacture and Analysis
 Complaints and Product Recall
 Self-Inspection
Compliance to GMP is mandatory prior to registration of any drug product.
1.1 GMP Inspection of Local Manufacturers

All local establishments desiring to engage in the manufacture, distribution, importation,
exportation, sale, offer for sale and transfer of any drug product, must first secure an LTO,
which serves as the establishment’s compliance to the required standard of good practice. For
manufacturer’s, compliance to GMP is required and is proved and continuously monitored
during inspection.
1.2 GMP Clearance/Certificate of Foreign Manufacturers

As with local manufacturers, foreign drug manufacturers must prove compliance to
GMP. However, in consideration of the GMP evidences of foreign manufacturers as applied
by select countries, the FDA has opened the opportunity to prove GMP compliance only
through desktop evaluation.
1.2.1 Documentation
The following documents are required upfront upon application:

 Letter of Request
 Foreign GMP Application Form
27
Administrative Order No. 2012-0008, “Adoption and Implementation of the Pharmaceutical Inspection
Cooperation Scheme (PIC/S) Guides for the Good Manufacturing Practice (GMP) for Medicinal Products”
- 23 -
 GMP Evidence
 GMP Evidence Dossier (required for Non-PIC/S countries)
 Affidavit of Undertaking
GMP evidence may either be:

 GMP Certificate (Certificate of GMP Compliance); or
 WHO Certificate of a Pharmaceutical Product; or
 Manufacturer's License or Manufacturing Authorization incorporating the specific
medicinal product(s)/dosage form(s)
For those manufacturers not coming from a PIC/S member country, a GMP evidence
dossier is required to be submitted, which consists of documents depending on the
manufacturing steps the said establishment engages with:
Manufacturing Steps
Documents Required Full Bulk
QC Testing
Packaging / Release for
Sterilization
Manufacture Manufacture Labeling supply
An original or notarized
copy of a GMP certificate
     
A copy of the last
inspection report and the
manufacturer’s response
     
to any deficiencies noted
A copy of the GMP
contract between the
manufacturer and the
Importer, including a list      
of the specific products
for supply in the
Philippines.
A copy of the Site Master
File or equivalent   
A copy of the Validation
Master Plan (covering
process, media fill (if
relevant), cleaning,
computerized systems, etc
as applicable and    
including a Risk
Assessment used to
determine the scope and
extent of validation)
Rationale for test method
validation, procedure for   
method transfer etc.
Copies of the procedures
for handling deviations
and out of specification
     
test results
Table 2. Documents Required for GMP Evidence Dossier
- 24 -
1.2.2 Process
The process of foreign GMP clearance begins with the submission of application by the
licensed local importer. Upon receipt of application, CDRR evaluates and determines
compliance of the establishment with the required standards of GMP. If the foreign
manufacturer has been inspected by a PIC/S-member country, inspection will no longer be
required; otherwise, the RFO evaluates the GMP evidence in preparation for the inspection.
Logistical preparations for inspection are coordinated with the applicant importer28. As part
of the commitment to transparency, the FDA publishes in the FDA website the list of foreign
manufacturers subject to inspection.29
If upon desktop evaluation it was found that the manufacturing site is compliant to GMP,
CDRR shall issue a GMP Clearance with validity similar to the evidence presented; if after
inspection it was found that the manufacturing site is compliant to GMP, FROO shall forward
to CDRR the results of inspection and recommendation to issue a GMP Certificate. The list of
foreign manufacturers compliant to GMP is also published in the FDA website.30
1.2.3 Review Period
For foreign manufacturers not requiring inspection: 15-21 working days; for foreign
manufacturers requiring inspection: 45-60 working days, exclusive of inspection.
2. Product Interchangeability
In line with the mandate of the Food and Drug Administration of ensuring the availability
of safe, efficacious and quality pharmaceutical products in the Philippines, the FDA
introduced the concept of Bioavailability/Bioequivalence to all stakeholders, highlight the
importance of establishing interchangeability between innovator (originator) and multisource
(generic) pharmaceutical products, and correspondingly require the submission of satisfactory
BA/BE as early 199731.
However, due to the unavailability of Philippine-based testing facilities and/or
bioanalytical test methods used in the conduct of the studies then, a selective moratorium on
this requirement was imposed. After several years, in 201332, the FDA was able to fully
implement the requirement of BE.
28
FDA Circular No. 2014-016, “Implementing Guidelines for Administrative Order No. 2013-0022 dated 13
August 2013, Subject: Guidelines for Current Good Manufacturing Practice (cGMP) Clearance and Inspection
of Foreign Drug Manufacturers”
29
http://www.fda.gov.ph/industry-corner/list-of-foreign-manufacturers-for-foreign-inspection
30
http://www.fda.gov.ph/industry-corner/list-of-manufacturing-site-with-gmp-clearance
31
Bureau Circular No. 01 s. 1997, Enforcement of the Requirement for Bioavailability Studies for Registration
of Products Included in the List B' (Prime) under Administrative Order No. 67 s. 1989 were issued to Study
Reports
32
FDA Circular No. 2013-014, “List of Products Requiring Bioequivalence (BE) Studies as part of the
Application Marketing Authorization in Addition to Rifampicin and the 11 Products Listed in Bureau Circular
No. 2006-008”
- 25 -
2.1 Products Covered
2.1.1 Products Requiring the submission of satisfactory BE Study Reports
1) Class 4 drugs (low solubility, low permeability) based on the revised World Health
Organization (WHO) criteria for Biopharmaceutics Classification Systems (BCS)
2) Class 2 drugs (high permeability, low solubility) not eligible for biowaiver based on
the revised WHO criteria for BCS
3) Subsequent generic products to be marketed after the patent expiration of the
innovator: Principle: The innovator drug has proven its safety and efficacy in view of
available satisfactory clinical data/studies. When its patent expires, pharmaceutical
manufacturers may produce generic versions of the innovator products, provided they
can establish product interchangeability through BE Studies or Biowaiver, whichever
is applicable.
4) All modified-release pharmaceutical products for oral administration designed to act
systemically.
2.1.2 Products that may avail of Biowaiver provided they meet all applicable
WHO criteria for application of the Biowaiver procedure (including certain
products covered in Bureau Circular No. 2006-008)
1) Class 1 drugs (high permeability, high solubility) based on the revised WHO criteria
for BCS
2) Class 2 drugs (high permeability, low solubility) with weak acidic properties based on
3) Class 3 drugs (low permeability, low solubility) based on the revised WHO criteria
for BCS
The list of molecules covered by the requirement is attached as Appendix 2 This list is not
exhaustive and may be changed from time to time.
2.2 BE Studies Conducted Abroad
Following the ASEAN Guidelines for the Conduct of Bioavailability and Bioequivalence
Studies, the FDA allows the submission of BE study reports conducted abroad so long as the
following are satisfied:
 All BE Study Reports shall be accompanied by a copy of the valid Certificate of
Accreditation of the foreign BA/BE testing center which conducted the study, issued
by the governing regulatory authority or in its absence, an independent accrediting
body. The BA/BE testing center's accreditation shall be based on satisfactory
compliance with Good Clinical Practice (GCP) and Good Laboratory Practice (GLP)
principles.
 The reference drug (comparator) shall be determined by the FDA. Generally, this is
the innovator drug registered and marketed in the Philippines. If there is no reference
- 26 -
drug, either a leading product in the market or the generic drug product(s) registered
after the innovator may serve as the alternative to reference drug.
 If a study has already used the same reference drug recognized by the FDA, but of a
different manufacturer or manufacturing site, a multi-comparative dissolution profile
between reference drugs from 2 different manufacturers/manufacturing sites shall be
provided together with the BE Study Report. The test shall be performed according to
the WHO guideline for in vitro test (e.g. using pH 1.2 HCl solution, pH 4.5 acetate
buffer, and pH 6.8 phosphate buffer in immediate-release oral dosage forms).
 Report Format: The BE Study Report shall follow the ASEAN Bioequivalence Study
Reporting Format
2.3 Enforcement of Requirement
BE requirement for BCS class 4 drugs took effect last 1 July 2013, expanded to other
products beginning 1 January 2014. For existing products, the FDA gave a conditional
approval of 2 years to complete the requirement; however starting 01 July 2016 full
implementation will begin which mean failure to comply shall result in recall and
cancellation of existing CPR.
3. Labeling Materials
In 1988, RA 6675 was enacted which required the use of generic terminology for drug
products. This led the Philippines to be one of the first few countries to implement a generic
labeling33 concept, emphasizing on the generic name of the product rather than its brand or
trade name. In March 2016, the revised rules and regulations for labeling requirements was
issued34, which is aligned with the requirements of ASEAN.
The minimum mandatory requirements include:
1) Product Name
2) Dosage Form and Strength
3) Pharmacologic Category
4) Formulation/Composition
5) Indication(s)
6) Dosage and Mode of Administration
7) Contraindication(s), Precaution(s), Warning(s) (if applicable)
8) Interactions
9) Adverse Drug Reaction(s)
10) Overdose and Treatment
11) Storage Condition(s)
12) Net Content or Pack Size
13) Name and Address of MAH
14) Name and Address of Manufacturer
33
One of the earliest to implement generic labelling concept through Administrative Order No. 55 s. 1988,
“Requirements for Labeling Materials of Pharmaceutical Products”
34
Administrative Order No. 2016-0008, Revised Rules and Regulations Governing the Generic Labeling
Requirements of Drug Products for Human Use
- 27 -
15) For prescription drug products, Rx Symbol and Caution Statement
16) ADR Reporting Statement
17) Registration Number
18) Batch Number and Lot Number (if any)
19) Expiration Date and Date of Manufacture
Details of the abovementioned minimum information required are attached as Appendix 3,

while the content per labeling requirement is attached as Appendix 4.
4. Certificate of Pharmaceutical Product
The Certificate of Pharmaceutical Product (CPP) describes the registration status of a

pharmaceutical product in the Philippines. It also certifies that the manufacturing plant in
which the product is produced undergoes periodic inspection and that it conforms to the
requirements of GMP.
CDRR issues a CPP to applicant companies who are planning to export a pharmaceutical
product as may be required by the drug regulatory authority of the importing country. The
CPP may be required by the importing country during the first importation and subsequently
if confirmation or updating is required. The requirements for the issuance of CPP are the
following:
1) Request letter with importing country
2) Copy of CPR and LTO of MAH
3) Immediate and secondary labeling materials
4) Unit Dose Formulation
5. Renewal of Drug Registration
CPRs issued by the FDA are given 5 year validity. For continuous marketing authorization
after the validity, the MAH shall apply for renewal of registration. Submission of the
application for renewal shall be on or 120 days before the expiration date of the CPR.
Renewal shall be accepted unless the prescribed renewal fee is paid.
There shall be automatic renewal of the CPR when the following conditions are satisfied:
 The application is filed before the expiration date of the registration;
 The prescribed renewal fee is paid upon filing of the application; and
 A sworn statement indicating no change or variation whatsoever in the product is
attached to the application.
For applications filed from within 120 days from its original expiry, the CPR shall be
considered valid and existing until a decision or resolution by the FDA is rendered on the
application for renewal.
Failure to market a pharmaceutical product, without legitimate reason, during an
uninterrupted period of at least 3 years from the date of issuance or renewal of the registration
or the last date of operation or marketing shall be a ground for cancellation of CPR.
Failure to apply for renewal registration shall mean cancellation of the CPR. If the
company wishes to reapply for renewal, then the corresponding surcharge will apply.
- 28 -
6. Post-approval Changes
It is understood that throughout the life cycle of a drug product, changes may occur on the
administrative and technical details in the registration dossier which may affect the safety,
efficacy, and quality of the product. In line with this, the product owner must seek approval
from the FDA to implement the change or provide notification depending on the type of
variation being proposed.
In the post-approval change (PAC) scheme of the FDA35, changes are classified either as
those falling under the ASEAN Variation Guidelines for Pharmaceutical Products, or those
falling under country specific requirements. PACs are also classified according to the risk
associated with the product:
6.1 Major Variation
This refers to a variation to a registered pharmaceutical finished product that may affect
significantly and/or directly the aspects of quality, safety and efficacy and it does not fall
within the definition of minor variation and new registration.
6.2 Minor Variation – Prior Approval (MiV-PA) and Minor Variation –

Notification (MiV-N)
This refers to a variation to a registered pharmaceutical finished product in terms of

administrative data and/or changes with minimal/no significant impact on the aspects of
efficacy, quality, and safety.
The list of PACs falling under each category is attached as Appendix 5.
35
FDA Circular No. 2014-008, Application Process and Requirements for Post-approval Changes of
Pharmaceutical Products
- 29 -
7. Fees
In 2001, the FDA issued its schedule of fees and charges36. As new requirements are
issued, separate fees are included. The table below summarizes the fees for the applications
covered in this document, exclusive of Legal Research Fee (LRF)37.
Fee (in PhP)

3839
LICENSE TO OPERATE Initial Renewal
(2 years) (3 years)
1. Drug Manufacturer (Repacker, Packer)
 <20M and below P20,000 P30,000
 20-50M P30,000 P45,000
 >50M P40,000 P60,000
2. Drug Trader
 <20M and below P6,000 P9,000
 20-50M P10,000 P15,000
 >50M P14,000 P21,000
3. Drug Distributor (Exporter, Importer, Wholesaler) P10,000 P15,000
4. Drugstore/Pharmacy/Botica and similar outlets P2,000 P3,000
5. Retail Outlet for Non-Prescription Drugs (RONPD) P2,000 P3,000
6. Contract Research Organization/Sponsor P10,000 P15,000
Fee (in PhP)
PRODUCT REGISTRATION Initial Renewal
(5 years) (5 years)
1. New P40,000
2. Generic Products40
 Unbranded Products P10,000 P7,500
 Branded Products P15,000 P10,000
3. Biotechnological Products
4. Other Drug Product Classification
36
Administrative Order No. 50 s. 2001, Revised 2001 Schedule of Fees and Charges for the Corresponding
Services Rendered by the Bureau of Food and Drugs
37
FDA Circular No. 2011-003, Collection of Legal Research Imposed by Republic Act No. 3870, as amended
by PD 200 and further amended by PD 1856
38
LTO fees are categorized according to the capital investment of the establishment
39
Fees for LTO differ in those provided under AO 50 as with the fees presented due to validity differences
40
Due to RA 6675, products identified by their generic name only and without trade names are given discounts
on the registration fee as their incentives
- 30 -
CLINICAL TRIAL, FOREIGN GMP,

Fee (in PhP)
CERTIFICATION AND OTHER FEES
1. Clinical Trial Protocol P2,500/phase
2. Amendment of Protocol P1,000/phase
3. Import Permit P500
4. Compassionate Special Permit P500
5. Certificate of Pharmaceutical Product P500
6. Initial Foreign GMP Clearance P10,000 (per importer per site)
7. Renewal Foreign GMP Clearance P2,000
8. Application for Foreign GMP Inspection P3,000
9. Inspection Fees
 ASEAN US$ 3,500 + UNDP-DSA
 Asia Pacific US$ 7,000 + UNDP-DSA
 Others US$ 10,000 + UNDP-DSA
Table 3. Fees and Charges for LTO, CPR, Clinical Trials, Foreign GMP, and Other
Certifications
In 2013, the FDA initiated the review of the existing fees and charges.
- 31 -
VI. References
Website
1. Republic of the Philippines, Food and Drug administration: http://www.fda.gov.ph/
2. Drug Establishment Licensing Requirements: http://www.fda.gov.ph/industry-

corner/downloadables/221-drug-establishment-licensing-requirements
3. Drug Registration Requirements: http://www.fda.gov.ph/industry-

corner/downloadables/217-requirements-for-drug-registration
4. Integrated Application Form and Process: http://www.fda.gov.ph/industry-

corner/downloadables/237-integrated-application-form-and-process
- 32 -
Appendix 1. Organization of ACTD
The registration dossier is organized into four parts as follows:

Sec. A Introduction
Sec. B Table of Contents
1. Application Form
2. Letter of Authorization (where applicable)
3. Certifications
4. Labeling
5. Product Information
Sec. C Guidance on the Administrative Data and Product Information
1. Application Form
2. Letter of Authorization (where applicable)
3. Certifications
For contract manufacturing:
a. License of pharmaceutical industries and contract manufacturer
b. Contract manufacturing agreement
c. GMP certificate of contract manufacturer
For manufacturing “under-license”
a. License of pharmaceutical industries
b. GMP certificate of the manufacturer
c. Copy of “under-license” agreement
For locally manufactured
a. License of pharmaceutical industries
b. GMP certificate (country specific)
For imported products
a. License of pharmaceutical industries/importer/wholesaler
(country specific)
b. Certificate of Pharmaceutical Product issued by the competent
authority in the country of origin according to the current WHO
format
c. Site Master File of the manufacturer (unless previously submitted
within the last 2 years) (country specific)
4. Labeling
5. Product Information
5.1. Package Insert
5.2. Summary of Product Characteristics (Product Data Sheet)
5.3. Patient Information Leaflet (PIL)
Part II: Quality

Sec. A Table of Contents
Sec. B Quality Overall Summary
- 33 -
Sec. C Body of Data
Drug Substance (S)
S1 General Information
S 1.1. Nomenclature
S 1.2. Structural Formula
S 1.3. General Properties
S2 Manufacture
S 2.1. Manufacturer(s)
S 2.2. Description of Manufacturing Process and Process Controls
S 2.3. Control of Materials
S 2.4. Control of Critical Steps and Intermediates
S 2.5. Process Validation and/or Evaluation
S 2.6. Manufacturing Process Development
S3 Characterization
S 3.1. Elucidation of Structure and Characteristics
S 3.2. Impurities
S4 Control of Drug Substance
S 4.1. Specifications
S 4.2. Analytical Procedures
S 4.3. Validation of Analytical Procedures
S 4.4. Batch Analyses
S 4.5. Justification of Specifications
S5 Reference Standards or Materials
S6 Container Closure System
S7 Stability
Drug Product (P)

P1 Description and Composition
P2 Pharmaceutical Development
P 2.1. Information on Development Studies
P 2.2. Components of the Drug Product
P 2.2.1. Active Ingredients
P 2.2.2. Excipients
P 2.3. Finished Product
P 2.3.1. Formulation Development
P 2.3.2. Overages
P 2.3.3. Physicochemical and Biological Properties
P 2.4. Manufacturing Process Development
P 2.5. Container Closure System
P 2.6. Microbiological Attributes
P 2.7. Compatibility
P3 Manufacture
P 3.1. Batch Formula
P 3.2. Manufacturing Process and Process Control
P 3.3. Controls of Critical Steps and Intermediates
- 34 -
P 3.4. Process Validation and/or Evaluation
P4 Control of Excipients
P 4.1. Specifications
P 4.2. Analytical Procedures
P 4.3. Excipients of Human and Animal Origin
P 4.4. Novel Excipients
P5 Control of Finished Product
P 5.1. Specifications
P 5.2. Analytical Procedures
P 5.3. Validation of Analytical Procedures
P 5.4. Batch Analyses
P 5.5. Characterization of Impurities
P 5.6. Justification of Specifications
P6 Reference Standards or Materials
P7 Container Closure System
P8 Product Stability
P9 Product Interchangeability
Part III: Nonclinical Document

Sec. B Nonclinical Overview
1. General Aspect
2. Content and Structural Format
Sec. C Nonclinical Written and Tabulated Summaries
1. Nonclinical Written Summaries
1.1. Introduction
1.2. General Presentation Issues
2. Content of Nonclinical Written and Tabulated Summaries
2.1. Pharmacology
2.1.1. Written Summary
2.1.1.1. Primary Pharmacodynamics
2.1.1.2. Secondary Pharmacodynamics
2.1.1.3. Safety Pharmacology
2.1.1.4. Pharmacodynamic Drug Interactions
2.1.2. Tabulated Summary
2.2. Pharmacokinetics
2.2.1.1. Absorption
2.2.1.2. Distribution
2.2.1.3. Metabolism
2.2.1.4. Excretion
2.2.1.5. Pharmacokinetic Drug Interaction
(Nonclinical)
- 35 -
2.3. Toxicology
2.3.1.1. Single-Dose Toxicity
2.3.1.2. Repeat-Dose Toxicity
2.3.1.3. Genotoxicity
2.3.1.4. Carcinogenicity
2.3.1.5. Reproductive and Developmental Toxicity
2.3.1.5.1. Fertility and Early Embryonic
Development
2.3.1.5.2. Embryo-Foetal Development
2.3.1.5.3. Prenatal and Postnatal
Development
2.3.1.6. Local Tolerance
2.3.1.7. Other Toxicity (if available)
3. Nonclinical Tabulated Summaries
Sec. D Nonclinical Study Reports
1. Table of Contents
2. Pharmacology
2.1. Written Study Reports
2.1.1. Primary Pharmacodynamics
2.1.2. Secondary Pharmacodynamics
2.1.3. Safety Pharmacology
2.1.4. Pharmacodynamic Drug Interactions
3. Pharmacokinetics
3.1.1. Analytical Methods and Validation Reports
3.1.2. Absorption
3.1.3. Distribution
3.1.4. Metabolism
3.1.5. Excretion
3.1.6. Pharmacokinetic Drug Interaction (Nonclinical)
3.1.7. Other Pharmacokinetic Studies
4. Toxicology
4.1.1. Single-Dose Toxicity
4.1.2. Repeat-Dose Toxicity
4.1.3. Genotoxicity
4.1.3.1. In-vitro Reports
4.1.3.2. In-vivo Reports
4.1.4. Carcinogenicity
4.1.4.1. Long Term Studies
4.1.4.2. Short or Medium Term Studies
4.1.4.3. Other Studies
4.1.5. Reproductive and Developmental Toxicity
- 36 -
4.1.5.1. Fertility and Early Embryonic Development
4.1.5.2. Embryo-Foetal Development
4.1.5.3. Prenatal and Postnatal Development
4.1.5.4. Studies in which the Offspring are Dosed
and/or further Evaluated
4.1.6. Local Tolerance
4.1.7. Other Toxicity Studies (if available)
4.1.7.1. Antigenicity
4.1.7.2. Immunotoxicity
4.1.7.3. Dependence
4.1.7.4. Metabolites
4.1.7.5. Impurities
4.1.7.6. Other
Sec. E List of Key Literature References
Part IV: Clinical Document

Sec. B Clinical Overview
1. Product Development Rationale
2. Overview of Biopharmaceutics
3. Overview of Clinical Pharmacology
4. Overview of Efficacy
5. Overview of Safety
6. Benefits and Risks Conclusions
Sec. C Clinical Summary
1. Summary of Biopharmaceutic Studies and Associated Analytical Method
1.1. Background and Overview
1.2. Summary of Results of Individual Studies
1.3. Comparison and Analyses of Results Across Studies
Appendix 1
2. Summary of Clinical Pharmacology Studies
2.1. Background and Overview
2.4. Special Studies
Appendix 2
3. Summary of Clinical Efficacy
3.1. Background and Overview of Clinical Efficacy
3.4. Analysis of Clinical Information Relevant to Dosing
Recommendations
3.5. Persistence of Efficacy and/or Tolerance Effects
Appendix 3
- 37 -
4. Summary of Clinical Safety
4.1. Exposure to the Drug
4.2. Adverse Events
4.3. Clinical Laboratory Evaluations
4.4. Vital Signs, Physical Finding, and Other Observations Related to
Safety
4.5. Safety in Special Groups and Situations
4.6. Post-Marketing Data
Appendix 4
5. Synopses of Individual Studies
Sec. D Tabular Listing of All Clinical Studies
Sec. E Clinical Study Reports (if applicable)
1. Reports of Biopharmaceutic Studies
1.1. BA Study Reports
1.2. Comparative BA or BE Study Reports
1.3. In vitro-In vivo Correlation Study Reports
1.4. Reports of Bioanalytical and Analytical Methods for Human
Studies
2. Reports of Studies Pertinent to Pharmacokinetics Using Human
Biomaterials
2.1. Plasma Protein Binding Study Reports
2.2. Reports of Hepatic Metabolism and Drug Interaction Studies
2.3. Reports of Studies Using Other Human Biomaterials
3. Reports of Human Pharmacokinetic (PK) Studies
3.1. Healthy Subject PK and Initial Tolerability
3.2. Patient PK and Initial Tolerability Study Reports
3.3. Population PK Study Reports
4. Reports of Human Pharmacodynamic (PD) Studies
4.1. Healthy Subject PD and PK/PD Study Reports
4.2. Patient PD and PK/PD Study Reports
5. Reports of Efficacy and Safety Studies
5.1. Study Reports of Controlled Clinical Studies Pertinent to the
Claimed Indication
5.2. Study Reports of Uncontrolled Clinical Studies
5.3. Reports of Analyses of Data from more than One Study, Including
any Formal Integrated Analyses, Meta-Analyses, and Bridging
Analyses
5.4. Other Clinical Study Reports
6. Reports of Post-Marketing Experience
7. Case Report Forms and Individual Patient Listing
Sec. F List of Key Literature References
- 38 -
Appendix 2. List of Molecules Requiring Proof of Interchangeablity
Classification of Selected Drugs belonging to the World Health Organization (WHO) Model
List of Essential Medicines (EML) Based on the Biopharmaceutics Classification System
I. Class 4 Drugs (low solubility, low permeability) based on the revised WHO criteria
for BCS
A. Substances on the WHO-EML

1) Acetazolamide
2) Albendazole (chewable tablet)
3) Artemether + Lumefantrine
4) Azithromycin
5) Cefixime
6) Clofazimine
7) Diloxanide furoate
8) Efavirenz
9) Erythromycin stearate and Erythrimycin ethylsuccinate
10) Furosemide
11) Glibenclamide
12) Haloperidol
13) Indinavir sulfate
14) Ivermectin
15) Lopinavir + Ritonavir
16) Mebendazole (chewable tablet)*
17) Mefloquine hydrochloride
18) Nelfinavir mesilate
19) Niclosamide (chewable tablet)*
20) Pyrantel embonate (chewable tablet)*
21) Pyrimethamine
22) Retinol palmitate
23) Ritonavir
24) Saquinavir
25) Spironolactone
26) Sulfasalazine**
27) Triclabendazole
B. Substances on the Complementary List of the WHO-EML

1) Artesunate
2) Azathioprine sodium
3) Ciclosporin
4) Etoposide
5) Mercaptopurine
6) Mifepristone
7) Oxamniquine
- 39 -
8) p-Aminosalicylic Acid
9) Sulfadiazine
10) Pyrimethamine in Sulfadoxine + Pyrimethamine
II. Class 3 Drugs (low permeability, high solubility) based on the revised WHO criteria
for BCS

1) Abacavir
2) Aciclovir
3) Amodiaquine
4) Atenlol
5) Clavulanic acid in Amoxicillin + Clavulanic Acid
6) Benznidazole
7) Biperiden hydrochloride
8) Chloramphenicol
9) Chlorphenamine hydrogen maleate
10) Chlorpromazine hydrochloride
11) Ciprofloxacin hydrochloride
12) Clomifene citrate
13) Clomipramine hydrochloride
14) Cloxacillin sodium
15) Codeine phosphate
16) Didanosine (Buffered chewable tablet, dispersible tablet)
17) Enalapril
18) Ergocalciferol
19) Ethambutol hydrochloride
20) Ethinylestradiol
21) Ethinylestradiol in Ethinylestradiol + Levonorgestrel
22) Ethinylestradiol in Ethinylestradiol + Norethisterone
23) Ferrous sulfate
24) Ferrous salt + Folic acid
25) Folic Acid
26) Glyceryl trinitrate (sublingual application)
27) Hydralazine hydrochloride
28) Hydrochlorothiazide
29) Isoniazid
30) Isoniazid + Ethambutol
31) Isosorbide dinitrate (sublingual application)*
32) Levamisole hydrochloride
33) Carbidopa in Levodopa + Carbidopa
34) Levothyroxine sodium
35) Metformin hydrochloride
36) Methyldopa
37) Metoclopramide hydrochloride
- 40 -
38) Morphine sulfate
39) Neostigmine bromide
40) Nifurtimox
41) Penicillamine
42) Pyrazinamide
43) Ranitidine hydrochloride
44) Isoniazid in Rifampicin + Isoniazid
45) Isoniazid in Rifampicin + Isoniazid + Pyrazinamide
46) Isoniazid in Rifampicin + Isoniazid + Pyrazinamide + Ethambutol
47) Ethambutol in Rifampicin + Isoniazid + Pyrazinamide + Ethambutol
48) Thiamine hydrochloride
49) Zinc sulfate

1) Chlorambucil
2) Cycloserine
3) Ethionamide
4) Ethosuximide
5) Flucytosine
6) Levamisole hydrochloride
7) Methotrexate sodium
8) Pentamine
9) Procarbazine hydrochloride
10) Pyridostigmine bromide
11) Quinidine sulfate
12) Sulfadoxine in Sulfadoxine Pyrimethamine
III. Class 2 Drugs (high permeability, low solubility) not eligible for biowaiver based on

1) Carbamazepine
2) Dapsone
3) Griseofulvin
4) Iopanoic acid
5) Nevirapine
6) Nitrofurantoin
7) Praziquantel
8) Sulfamethoxzole + Trimethoprim
9) Trimethoprim
10) Verapamil hydrochloride
IV. Class 2 Drugs (high permeability, low solubility) with weak acidic properties based
on the revised WHO criteria for BCS
- 41 -
1) Ibuprofen
2) Phenytoin sodium
V. Class 1 Drugs (high permeability, high solubility) based on the revised WHO criteria
for BCS

1) Acetylsalicylic acid
2) Allopurinol
3) Amiloride hydrochloride
4) Amitriptyline hydrochloride
5) Amlodipine
6) Amoxicillin
7) Ascorbic acid
8) Chloroquine phosphate and Chloroquine sulfate
9) Diazepam
10) Digoxin
11) Doxycycline hydrochloride
12) Fluconazole
13) Lamivudine
14) Levonorgestrel
15) Lithium carbonate
16) DL-Methionine
17) Metronidazole
18) Nicotinamide
19) Noethisterone
20) Paracetamol
21) Phenobarbital
22) Phenoxymethyl penicillin potassium
23) Potassium iodide
24) Prednisolone
25) Primaquine diphosphate
26) Proguanil hydrochloride
27) Promethazine hydrochloride
28) Propranolol hydrochloride
29) Propylthiouracil
30) Pyridoxine hydrochloride
31) Quinine bisulfate and Quinine sulfate
32) Riboflavin
33) Salbutamol sulfate
34) Stavudine
35) Valproic acid sodium
36) Warfarin sodium
37) Zidovudine
- 42 -
1) Calcium folinate
2) Clindamycin
3) Cyclophosphamide
4) Diethylcarbamazine dihydrogen citrate
5) Levofloxacin
6) Ofloxacin
7) Prednisolone
8) Tamoxifen citrate
- 43 -
Appendix 3. Details on the Minimum Labeling Information
1) Product Name
(a) The product name shall indicate the generic name and the brand name (if any) of the
drug product.
(b) The generic name shall be as the active moiety based on the International Non-
proprietary Name (INN), and consistent with the dosage strength indicated; for
prodrugs, the generic name shall be the INN of the prodrug itself and not its active
chemical (metabolite) form.
(c) The generic name shall appear prominently with an outline box, with the generic
name’s prominence over the other information being clearly and distinctly readable
by normal vision as may be determined by common visual sense.
(d) For herbal medicines and traditionally-used herbal products, the generic name shall
be the botanical origin or as recognized by the FDA.
(e) If a product is identified by a brand name together with its generic name, the generic
name enclosed in an outline box shall in all cases appear immediately above the
brand name; for narrative texts (whether in the unit carton, primary label or insert),
the brand name shall in all cases be preceded by the generic name and enclosed in
parentheses or brackets.
(f) For products with multiple APIs, the product name shall indicate all of the APIs,
enumerated in the order of decreasing pharmacologic activity and placed inside the
box in either of the given format:
E.g.:
Iron
Folic Acid
Brand Name
Iron / Folic Acid

Brand Name
Iron + Folic Acid

Brand Name
If the APIs have more or less similar pharmacologic activity, they shall be
enumerated in the order of decreasing potency and strength; provided, that if there
exists a single approved name for fixed-dose combination (e.g. Cotrimoxazole for
the standard formulation Sulfamethoxazole / Trimethoprim), the single approved
name shall be used; provided further, that if there is no single approved name but
there exist a generic class name (e.g. Multivitamins for multi-vitamin containing
preparations, as approved by the FDA), the generic class name shall be used.
The individual components of the single approved name and generic class name
shall be enumerated under Formulation.
- 44 -
(a) The label shall specify the (i) dosage form of the product such as tablet, capsule,
suspension, ointment, etc., (ii) the specific delivery system, if any, such as modified
release, and (iii) specific mode of administration, if any, and appropriate, such as
vaginal/rectal suppository, etc., as approved by the FDA. If there is no qualifier for
tablets, it is understood as an oral, uncoated, immediate release tablet.
(b) The label shall specify the dosage strength of the product which shall be expressed
in metric units reduced to lowest terms and in the number of the largest unit
specified (e.g. 500 mcg, not 0.5 mg).
(c) The FDA, as deemed necessary and appropriate, shall allow the strength of certain
dosage forms (e.g. semisolid, ophthalmic, otic, nasal, and topical preparations) to be
expressed as percentage.
(d) For products with multiple APIs, the dosage strength shall be stated in accordance
with the generic name indicated: for multiple APIs, the individual strengths shall be
indicated, separated by a slash sign (/); if a single approved name is used, the dosage
strength shall be indicated as the sum.
E.g.:
Piperacillin / Tazobactam
Brand Name
4 g / 500 mg Powder for Injection (IV)
Piperacillin + Tazobactam
Brand Name
Piperacillin
Tazobactam
Brand Name
Cotrimoxazole
Brand Name
960 mg Tablet
The pharmacologic category shall be as determined by the FDA, taking into
consideration current acceptable standards for therapeutic categories.
(a) The label shall state the name and strength of all APIs present per unit dose of the
product, which shall be arranged in decreasing pharmacologic activity, or if having
more or less similar pharmacologic activity, in decreasing potency and strength.
(b) The generic name of the API shall be stated in full (including salts and esters, if any)
and correlated to the active moiety, when applicable. The name of the API shall be
in accordance with its INN; for herbal medicines and traditionally-used herbal
- 45 -
products, the official Philippine Pharmacopoeia name shall be used, or as
determined by the FDA.
(c) The reference monograph recognized by the FDA (e.g. USP, BP, EP, JP, PP, Ph. Int)
used for the analysis of the finished drug product shall be indicated immediately
after the API, unless a non-official method is used; for multiple APIs, it shall be
indicated after the first API.
E.g.:
Each tablet contains:
Sodium Ascorbate, USP....................................562.5 mg
(equivalent to Ascorbic Acid 500 mg) (Vitamin C)

Calcium Carbonate, BP.........................................750mg
(equivalent to elemental Calcium 300 mg)
Each capsule contains:

Amoxicillin (as Trihydrate), USP..........................500mg
Each vial contains:

Omeprazole (as Sodium) ........................................40mg

Sulfamethoxazole, USP.........................................800mg
Trimethoprim.........................................................160mg
(d) Alcohol, when present in the product shall also be indicated, expressed as a
percentage (%). The name “alcohol” without qualification shall mean ethyl alcohol.
(e) The coloring, antimicrobial, and antioxidant agents, and preservatives used in the
manufacture of the product that may cause hypersensitivity and/or other adverse
drug reactions shall also be indicated, with the amount expressed in the same manner
as the API.
5) Indication(s)
The indication(s) stated in the labeling materials shall include only the FDA-approved
clinical use(s) of the drug product.
6) Dosage and Mode of Administration

(a) The label shall contain full information on the product’s recommended dosage,
including the (i) initial or loading dose, (ii) optimal use or usual dose, (iii) frequency
interval, (iv) duration of treatment, (v) dosage adjustment, and other pertinent
aspects of drug therapy, if applicable.
(b) Relevant information regarding dilution (e.g. the specific volume of diluent to be
added), reconstitution, preparation, and administration shall also be included (such
- 46 -
as “Shake well before use” for suspensions, “Do not crush” for tablets with special
delivery system, etc.) in all labeling materials. The label shall include a description
of the reconstituted preparation.
(c) Separate directions for use by special populations, adults, and children shall be
stated. If the product is not recommended for children, the dosage shall be clearly
identified as “Adult dose”, or any statement to that effect.
7) Contraindication(s), Precaution(s), Warning(s)

(a) The label shall contain full information regarding the contraindication(s) of the drug
product, as well as the precaution(s) to be observed in its administration and use.
(b) The label shall include warning statements, as required and/or specified by the FDA
(e.g. “Flammable,” “For external use only,” “Keep out of reach of children”). Other
specific additional instructions shall be issued by the FDA in appropriate regulations.
(c) Where the contents of a container are to be used on one occasion only, the label shall
include the statement, “Single use only”, “Single dose”, “Use only once”, “Discard
any remaining portion”, or any statement to that effect.
8) Interactions
The label shall include drug-drug, drug-food, drug-laboratory testing interactions, as well
as other relevant interactions, if applicable.

The label shall include detailed information on adverse drug reaction(s) for a drug
product arranged by system organ class.

The label shall include signs and symptoms of overdose, as well as possible treatment.

(a) The label shall indicate appropriate storage condition(s) and special instructions for
handling of the drug product.
(b) Special labeling instructions shall be added for drug products with the following
properties:
Properties Special labeling instructions
Cannot tolerate refrigeration “Do not refrigerate or freeze”
Cannot tolerate freezing “Do not freeze”
Light-sensitive “Protect from light”
Cannot tolerate excessive heat, “Store and transport not above
e.g. suppositories 30 °C”
Hygroscopic “Store in dry conditions”
12) Pack Size or Net Content

(a) The unit carton shall indicate the pack size of the drug product expressed in terms
of the number of units in the pack or the volume of each unit, e.g. 60 mL (for
- 47 -
liquids), 10 blister packs x 10 tablets (for tablets), 100 tablets, 12 sachets x 5 g, etc.;
Provided, that in case of drug products for reconstitution for oral administration, the
pack size shall reflect the volume of the product as reconstituted.
(b) For the primary label excluding blisters and foil strips, the net content of the
product, stating the total amount/quantity/number of the dosage form in a given
container shall be expressed in metric units, e.g. 60 mL (for liquids), 5 g (for sachets)
13) Name and Address of Marketing Authorization Holder

The label shall state the name and full address of the MAH of the drug product.

The label shall state the name of the manufacturer and full address of the specific
manufacturing site of the drug product as determined by the FDA.
15) Rx Symbol and Caution Statement

(a) The labeling materials of prescription drug products shall always include the Rx
symbol, which shall be prominently displayed. The Rx symbol may be allowed to be
over-printed or superimposed, provided, that such will not result in the obliteration
by or being rendered less legible than other required labeling information.
(b) The caution statement, “Foods, Drugs, Devices, and Cosmetics Act prohibits
dispensing without prescription.” shall always be included in the package insert,
unit carton, primary label except blister pack, foil strip, and small containers of
prescription drug products. In addition, for products classified as Dangerous Drug as
per Republic Act No. 9165, the caution statement shall be followed by an additional
statement as specified by the Philippine Drug Enforcement Agency (PDEA).

For the product information sheet and the unit carton or primary label except
blister pack, foil strip, and small containers of products intended to be sold without
a unit carton, the statement “For suspected adverse drug reaction, report to the FDA:
www.fda.gov.ph” shall appear. In addition, a statement instructing the patient to seek
medical attention immediately at the first sign of any adverse drug reaction shall appear.
The MAH may also include a reporting statement for their own pharmacovigilance
system.

The label shall indicate the registration number assigned by the FDA to the product,
which is denoted by a combination of letters and/or numbers.
18) Batch Number and Lot Number

The label shall indicate the product’s batch number; provided, that if the entire batch is
marketed by one drug establishment, only the batch number shall be indicated. However,
if a batch is divided into lots marketed by different drug establishments, the lot number
and corresponding batch number shall be indicated.
- 48 -
(a) The label shall bear the month and year of the product’s manufacturing and
expiration date either in letters or words and numbers, or in numbers alone; if
expressed in numbers alone, the year shall be stated completely in order to
distinguish it from the month; and if the day is specified, the month shall be spelled
out, as shown below:
 June 2007 or Jun 2007
 06/2007
 03 June 2007 or 03 Jun 2007
(b) Unless a certain day of the month is specified, the last day of the stated month shall
be deemed as the date of the product’s expiration/manufacturing date.
(c) For products reconstituted prior to use and those which can be administered multiple
times (e.g. suspensions), the label shall include the period of guaranteed safety,
efficacy, and quality of the reconstituted preparation/after first opening at a given
storage condition(s).
- 49 -
Appendix 4. List of Information Required per Labeling Material
A. Unit Carton
The unit carton shall contain the following minimum information:
1) Product Name
5) Indication(s)
6) Warning(s) (if applicable)
7) Storage condition(s)
8) Pack Size
11) For prescription drug products, the Rx Symbol and Caution Statement
B. Primary Label excluding blister pack, foil strip and small containers
The primary label shall contain the following minimum information:
1) Product Name
5) Indication(s)
6) Warning(s) (if applicable)
7) Storage condition(s)
8) Net Content
11) For prescription drug products, the Rx Symbol and Caution Statement
12) ADR Reporting Statement (if without accompanying unit carton)
C. Blister Packs/Foil Strips

The standard blister pack/foil strip packaging of a drug product shall contain the
following minimum information:
1) Product name on each unit for single API, or every two (2) units for multiple
APIs
- 50 -
2) Dosage form and strength of API on each unit for single API, or every two (2)
units for multiple APIs
3) Name and/or logo of the Marketing Authorization Holder on each unit for single
API, or every two (2) units for multiple APIs (for unbranded products only)
4) Rx symbol on each unit for single API, or every two (2) units for multiple APIs.
5) Batch number and expiration date on every standard blister pack/foil strip, provided
that, when the pharmaceutical product is not restricted to be dispensed in quantities
less than the standard blister pack or foil strip, the batch or lot number and expiration
date shall be indicated on each unit
D. Primary label of small containers

The primary label of small containers shall contain the following minimum information:
1) Product name
3) Net Content
4) Name and/or Logo of Marketing Authorization Holder
5) Rx Symbol (if applicable)
8) Batch and/or Lot Number (if any)
Due consideration may be given in view of limited space on the label.
E. Package Insert
The package insert shall contain the following minimum information:
1) Product Name
4) Product Description
6) Pharmacodynamics and Pharmacokinetics
7) Indication(s)
8) Dosage and Mode/Route of Administration
9) Contraindication(s), Precaution(s), Warning(s) (if applicable)
10) Pregnancy and Lactation (if applicable)
11) Interactions
15) Dosage Forms and Packaging Available (pack size)
16) Instructions and Special Precautions for Handling and Disposal (if applicable)
19) Caution Statement
- 51 -
22) Date of First Authorization/Renewal of the Authorization
23) Date of Revision of Package Insert
Products with varying strengths may opt to use a common insert, provided that individual
product description, packaging, formulation, or other differing information between the
strengths are included.
F. Patient Information Leaflet

PIL shall be prepared and written in layman’s terms, and shall contain the following
minimum information:
1) Name of the Product
2) Description of the Product
3) What is in the Medicine?
4) Strength of the Medicine
5) What is this Medicine used for?
6) How much and how often should you use this Medicine?
7) When should you not take this Medicine?
8) Care that should be taken when taking this Medicine?
9) Undesirable Effects of this Medicine
10) What other medicine or food should be avoided while taking this Medicine?
11) What should you do if you miss a dose?
12) Signs and Symptoms of Overdose
13) What to do when you have taken more than the recommended dosage?
14) How should you keep this Medicine?
15) When should you consult your doctor?
20) Date of First Authorization/Renewal of the Authorization
21) Date of Revision of Patient Information Leaflet
- 52 -
Appendix 5. List of Post Approval Changes
A. ASEAN Variation Guidelines
MAJOR VARIATION (MaV)

MaV-1 Change and/or additional indication/dosing regimen/patient
population/inclusion of clinical information extending the usage of the
product
MaV-2 Change of content of product labeling
MaV-3 Change and/or addition of alternative manufacturer/site of drug substance
[where European Pharmacopoeial Certificate of Suitability (CEP) is not
available]
MaV-4 Addition or replacement of the manufacturing site of the drug product
MaV-5 Addition or replacement of the alternative site for the primary packaging
(direct contact with drug product)
MaV-6 Change of the specification drug substance and/or drug product [where
European Pharmacopoeial Certificate of Suitability (CEP) is not available]
MaV-7 Change of batch size of sterile drug product
MaV-8 Change of batch size of non-sterile drug product
MaV-9 Major change in the manufacturing process for the drug product
MaV-10 Qualitative or quantitative change of excipient
MaV-11 Quantitative change in the coating weight of tablets or weight and/or size of
capsule shell for modified release oral dosage form
MaV-12 Change in primary packaging material for sterile product a) Qualitative and
quantitative composition and/or
b) Type of container and/or
c) Inclusion of primary packaging material
MaV-13 Change or addition of pack size/fill volume and/or change of shape or
dimension of container or closure for a sterile solid and liquid drug product
MaV-14 Inclusion or replacement of the solvent/diluent for the drug product
MaV-15 Extension of shelf-life of the drug product
MaV-16 Change of storage conditions of the drug product (Lowering from the
current approved storage condition)
MINOR VARIATION PRIOR APPROVAL (MiV-PA)
MiV-PA1 Change of drug product name
MiV-PA2 Change of product labeling (in accordance to country specific labeling
requirement)
MiV-PA3 Addition or replacement of the company or party responsible for batch
release
MiV-PA4 Change and/or addition of alternative manufacturer/site of drug substance
[where European Pharmacopoeial Certificate of Suitability (CEP) is
available]
MiV-PA5 Change of batch size of drug substance [where European
Pharmacopoeial Certificate of Suitability (CEP) is not available]
- 53 -
MiV-PA6 Change of in-process controls applied during the manufacture of the drug
substance [including tightening and addition of new in- process test and
where European Pharmacopoeial Certificate of Suitability (CEP) is not
available]
MiV-PA7 Change of manufacturing process of the drug substance [where European
Pharmacopoeial Certificate of Suitability (CEP) is not available]
MiV-PA8 Change of the specification of drug substance
MiV-PA9 Change of the test procedure of non-compendial drug substance
MiV-PA10 Change of shelf-life or retest period for drug substance
MiV-PA11 Change of storage condition for drug substance
MiV-PA12 Revision of European Pharmacopoeial Certificate of Suitability
(CEP) of drug substance
MiV-PA13 Change of batch size of non-sterile drug product
MiV-PA14 Reduction or removal of overage
MiV-PA15 Qualitative or quantitative change of excipient
MiV-PA16 Quantitative change in coating weight of tablets or weight and/or size of
capsule shell for immediate release oral dosage form
MiV-PA17 Change of the colouring/flavouring agent of the product [addition, deletion
or replacement of colourant(s)/flavour(s)]
MiV-PA18 Deletion of the solvent/diluent for the drug product
MiV-PA19 Change of in-process controls applied during the manufacture of the drug
product (including tightening and addition of new in- process test)
MiV-PA20 Minor change of the manufacturing process for non-sterile product.
MiV-PA21 Change of specifications of an excipient
MiV-PA22 Change of a test procedure for an excipient, including replacement of an
approved test procedure by a new test procedure
MiV-PA23 Change in the source of empty hard capsule
MiV-PA24 Change of release and shelf-life specifications of the drug product
MiV-PA25 Change of imprints, bossing or other markings on the tablets or printing on
capsules including addition or change of inks used for product marking
MiV-PA26 Change of dimensions and/or shape of tablets, capsules, suppositories or
pessaries without change in qualitative and quantitative composition and
mean mass
MiV-PA27 Change in the test procedure of the drug product (including replacement or
addition of a test procedure)
MiV-PA28 Change in primary packaging material for non-sterile product a) Qualitative
and quantitative composition and/or
b) Type of container and/or
c) Inclusion of primary packaging material
MiV-PA29 Addition or replacement of a manufacturer for secondary
packaging
MiV-PA30 Change of pack size/fill volume and/or change of shape or dimension of
container or closure for non-sterile product
- 54 -
MiV-PA31 Change of outer carton pack sizes for a drug product
MiV-PA32 Change in any part of the (primary) packaging material not in contact with
the finished product formulation (such as colour of flip- off caps, colour
code rings on ampoules, change of needle shield (different plastic used)
MiV-PA33 Addition or replacement of measuring device for oral liquid dosage forms
and other dosage form
MiV-PA34 Reduction of shelf-life of the drug product
MiV-PA35 Change of storage conditions of the drug product (Increasing from the
current approved storage condition)
MINOR VARIATION NOTIFICATION (MiV-N)
MiV-N1 Change in name and/or address of the marketing authorization holder
MiV-N2 Change of product owner
MiV-N3 Change in ownership of manufacturer
MiV-N4 Change of the name or address (for example: postal code, street name) of
the manufacturer of drug product
MiV-N5 Change of the name or address (for example: postal code, street name) of
the company or manufacturer responsible for batch release
MiV-N6 Change of the name and/or address (for example: postal code, street name)
of a manufacturer of the drug substance
MiV-N7 Withdrawal/deletion of the alternative manufacturer(s) (for drug
substance and/or drug product and/or packager)
MiV-N8 Renewal of European Pharmacopoeial Certificate of Suitability
(CEP)
MiV-N9 Change of release and shelf-life specifications of the drug product and/or
drug substance and/or excipient, following the updates in the compendium
MiV-N10 Deletion of pack size for a product
B. Country Specific Post-approval Changes
MAJOR VARIATION (MaV)

MV-PH1 Additional route of administration
MV-PH2 Change of manufacturing site (same subsidiary) of the drug product
MINOR VARIATION PRIOR APPROVAL (MiV-PA)
MV-PH3 Change of capsule color
MV-PH4 Change of brand name
MV-PH5 Change of MAH
MV-PH6 Reclassification (ex. Over-the-counter [OTC] to Prescription, OTC to
household remedy [HR])
- 55 -

Drug Approval System of The Philippines PDF

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Drug Approval System of

APEC Harmonization Center

ACTD: ASEAN Common Technical Dossier

2. This document is limited only to pharmaceutical products, not

3. When referring to the contents of this document, check the up-to-

I. Drug Regulatory Agency ···························································· 5

III. Pharmaceutical Products and its Classification································ 10

IV. Drug Approval System······························································ 12

Figure 1. Organization of the Food and Drug Administration1

1) Internal Management Office

2) Field Regulatory Operations Office

3) The RFOs have the following functions:

4) Policy and Planning Service

6) Common Services Laboratory

1.3 Contact Information

The FDA is also guided by the following RA:

In the Philippines, drug products are classified into the following:

For Purposes of this paper, the following shall be covered:

New drugs are registered under monitored-release status.

Generic drug is a product considered to be essentially similar or bioequivalent to a

1.1 Establishments Authorized to Conduct Clinical Trial

Establishments authorized by the FDA include Sponsors and Clinical Research

Entities involved in the procurement/importation, storage, and/or distribution of

1.2 Clinical Trial Application Requirements

A clinical trial dossier is required, consisting of the following documents:

Part A: Clinical Trial Protocol and other documents

Part B: Pharmaceutical Data

Part C: Investigator’s brochure (Efficacy and Safety data)

1.3 Clinical Trial Approval Process

If the protocol is found to be acceptable, a Clinical Trial Protocol Approval is issued by

1.5 Review Period

For a company to be able to market a drug product in the Philippines, securing a

Issuance of CPR NOD/LOD

Figure 2. Overview of Drug Registration Process

3. New Drug Application

3.1 Application Dossier

Part I: Administrative Data and Product Information

Part II: Quality

Part III: Nonclinical Document

Part IV: Clinical Document

Country specific requirement include submission of foreign GMP Clearance 24 for

3.2 Processing Timelines

4.1 Application Dossier

Part I: Administrative Data and Product Information

Part II: Quality

For over-the-counter (OTC) preparations and household remedy (HR) products,

4.2 Processing Timelines

The requirements for securing a CSP are the following:

A maximum of 15 calendar days is given by the FDA in the processing of CSP.

The FDA provides a facilitated registration of applications following certain categories:

A maximum of 90 calendar days is given by the FDA for facilitated applications,

1. Good Manufacturing Practice

Compliance to GMP is mandatory prior to registration of any drug product.

1.1 GMP Inspection of Local Manufacturers

1.2 GMP Clearance/Certificate of Foreign Manufacturers

The following documents are required upfront upon application:

GMP evidence may either be:

1.2.3 Review Period

2.1.1 Products Requiring the submission of satisfactory BE Study Reports

2.2 BE Studies Conducted Abroad

2.3 Enforcement of Requirement

Details of the abovementioned minimum information required are attached as Appendix 3,