Regulation of Drug Products: Role of the FDA
Transcript of Regulation of Drug Products: Role of the FDA
Republic of the Philippines Department of Health
Food and Drug Administration
Regulation of Drug Products: Role of the FDA
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Center For Drug Regulation and Research FDA Philippines
I. Legal Bases for Regulation
II. The Food and Drug Administration
III. Regulatory Framework A. Licensing and Inspection of establishments
B. Pre-marketing assessment
C. Post-marketing surveillance
D. Communication, Coordination, and Collaboration
IV. The Way Forward
Presentation Outline
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Republic of the Philippines Department of Health
Food and Drug Administration
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I. LEGAL BASES FOR REGULATION
• Republic Act No. 9502 – Universally Accessible Cheaper Quality Medicines Act of 2008
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Legal Bases
• Republic Act No. 10354 – The Responsible Parenthood and Reproductive Health Act of 2013
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Legal Bases
• Republic Act No. 7277 (as amended) – Magna Carta for Disabled Persons
• Republic Act No. 9165 – Comprehensive Dangerous Drugs Act of 2002
• Republic Act No. 9994 – Expanded Senior Citizens Act of 2010
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Legal Bases
• Republic Act No. 10532 – Philippine National Health Research System Act of 2013
• Republic Act No. 10747 – Rare Diseases Act of the Philippines
• Republic Act No. 10767 – Comprehensive Tuberculosis Elimination Plan Act
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Legal Bases
Republic of the Philippines Department of Health
Food and Drug Administration
II. The Food and Drug Administration
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The Food and Drug Administration
• Office under the Department of Health
• Created in 1963 by virtue of Republic Act 3720 as amended by Executive Order No. 175, and subsequently Republic Act No. 9711
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• To ensure the safety, efficacy, and quality of health products
– Food, drugs, cosmetics, devices, biologicals, vaccines, in-vitro diagnostic reagents, and household/urban hazardous substances and/or a combination of and/or a derivative thereof
Mandate 17
Drug
1. any article recognized in the official USP-NF, official HPUS, PP, PNDF, BP, EP, JP, IP, 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;
Drug
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;
Drug 5. herbal and/or traditional drugs
which are articles of plant or animal origin used in folk medicine which are:
i. recognized in PNDF
ii. intended for use in the treatment or cure or mitigation of disease symptoms, injury or body defects
in humans
Drug 5. herbal and/or traditional drugs
which are articles of plant or animal origin used in folk medicine which are:
iii. other than food, intended to affect the structure or any function of the human body
iv. in finished or ready-to-use dosage form; and
v. intended for use as a component of any of the articles specified in clauses (i), (ii), (iii) and (iv)
• Drug Products include:
Mandate 22
1. New chemical entities 2. Generic products 3. Biological products
(including biosimilars and vaccines)
4. Household remedies 5. Over-the-counter products
6. Traditionally-used herbal products
7. Herbal medicines 8. Medical gases 9. Veterinary Drugs 10. Stem Cell Products
To ensure the safety, efficacy, purity, and quality of products we regulate through effective implementation of the national regulatory framework consistent with international best practice
MISSION 23
VISION
To be an internationally recognized center of regulatory excellence safeguarding the health of the Filipinos
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QUALITY POLICY
Our highest commitment is to ensure the safety, efficacy and quality of health products.
Toward this end, we commit to maintain and establish science-based policies based on national and international standards as basis for regulatory policies, to continually improve and maintain our competencies in relation to our regulatory function, and to deliver quality public service with integrity and efficiency.
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Republic of the Philippines Department of Health
Food and Drug Administration
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III. Regulatory Framework
A. Licensing and Inspection of establishments
B. Pre-marketing assessment
C. Post-marketing surveillance
D. Communication, Coordination, and Collaboration
Regulatory Framework Elements
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Republic of the Philippines Department of Health
Food and Drug Administration
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III. Regulatory Framework: A. Licensing and Inspection of
Establishments
Establishments must comply with the requirements of different good practices:
• Good Manufacturing Practice
• Good Distribution Practice
• Good Storage Practice
• Good Laboratory Practice
• Good Clinical Practice
• Good Tissue Practice
Licensing and Inspection of Establishments
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AO 2012-0008
AO 2013-0027
FC 2013-018
AO 2013-0012
I. Drug Manufacturer II. Drug Distributor III. Drugstore/Pharmacy/Botica IV. Retail Outlet for Non-prescription
Drug (RONPD) V. Sponsor VI. Contract Research Organization
(CRO)
Classification
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engaged in any or all operations involved in the production of drug products including preparatory processing, compounding, formulating, filling, packaging, repackaging, altering, ornamenting, finishing and labeling with the end in view of its storage, sale or distribution; provided, that the term shall not apply to the compounding and filling of prescriptions in drugstores and hospital pharmacies.
Drug Manufacturer 35
Procures raw materials, active ingredients and/or finished products to other drug establishment whether through import, export, or local wholesale
Drug Distributor 36
Drugstore/ Pharmacy/Botica
including hospital pharmacy and institutional pharmacy shall refer to drug establishment where registered drugs, chemical products, dental, medicinal and household remedies are dispensed directly to the general public on a retail basis.
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RONPD
drug establishment such as a supermarket, convenient store and other similar retail establishment authorized to sell only Over-the-Counter (OTC) and household remedy products directly to the general public on a retail basis.
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an individual, company, institution, organization or an entity which takes the responsibility for the initiation, management, and/or financing of a clinical trial.
Sponsor 39
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.
CRO 40
General Rule (1)
All establishments shall first secure an LTO from FDA prior to engaging in the manufacture, import, export, sell, offer for sale, distribute, transfer, promote, advertise and/or sponsor of any activity that involves drug product
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General Rule (2)
Likewise, no CRO and/or Sponsor shall be involved in the conduct of clinical trial without a license from FDA.
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All establishments must continuously comply with the existing requirements, regulations and standards, otherwise the they may be ordered closed or their licenses suspended or revoked motu proprio or upon petition by any person. A violation with any of the terms and conditions of the LTO may result in the suspension, revocation, or cancellation of the LTO, or disapproval of its application for renewal.
General Rule (3) 43
All establishments must continuously comply with the existing requirements, regulations and standards, otherwise the they may be ordered closed or their licenses suspended or revoked motu proprio or upon petition by any person. A violation with any of the terms and conditions of the LTO may result in the suspension, revocation, or cancellation of the LTO, or disapproval of its application for renewal.
General Rule (3) 44
GMP
GDP
GSP
GCP
General Rule (4)
The FDA shall have the authority to enter any establishment for (1) inspection and/or (2) verification of documents submitted in support of its application for license.
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The responsibility of ensuring the safety, quality, efficacy, and/or purity of any drug product shall rest upon all the establishments or persons involved in the production, sale, handling, transport, distribution, trading and storage thereof
General Rule (5) 50
General Rule (6)
All drug establishments engaged with vaccines, biologics, and other temperature-sensitive drug products shall comply with the cold chain management requirements.
All drug establishments shall be under the supervision of a registered pharmacist as required by pertinent rules and regulations.
General Rule (7) 54
All FDA-required information, education and communication campaign material shall be displayed in the establishment’s conspicuous area.
General Rule (8) 57
Foreign GMP Clearance
• Previously, FDA relies solely on the documentary evidence from DRA of the country of origin for GMP evaluation of foreign manufacturers
• New policy – empowers FDA to inspect foreign manufacturers
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Foreign GMP Clearance
• Foreign manufacturers inspected by PIC/S – GMP Clearance
• Foreign manufacturers not inspected by PIC/S – requires inspection
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Republic of the Philippines Department of Health
Food and Drug Administration
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III. Regulatory Framework: B. Pre-Marketing Assessment
• Product Type 1. New Chemical Entities
Not previously authorized for marketing for any pharmaceutical use
2. Biotechnological Products (including biosimilars and vaccines) Any product of biological origin, prepared with biological
processes, derived from human blood and plasma, or manufactured by biotechnology consisting of substances of high MW whose purity, potency, and composition cannot readily be determined by chemical or physicochemical analysis
3. Generic Drugs Intended to be interchangeable with the innovator product
Drug Class
• Formally adopting the ASEAN Common Technical Dossier (ACTD) and Requirements (ACTR) for the registration of new chemical entities, biotechnological products, and prescription generic products
• 4 parts: Administrative, Quality, Nonclinical, Clinical document with RMP
• With consideration for ICH CTD
ACTD/ACTR
• Product Type 4. Traditionally-used Herbal Products
preparations from plant materials whose claimed application/s is/are based only on traditional experience of long usage which should be at least five (5) or more decades as documented in medical, historical and ethnological literature
5. Herbal Medicines finished, products that contain as active ingredient(s) aerial or
underground part(s) of plants or any other plant material, or combination thereof, whether in the crude state or as plant preparations
have specific therapeutic claim(s) intended for use in the diagnosis, alleviation, cure or treatment of disease, promotion of health or intended to affect or modify the structure or any function of the body of humans or animals
Drug Class
• Product Type 6. Household Remedies
containing pharmaceutical substances of common or ordinary use to relieve common physical ailments which may be dispensed without a medical prescription in original packages, bottles or containers, the nomenclature of which has been duly approved by FDA in the process of registration. A household remedy preparation should have no history of or recognized adverse reaction after being marketed and used for at least twenty (20) years according to its indication
7. Over-the-Counter Preparations drug products or preparations that can be dispensed even
without the written order of a licensed physician or dentist
Drug Class
Republic of the Philippines Department of Health
Food and Drug Administration
Registration Requirements
I. Administrative Requirements
II. Quality Data
III.Non-clinical Data
IV.Clinical Data
Registration Requirements
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• Labeling materials and product information
• GMP Certificate of foreign manufacturer(s)
• Certificate of Pharmaceutical Product (or Certificate of Free Sale)
• Site Master File
Major Administrative Data
• GMP Clearance issued by FDA after review of foreign GMP application,
• Or as issued by FDA for local manufacturers
GMP Certificate
• Establishes:
– Product is manufactured compliant to GMP
– Product is freely sold either in the country of origin or another country
– Product is
Certificate of Pharmaceutical Product
Major Quality Documents
• API: Manufacturing process and controls
• API: Process validation and process development
• API: Characterization
• API: Specifications, procedures, analytical validation
• API: Batch analyses
• API: stability
New Chemical Entities and Biotech Products
Major Quality Documents • FP: Pharmaceutical development – formulation
development, physicochemical and biological properties
• FP: Manufacturing process development, • FP: microbiological attributes • FP: batch formula • FP: manufacturing procedure and process control • FP: process validation
New Chemical Entities and Biotech Products
Major Quality Documents
• FP: control of excipients – specifications and procedures
• FP: Specifications, procedures, analytical validation
• FP: Batch analyses
• FP: Characterization of impurities
• FP: Stability
New Chemical Entities and Biotech Products
Major Safety and Efficacy Documents
• Pharmacodynamics (effects, mode of action)
• Safety pharmacology (potential side effects)
• Drug interactions
• Pharmacokinetics (ADME)
• Toxicology (single/repeat-dose, genotoxicity, carcinogenicity, reproductive and developmental toxicity, tolerance) (onset, severity, and duration)
New Chemical Entities and Biotech Products
Major Safety and Efficacy Documents
• Biopharmaceutic studies (bioavailability, bioanalytical studies)
• Clinical pharmacology studies (protein binding, hepatic metabolism, health and patient subjects)
• Clinical Efficacy and Safety (controlled and uncontrolled studies)
• Post-marketing experience
New Chemical Entities and Biotech Products
• In lieu of clinical trials to prove safety and efficacy, product interchangeability
Generic Products
Prior to the marketing of products:
1. The conduct of clinical trials must comply with ICH GCP
2. Proof of safety, efficacy, and quality must pass the requirements of FDA • For innovative drugs – full quality, safety, and efficacy review,
compliant with ASEAN reqts
• For generic drugs – full quality plus proof of interchangeability
Pre-marketing Assessment 87
Also included:
• Sample submission and evaluation
• Labeling review
• Review and imposition of post marketing commitments (where applicable)
Pre-marketing Assessment 88
Republic of the Philippines Department of Health
Food and Drug Administration
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III. Regulatory Framework: C. Post-marketing surveillance
Post-Marketing Surveillance
1. Pharmacovigilance
Safety monitoring of drugs on the market for unexpected health risks and informing the public of risks posed by specific drugs and other health products;
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Post-Marketing Surveillance
2. Monitoring, collecting, sampling and testing of drugs
3. Audits and inspection of manufacturers/ distributors/ retail outlets
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Post-Marketing Surveillance
4. Advertisements and claims monitoring
Monitor of advertisements, promotions, sponsorship and other marketing activities on health products to protect consumer against misleading, deceptive, false, and erroneous impressions
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Post-Marketing Surveillance
5. Product recall / Labeling revision/ restrictions on use
6. Other administrative sanctions
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Republic of the Philippines Department of Health
Food and Drug Administration
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III. Regulatory Framework: D. Communication, Coordination, and
Collaboration
Communication, Coordination, and
Collaboration
1. International Collaboration
• World Health Organization (WHO)
• United States Pharmacopeia – Promoting the Quality of Medicines (USP-PQM)
• European Union
• Asia Pacific Economic Cooperation (APEC)
• International Council for Harmonization (ICH)
• Other Drug Regulatory Authorities (DRAs) such as Taiwan FDA, MFDS Korea, HSA Singapore, US FDA 104
Communication, Coordination, and
Collaboration
2. Alignment with other government agencies
• DOH offices such: Pharmaceutical Division
Health Facilities and Services Regulatory Bureau (HFSRB)
Disease Prevention and Control Bureau (DCPB; formerly NCDPC)
Epidemiology Bureau (EB; formerly NEC/EPI)
Philippine Health Insurance Corporation (PhilHealth)
Philippine Institute of Traditional and Alternative Health Care (PITAHC) 105
Communication, Coordination, and
Collaboration
2. Alignment with other government agencies
• Philippine Drug Enforcement Agency (PDEA) and the Dangerous Drug Board (DDB)
• Professional Regulation Commission (PRC) and Professional Regulatory Boards such as: Board of Pharmacy
Board of Medicine
• Technical Education and Skills Development Authority (TESDA)
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Communication, Coordination, and
Collaboration
2. Alignment with other government agencies
• Department of Trade and Industry (DTI) offices, such as: Philippine Economic Zone Authority (PEZA) and Board of
Investments (BOI)
Bureau of Product Standards (BPS)
Philippine International Trading Corporation (PITC)
Intellectual Property Office of the Philippines (IPOPHL)
Philippine Accreditation Bureau (PAB)
• Bureau of Customs (BOC) 107
Communication, Coordination, and
Collaboration
2. Alignment with other government agencies
• Department of Agriculture offices, such as: Bureau of Animal Industry (BAI)
Bureau of Fisheries and Aquatic Resources (BFAR)
• Department of Science and Technology (DOST), such as: Philippine Council for Health Research and Development
(PCHRD)
Philippine Health Research Ethics Board (PHREB)
Philippine Health Research Registry (PHRR) 108
Communication, Coordination, and
Collaboration
2. Alignment with other government agencies
• Other enforcement partners, such as: National Bureau of Investigation (NBI)
Philippine National Police (PNP)
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Communication, Coordination, and
Collaboration
3. Partnerships with professional associations and private institutions
• Philippine Pharmacists Association
• Philippine Medical Association
• Ad Standards Council
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Republic of the Philippines Department of Health
Food and Drug Administration
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IV. THE WAY FORWARD
• Electronic Processing of applications for registration
• Introduction of risk-based processing from bench-mark countries
• Shift from pre-market to post-market, with emphasis on public health
• Regulatory convergence
The Way Forward
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