As pharmaceutical supply chains become more globalized and complex, regulatory oversight increases as well in complexity, on top of an increasing need for financial and technical resources. It is, therefore, strategic to establish regulatory reliance and cooperation practices among national regulatory authorities, in order to address individual regulatory gaps in a more efficient and effective manner. With the issuance of Administrative Order (AO) No. 2020-0045, entitled, “Establishing Facilitated Registration Pathways for Drug Products, including Vaccines and Biologicals”, the Food and Drug Administration (FDA) recognized that instituting good reliance practices would be impactful toward facilitating access to drugs by producing more efficient regulatory mechanisms.
The World Health Organization, in its Technical Report Series No. 1033, Annex 10 – Good reliance practices in the regulation of medical products: high-level principles and considerations, defines reliance as “the act whereby the regulatory authority in one jurisdiction takes into account and gives significant weight to assessments performed by another regulatory authority or trusted institution, or to any other authoritative information, in reaching its own decision. The relying authority remains independent, responsible, and accountable for the decisions taken, even when it relies on the decisions, assessments, and information of others.”
In applying regulatory reliance, the FDA shall be streamlining its regulatory review to accelerate the registration process of drug products by leveraging against product regulatory assessments made by reference drug regulatory agencies (RDRAs). Simultaneously, strengthened post-marketing surveillance shall ensue and continuous improvement in building FDA’s institutional capacity to effectively oversee innovative and complex advancements of drug products shall remain in the long term. Thus, pursuant to Republic Act (RA) No. 3720 as amended by RA No. 9711, the FDA hereby provides the implementation arrangements for the abridged and verification review pathways stipulated in AO No. 2020-0045 through this Circular as a pragmatic approach to institutionalizing regulatory reliance.
This Circular aims to provide the implementing guidelines of AO No. 2020-0045 on the facilitated registration pathways (FRPs) through abridged review or verification review of new drugs, including vaccines and biologicals.
III. SCOPE AND COVERAGE
This Circular covers applications of new drugs including vaccines, and biologicals as defined in Section IV below, and shall apply to all licensed drug distributors intending to place in the local market or apply for post-approval changes of drug, vaccine, and biological products with existing and valid approval/s from RDRA/s.
This Circular only covers the abridged review and verification review types of FRP. For the collaborative procedure under AO No. 2020-0044 or the Adoption of the Collaborative Procedure for the Accelerated Registration of World Health Organization (WHO) – Prequalified Pharmaceutical Products and Vaccines, the implementing guidelines shall be covered by a separate Circular.
IV. DEFINITION OF TERMS
Abridged review refers to a limited independent assessment of specific parts of the dossier, or submission for suitability of use under local conditions and regulatory requirements while relying on prior assessment from an RDRA to inform the local decision. The review is based on a complete assessment report, including question and answer documents, and the dossier including the stability data.
Verification review refers to an assessment process by which the submission has been evaluated and approved by at least two (2) RDRAs, and the FDA only validates the submission and ensures that the product conforms to the registration conditions, standards, and requirements as approved by the RDRAs.
A new drug application refers to a local registration application for a product that contains new chemical and/or biological entities proposed to be used in the diagnosis, cure, mitigation, treatment, or prevention of disease, new dosage forms, new dosage strengths, new routes of administration, and new indications. All generic products with FDA-approved equivalents shall not be considered new drugs.
Reference Drug Regulatory Agency (RDRA) refers to a national or regional regulatory agency for drugs, vaccines, and biologicals being relied upon by the FDA for a more efficient approach at arriving at a decision thereby improving and expediting quality assured, effective, and safe products.
Assessment Report refers to the complete, unredacted, or unedited copy of the assessment reports of the marketing authorization application and evaluated by the RDRA. The Assessment Report details and explains how the RDRA assessed the safety, quality, and efficacy data and information within the submitted dossier to inform its final decision on the regulatory action. The Assessment Report outlines the area of concerns, questions and answers, and clarifications which the RDRA raised and how these were addressed by the applicant and includes the product approval conditions, the final and approved product labeling, and all other annexes.
V. IMPLEMENTING GUIDELINES
A. Eligibility Criteria
The eligibility criteria provided under Sec. IV.B of AO No. 2020-0045, reiterated with necessary clarifications as follows, shall apply to applicants availing of the FRP:
- The applicant shall be a holder of a valid License to Operate (LTO) issued by the FDA;
- The applicant may avail of the following submission pathways, subject to certain conditions.
a. Abridged review may be availed when the drug product, vaccine, or biological has been approved by an RDRA and the product application is within three (3) years from the date of approval of the RDRA.
b. Verification review may be availed when the drug product, vaccine, or biological has been approved by at least two (2) RDRAs and the product application is within three (3) years from the date of approval of the RDRA/s.
c. The applicant may choose to avail of only one (1) type of FRP per application based on compliance with the requirements. If the requirements of any of the FRP cannot be complied with, the application shall be processed following the regular review pathway.
- The eligible product shall be the same as the product duly approved or registered in the RDRA/s identified by the applicant.
a. All aspects of the drug product’s quality, including but not limited to the formulation, manufacturing site/s, release and shelf-life specifications, and primary packaging, must be the same as those currently approved by the identified RDRA/s at the time of submission.
b. The proposed indication/s, dosing regimen/s, patient group/s, and/or direction/s for use should be the same as those approved by the identified RDRA/s.
- The product and its intended use have not been rejected, withdrawn, suspended, revoked, or has pending deferral by any RDRA due to quality, safety, or efficacy reasons.
- The information on the proposed Package Insert/Patient Information Leaflet shall be identical to that of the approved by the RDRA with the addition of country-specific information stipulated in the current FDA labeling requirements.
- All documents to be submitted shall be written/translated into the English language.
B. Documentary Requirements
- Applications for new drugs, vaccines, and biologicals
a. A formal, written request from the applicant drug distributor notifying the FDA of its intent to avail of the abridged or verification review, identifying the RDRA/s.
b. Assessment Report from each of the identified RDRA/s.
c. A valid Certificate of Pharmaceutical Product (CPP) following the WHO Certification Scheme or its equivalent from the identified RDRA/s. If the product is not marketed in the jurisdiction of the identified RDRA/s, then a valid CPP or its equivalent from any of the RDRA/s as listed in Annex A may be provided.
d. Complete International Council for Harmonisation of Technical Requirements for Pharmaceutical for Human Use (ICH) Common Technical Document (CTD) or ASEAN Common Technical Dossier (ACTD) data requirements following existing guidelines.
e. A report of stability studies conducted under climatic Zone IVB (hot and very humid), with the required minimum time period covered by data at submission, the minimum number of batches, and storage conditions for accelerated and long-term conditions shall be provided unless otherwise justified.
f. Proposed Package Insert/Patient Information Leaflet identical to that approved by the RDRA with the addition of country-specific information stipulated in the current FDA labeling requirements.
- Applications for RDRA/s post-approval changes
- A formal, written request from the applicant drug distributor notifying the FDA of its intent to avail of the abridged or verification review, identifying the RDRA/s that approved the post approval changes.
Note: The date of RDRA approval to be reflected in Annex B shall be the date the post-approval change/s was/were approved by the RDRA.
- Official approval letter or notification of the post-approval change/s from the identified RDRA/s.
- For changes and/or additional indication/dosing regimen/patient population/inclusion of clinical information extending the usage of the product (categorized as major variation [MaV]-1 based on the ASEAN Variation Guideline for Pharmaceutical Products and as adopted through FDA Circular No. 2014-008 or any amendment or latest issuance thereafter), Assessment Report from each of the identified RDRA/s shall be required.
In addition to the foregoing requirements for applications for new drugs, vaccines, and biologicals and post-approval changes, all applications should be accompanied by a Sworn Assurance and (Annex B) signed exclusively by the Head of Regulatory Office of the product owner stating the following: (1) the product being applied is the same in all respects as the product approved by the RDRA, (2) the product and its intended use has not been rejected, withdrawn, suspended, revoked, or has pending deferral by any RDRA due to quality, safety, or efficacy reasons, and (3) that there is full compliance with the eligibility requirements provided under this Circular.
The applications shall comply with rules on filing and receiving pursuant to the latest issuances until such time that an automated system has been developed and launched.
C. Review and Evaluation
- The abridged review or verification review shall be based on a limited independent assessment of specific parts of the dossier. The complete Assessment Report/s, including all annexes, and the dossier including the stability data shall be reviewed and evaluated. Suitability of use under local conditions and regulatory requirements while relying on the prior assessment/s of the RDRA/s shall be assessed. The FDA may request additional supporting documents, as deemed necessary, to ensure the safety, efficacy, and quality of the product intended for registration.
- The FDA shall consider the benefits and risks as they apply to the Philippine context based on the available data provided by the applicant.
- The FDA may consider seeking opinions from clinical experts as necessary.
|Type of Application / Pathway||Timeline|
|Abridged Review||not more than 45 working days|
|Verification Review||not more than 30 working days|
The turnaround time shall start after receipt of the proof of payment with the complete application dossier.
These timelines are not applicable to registration applications of reproductive health products which are required to undergo the complete process stipulated in the Implementing Rules and Regulations of Republic Act No. 10354 or the Responsible Parenthood and Reproductive Health Act of 2012.
The appropriate fees as prescribed under existing regulations shall apply, including a Legal Research Fee (LRF), following AO No. 50 s. 2001 or any amendment or latest issuance thereafter.
VII. PROCESSING OF PENDING APPLICATIONS
All pending applications which qualify for Abridged Review or Verification Review, and which were received on or after 30 October 2020, the effectivity of AO No. 2020-0045, if so desired, shall submit the additional requirements as described under Section V. B of this Circular.
VIII. PENALTY CLAUSE
The applicable penalties under Republic Act No. 9711 and its Implementing Rules and Regulations and other laws shall apply for any violations of this Circular or of AO No. 2020-0045.
IX. IMPLEMENTATION REVIEW
The FDA shall conduct a review of the implementation of this Circular after a period of five (5) years from its effectivity or earlier as needed.
X. SEPARABILITY CLAUSE
If any provisions in this Circular, or application of such provision to any circumstances, are held invalid, the remainder in this Circular shall not be affected.
This Circular shall take effect fifteen (15) calendar days after publication in one (1) newspaper of general circulation and upon filing with the University of the Philippines, Office of the National Administrative Register (ONAR).