Asia/ROW BioPharma Regulatory 2023 News/Updates recap

Asia

China

NMPA Tightens Regulation on Outsourced Manufacturing for MAHs

NMPA issued the Notice on Enhancing the Supervision and Management of Outsourced Manufacturing for Drug Marketing Authorization Holders (MAHs) (referred to as the Notice), which took immediate effect.  The Notice came out in response to the growing trend R&D institutions and contract sales organizations (CSOs) utilize the MAH system to obtain drug marketing authorizations and subsequently outsource manufacturing activities to contract manufacturing organizations (CMOs). However, some of these MAHs lack qualified personnel for quality assurance, raising doubts about their ability to effectively oversee the manufacturing activities of CMOs.

ANDAs Without RLDs should Demonstrate Clinical Value

NMPA announced regulations on generic drug registration / abbreviated new drug application (ANDA) have no reference listed drugs (RLDs). ANDA without RLD means that the applicant plans to copy a drug that is not in the RLD Catalog. For such a generic candidate, NMPA requires the applicant to fulfil the following requirements: Conducting chemistry, manufacturing, and controls (CMC) studies to prove the proposed generic drug’s equivalence to the marketed drugs with the same active pharmaceutical ingredient (API); Assessing and demonstrating the proposed drug’s clinical value; Submitting a communication application for having a type-III meeting with CDE.

Adopting ICH Guidelines S12: Nonclinical Bio distribution Considerations for Gene Therapy Products

To align the technical standards for drug registration with international standards, the NMPA has decided upon deliberation to adopt the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guidelines S12: Nonclinical Biodistribution Considerations for Gene Therapy Products (hereinafter referred to as S12). The relevant items are hereby announced as follows: Nonclinical studies starting from the issuance of this Announcement shall be applied to S12. The determination of the starting date of nonclinical studies shall be in accordance with the relevant provisions of the Good Laboratory Practice for drugs.

NMPA Announcement on Adopting ICH Guidelines M10 Q&As and FAQs

To align the technical standards for drug registration with international standards, the NMPA upon deliberation decided to adopt the ICH(International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) Guidelines M10: Bioanalytical Method Validation And Study Sample Analysis (hereinafter referred to as M10) Q&As documents and FAQs documents. The relevant items are hereby announced as follows: The relevant studies starting from July 29, 2023 (based on the original record time of biological sample analysis) are applicable to M10 Q&As documents and FAQs documents.

NMPA becomes the applicant for PIC/S

In late September 2023, the National Medical Products Administration (NMPA) submitted the formal application to the Pharmaceutical Inspection Co-operation Scheme (PIC/S). On Nov 8, 2023, PIC/S sent a letter to NMPA confirming the applicant status.Following this confirmation, NMPA will strengthen communication and cooperation with the PIC/S, promote itself to become a full member of PIC/S, and take this opportunity to continuously improve the country’s drug inspection system and standards, to constantly enhance its drug inspection quality management system and to steadily promote the development of its inspectors’ team, so as to modernize the national drug regulation in China.

Malaysia

Malaysia’s NPRA posts analysis of GMP deficiencies

Malaysia’s National Pharmaceutical Regulatory Authority (NPRA) has released an analysis of the good manufacturing practice (GMP) inspections it conducted at home and abroad last year, revealing trends in the types of deficiencies identified by its staff during routine assessments of production facilities. Last year, NPRA conducted 52 GMP inspections of pharmaceutical facilities, two of which were found to be unacceptable and faced regulatory actions. NPRA divided its analysis of the deficiencies identified by its inspectors based on the Pharmaceutical Inspection Co-operation Scheme’s (PIC/S) guide to GMP for medicinal products.

Guideline On Electronic Labelling (E-Labelling) For Pharmaceutical Products in Malaysia

This document serves as a guide for the implementation of voluntary e-labelling. The document shall be reviewed when necessary. The implementation of e-labelling is voluntary and applies to new drug products, biologics and generic products containing scheduled poisons for human use only. Extension of e-labelling to other product categories will need to be further reviewed.  Acceptable e-labelling formats E-labelling shall be presented in a QR code on the outer carton/inner label of the product that translates to NPRA QUEST3+ page which displays the same product information in a pdf format. The format would allow optimized viewing on any electronic devices such as smartphones/ laptops/ tablets.

Malaysia’s NPRA creates declaration of worldwide registration status for generic medicines

Malaysia’s National Pharmaceutical Regulatory Agency (NPRA) has created a template for declaring the worldwide registration status of generic medicines in its Quest online submission system. The template asks users to provide information including the name of the product, its application status, and the application type and registration number in the registered country. If the application type is the decentralized procedure, NPRA wants the applicant to include the reference member state on the form. The template supports the provision of information about multiple products. NPRA has designed the template for use with all new applications for prescription generic medicines. The creation of the template follows NPRA’s publication of a guide to uploading bioequivalence study reports to the Quest 3+ online portal and its updating of the guidance notes for active pharmaceutical ingredient information for product registration.

Guideline for Facilitated Registration Pathway (FRP)

NPRA revised Guideline for Facilitated Registration Pathway (FRP). The revised pathway includes registration schemes that may be considered for abbreviated and verification review as well as the inclusion of additional Drug Control Authority (DCA) reference agencies. The scope is broadened to include generic medicines in addition to new drug products and biologics (including CGTP). Eligibility criteria, documents required and the timeline for registration process are revised according to type of review. Dossier checklists and process flowcharts were included.

Pakistan

DRAP invites Comments on Draft Guideline for Storage and Destruction of Substandard-Falsified (SF) and recalled Therapeutic Goods

The Drug Regulatory Authority of Pakistan (DRAP) has drafted a guideline on the storage and destruction of recalled therapeutic goods, which are medicines, medical devices, and health products that do not meet the quality standards or are deliberately misrepresented. The guideline aims to provide a framework for the safe and effective management of such goods, from their identification and reporting to their disposal and documentation.

DRAP Added New eService for Online Data Submission for Registration of Pharmaceutical and Biological Product

The Drug Regulatory Authority of Pakistan (DRAP) is pleased to announce the addition of a new e-service for online regulatory data submission registration/marketing authorization of human drugs for local manufacturing, import and export. The Licensing Operations of all [pharmaceutical and biological manufacturers are already enabled through the same platform. This e-service is part of the transformation strategy of the Drug Regulatory Authority of Pakistan which aim to ensure the quality, safety and efficacy of therapeutic goods in Pakistan. The e-service requires applicants to submit their data in a standardized format

DRAP finalized the 2nd Edition of Guidelines on Post-Registration Variation of Drug Products

DRAP has finalized the second edition of its guidelines on procedure and data requirement for post registration variation of drugs. Registration / Marketing Authorization holders are responsible for the safety, efficacy, and quality of drug products that are placed on the market throughout their approved life cycle. These guidelines are intended to provide information for submission of post-registration variation application by the registrations / marketing authorization holders of drug products. It includes categories of variations and the required documentation & procedures for submission of an application for a particular variation.

S.R.O. 1067(I)12023: Schedule of Charges for GMP Certificate and Panel Inspection

ln exercise of the powers conferred by sub-section (l) of section 20 of the Drug Regulatory Authority of Pakistan Act, 2012 (X.XI of 2012) read with sub-rule (3) of rule 4 of the Drug Regulatory Authority of Pakistan (Fee and Levy) Rules, 2022, and in partial modification of its previous Notification No. S.R.O.496(|)/2023 dated the 17tr day of April, 2023, the Drug Regulatory Authority of Pakistan, with the approval of the Policy Board, is pleased to direct that the fee specified

Relocation of Manufacturing Units from Residential Area to Industrial Area

DRAP issued directions to the manufacturers vide No.F.1-78/2018-DD(H&OTC)(Pt) dated 2nd September, 2019 for those whose manufacturing units were situated in the residential area to relocate their manufacturing sites to the industrial areas to ensure the environmental safety and protection of public health. Following DRAP guidelines, another large manufacturer of alternative medicines has relocated its facility from a residential to an industrial area. Consequently, EEC has cancelled previous enlistment certificates (Form-6 and Form-7) and issued revised enlistment certificate for the new manufacturing site in the residential area.

Application (Form II-A) for approval and registration of bio-equivalence or bio-availability study

DRAP published Application (Form II-A) for approval and registration of bio-equivalence or bio-availability study.

Applications for Registration of Multiple Strength and Volume Drugs (Pharmaceutical) on Form-5F

Drug Regulatory Authority of Pakistan, on the recommendations of the Registration Board has issued guidance for submitting applications for registration of pharmaceutical product with multiple strengths and different fill volumes on form -5F.

Application on Form-5F (CTD) for Extension in the Contract Manufacturing Permission of Drugs

Drug Regulatory Authority of Pakistan on the recommendation of the Registration Board has revised the data requirement for submitting applications for extension in the contract manufacturing permission of the drugs for those product where CTD dossiers has already been submitted and approved by the Registration Board.

Philippines

Pharmacovigilance 101 (PV – HCP) (for Healthcare Professionals)

This program aims to provide discussions in pharmacovigilance, its brief history and importance in drug reporting mechanisms/guidelines and requirements, what to report, how to report and what happens to the reports and your contribution in ensuring the safety of drug products. All successful registrants/applicants shall wait for the email from the FDA Academy for the issuance of Couse Assessment Slip (CAS) and payment instruction pursuant to FDA Circular 2021-007. Payments made without the required registration and Course Assessment Slip (CAS) shall automatically be forfeited in favor of the government and shall be non-refundable/non-transferable.

Updated Guidelines on the Application for License to Operate of Health Product Establishments with the Food and Drug Administration

The Food and Drug Administration (FDA) is mandated to issue standards and appropriate marketing authorizations (MAs) to all its covered establishments, facilities, and health products. Through this endeavor, the FDA streamlined its processes through the establishment of various online application platforms for the issuance of MAs including License to Operate (LTO) for Manufacturers, Distributors, Traders, Drug Outlets, Retailers, Clinical Research Organizations, and other health establishments as determined by the FDA.

Singapore

HSA Singapore Designated as WHO-Listed Authority for its Medicines Regulatory System

The Health Sciences Authority (HSA) has been designated by the World Health Organization (WHO) as a WHO-Listed Authority (WLA) on 26 October 2023 for its medicines regulatory system. This means that HSA is now recognised globally as operating at an advanced level of regulatory performance, ensuring that medicines in Singapore meet high safety, efficacy and quality standards.  In January 2022, HSA had attained the WHO Maturity Level 4[1] based on our operational efficiency. The subsequent assessment for WLA included a thorough review of the quality of regulatory assessments, the scientific soundness of the decision-making and their consistent implementation. WHO’s comprehensive assessment of HSA’s core functions and operations, conducted by a team of 10 international assessors and WHO officials, took place from October 2022 to March 2023.

Implementation of Good Manufacturing Practice (GMP) Evidence for Drug Substance (DS) manufacturers

The implementation will apply prospectively to New or Generic Drug Applications (NDA/GDA) and Minor Variation Applications (MIV-1) for addition of a new DS manufacturer. Effective 1 October 2024, NDAs, GDAs, and MIV-1 applications (Addition of new DS manufacturer) are to be supported by the required GMP Compliance Evidence for DS manufacturers. Applications submitted on or after 1 October 2024 without the required GMP evidence will not be accepted.

Guidance on therapeutic product registration in Singapore

This guidance document describes the procedures and requirements for submitting an application to register a therapeutic product, or to make a variation application to a registered therapeutic product. A therapeutic product registered under the HPA is specific to the product with respect to its: proprietary or brand name; pharmaceutical formulation; pharmaceutical dosage form (i.e. physical presentation) and strength; and indication(s) and dosing regimen.

HSA updates ICH CTD, ACTD checklists, submission requirements specific for MIV applications

Health Sciences Authority updates Appendix 2A – Application checklist for NDA and GDA (ICH CTD), Appendix 2B – Application checklist for MAV (ICH CTD), Appendix 3A – Application checklist for NDA and GDA (ACTD), Appendix 3B – Application checklist for MAV (ACTD), Appendix 12 – MIV self-guided tool for post-approval Variation Selection.

Guideline on prism submission

HSA updates appendix 17, Guideline on prism submission. This appendix primarily describes the processes for: Submitting a new product application, submitting a variation product application, responding to Input Request (IR) from HAS, Withdrawing a pending application.

ROW

Australia

New medicine adverse event search for sponsors

TGA has launched a new search functionality in the Adverse Event Management System (AEMS)- external site web portal.  Sponsor can now access TGA-held adverse event reports relevant to the medicines and biologicals in a self-serve manner. Sponsor can: search for reports, filter results using multiple data attributes, download de-identified Public Case Detail (PCD) and Case Line Listing (CLL) reports for inclusion into their own pharmacovigilance systems.

Directions of Registration Board on Reference Product data submissions for conducting Pharmaceutical Equivalence and Comparative Dissolution Profile Studies

Registration Board of DRAP has issued a Guidance document for applicants on submission of application on form 5-F (CTD) for registration of pharmaceutical drug products for human use. Submission of data of pharmaceutical equivalence and Comparative Dissolution Profile (CDP) is required under section 3.2.P.2.2.1 (Formulation Development) of Form 5F (CTD).

Directions of Registration Board on the Drug Substance (DS) for Product Development, R&D, and Stability Testing

The Registration Board of Drug Regulatory Authority of Pakistan grants registration to pharmaceutical and biologicals drug products for human and veterinary use. The Drugs (Licensing, Registering and Adverting), Rules, 1976 as amended requires that applicant shall submit applications for human use on Form 5F (CTD), along with submissions of product development, and stability studies, etc. under the relevant modules. For these studies, applicants firms have to procure the Drug Substance / Active Pharmaceutical Ingredient (API) from licensed pharmaceutical manufacturers only having valid Good Manufacturing Practices (GMP) Certifications and/or Drug Manufacturing Licenses form the relevant Regulatory Authority of the Country of origin.

New reporting requirements for medicine shortages

Companies supplying medicines in Australia will be required to provide additional information to the Therapeutic Goods Administration (TGA) if their products go into shortage. Upcoming changes to reporting requirements will assist health professionals and patients in managing shortages by keeping our Medicine Shortage Reports Database as up-to-date as possible. From 22 September 2023, companies supplying medicines (known as ‘sponsors’) will be required to specify the period of each medicine shortage in Australia. This follows changes to the Therapeutic Goods Act 1989- external site (Act) that came into force in March 2023. A six-month grace period allowed sponsors to refine their internal shortage reporting processes to manage the change.

Submitting data in the eCTD format

TGA published guidance on how to submit data in the electronic Common Technical format. This information is for sponsors and manufacturers wanting to submit data in the electronic Common Technical Document (eCTD) format. Minor edit for clarification on naming convention of submission file.

Brazil

Anvisa publishes new import manual by postal shipment

The document aims to guide the population on the purchase of products subject to health surveillance (such as medicines, cosmetics, medical equipment and cigarettes, for example) that are transported and delivered by the Post Office. In the manual you can find out more about this type of import, what can and cannot be imported and what to do if your merchandise is detained during inspection. The Agency also gives tips on what to check when importing this type of product.  

Anvisa clarifies doubts about carrying out clinical analysis tests in pharmacies

The document presents the answers to the main questions received through Anvisa’s communication channels regarding the Resolution of the Collegiate Board (RDC) 786/2023.  The standard provides for the technical- sanitary requirements for the operation of clinical laboratories, pathological anatomy laboratories and other services that carry out activities related to clinical analysis exams (EACs). The resolution, which came into force on August 1st, allows clinical analysis tests to be carried out, on a screening basis, in pharmacies and offices.

Mexico

Cofepris offers regulatory certainty for the development of biotechnological medicines

The Federal Commission for the Protection against Sanitary Risks (Cofepris) launches actions to provide regulatory certainty to companies in the biotechnology pharmaceutical sector, which represents medical innovations and productive development in the Mexican market. With the aim of promoting the development, manufacturing and marketing of biotechnological and biosimilars in our country, this health authority has developed a work plan with a four-year horizon, considering the life cycle of the pharmaceutical product.

New Zealand

New Zealand’s new database aims to improve ADR turnaround time

Authorities in New Zealand are transitioning the collection and storage of adverse reaction (ADR) reports to a new database to improve efficiency and shorten processing time. The original system used by New Zealand’s Centre for Adverse Reactions Monitoring (CARM) and Medicines and Medical Devices Safety Authority (Medsafe) was established by the University of Otago in 1965. CARM and Medsafe began using an early version of the system late last year to process ADRs for vaccines against COVID-19 and Mpox. They have now completed work on the new system.

New Zealand clarifies acceptable overseas evidence of GMP in updated medicine guidelines

The New Zealand Medicines and Medical Devices Safety Authority (Medsafe) has published the fifth version of its guidelines on the manufacture of medicines. Medsafe used the update to clarify examples of acceptable evidence from audits by authorities in the United States and European Union. New Zealand accepts any good manufacturing practice (GMP) certification document issued by a recognized authority that confirms compliance. The updated guidelines expand the list of recognized authorities to include Bulgaria, Croatia, Cyprus, Estonia, Latvia, Lithuania and Slovenia, and clarify the information about using evidence from US Food and Drug Administration (FDA) audits. 

South Africa

Clinical Trials Committee and Submission Dates for 2024

This communication is for Stakeholders to be aware of the South African Health Products Regulatory Authority (SAHPRA) Clinical Trials Committee meeting dates and the submission dates for the year of 2024. Applicants are advised to submit clinical trial applications before the due date. Applications submitted after the due date will not be accepted.

ECTD validation and technical screening for Renewals

The Validation Template is used on receipt of an application to verify that all required information has been supplied to SAHPRA in order to evaluate an application for the renewal of registration of a medicinal product for human or veterinary use submitted in eCTD format. The applicant must ensure that all relevant fields are completed. For products registered in the year 2017 and dating further back, a full eCTD baseline (0000) submission in line with the General Information guideline for registration will be required (only if the dossier has not yet been converted to eCTD): Complete and submit only Sections A.1; A.3 and C for the baseline sequence.

Follow-up sequences (related to the renewal application): Complete and submit only Sections A.1 A.3; B; D and E.

Renewal and registration of human and veterinary medicines

The guideline presents SAHPRA’s current thinking on technical requirements necessary to facilitate renewal of registration of medicinal products. This guideline is divided into three major parts stipulating the general requirements and application procedures for human and veterinary medicinal products; processing of applications; and technical requirements for application for renewal of medicinal products.

Adverse Drug Reactions and Quality Problem Reporting Form

SAPHRA published Adverse Drug Reactions and Quality Problem Reporting Form – for both public and private sector and includes herbal products.

Saudi Arabia

SFDA Guideline on Classification of Advanced Therapy Medicinal Products

This guideline provides definitions for Advanced Therapy Medicinal Product (ATMP) in Saudi Arabia. The aim of ATMP Guideline on classification of ATMPs is to provide guidance on the ATMP definitions, as well as on the interpretation of key concepts of the definition of gene therapy medicinal products and cell based medicinal products, and combined advanced therapy medicinal products. ATMP classification will be based on the evaluation of whether a given product fulfills one of the definitions of Gene Therapy Medicinal Product (GTMP) or Cell Based Medicinal Product (CBMP), and whether the product fulfills the definition of a combined ATMP or not.

Breakthrough medicines program

Breakthrough medicines program aims to facilitate and accelerate development and review of new drugs that address unmet medical need in the treatment of serious or life-threatening conditions. The program is voluntary and based on enhanced interaction and early dialogue with drug developers, to optimise development plans and speed up evaluation and ensure that promising medicines are available as soon as it can be concluded that the medicines’ benefits justify their risks. Under the breakthrough medicine program, the designation request may submitted by the end of phase 2 or at any time after. The SFDA will assess the application and provide a guidance based on the stage of drug development and provided data at submission time.

SFDA Guideline on Classification of Advanced Therapy Medicinal Products

This guideline provides definitions for Advanced Therapy Medicinal Product (ATMP) in Saudi Arabia. The aim of ATMP Guideline on classification of ATMPs is to provide guidance on the ATMP definitions, as well as on the interpretation of key concepts of the definition of gene therapy medicinal products and cell based medicinal products, and combined advanced therapy medicinal products.

Guideline on the Braille Requirements for Labeling Information of Medicinal Products for Human Use

This guidance interprets the requirements for Braille on the packaging of human medicinal products to be available in formats for blind and partially sighted people. For new medicinal products seeking marketing authorization, the final version of this document is effective after 3 years following the adoption date of the guideline. After 5 years of publishing the final version of this document, the implementation is mandatory for all registered products.

The Registration Rules of Pharmaceutical, Herbal and Health Product Manufacturers and their Products

the Registration Committee of Manufacturers of Pharmaceuticals and their Products has approved the updated the Registration rules of Pharmaceutical, Herbal and Health Product Manufacturers and their Products, based on Article (20/4) of the Implementing Regulations of the Law of Pharmaceutical and Herbal Establishments and Products, which stated that the registration committees must conduct the update tasks for the Registration rules of Pharmaceutical and Herbal Products.

Sri Lanka

GMP certificates validity period extension for Medicines (only for the category B)

As per the announcement published on 25.08.2023 at NMRA official website, applicants are informed to submit following documents.1. Request letter for the certificate extension,2. Original GMP Certificate,3. Copy of the latest GMP report. Applicant can submit above mentioned documents on every Monday at the dossier accepting point to the manufacturing regulatory division’s officials.