Biosimilars & Vaccines Regulatory Support

Our Expertise in Biosimilars & Vaccines

  • Skilled resources with core biopharmaceutical industry experience, having in-depth understanding of biologics (biosimilars and vaccine) development processes and regulatory requirements at different phases of product life cycle.
  • Technical competencies to support regulatory activities related to different recombinant expression systems and mammalian cell lines (E.Coli, Yeast rCHO etc.) for biosimilar product development and various platform technologies (egg based, cell based, recombinant) for vaccine development.
  • Specialized team for regulatory CMC authoring, dossier compilation, review and submissions, addressing deficiency responses from various Health Authorities.
  • Expertise in generating biosimilar and vaccine intelligence reports.
  • Strong connect with regulatory and marketing experts across BRICS-TM countries, ACCESS countries, Asia, Africa (including MENA), GCC and Latin America.

Where can Metina support?

Development phase (CMC)

  • Regulatory guidance on upstream and downstream process development (DS) and product development (DS & DP) for biosimilars & vaccines.
  • Review and advice for establishing biosimilarity – CMC, analytical comparability protocol (physicochemical & biological characterization), setting specification, validation, stability studies etc.
  • Regulatory advice on vaccine development .
  • Regulatory support for technology transfer package – review of package, gap identification etc.
  • Support for pre-submission advisory meetings/ Scientific advice packages, agency meetings

Non-clinical Phase

  • Guidance and review of non-clinical study protocols & reports, authoring Dossier sections
  • In vitro – Functional assays, receptor binding assays, cell based assays
  • In vivo – PK/PD, Comparative repeat dose toxicity, Immunogenicity (dose, dosing regimen, ROA) and Local tolerance studies, Challenge studies

Phase I

  • Guidance and review of Phase I (PK/PD) clinical study protocol & report
  • Support for pre-submission advisory meetings/ Scientific advice packages

Phase II (for vaccines)

  • Guidance and review of Phase II clinical study protocol & report (evaluating short-term side effects & immune responses)
  • Support for pre-submission advisory meetings/ Scientific advice packages

Phase III

  • Guidance and review of Phase III clinical study protocol & report
  • Support for pre-submission advisory meetings/ Scientific advice packages
  • Authoring/ Compilation/ review of Non-clinical section of the dossier [Module 2 (2.5, 2.7), Module 5]

Marketing authorization

  • Regulatory Gap assessment of the dossier
  • Detailed review of all official applications to regulatory agency
  • Dossier submission (authoring/ compilation, review and submission) support for registration in BRICS-TM, WHO & other RoW markets, Regulated markets
  • Dossier submission (authoring/ compilation, review and submission) in regulated markets (US, EU, Australia, Canada, Switzerland).
  • Addressing queries from health authorities
  • Representing MAA review committees at agency level

Regulatory strategies for global regulatory submissions of Biosimilars and Vaccines

BRICS-TM

Brazil, Russia, India, China, South Africa, Turkey and Mexico

WHO

World Health Organization

Other ROW/ EM

Rest of the world /Emerging Markets

US

United States

EU

European Union

ACCESS

Australia, Canada, United Kingdom, Singapore and Switzerland

BRICS-TM countries

End-to-end regulatory support for MAA submission in Brazil, Russia, India, South Africa, Turkey, Mexico

  • Regulatory guidance on compliance to current regulations across BRICS-TM, gap assessment and devising regulatory strategy
  • Support for dossier preparation, review and submission in BRICS-TM countries
  • Evaluation of applications for registration of biological medicines, including;
    • Review of dossiers for registration of biological medicines;
    • Handling all matters relating to biological medicines during review of applications for registration.
    • Addressing queries from regulatory agencies and supporting product registration
  • Evaluation of applications for amendments to registered biological medicines
  • GMP inspection and compliance support
  • MA holding and life cycle management

INDIA Regulatory Support

Import & Manufacture of New Drugs (CDSCO/SLA)

Registration & Import Licenses (CDSCO/ SLA)

Preclinical Protocol and Report submission & Approval (RCGM)

Clinical trial Protocol and Report Submission & Approval (CDSCO/DCGI)

Sample testing & Batch Release Certificate (CDL, Kasauli)

Marketing Authorization Application Submission & Approval (CDSCO/ DCGI)

  • End-to-end regulatory support including licensure for import/export, test, examination, manufacture and approval – Form 10, 28D, 29, 46, etc.
  • RCGM submissions/approval (IBK Portal) – Preparation of packages for Preclinical studies permission & approval (Form C3/C4), Submission & approval of preclinical study report (Form C5/C6)
  • DCGI submissions (SUGAM portal) – Phase 1, Phase 2 and Phase 3 CTA submission package (as per New Drug Clinical Trial Rules, 2019) (Form 44)
  • MAA submission support – CTD authoring/compilation, review and submission (Form 27D/28D)
  • Regulatory support for filing of variations/amendments
  • MA holding and lifecycle management
  • Support for sample testing for biosimilar products and vaccines (CDL, Kasauli)

WHO Prequalification Programme & Other ROW/ Emerging Markets

1

Submission to WHO Prequalification programme (PQP) for Biologics

1

Submission to WHO Prequalification programme (PQP) for Biologics

2

Based on Stringent regulatory agency (SRA) approval (1) Full assessment pathway (2) Abridged assessment pathway

2

Based on Stringent regulatory agency (SRA) approval (1) Full assessment pathway (2) Abridged assessment pathway

3

GMP inspection/ Sample analysis (depends on the filing pathway)

3

GMP inspection/ Sample analysis (depends on the filing pathway)

4

Product dossier assessment by WHO

4

Product dossier assessment by WHO

5

Products assessed and placed in WHO’s list of prequalified medicines

5

Products assessed and placed in WHO’s list of prequalified medicines

6

Accelerated registration in other low-and-middle-income countries (LMICs)

6

Accelerated registration in other low-and-middle-income countries (LMICs)

7

Enables procurement by many NRAs and other UN agencies

7

Enables procurement by many NRAs and other UN agencies

Regulatory Support from Metina

  • Regulatory advice and complete regulatory support for application to WHO PQP in compliance with WHO-PQP product specific guidelines & other guidance documents under WHO Technical Report Series
    • WHO Pilot Procedure for Prequalification of Biotherapeutic Products: Rituximab and trastuzumab, Version 10, February 2020
    • WHO Pilot Procedure for Prequalification of Biotherapeutic Products: Human Insulin, Version 10, February 2020
    • Procedure for assessing the acceptability, in principles, of vaccines for purchase by United Nations agencies (2013); WHO Technical Report Series, No. 978, Annex 6.
  • Support for GMP inspection/ compliance and sample testing.
  • End-to-end regulatory support for filing to other ROW markets based on prequalification by WHO

Regulated Markets - US & EU

  • Regulatory strategy and gap assessment for biologic/ biosimilar development for US & EU
  • Regulatory support for BLA filing under 351(k) pathway of the PHS Act- authoring, review and submission
  • Regulatory support for MAA submission via Centralized procedure under Article 10(4) application – authoring, review and submission
  • Pre-submission guidance and support for preparation of briefing packages (BPD meetings) and scientific advice packages
  • Preparation for pre-IND/ scientific advisory meetings and support for IND/IMPD package preparation and submission
  • Support for GMP inspection

ACCESS Consortium

End–to–end regulatory support for dossier submission to ACCESS countries

The 'ACSS' consortium, formed in 2007, comprises of the national regulatory authorities of Australia, Canada, Singapore and Switzerland. ACCESS – In October 2020, the United Kingdom regulator – the Medicines and Healthcare products Regulatory Agency (MHRA) – joined the consortium and the group's name was changed to 'Access’. The consortium's goal is to maximize international cooperation, reduce duplication, and increase each agency's capacity to ensure patients have timely access to high quality, safe and effective therapeutic products. Pharmaceutical companies that submit applications to some or all Access countries will benefit from having their products evaluated for marketing in those countries simultaneously, with reduced evaluation times.

TGA - Australia
Regulatory guidance & advice on TGA Biosimilar guidelines “Biosimilar Medicines Regulation, Version 2.2, 2018”
HC-BRDD - Canada
Regulatory guidance & advice on HC/BRDD Biosimilar guidelines “Guidance Document: Information & Submission requirements for Biosimilar Biologic drugs, 2017”
MHRA - United Kingdom
Regulatory advice on “MHRA guidance on the licensing of biosimilar products, October 2020”
HSA - Singapore
Regulatory guidance & advice on “Guidance on Therapeutic Product Registration in Singapore, December 2020”
SWISSMEDIC - Switzerland
Regulatory guidance on Swissmedic Biosimilar guidelines “ZL101_00_012e_WL Guidance document Authorization biosimilar HMV4, V3.1,2021”

GMP Compliance Support for Biological Facilities

Support for EU GMP and PIC/S GMP inspection (Via NPRA, Malaysia)
GMP upgradation advice for biologics/ biosimilar manufacturing sites
Gap Analysis, Auditing and Report

Inspection Readiness Support

Preparation of GMP inspection application

Support throughout inspection, CAPA, approval & renewal