Implementation of the CTD:Implementation of the CTD:CBER’S PerspectiveCBER’S Perspective

Implementation of the CTD:Implementation of the CTD:CBER’S PerspectiveCBER’S Perspective

May 8, 2001

Joan Wilmarth Blair, M.A.International Affairs Advisor

CBER/FDA

May 8, 2001

Joan Wilmarth Blair, M.A.International Affairs Advisor

CBER/FDA

CC BB

EE RR

International Conference on

Harmonisation of TechnicalRequirements for the Registration ofPharmaceuticals for Human Use

International Conference on

Harmonisation of TechnicalRequirements for the Registration ofPharmaceuticals for Human Use

International Conference on

Harmonisation of TechnicalRequirements for the Registration of

Pharmaceuticals for

Human Use

International Conference on

Harmonisation of TechnicalRequirements for the Registration of

Pharmaceuticals for

Human Use

BIOLOGICAL PRODUCTSREGULATED BY CBER

Whole BloodWhole BloodSomaticSomatic

Cell & GeneCell & GeneTherapyTherapy

BloodBloodComponentsComponents

Allergenic ExtractsAllergenic Extracts

Plasma DerivativesPlasma Derivatives VaccinesVaccines

Monoclonal AntibodiesMonoclonal AntibodiesBiotech DerivedBiotech Derived

TherapeuticsTherapeutics

TissuesTissues XenotransplantationXenotransplantation

Blood Related DevicesBlood Related Devices

PeptidesPeptidesPeptidesPeptides

Q6B: Specifications,Test Procedures & Acceptance Criteria for Biotechnological/Biological Products

Q6B: Specifications,Test Procedures & Acceptance Criteria for Biotechnological/Biological Products

Scope: “…apply to proteins & polypeptides, theirderivatives, & products of which they are components (e.g., conjugates)”

“…does not cover antibiotics, syntheticpeptides & polypeptides, heparins, vitamins, cell metabolites, DNA products, allergenic extracts, conventional vaccines, cells, whole blood, and cellular blood components”

Scope: “…apply to proteins & polypeptides, theirderivatives, & products of which they are components (e.g., conjugates)”

“…does not cover antibiotics, syntheticpeptides & polypeptides, heparins, vitamins, cell metabolites, DNA products, allergenic extracts, conventional vaccines, cells, whole blood, and cellular blood components”

BIOLOGICAL PRODUCTSREGULATED BY CBER

Whole BloodWhole BloodSomaticSomatic

Cell & GeneCell & GeneTherapyTherapy

BloodBloodComponentsComponents

Allergenic ExtractsAllergenic Extracts

Plasma DerivativesPlasma Derivatives VaccinesVaccines

Monoclonal AntibodiesMonoclonal AntibodiesBiotech DerivedBiotech Derived

TherapeuticsTherapeutics

TissuesTissues XenotransplantationXenotransplantation

Blood Related DevicesBlood Related Devices

ICHICH PeptidesPeptidesPeptidesPeptides

Whole BloodWhole BloodSomaticSomatic

Cell & GeneCell & GeneTherapyTherapy

BloodBloodComponentsComponents

Allergenic ExtractsAllergenic Extracts

Plasma DerivativesPlasma Derivatives VaccinesVaccines

Monoclonal AntibodiesMonoclonal AntibodiesBiotech DerivedBiotech Derived

TherapeuticsTherapeutics

TissuesTissues XenotransplantationXenotransplantation

Blood Related DevicesBlood Related Devices

ICH CTD?ICH CTD? PeptidesPeptidesPeptidesPeptides

CTD application format only applicable to BLAs for this subset of products?

CTD application format only applicable to BLAs for this subset of products?

BLA - Section 601.2Application for Biologics Licenses

Describes content of application

Describes procedures for filing

NDA - Section 314.50Content and Format of Application

Describes form and content, e.g., – Application form– Numbers of copies (archival copy)– Index – Summaries– Case report tabulations – Case report forms– Labeling– etc.

The question is NOT “Will CBER be accepting the CTD instead of the BLA?”

The question is NOT “Will CBER be accepting the CTD instead of the BLA?”

The question being asked is “Will the CTD application format be applicable to all BLAs?”

The question being asked is “Will the CTD application format be applicable to all BLAs?”

Application Format - Regulatory Requirements?

NDA - Section 314.50

Describes content of application

Describes procedures for filing

Describes format

BLA - Section 601.2

Describes content of application

Describes procedures for filing

DOES NOT describe format

BLA req’mentsand Form 356hformat

BLA req’mentsand Form 356hformat

ELA/PLA Req’ments

ELA/PLA Req’ments

Migration from ELA/PLA to BLA ConstructMigration from ELA/PLA to BLA Construct

Issue guidancefor content & format for productcategories

Issue guidancefor content & format for productcategories

BLA/Form 356h Issuance of Guidances

8/96: Therapeutic rDNA-derived products and monoclonal antibody products for in vivo use

1/97: Autologous somatic cell therapy products 1/99: Vaccines & related products 2/99: Plasma derivatives, animal plasma,

serum-derived products 3/99: Biological in-vitro diagnostics 4/99: Allergenic extracts or allergen patch tests 5/99: Human blood & blood components

CTD BLACTD BLA

BLA ContentReq’ments• “CMC” guidance• “CMC” guidance• “CMC” guidance

BLA ContentReq’ments• “CMC” guidance• “CMC” guidance• “CMC” guidance

Formatting of BLA to CTD ConstructFormatting of BLA to CTD Construct

Revise guidancefor new format

Revise guidancefor new format

CBER’s Acceptance of CTD

Question of acceptance of CTD format prior to issuance of guidance

Use of CTD format not precluded in advance of guidance

URGE early communication -- assure all required content included in submission

CBER’s CTD Implementation Process

Revise “CMC” guidances to map CTD to BLA

“Specified Products” currently in process

Staff training Workshops likely

Integration of CTD with Applications for Product Approval