Biological Products Regulated Under Section 351 of the Public Health Service Act

1
Biological Products Regulated Under Section 351
of the Public Health Service Act

• Open Public Meeting
• September 2, 1998
• Rebecca A. Devine, Ph.D.

2
Legal Authority

• Section 351 of the PHS Act
• Food and Drug Administration Modernization Act of
  1997 (FDAMA)
• November 21, 1997
• Section 123 Amends Section 351 of the PHS Act

3
FDAMA Section 123

• A biologics license shall be in effect
• Prior to such product being introduced into
  interstate commerce
• Codifies the Rego initiative
• FDA shall approve a biologics license
  application
• Product is demonstrated to be safe, pure and
  potent
• Facility meets standards designed to assure
  continued safety, purity and potency

4
Regulatory Standards

• Biologics Regulations 21 CFR 600-680
• Drug GMPs 21 CFR 21, 211
• Device GMPs 21 CFR 810, 811
• Standards agreed to in the license application
• Establishment means same as facility in FDAMA

5
FDAMA (cont)

• Steps intended to minimize differences
• PHS products and NDA products

6
BLA Regulations Proposed Rule

• Eliminates all references to
• establishment and products license applications
• establishment and product licenses
• Requires submission of a Biologics License
  Application
• Uses the form FDA 356h
• Harmonizes application procedures
• Updates the format of certain regulations

7
Administrative Issues

• Approval letter will be functional equivalent of
  the license
• No physical certificate
• Listing of all manufacturing locations in the BLA
• Multiple products in some BLAs

8
Multiple Products in BLAs

• Blood and Blood Components
• Non-Standardized Allergenic Extracts

9
Specified Biotechnology Products

• Remains essentially unchanged
• Still exempt from
• 600.10(b) and (c)
• 600.11
• 600.12
• 600.13
• 610.11
• 610.53
• 610.62

10
Radioactive Biological Products

• Revised 601.2(b)
• Clarify current procedures
• Intercenter agreements
• NDA vs BLA

11
Blood and Blood Components

• Currently 10 forms
• Whole Blood, Platelets, Plasma, Red Blood Cells,
  Cryoprecipitate, Source Plasma
• One BLA would cover all above products
• Eliminates duplication in individual ELAs/PLAs
• Simplifies supplement submission

12
Allergenic Products

• Non-standardized single BLA
• Standardized - Individual BLAs
• Detailed product specifications
• Detailed establishment information

13
Deemed Biologics Licenses

• Existing Product and Establishment License
  holders
• Upon effective date
• Will be considered to have Biologics Licenses
• No submissions necessary to FDA
• Portions of the PLA/ELA will constitute the BLA

14
Current Good Manufacturing Practices

• Compliance with GMPs
• Required for licensure
• Regulation (601.2 (d)) clarifies this requirement

15
Implementation of the 356h

• Currently using 356h
• Specified products
• Autologous somatic cell therapy
• Start to use 356h
• When FINAL CMC documents issue
• FR notice will advise applicants

16
What to do in the meantime?

• Continue to use the current forms
• PLAs and ELAs
• Until and FR notice indicating use of 356h

17
BLA Tracking Number

• BLxxxxxx/yyyy.zzzz
• First level (xxxxxx) identifies the application
• Second level (.yyyy) identifies submissions to
  the approved application
• Third level (.zzzz) identifies amendments to a
  pending submission

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BLA Tracking Number

• New BLA for panacea - 000345/0000.000
• First amendment to the pending BLA
  000345/0000.0001
• First supplement to the approved BLA
  000345/0001.0000
• First amendment to that pending supplement
  000345/0001.0001

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Transition Grace Period

• Ten months after the effective date of the final
  rule
• All applicants should use the BLA/356h
• During the ten months
• PLAs and ELAs will be accepted
• BLAs will be accepted
• All information in 356h needed
• Administratively handled as BLAs

20
Issuance of Biologics License

• Began February 19, 1998
• Regardless of application type submitted

21
Licensed Establishments

• As specified in the regulations
• No establishment license issued
• Establishments listed in BLA
• Engaged in manufacture (any part)
• Considered licensed establishments
• Includes contract manufacturers
• Short suppliers

22
Licensed Manufacturer

• Any legal person or entity
• Holding an unsuspended or unrevoked Biologics
  License
• Ultimately responsible for compliance
• Will have US license number
• Holds the Biologics License

23
BLA Tracking Number

• New internal tracking number
• Similar to NDA number
• Will remain with BLA thru its life
• Currently approved will have BLA numbers assigned
• Use in all correspondence for product
• Supplements will be added in sequence

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US License Number

• PHS Act requires it on labeling
• Applicant (Manufacture) receives US license
  number
• Will be used as current Establishment License No.
• Already licensed manufacturers
• Retain same license no.
• There will be NO Biologics License Number
• Approval letter will issue the number for new
  applicants

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Parts Of Regulations Affected

• 3 Product Jurisdiction
• 5 Delegations of Authority
• 10 Administrative Practices and Procedures
• 20 Public Information

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Parts Of Regulations Affected (cont)

• 207 Registration of Producers of Drugs and
  Listing of Drugs in Commercial
  Distribution
• 310 New drugs
• 312 Investigational New Drug Application
• 316 Orphan Drugs

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Parts Of Regulations Affected (cont)

• 600 Biological Products General
• 601 Licensing
• 607 Establishment Registration and Product
  listing For Manufacturers of Human Blood and
  Blood Products

28
Parts Of Regulations Affected (cont)

• 610 General Biological Product Standards
• 640 Additional Standards for Human Blood and
  Blood Products
• 660 Additional Standards for Diagnostic
  Substances for Laboratory Tests