Federal Regulations and Industry Stewardship of PMPs

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Federal Regulations and Industry Stewardship of
PMPs

• Dr. Michael J. Phillips
• Vice President, Food and Agriculture, Science and
  Regulatory Affairs
• Biotechnology Industry Organization, Washington,
  D.C.
• May 31, 2006

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About BIO

• BIO represents more than 1,100 biotechnology
  companies, academic institutions, state
  biotechnology centers and related organizations
  across the United States and 31 other nations.
  BIO members are involved in the research and
  development of healthcare, agricultural,
  industrial and environmental biotechnology
  products.
• Biotechnology Industry Organization (BIO)
• 1225 Eye Street, N.W., Suite 400
• Washington, D.C. 2005
• 202.962.9600 www.bio.org

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Regulatory Pathway for Plant-Made Pharmaceuticals
Is Defined

• USDA APHIS Regulate plant growth, definition of
  appropriate safeguards for regulated products,
  transport of product constituents
• FDA CFSAN CVM Consultation on food and feed
  safety
• FDA CBER/CDER Regulate biologic products, their
  manufacture and distribution
• PMP Companies Safety Assessments, Drug Master
  Files, Chemistry Manufacturing Controls
  Biologics License Agreement for clients drug
  registration, Field Production CACCP Plan

USDA FDA
FDA
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Regulating PMP Field Production
Plant-Made Pharmaceutical Permit Process
Letter, Permit Proposed Conditions Sent to the
State
Permit Application Received
Scientist Reviews
Permit Complete
Successfully
Deficiencies Identified Applicant Responds
State Adds Conditions Concurs
State Denies
Unsuccessfully
Permit Denied
Permit Issued with Conditions
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Industry Self-Regulation CACCP

• CACCP Plan
• Containment Analysis and Critical Control Point
  Plan
• Developed in 2003 by BIO and its members
• Created with input from the Food Products
  Association, Grocery Manufacturers Association,
  the National Corn Growers Association, and the
  North American Millers Association
• Ensures compliance with federal regulations for
  the confinement of PMPs
• Identifies potential hazard points and develops
  confinement strategies for those points
• Modeled on the Hazard Analysis and Critical
  Control Points (HACCP) approach used in the food
  and pharmaceutical industries

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7 Principles of CACCP

• Conduct loss of containment analysis
• Determine critical control points
• Establish critical limits
• Establish monitoring procedures
• Establish corrective actions
• Establish verification procedures
• Establish record keeping and documentation

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Consumer Questions

• Are PMPs safe?
• As plants, they are grown under strong permit
  regulations and monitored by USDA
• Therapeutic proteins, once extracted for use in
  pharmaceuticals, are regulated and approved by
  FDA, similar to other biopharmaceuticals
• Strict confinement measures ensure that food and
  feed supply do not commingle with PMPs

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Consumer Questions

• How are PMPs different from biotech crops?
• PMPs are not value-added opportunities for
  agriculture or many growers
• PMPs are not sold as seed to growers
• PMPs are production factories and are one step
  in the pharmaceutical manufacturing process
• PMPs are handled completely outside of the
  commodity food and feed stream
• Commodity biotech crops are grown on hundreds of
  millions of acres in the U.S. in 2002, PMPs were
  grown on 130 acres in the U.S.

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Commercial Crop Biotechnology

• Harness biotechnology to improve crops in an
  expedited manner these plants are specifically
  designed for food, feed, and fiber use.
• Over 100 million acres of biotech corn and
  soybeans grown each year in the United States
• No adverse health events in humans or animals
  from any biotech crops
• Regulated by three federal agencies USDA, FDA,
  and EPA
• Grown on over 200 million acres in 18 countries
• Six major crops corn, cotton, soybean, papaya,
  squash, and canola

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PMP Production

• Is not a commodity agricultural production
  system
• Contained process
• Outside commercial grain channel
• Limited acreage, location
• Controlled articles
• Grown and processed under USDA permit conditions

• Is like any other pharmaceutical production
  system
• Regulated and subject to mandatory conditions
• Well characterized
• Stable
• Productive
• Produces safe, pure, potent, consistent product

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Commodity Crops vs. PMPs

• Plant-Made Pharmaceuticals
• Used to manufacture therapeutic proteins, which
  are extracted, refined and used in regulated
  pharmaceuticals
• Can only be grown under USDA/APHIS permit
  conditions, and will never be de-regulated
• APHIS and/or state officials inspect records,
  facilities, and each field site is inspected at
  least 7 times over 2 years
• Only a few select and trained growers under
  contract, with APHIS approval, can grow PMPs
• Most equipment that comes into direct contact
  with must be dedicated for PMP production only
  and cannot be used with any crops intended for
  food, feed or fiber use
• Confinement measures are based on the type of
  plant, specific target protein, and location of
  production area

• Commodity Agriculture
• Harvested food, feed, and fiber use
• Permits only required for field trial phase of
  biotech crops after federal approval is granted,
  no permits are required
• Inspections required for field trial phase once
  federal approval is granted, no inspections are
  required
• Any farmer can plant biotech crops
• Hundreds of millions of U.S. acres are planted
  with biotech crops
• No dedicated equipment needed for biotech crops
• Confinement measures are only needed during field
  trial phase

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Consumer Questions

• Why are food plants used in PMP technology?
• Researchers have extensive agricultural knowledge
  and familiarity with these plants, as well as
  experience with their growth
• Scientists have a vast understanding of genetics,
  agronomics, and the environmental impact these
  plants have, as well as their composition
• Considerable knowledge is needed to confine and
  manage these plants
• Sometimes, these plants are best suited for the
  specific target protein
• Non-food crops are also used for protein
  production in plants

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Consumer Questions

• Will PMPs end up in the food supply?
• USDA APHIS has set up strict confinement
  requirements that are based on scientific risk
  assessments
• Confinement measures include both spatial
  isolation and temporal separation
• Machinery used for PMPs is unique to these
  purposes and cannot be shared with conventional
  crops
• Comprehensive education programs for personnel
  working with PMPs
• BIO and its members have developed a Containment
  Analysis and Critical Control Point (CACCP) Plan
  to identify hazards and critical control points,
  and establish procedures for maintaining these
  points

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Consumer Questions

• Why cant the public know where PMPs are grown?
• Confidentiality the location of fields is
  considered confidential business information
  (CBI) this is not an unusual practice for any
  industry
• Safety there is a history of vandalism by
  activists when field trial locations are
  discovered the safety of the plants, as well as
  employees and growers, are at risk
• No need state and federal governments are
  familiar with the locations and conduct regular
  audits to ensure that permit requirements are
  followed

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• For More Information
• www.bio.org