|
Government Regulation of Plant-Made Pharmaceuticals: Frequently Asked Questions
|  Printer Friendly |
Which government agencies oversee the production of plant-made pharmaceuticals?
Plant-made pharmaceutical (PMP) production is regulated under stringent requirements of the U.S. Department of Agriculture (USDA) and the Food and Drug Administration (FDA). Several agencies within USDA and FDA regulate and monitor PMPs, including USDA's Animal and Plant Health Inspection Service (APHIS) under the Biotechnology Regulatory Services (BRS), the FDA Center for Biologics Evaluation and Research (CBER), FDA Center for Drug Evaluation and Research (CDER), FDA Center for Food Safety and Applied Nutrition (CFSAN) and FDA Center for Veterinary Medicine (CVM).
How is PMP production regulated?
APHIS requires companies to obtain permits for the production of field trials for pharmaceutical protein production. New permit conditions for the 2003 growing season were announced by APHIS in March 2003. These rigorous regulations, which are science-based, are available for public review as a Federal Register notice.
Prior to issuing a test permit, APHIS reviews all plans for seed production, timing of pollination, harvest, crop destruction, shipment, confinement and the storage and use of equipment. Permits are then issued for the importation, interstate movement and field testing of the plants.
APHIS or state officials inspect records and facilities (including laboratories and greenhouses), and each field site is inspected at least five times during the growing season, with those inspections corresponding to critical times in production, such as pre-planting site location evaluation, planting, mid-season, harvesting and post-harvesting. A sample inspection plan might include five site visits made during the growing season, with an additional two inspections to assess any potential volunteer plants in the following year. Records also are required for all activities specified by the permit, including planting dates of regulated and adjacent crops if applicable, and dates of bagging and assessment. APHIS will use these records to oversee and audit the field tests.
Permit reporting requires field test reports six months after field test termination. Interim reports also may be required. Additionally, APHIS must be notified by phone within 24 hours of an unusual occurrence or suspicion of a breach of confinement, followed by a written report within five business days.
Trials grown under containment, such as in a greenhouse, must meet FDA good manufacturing practices and may be subject to APHIS regulations as well, depending on the plant grown and the protein expressed.
What confinement measures are in place to ensure there is no commingling with food or feed crops?
Confinement includes procedures to prevent commingling with food or feed crops, the environment, humans and non-target organisms. Confinement procedures are based on scientific risk assessments that evaluate the potential for and impact of exposure, and are modeled after Hazard Analysis and Critical Control Point (HACCP) principles. HACCP is a system currently in use in the food industry and identifies hazards and critical control points, and then establishes procedures for maintaining those points. The PMP industry has named its risk assessment Containment Analysis and Critical Control Point (CACCP).
These risk assessments developed for plant-made pharmaceuticals take into account the crop, the specific protein, the spatial setting or location of the intended production area and agronomic and crop handling practices. Confinement measures include both spatial isolation and temporal separation. Spatial confinement defines the distance between plots for plants producing pharmaceutical proteins and conventional crops used for food and feed. Temporal boundaries define the time separating the flowering and pollination between plants producing pharmaceutical proteins and nearby conventional crops of the same or related species.
Additionally, there is a perimeter fallow zone (an area not in production) around the field test site of 50 feet. This fallow zone ensures that farm machinery and equipment can freely access the test plot without affecting nearby fields.
Some plants, such as corn grown to produce pharmaceutical proteins, have unique confinement conditions as required by the 2003 APHIS permit guidelines. Due to corn's unique pollination cycle, no conventional corn can be grown within one mile of a field test that involves open-pollinated pharmaceutical corn. If pollination is controlled within the field test plot (through detasseling or bagging the corn stalks), then spatial confinement is reduced to half a mile, with a temporal buffer of 28 days. For example, controlled transgenic corn producing pharmaceutical proteins must be planted either 28 days before or 28 days after planting or harvesting of any other corn growing within a half mile of the test plot.
Test Plot Confinement Requirements for Open - Pollinated Corn
Test Plot Confinement Requirements for Corn Produced Under Controlled Pollination (Using Detasseling or Bagging Procedures)
Do PMPs require dedicated equipment?
Dedicated equipment is machinery that is solely used for plants producing pharmaceutical proteins and not for any other plants or crops. APHIS permit conditions require dedicated equipment to be used for planting and harvesting for the duration of the growing season for the pharmaceutical plants. This includes harvesters and planters. Tractors or tillage equipment can be used in other fields following APHIS-approved cleaning procedures. Additionally, dedicated facilities for the storage of equipment and regulated articles for the duration of the field test are required. Dedicated equipment can be decommissioned after a thorough cleansing process that has been approved by APHIS.
Are farm workers and other personnel specially trained to work with PMPs?
The annual training of contract growers and all other individuals involved with the development and production of PMPs is an APHIS regulatory requirement. An APHIS-approved training program ensures personnel are prepared to successfully implement and comply with all permit conditions.
What is the process for obtaining a permit?
While each permit issued by APHIS is unique and approval is granted on a case-by-case basis, the process for obtaining a permit is the same for all parties and involves both federal and state agriculture department approvals. In general, it takes approximately 120 days from the time the permit application is received until the permit is either denied or issued.
APHIS permitting requirements can be found online at http://www.aphis.usda.gov. Additionally, all permit information for companies involved with PMP technology and
their field tests are publicly available from USDA at http://www.aphis.usda.gov/bbep/bp/status.html.
Plant-Made Pharmaceutical Permit Process
How many PMP test plots are there in the United States and where are they?
APHIS reports that in 2002 total U.S. test trials consisted of 20 permits governing 34 field sites for a total of 130 acres. Plants growing pharmaceutical proteins can only be grown under USDA permit. Permits have been issued in the following 14 states since 2001: Arizona, California, Florida, Hawaii, Iowa, Kansas, Kentucky, Missouri, Nebraska, South Carolina, Texas, Virginia, Washington and Wisconsin.
What happens if regulations are violated?
In the event that permits are violated, APHIS will conduct a full-scale investigation governed by the Plant Protection Act. In the event a violation occurs, the Act provides for both criminal and civil penalties that may be leveled against the company or individuals that violate the act. Companies or individuals that violate the act and permit conditions face civil penalties of up to $250,000 per violation and/or imprisonment for up to five years, or $500,000 per adjudication, and may result in having their permits revoked. Additionally, if necessary, to protect the environment or public health, the transgenic plants can be subjected to the application of remedial measures (including disposal); if the owner fails to take such action, APHIS can take the action and recover the cost of the action from the owner.
Will PMPs ever be de-regulated?
PMP field production will always be under federal oversight and will not be de-regulated. Even when PMPs enter into commercial production, they will continue to be strongly regulated.
Is the public allowed to voice opinions on permit requirements?
As reported in the Federal Register notice, APHIS recognizes the need to provide additional information about field testing to the public and is in the process of determining how to make information about specific permits and necessary confinement standards available for each field test under permit. The Federal Register notice provides permit condition changes in a more formal way to the public and allows the public to respond during an open comment period. All current rules were developed with notice and comment rulemaking in accordance to the Administrative Procedures Act (APA).
Does the biotechnology industry support the permit requirements?
The PMP biotechnology industry views USDA's approach to establishing new guidelines for field trials of PMPs as a model for establishing a transparent and informative approach to invite public participation in the oversight of an emerging technology. As a whole, the biotechnology industry supports a regulatory system that is grounded in science and believes USDA's guidelines reflect established science and ensures plants grown for pharmaceutical protein production can be isolated for their intended use only. Manufacturers of PMPs recognize their responsibility to maintain the safety of the manufacturing process. They are ready to provide regulatory authorities with validated analytical methods and tools for detecting PMPs and are fully cooperaing with regulatory agencies in reviews and audits of confinement procedures.
In addition to adhering to USDA regulations, the PMP biotechnology industry is committed to strict, self-imposed guidelines with a goal to create a uniform code of conduct throughout the industry. Thus, each manufacturer has developed standard operating procedures that cover every aspect of production and handling of PMPs, from pre-planting preparation to the delivery of the plant material or the product derived from plant material to a processing facility. A central focus of the standardized procedures is a confinement system intended to ensure that neither humans nor the environment are unintentionally exposed to PMPs. These plants are used exclusively to produce pharmaceutical proteins and are not intended for food or feed consumption.
| 
