Regulatory Approvals and Permits

USDA Inspection report 01/24/2017  No non  compliant items identified.   Pass

USDA VS inspection 11/09/2017 Pass , inspection report 93-R-0434 PASS

IBC Approval 10/02/2019 1999-471 Approved 3 year 

IACUC inspection Jan-16-2019 to Jan-16-2022 UC Irvine Pass

Biological Materials Permits

USDA permits

MIT cheat sheet for permitting biological materials

Permits and Field work 

Duke Permits and Procedures for Field work

Guidelines for Shipping/Receiving Biological Materials

Unv Minn Guidelines

https://www.aphis.usda.gov/aphis/resources/permits

Apply for ePermit access and authenticate.   You may need to authenticate in person.

Fill out online questionnaire according to permit type and submit,.  You can check status https://www.aphis.usda.gov/aphis/ourfocus/biotechnology/sa_permits_notifications_and_petitions/sa_check_status

sample of status check

FDA and EPA would be for live mosquitoes.   The constructs should go through IBC and EHS locally, IATA...etc.

As of January 2017 the FDA defines GMO Mosquitoes as;

1. Examples of New Animal Drugs a. Products intended to reduce the virus/pathogen load within a mosquito, including reduction in virus/pathogen replication and spread within the mosquito and/or reduction in virus/pathogen transmissibility from mosquitoes to humans. b. Products intended to prevent mosquito-borne disease in humans or animals.  (FDA)

     It recommends approvals from both agencies (FDA and EPA) to assure due diligence.

https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM533600.pdf

2. Example of Pesticide Products a. Products intended to reduce the population of mosquitoes (for example, by killing them at some point in their life cycle, or by interfering with their reproduction or development)5 . (EPA)

https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/epas-regulation-biotechnology-use-pest-management#applying

UCI IRB does not have specific guidance for GMO mosquitoes, however it would expect documentation of community consent prior to any release.

SITE Regulatory plan

Based upon WHO Guidance for vector approvals, NASEM, FNIH and UCI MI project plan

1)     Determine final site. Finalize decision on partner institution and local PI, who should represent the project in stakeholder engagement with the PNLP of Comoros and STP, (Programme National de Lutte contre le Paludisme)

1. Contact to see if there is interest and capacity to begin
2. Compile contact listing
3. Send out introduction emails, letters etc.
4. Arrange meeting
5. Draft agreements
6. Chart responsibilities
7. Local informational workshop venue
8. Presentations
9. Materials
10. Hire local staff
11. PI approvals
12. Finalize contracts

2)     Complete TPP

3)     Field protocols

4)     Laboratory approvals

5)     Train staff

UC I Þ SITEÞINTERNATIONAL AND NGO

6)     Make contact with Biosafety Clearing House focal point for Comoros, who can help clarify the regulatory pathway for LMOs (Will check with Tony on this). Mlle Assani Moinahalima

            Spécialiste en Gestion et Conservation de la Biodiversité

            Direction Générale de l'Environnement et des Forêts

Ministère de l'Agriculture, de la Pêche, de l'Environnement, de l'Aménagement du territoire et de l'Urbanisme    BP 5414            Moroni Comoros

Phone:             +260 334 31 02

Email:               assanimoinahalima@yahoo.fr

3. Determine status of national biosafety law, application and review process (There are none in the Comoros, not even for agriculture, they do not restrict GMO)

4. Encourage national authorities to request training and support from AUDA-NEPAD –(Requested that our Community Engagement consultant, Ana Kormos engage on the subject with our partners in the Comoros)

5. Focus initially on requirements for contained use

6. Establish IBC at partner (Local PI)  University (STP or Comoros )

7. Determine requirements of Comoros/STP responsible authority (Ministry of Environment?) for certification of contained use facility for gene drive mosquitoes, Adapt crop policy, such as exists in Burkina faso.

a. Comoros has no GM rules or guidance

b. Sao Tome has no capacity to enforce

8. Establish plan and timeline for building containment facility at partner institution. (ACL2 + should be a priority and be complete  before training of local postdocs or scientist)

9. Identify trainee candidates and establish timeline for training that correlates with completion of containment facility.

10. Check with the university/PNLP to make sure they understand the technology (especially the persistence issue) and feel comfortable that their insurance adequately covers the field work

11. CISRO will be unable to hold a slot for Risk assessment and we should consider engaging with them soon for a projected time frame for assessment.

•          Consider reaching out to Tanzania

 12. Obtain copies of previously approved ACL2 + laboratories in Africa

 13. Conduct hazard analysis with the research team (including representatives from the field site) and any external experts desired by the project. The project may choose to stop there.

“Hazard analysis is the first step in risk assessment.  A hazard analysis is a systematic exercise to think collectively about everything that could potentially go wrong with the system, no matter how unlikely.  The hazard analysis will include consideration of the possible steps that would have to occur for each of these hazards to occur (the pathway to harm).  Early hazard analysis is a benefit to the project.  The utility is that it helps the project identify data or information that may be needed to predict the probability that any of the steps in the pathway to harm might occur.  Prediction of the probability that a hazard will occur, and the consequence if it does, is part of risk assessment.  If risk assessment determines that a particular hazard has a high level of probability, or a high level of uncertainty, this may cause the project to have to stop and go back to collect missing data, which could result in serious delays.”

14. Risk assessment will be conducted by national regulatory authority(ies) in any case, but this is unlikely to conform to the NASEM recommendation for probabilistic ecological risk assessment of gene drive organisms.  An external risk assessment that is made public by the project can help with transparency issues later on and provide information that may be useful to national authorities in their own risk assessment. (Review Mark Benedick Pathway to Development)

15. Local Approvals and requirements

            Permits

            Scientific Review

            Contracts

            Visas

Approvals

16. Initiate WHO l approvals

Assesses Quality, Safety, and Efficacy of manufacturing facilities (Continuous)

1. WHO Prequalification Team Vector control products MVP/EMP/RHT/PQT World Health Organization 20, Avenue Appia 1211  Geneva 27 Switzerland

1. Single point of entry (PQT-VC) Electronic submission and one hard copy.
2. Service Code
3. Service
4. PQ100 Request for Determination of Pathway
5. PQ200 Protocol Review
6. PQ300 New Vector Control Product PQ301 New Equivalent Vector Control Product
7. PQ400 Active Ingredient: New Manufacturing Site PQ401 New Active Ingredient Hazard Assessment via JMPR
8. PQ40 New Active Ingredient Hazzard Assessment via JMPR
9. PQ500 Post PQ Change: Major PQ501 Post PQ Change: Minor
10. PQ501 Post PQ changes Minor/Major

New interventions Pathway

­­

1)     Cover letter requesting Service PQ100

2)     Dossier, letters forms, studies, data, (living document using GLP)

1. Cover letter
2. Application form
3. Table of Contents
4. Letter(s) of authorization
5. Letter(s) of access
6. Declaration of Labelling

3)     Request for Determination of Pathway Form ◦ Handout

4)     Draft Label (if available)

5)     Additional supporting documentation

6)     Submit to the PQT-VC Case Managers via pqvectorcontrol@who.int

7)     http://www.who.int/pq-vector-control/resources/presubmission/en/

8)     Meeting requests, Submit to the PQT-VC Case Managers via pqvectorcontrol@who.int

Dossier requirements

Example of cover letter

1. University of California Approvals
2. Site Ministry Approvals
   1. Community Consent
   2. International and NGO approvals

Example of Letter of Authorization

Example of Letter of Access

Example of labeling

Appendix 1 Guiding Principles

Engagement with colleagues, partners, all stakeholders

• Practice openness and transparency

• Collaborate, engage, and listen through proactive/constructive 2-way communication

• Demonstrate integrity (judgement/confidentiality/tact/consistency)

• Be respectful and demonstrate respect

Process and Decision Making

• Action oriented, i.e., value-added processes which focus on end user access to products

• Evidence-based

• Adhere to established roles and responsibilities

• Transparent

• Timely

• Well documented policies and decisions

• Continuous evaluation and process improvement

Broader Impact

• Embrace innovation and creativity

• Apply a global perspective to meet varying geographic and disease needs

• Monitor and evaluate current approaches to meet changing global needs, i.e., remain relevant

Summaries:

1)     Summary of Quality Dossier

1. Physical/Chemical Data
2. Declaration of Product Formulation
3. Description of Manufacturing Process
4. Declaration of Manufacturing Sites
5. Confidential Appendices

2)     Summary of Safety Dossier

1. *Acute toxicology (6-pack) - Acute Inhalation - Acute Oral - Acute Dermal - Primary Eye Irritation - Primary Skin Irritation - Dermal Sensitization
2. Product Risk Assessment (Occupational and Residential Exposure)
3. AI Specific Hazard Assessment (or summary of publically available information)

3)     Summary of Efficacy Dossier

1. Lab studies
2. Field studies
3. Supporting Documentation

*TPP