2. Background: Current Responses Are Insufficient
- Marketing and promotion
- Perverse incentives
- Supply initiation and continuity
- Surveillance—data collection and disclosure (sales and emerging resistance)
- Formulary controls
- Post-market (clinical) data generation
- Environment (supply chain pollution)
- Non-human use
- Third-party control of the product
- Availability challenges
- Sub-optimal clinical use
- Supply chain challenges and risks
- Off-label use
- Substandard/spurious/falsely-labelled/falsified/counterfeit medical products (SSFFC)
- Market authorization and labelling
- Pricing and reimbursement
- ‘Clear opportunities’ for action: In optimizing clinically appropriate use. Between the current situation (where we are now) and the desired situation (where we would like to be).
- No likely lego-regulatory response: Anticipated to address the issue in the next decade. The likely absence of a legislative or other system-wide mechanisms increases the imperative to tie the issue to a specific R&D incentive.
- Reasonable industry influence: Over the issue given their role in the antibiotic lifecycle (product development, production, and global sales and distribution). For each domain, do developers have ‘reasonable’ responsibility or influence? To what degree could a condition be considered reasonable and practical bearing in mind the comparative advantage and cost relative to other stakeholders who could potentially take on a greater role in sustainable use in this space.
- Realistic to address early in product development: Are the risks presented by the identified domain largely general to the high unmet need antibiotic class and the general pharmaceutical business model? Are they conceivable and hence could they be, at least, mitigated through an early-defined condition that would be potentially blunt and non-specific but would maximize early developer certainty.
4. Findings and Discussion
5. Domain 1—Marketing and Promotion
5.1. Background and Justification for Inclusion in Developer Conditions
5.2. Considerations for Condition Design
- To be supported by an enhanced role of public health bodies in informing practitioners etc.
- A globally accessible, anonymous, whistleblower facility (supported by a policy of non-retaliation and by qui tam style financial incentives).
6. Domain 2—Perverse Incentives
6.1. Background and Justification for Inclusion as a Developer Condition
6.2. Consideration for Condition Design
7. Domain 3—Supply Initiation and Continuity
7.1. Background and Justification for Inclusion as a Developer Condition
- Minimum national safeguards: the risk to waning product efficacy from being used in countries without minimum product-specific SU safeguards in place (risk of oversupply where there is an insufficient ability to provide the product in an appropriate manner).
- Supply continuity: the risk to appropriate stewardship from disruptions in the supply of the novel product (risk of undersupply when the product is in routine use).
7.2. Supply Initiation and SU-Safeguards
7.3. Supply Continuity
- Lack the ability to distribute/prescribe appropriately (unless this is guaranteed by a third-party) and/or
- Do not have an effective national supply control and stewardship plan in place.
8. Domain 4—Surveillance—Data Collection and Disclosure (Sales Data and Evidence of Emerging Resistance)
8.1. Background and Justification for Inclusion in Developer Condition
8.2. Considerations for Condition Design
9. Domain 5—Formulary Controls
9.1. Background and Justification for Inclusion in Developer Condition
9.2. Considerations for Obligation Design
10. Domain 6—Post-Market (Clinical) Data Generation
10.1. Background and Justification for Inclusion in Developer
10.2. Considerations for Condition Design
11. Domain 7—Environment (Supply Chain Pollution)
11.1. Background and Rationale for Condition
11.2. Contractual Condition
12. Domain 8—Non-Human Use
12.1. Background and Justification for Inclusion in Developer Condition
12.2. Considerations for Condition Design
13. Domain 9—Third-Party Control of Product
13.1. Background and Justification for Inclusion in Developer Condition
13.2. Considerations for Condition Design
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|Possible Regulatory Action||Examples of Use|
|Refuse animal marketing authorization||Fluoroquinolones, Australia EMA tigecycline |
|Restrict animal marketing authorization||extra-label use of cephalosporins in food-producing animals  in the USA|
|Revise animal marketing authorization||Colistin, EMA , introduced restrictions based on new information|
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