This content is current only at the time of printing. This document was printed on 24 June 2021. A current copy is located at http://www.plural-consulting.com/node/71651
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Guidance on veterinary drug joint reviews
International regulatory cooperation comes in many forms—from formal treaties to informal information exchanges, to simultaneous and joint reviews, and more. Collaboration with partner regulators in the pre-market and post-market context promotes harmonisation of regulatory practices and standards, leverages resources, and facilitates timely access to safe and effective veterinary drugs. Veterinary drug regulators have for many years worked on harmonising requirements and systems, and on the development of internationally-recognised guidance through a number of international forums, such as VICH and CODEX. This important foundational work enables international collaboration in the review of veterinary drug submissions.
Partner regulators are working together to explore ways to review veterinary drug submissions jointly. This guidance covers joint reviews between the Australian Pesticides and Veterinary Medicines Authority (APVMA), the New Zealand Ministry for Primary Industries, and Health Canada’s Veterinary Drugs Directorate to enable simultaneous access to animal drugs in three major markets, leading to improved animal health and food safety. More partner regulators in other countries may be added to the joint review context over time.
Strong relations and dialogue with partner regulators are important in achieving program objectives in an increasingly complex regulatory world, while also addressing the challenges of globalisation, new technologies and timely approval of new medicines. For partner regulators, joint reviews promote increased effectiveness in achieving policy objectives, while providing more timely access to market for industry applicants and end users.
Following several successful joint reviews between Australia, New Zealand and Canada, there has been interest by others within industry to explore this as a model for bringing new veterinary drug products to market. Industry has been keen to understand how to initiate discussions and how the overall process would work. This content is therefore provided as guidance for industry about the joint review process for veterinary drugs. Note that guidance documents are administrative instruments not having the force of law.
2. What is a joint review
A joint review is the evaluation of a veterinary drug submission shared by two or more countries. Joint reviews also allow for the possibility of another regulatory agency to participate as an observer only. Each participating partner regulator is assigned a technical section of the submission (eg, target animal safety, efficacy, quality and human food safety), and each review report is peer-reviewed by the other countries’ regulators.
A joint review requires simultaneous submission filing to all participating partner regulators. This is a formal process in which timelines and work allocation are negotiated in advance. Data reviews are exchanged and peer-reviewed, and there is agreement on both the documentation to be produced and the decision-making target date, ie the date on which the decision (or proposed decision) is communicated to the applicant. One country will serve as a Project Lead with responsibility for preparing the project plan, establishing the documentation and communication tracking system/approach, and coordinating the joint review planning (refer to sections 5 and 6 below for more details).
At the end of the joint review process, each partner regulator makes its own sovereign decision based on recommendations contained in the review reports and its own legislative and regulatory context.
3. Context overview
This guidance outlines the process for regulator partners and industry applicants going forward. Joint reviews offer the following benefits without compromising domestic standards and scientific rigour:
- Reduces administrative burden for industry by harmonising data requirements, and offering transparent and predictable regulatory processes.
- Simultaneous access to multiple major markets for veterinary drug manufacturers.
- Consistent and robust regulatory decisions.
- More choices for animal owners and food producers by supporting faster access and expanding the number of treatment options available.
- Maximises efficiency for partner regulators by sharing the work.
- Builds a stronger global review community that allows partner regulators to work across jurisdictions to share knowledge and expertise.
- Independent, sovereign decision-making by each partner regulator while striving for harmonisation.
4. Eligible products
The scope of the joint review process includes veterinary drug new chemical entities and generics. New biologic entities and bio-similars will be handled on a case-by-case basis depending on the regulatory authority. Submissions for drugs for minor uses/minor species (MUMS) are especially encouraged.
Submissions may be for new drugs or for new uses of existing products that already hold marketing authorisations in all participating countries, provided it has not been subject to relevant or significant safety-related regulatory action in any country. The product must be identical in formulation and manufacturing, including the source of the active ingredient in all participating countries. There may be differences in product labels.
Multi-national collaboration on veterinary drug joint reviews is supported by Heads of Agency of the partner regulators. The Heads of Agency will select one partner regulator to be the Project Lead for the drug submission, which will serve as a single window point of contact and project manager.?
The Heads of Agency, with the support of the Project Lead, provide oversight and support the following key phases of the joint review process, which are further described in the guidance below:
- Pre-submission phase: Advance notice/expressions of interest by industry and early interactions with partner regulators.
- Submission filing phase: Coordinated and consistent (with the exception of select nation-specific requirements) submission filing by industry to each partner regulator where a market authorisation is intended.
- Submission review phase: Planned, transparent and coordinated review by partner regulators.
- Sovereign decisions: Partner regulators endeavour to issue sovereign decisions within agreed-to timelines.
6. Phases of a joint review
This section outlines the key steps and considerations for a joint review. It is based on the OECD Pesticides Guidance Document on the Planning and Implementation of Joint Review of Pesticides (OECD Environment, Health and Safety Publications Series on Pesticides no. 60). This guidance provides high-level direction while allowing for the flexibility required in the conduct of joint reviews.
6.1. Pre-submission phase
6.1.1. Expression of interest
Early interactions by industry with partner regulators are important, and will assist in the joint review feasibility and admissibility process. Expressions of interest should be signalled at the earliest opportunity. Applicants may signal their interest by sending a letter or email to each of the partner regulators.?
The expression of interest should also include a request for a pre-submission discussion. The request should, as a minimum, provide basic information on the proposed product and indicate the scientific disciplines that the applicant wishes to discuss, as well as any specific issues/questions to be addressed by partner regulators. The Project Lead will then work with the applicant and the partner regulators to schedule these discussions.
6.1.2. Pre-submission discussions
Pre-submission discussions are required to inform a decision on admissibility. The purpose of a pre-submission discussion where presentations are made by the applicant to partner regulators is to introduce their new drug product and to discuss whether it is a good candidate for the joint review initiative. This teleconference is of a scoping/exploratory nature, between the applicant and all partner regulators at the same time.
Discussions can confirm and clarify data requirements and product testing, address submission formatting, and provide feedback from partner regulators on study protocols proposed by applicants. The discussions are also an opportunity to clarify any national requirements.
The applicant is responsible for recording the meeting notes and seeking any comments, clarifications or corrections from meeting participants in a timely manner; revised and finalised meeting notes should be shared with partner regulators for approval and future reference.
6.1.3. Decision on admissibility
If a submission is deemed to be an appropriate candidate, the Project Lead will be established. They will request a formal letter from the applicant seeking a joint review.
Based on the information gathered through the pre-submission discussions and the formal request from the applicant, the partner regulators will consider a variety of factors before deciding to proceed with a joint review. The partner regulators will communicate the decision on admissibility to the applicant via formal letter from the Project Lead.
6.1.4. Timelines for review
Each partner regulator may have different national performance standards or targets for submission reviews that are established through policy or regulations. In order to ensure national regulations are respected, the timeline for a joint review will therefore be determined based on the partner regulator with the shortest applicable performance standard. This timeline will be communicated to the applicant prior to submission filing.
6.2. Submission filing phase
6.2.1. Coordinated filing
Applicants must file separate submissions to each regulator where a market authorisation is intended—independently within five working days of each other. This will facilitate coordination for regulators and advance project planning, while recognising that industry may need time between country‐specific filing to address select nation‐specific requirements.
The content of the applications should be consistent, unless there is a select nation-specific application requirement. Submissions should also include any administrative documentation or fees payable, as per national regulatory requirements, policies or processes. Applicants are encouraged to confirm applicable fees with each partner regulator prior to submission.
To facilitate submission completeness checks and to enable a coordinated joint review, it is strongly recommended that applicants file their submission in one regulator’s format, supported by a covering note or cross-walk of the submission technical sections (eg parts, volumes). Cross-walks should clearly indicate the location of the technical sections and highlight country-specific deviations. Although not the preferred option, applicants may also choose to file the submission in the unique format of each partner regulator, supported by a cross-walk of the submission technical sections to the other two regulatory formats. Applicants may seek advice on submission format during the pre-submission discussions and by contacting the Project Lead. Applicants may also propose a format for regulator consideration and further guidance.
To enable the joint review process, data and other information (including confidential business information) provided by the sponsor will be shared between participating regulators. Sponsors are asked to provide a letter authorising this exchange of information.
6.2.2. Submission completeness check
Each partner regulator will perform technical and administrative screening of the submission to ensure that their legislation and data requirements are met (eg application forms and fees) to be accepted for review.
If partner regulators have questions about the content of the submission during the completeness check, particularly for national requirements, they may contact the applicant directly. Where feasible, partner regulators will coordinate questions. If a partner regulator requests technical information or data, the applicant is asked to ensure that all partner regulators receive the same information.
At the end of the submission completeness check, each partner regulator will send a communication to the applicant informing them of the acceptability of the submission for review.
6.3. Submission review phase
Partner regulators will conduct the primary review of the technical section(s) for which they were identified as lead reviewer and draft an assessment report. All partner regulators will conduct a secondary peer-review of this report. Together, they will develop a combined list of questions for the applicant.
The applicant will be provided with an established amount of time in which to submit completed responses. The amount of time provided to respond to questions or deficiencies may be subject to specific requirements of partner regulators and should be confirmed with the Project Lead. These responses will be shared with all partner regulators.
Responses undergo primary review by the lead reviewers for the applicable technical section and secondary peer-reviews by the other regulator partners. As part of finalising the reports, opportunities to harmonise maximum residue limits (MRLs) and better alignment of labelling will be considered.
6.4. Sovereign decision
Each partner regulator makes its own sovereign decision informed by recommendations contained in the review reports and its own legislative and regulatory context.
Each partner regulator will undertake the necessary national administrative and/or legal steps relating to the issuance of a market authorisation or negative decision. To the extent possible, partner regulators will synchronise the timing and communication related the issuance of decisions.
In the event of a negative decision, by one or all of the regulators, the applicant is encouraged to discuss available options and the administrative process to address deficiencies with the relevant partner regulator(s), based on their regulatory frameworks.
7. Additional considerations
Should an applicant wish to withdraw a submission from review or cancel the joint review, they are encouraged to contact all partner regulators at the earliest opportunity prior to cancellation to discuss any concerns and regulatory considerations.?
Once a product has received market authorisation, it is the responsibility of the applicant to adhere to all applicable national post-market regulatory requirements. Partner regulators will continue to collaborate and exchange information to support post-market monitoring, risk assessment and risk management activities, as appropriate.
8. Contact information
Any nation-specific questions relating to joint reviews can be directed to:
Australian Pesticides and Veterinary Medicines Authority
GPO Box 3262
Sydney NSW 2001
Phone: +61 2 6770 2300
International Liaison Officer
Veterinary Drugs Directorate
Health Products and Food Branch
Ground Floor, Suite 14—Holland Cross Complex
11 Holland Avenue
Ottawa, Ontario K1A 0K9
Postal Locator 3000A
Principal Adviser ACVM
New Zealand Food Safety
PO Box 2526
New Zealand 6140
Phone: +64 4894 2560