Mock-up of Application Form for Confirmation of Change Management Protocol, etc. Related to Change of Strains for Influenza Vaccine or COVID-19 Vaccine — PMDA Early Consideration Summary

In Plain Language

This document is a set of mock-up forms and supporting examples for managing repeated changes to influenza or COVID-19 vaccine strains using a post-approval change management protocol (PACMP). It shows how a sponsor might apply for confirmation of a protocol before a strain change, then notify PMDA about changes made under that confirmed protocol. The examples also show how to describe planned manufacturing and testing changes, assess product quality, and present results against criteria established in advance. The goal described in the document is to make regulatory procedures for recurring strain changes more reasonable and predictable. The examples are not a complete, one-size-fits-all application: information and data are to be determined for each product.

What This Guidance Covers

The document is an administrative notice from PMDA containing mock-ups and points to note for preparing application and notification materials related to strain changes in influenza vaccines or COVID-19 vaccines. It applies only to those vaccine types. It describes use of a strain change PACMP in the context of procedures for changing approved items according to a protocol.

The mock-ups cover four types of material: an application form and a table comparing old and new text; data attached to the application; the change management protocol itself; and a notification form for changes made according to the protocol. The examples show a sequence in which the sponsor seeks confirmation for one season, submits a Step 2 notification for that season, and later submits another Step 2 notification for a subsequent season.

The document expressly cautions that it presents examples only. It is not intended to be the sole basis for preparing an application form or related materials, and it does not cover every possible content item. The information and data to include should be determined for each product. The document also says it was prepared based on knowledge and information available as of October 2025 and may change as knowledge and information change.

Why It Matters

The document describes a recurring timing challenge. Production strains or antigen strains used for seasonal influenza vaccines and COVID-19 vaccines are recommended or selected around spring each year by the World Health Organization (WHO) or Japan’s Ministry of Health, Labour and Welfare (MHLW). If a strain change is considered necessary, regulatory procedures should be completed promptly by autumn.

For vaccines that may need repeated strain changes, the cited handling procedures describe use of a PACMP to support reasonable and highly predictable regulatory procedures. This mock-up aims to make that approach easier to understand by showing the kinds of application forms, comparisons, protocols and supporting data that may be assembled. Its focus is on how to express and document the proposed process; it does not replace product-specific assessment or the procedures named in the document.

Key Recommendations

The material below summarises the document’s main points. Since it is a mock-up, its tables and example content illustrate possible presentation rather than prescribing a single format or universal set of tests.

1. Use the examples as models, not as a complete template. The document says the contents of the application and attached data should be determined individually for each product. The comparison table may also be arranged differently if another format better represents the parts that could change in future strain changes.
2. Make the Step 1 application reflect the current approval. The example says the Application for Confirmation of Change Management Protocol (Step 1) should include the contents of the approval certificate at the time of application. In the example, production strains for the coming season have not yet been determined, so the pre-change and post-change fields show the same strains; the production strains expected to change are underlined.
3. Show how the confirmed protocol is used in Step 2 notifications. The example for the season with confirmation granted identifies the strain change made in that season and underlines the changed clade in the comparison table. For a later season, the “Pre-change” field reflects the condition after the previous Step 2 notification. The document notes that this difference from the original Step 1 application does not require a procedure to change the change management protocol.
4. Describe the planned change and what stays the same. In the example protocol, the virus seed (template DNA) changes, while the other parts of the manufacturing method remain unchanged. For specifications and testing methods, the example identifies changes to primers and reference sequences used for identification, and to the primary antibody and reference materials used for the titer assay. Details and reasons are to be provided for changed parts, and the unchanged status of other parts is to be explained.
5. Set out an evaluation plan based on risk assessment and existing knowledge. The protocol example includes studies or investigations to assess potential effects of the strain change on quality, their methods and acceptance criteria. It also describes how the results will show whether the approved control strategy remains applicable, or how discussion of potential changes to that strategy will be planned.
6. Include the relevant supporting materials. The application attachment examples include a draft post-change approval certificate and comparison table, the change management protocol and its evaluation plan, other supporting material, and copies of relevant prior approvals or minor change notifications where applicable. The Step 2 notification example includes study results, relevant draft approval-certificate text, the current protocol, prior certificates and notifications where applicable, a statement about data collection and preparation, and draft revised product information and risk management documents where relevant.
7. Present the work and regulatory schedule clearly. The protocol example includes a representative schedule for manufacturing, evaluation, stability work and notifications. If activities follow a different schedule, or if particular additional procedures affect the supporting data, the document encourages timely sharing of the schedule with PMDA. It says this should occur immediately after the marketing authorization holder decides to change the strain through the Step 2 notification, taking account of strains recommended or selected by MHLW.

Practical Implications

Interpretation: For a sponsor, the examples imply that planning should connect the proposed future strain changes to the approved product information and to the evidence that will be generated. The application is not just a description of a new strain: the illustrated protocol also explains expected manufacturing and testing changes, the evidence plan, and how results will be presented against agreed criteria.

Interpretation: Regulatory teams may find it helpful to track the product’s state from one season to the next. The mock-up makes clear that the post-change status established by a prior Step 2 notification becomes the next season’s “Pre-change” status. The document specifically says that reflecting this status in the later comparison table does not itself require a change-management-protocol update procedure.

Interpretation: Quality and analytical teams can use the protocol example to organise work by material and purpose: virus seed, active substance, vaccine product, analytical procedure, reference material and stability. The examples distinguish characterization from batch analyses and show that analytical-procedure validation is relevant when a strain change requires changes in testing procedures, reagents or reference materials. If no testing-method changes associated with the strain change are planned, the example says validation data are exempted from submission.

Interpretation: Clinical operations are not the main focus of this document. Its practical emphasis is on manufacturing, quality evaluation and regulatory materials. The examples nonetheless provide a planning sequence across seasons, including when studies, long-term storage work and notifications may occur. This should be read as an illustrative schedule, not as a universal calendar for every product.

Technical Details

Terms used in the document. A PACMP is a “Post Approval Change Management Protocol” or a “protocol to change a part of approved items for approved products.” The document uses “Application for Confirmation of Change Management Protocol (Step 1)” for an application for confirmation under the first sentence of Article 14-7-2, Paragraph 1 of the Act. “Notification for Changes Made According to Change Management Protocol (Step 2)” refers to a notification under Article 14-7-2, Paragraph 6 of the Act. These are the terms and descriptions given in the document.

The example attachments illustrate the sequence as follows:

Protocol and quality evaluation. The sample protocol is intended to demonstrate that the same manufacturing method as for the pre-change product produces a post-change product comparable to it, except for a difference in amino acid (base) sequence caused by the strain change. It describes the virus seed (template DNA) as changed or added, with the other manufacturing method unchanged in the example. It also gives examples of changes to identification and titer testing materials. These are illustrations; the document says test items and analytical procedures should be selected to suit the product and the purpose.

The evaluation plan is to list studies or investigations addressing potential quality impacts, together with testing methods and acceptance criteria, based on risk assessment. For characterization and batch analyses, the example uses at least 3 lots each of active substance and vaccine product manufactured at commercial scale after the strain change. The document qualifies this by saying the number of lots is determined for each product according to the extent of existing knowledge. If the strain change requires evaluation of manufacturing-process performance, a plan for that evaluation is also provided.

For test items, methods and acceptance criteria, the example says these are established using existing knowledge about pre-strain-change products. Test items and methods remain unchanged from those for the pre-change product in principle. Criteria for attributes expected to change are set to confirm expected changes, such as a change in base sequence; criteria for attributes expected to remain unchanged are established in principle from manufacturing results for pre-change materials. This logic is shown for virus seed, active substances and vaccine product.

Analytical validation and stability. The example includes validation of identification and titer-assay procedures when a strain change leads to changes in testing procedures, reagents, reference materials or related operations. It lists characteristics such as specificity, and, for the titer assay, range, accuracy and precision, including repeatability and intermediate precision. The example states that validation data are not submitted if no testing-method changes associated with the strain change are planned.

Stability plans are also illustrated for active substances and vaccine product. The example tables show long-term storage at -20°C, with sampling at Months 1, 3, 6, 9, 12, 15, and 18, and an accelerated condition of 2 to 8°C, with sampling at Months 1, 3, and 6. Each example lists 1 lot. The document explicitly presents these as examples and says the plan and test items should be developed based on the product and existing knowledge; it also says to clarify which test items are performed at each sampling point when the list is reduced. The protocol example concludes that the long-term storage study continues after the strain change to confirm no impact on stability.

Who Should Read It

This document is most relevant to marketing authorization holders and their regulatory affairs, quality, analytical development, manufacturing and CMC teams working on influenza or COVID-19 vaccines that may undergo repeated strain changes. It may also help project teams coordinating protocol confirmation, production planning, study data and seasonal notifications understand how the example materials fit together.

It is particularly useful when preparing or reviewing a strain change PACMP, deciding how to show pre-change and post-change product information, planning quality evaluations, or assembling a Step 2 notification. Readers should bear in mind that the document is a mock-up, is limited to the vaccine types it names, and says product-specific content should be determined individually.

Official PMDA Source

• Official title: Mock-up of Application Form for Confirmation of Change Management Protocol, etc. Related to Change of Strains for Influenza Vaccine or COVID-19 Vaccine (Early Consideration)
• Issuing body: Pharmaceuticals and Medical Devices Agency, Office of Vaccines and Blood Products
• Date printed on the document: October 3, 2025
• English version: Provisional Translation (as of April 2026)
• PMDA PDF: Download the PMDA document
• PMDA Early Consideration list page: View the PMDA list page

Source: Pharmaceuticals and Medical Devices Agency (PMDA) website, PMDA Early Consideration list page. This page was created by editing and summarising the PMDA document.

Consult the official document for the full text and examples; this summary does not replace it. PMDA provides the English version for reference purposes, and the Japanese original prevails if the two differ. PMDA describes Early Consideration documents as reference information reflecting the Agency’s views at the time of publication; they may change as scientific knowledge develops.

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