Benefits and Challenges of Change Protocol Approach: An EU Agency Perspective

Transcription

1 Benefits and Challenges of Change Protocol Approach: An EU Agency Perspective Ann Johnsson, Senior Expert Medical Products Agency (MPA), Uppsala, Sweden

2 Post Approval Change Management Protocols (PACMPs) Introduced in the EU legislation 2010 (2010/C 17/01 ) Option for a faster and more predictable implementation of changes post-approval. Uses a step-wise procedure starting with an evaluation of the strategy for the change followed by a separate evaluation of the data produced based on the agreed strategy.

3 Post Approval Change Management Protocol (PACMP) Apply to all medicinal products for human and veterinary use including biotechnological or biological products. Irrespective of whether a traditional or enhanced Quality by Design (QbD) approach has been used for product development.

4 Post Approval Change Management Protocol (PACMP) May be included in an original marketing authorisation application or (line) extension application, or be submitted as a stand alone variation. Not feasible for biological medicinal products where non-clinical/clinical data are needed as part of the comparability exercise. A PACMP should not include changes that would result in a line extension.

5 Post Approval Change Management Protocol (PACMP) Protocols should be specific to a product although the same management strategies may be applicable to other products and processes. Companies are recommended to submit PACMPs only for those changes that they are highly likely to implement and whose feasibility has already been investigated and is supported by relevant data. Inclusion of several PACMPs may cause problems

6 Post Approval Change Management Protocol (PACMP) In principle, a PACMP could be applied already at the time of identification of a need for a change. It has, however, been found difficult to introduce them at an early stage as it results in too complex protocols to be functional in practice.

7 Post Approval Change Management Protocol (PAMPC) - Content of the protocol EU guideline on Quality: Questions and Answers Post approval change management protocols (EMA/CHMP/CVMP/QWP/586330/2010)

8 Post Approval Change Management Protocol (PAMPC) - Content of the protocol Justification for the need for a specific change(s) within a reasonable timeframe. Commitment to update the approved protocol, due to significant changes to test methods/acceptance criteria or new knowledge or regulatory requirements.

9 Post Approval Change Management Protocol (PAMPC) - Content of the protocol Justification for the need for a specific change(s) within a reasonable timeframe. Commitment to update the approved protocol, due to significant changes to test methods/acceptance criteria or new knowledge or regulatory requirements. A detailed description of the change. Data from development or pilot scale studies supporting that proposed approach is feasible. Risk assessment of the impact of the change on product quality. Identification for potential risks and details on the strategy of how the risks will mitigated or managed. Appropriateness of the approved control strategy and additional tests needed

10 Post Approval Change Management Protocol (PAMPC) - Content of the protocol, continued Description of the studies to be performed, and the test methods and acceptance criteria that will be used For biologics, the approach to be used to demonstrate the comparability of the pre- and post- change product (IPC test, spec s and extended characterisation studies). A plan for stability studies should be included, if appropriate;

11 Post Approval Change Management Protocol (PAMPC) - Content of the protocol, continued Description of the studies to be performed, and the test methods and acceptance criteria that will be used For biologics, the approach to be used to demonstrate the comparability of the pre- and post- change product (IPC test, spec s and extended characterisation studies). A plan for stability studies should be included, if appropriate; For chemical medicinal products, a proposal of how the implementation of the change will be reported, as a Type IA / IAIN variation or Type IB variation For biological medicinal products the reporting shall always be made as a Type IB variation

12 Post Approval Change Management Protocol (PAMPC) - Content of the protocol A prerequisite for the implementation of a change described in an approved protocol is that all studies described in the protocol have been performed, and the results of the studies comply with the predefined criteria set out in the protocol. The variation procedures used for reporting of data cannot include e.g. justifications for deviations to an established protocol or the pre-defined acceptance criteria.

13 PACMP procedure for biological products

14 PACMPs limitations and opportunities Besides aspects of providing an option for a faster and more predictable implementation of changes post-approval for procedures that can be run without longer clock-stops, the PACMP procedure provides clear benefits in process of the introduction of more complex changes.

15 PACMPs limitations and opportunities Besides aspects of providing an option for a faster and more predictable implementation of changes post-approval for procedures that can be run without longer clock-stops, the PACMP procedure provides clear benefits in process of the introduction of more complex changes. The data package included in the Type II variation submission would give indications of if e.g. Clinical or pre-clinical studies would be required?

16 PACMPs limitations and opportunities Besides aspects of providing an option for a faster and more predictable implementation of changes post-approval for procedures that can be run without longer clock-stops, the PACMP procedure provides clear benefits in process of the introduction of more complex changes. The data package included in the Type II variation submission would give indications of if e.g. Clinical or pre-clinical studies would be required? Changes introduced in conjunction with a process transfer would be seen as an establishment of an alternative process?

17 PACMPs limitations and opportunities Particularly for small companies, the option for submission of a PACMP provides means to introduce a change in production while still maintaining production to ensure market supply.

18 PACMPs experience so far Primarily used for biotechnological/biological products 29 applications for biotech products in the centralized procedure Several in pipe-line < 10 applications for chemical products in the centralized procedure No official figures available on national/mrp applications but according to the SE experience a similar overweight is seen for biotech products.

19 PACMPs experience so far Most applications have referred to process transfers to new manufacturing sites. Some for changes of the manufacturing process such as Reorganisation of the process Change of column matricides/filters Change of other raw materials Up-scale of production

20 PACMPs experience so far Problems seen so far: Primarily linked to the timing of the application of the PACMP Changes not described in sufficient detail Too limited data to support that the change is feasible Too limited data to support the proposed strategy for definition of acceptance criteria Content of the follow-up, Type IB variation