Influenza vaccines – Quality module

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Recently, EMA (European Medical Agency) published a Guideline on Influenza Vaccines – Quality Module.

Though the main focus of this EMA guideline was not QbD or PAT, one section – 4.1.1.6. Characterisation – was relevant to QTPP, CQA, CPP and hints on the details of the design space (albeit at high level).

From the original document:

“4.1.1.1.6. Characterisation

While it is appreciated that certain characteristics may be strain specific, extended characterization studies can contribute to an enhanced process and product understanding and may provide information about product consistency from one season to another. This enhanced product knowledge may allow relevant specifications to be established and may support the scientific evaluation of comparability after product or process changes have been introduced.

The kind of characterization studies needed will depend on the nature of the vaccine, e.g. whole virion, split virion or subunit.

The components, i.e. active substance(s) and process related impurities, contained in the drug substance should be investigated and characterized as appropriate. The biological, immunological and physicochemical properties of the HA antigen should be verified
using a wide range of state-of-the-art analytical methods3.

As required by Ph. Eur., the presence, and type of NA antigen should be confirmed by suitable enzymatic or immunological methods on the
monovalent pooled harvests. Considerations should be given to characterize and quantify antigens (other than HA) that may contribute to vaccine immunogenicity, as far as technically feasible.

New analytical technology and modifications to existing technology are continually being developed and should be utilized when appropriate. Marketing authorisation holders should take account of scientific and technical progress and update the relevant sections of the marketing authorisation dossiers regularly via appropriate regulatory procedures (but not as part of the Annual Update).

Where present in the drug substance and/or drug product, aggregates should be investigated, e.g. in terms of diameter, composition, content, and dissolution profile. Considerations should be given to the safety and immunogenicity of a formulation containing such particles.

Process related impurities (e.g. ovalbumin for egg-derived influenza vaccine/host cell protein, residual host cell DNA for cell culture-derived vaccine, downstream-derived impurities such as reagents used for inactivation/splitting) should be identified, quantified and data used to set release specifications.”

Below is the entire document:

Quality Module on Influenza Vaccines – EMA 2017