manufacturing, and raises the
quality of understanding of
released batches. It is, therefore,
of broad applicability across
organizations of all sizes.
Q: Molecule characteristics
can vary at multiple
production sites even within
the same company for the
same drug. How is the MAM
data compiled and shared
when multiple sites are
involved in biopharmaceutical
development and complex
Josephs: MAM data acquisition
and processing uses established
CFR 21 part 11 enterprise based
software that can be deployed
While data is acquired into
a ‘vault’ to ensure raw data
integrity, raw and processed data
may be shared throughout or
Q: How has MAM aided
companies in the preparation
of data for submission to
regulatory authorities? When
different regulatory bodies
are involved (FDA, EMA, etc.)
does that complicate the data
compilation methods so each
data set satisfies the different
Josephs: For regulatory filings
there have been attempts by
regulatory agencies to harmonize
certain aspects. The requirements
of each agency do differ and any
one filing will be adjudicated by
potentially different reviewers.
The general guidance often
provided by agencies is on a
‘case-by-case basis’ and ‘based
on scientific merits.’
In general terms, MAM is
no different than any other
analytical assay used in a filing.
If it meets the requirements for
the attributes being measured,
and measurement of those
attributes answer reviewers
concerns for safety and efficacy,
it is being seen as a scientifically
Essentially, MAM is a ‘platform
method’ and therefore once
established should not be any
more complicated to use in a filing
than any other accepted assay.
Q: On a quantitative basis,
how has MAM improved the
instances of FDA, EMA, and
other regulatory approvals
since the development of the
Josephs: This question really is
not easy to answer. Over time
the agencies have been setting
higher standards for submissions
than were previously acceptable.
Therefore, it is really not
possible to answer this question.
The agencies are asking for
more information and the MAM
method can be more informative.
It, therefore, is well aligned with
the agencies’ desire to use state-of-the-art analytical methods.
Q: How closely do the
regulatory authorities monitor
the MAM technique in use?
Do they inspect it regularly or
require certain procedures to
validate the technique?
Josephs: The regulatory agencies
do not set different criteria for
how closely they monitor any
particular analytical technique.
They ask scientific and technical
questions and they also conduct
site inspections for compliance
regardless of what analytical
technique might be employed.
Q: Mass spectrometry’s use
has expanded in biologics
development. Are there other
areas on the radar screen for
this technique in pharma in
Josephs: Mass spectrometry
has in general been showing
ever increasing applications in
Pharma and BioPharma.
MAM is applicable across
the Discovery to Development
continuum through to
biopharmaceuticals, is MAM
being targeted toward other
markets going forward?
Josephs: MAM is essentially a
modality independent analytical
technique applicable to all
proteins and, as such, could be
applied wherever detailed analysis
of proteins is required.