New & existing cleanroom

facilities - what's the impact

of draft Annex 1?
Presented by Ashley Isbel, 7 August
2018

Slide 1 © PharmOut 2018

A long, long time ago …

• Concept paper on the revision of annex 1 of the guidelines on good

manufacturing practice – manufacture of sterile medicinal products, 8 January
2015

Slide 2 © PharmOut 2018

Resources?

Environmental monitoring expectations are increased

Contamination control strategy to be instituted, and maintained

Risk management expectations are increased

Requirements for training, manual visual inspection increased

Requirements for certain validations (materials transfers, disinfection processes, etc.)

increased

Slide 3 © PharmOut 2018

The bar has been raised …

The authors may argue that in the majority of

cases, they are merely reflecting expectations
that already exist. But expectations and
requirements are different things …

Slide 4 © PharmOut 2018

But what about “costs”?

Capital
costs?

Operating
costs?

Slide 5 © PharmOut 2018

We are still only guessing the impact …

The concept paper implied that there would be a

implementation period before full compliance is expected …

Regulators have given no firm indication of how new

requirements will be interpreted for legacy facilities

The draft has received 6500 responses … what we see now

will change!

So lets take some guesses!

Slide 6 © PharmOut 2018

Interlocked Doors

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Retrofit of non- Mandate Low $5-10K per Similar, Low
interlocked doors interlocked airlock airlock slightly lower
doors than legacy

Slide 7 © PharmOut 2018

Air pressure monitoring

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Retrofit of Mandate $15K and Similar, but
automated ΔP automated EMS Moderate upwards possibly more, Moderate
warning system (200K+) depending on
depending on sophistication
size of facility of system

Slide 8 © PharmOut 2018

 Grade B room interfaces

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Grade C interface Grade C interface $100Ks to $Ms Low $10Ks to
only - Significant only - Lower Very High $100Ks Uncertain
redesign/ flexibility in design dependent on
reconfiguration facility size

Slide 9 © PharmOut 2018

 Separate personnel and material flows

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Redesign/ Would normally be $10Ks - NA Uncertain for
reconfigure of compliant Low $100Ks legacy
materials depending on facilities
transfer facility size

Slide 10 © PharmOut 2018

Separate entry and exit

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Retrofit of Mandate $15K and Similar, but
automated ΔP automated EMS Moderate upwards possibly more, Moderate
warning system (200K+) depending on
depending on sophistication
size of facility of system

Slide 11 © PharmOut 2018

Actively ventilated pass throughs

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Possible upgrade All pass through $5K-10K per $5K per hatch
of most critical hatches to be hatch upgrade upgrade
hatches (e.g. actively ventilated
into aseptic Moderate Moderate
areas).
Procedural
enhancements
for others

Slide 12 © PharmOut 2018

HEPA filtration in Grade D

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Retrofit Grade D Upgrade of Grade $20K-$100Ks Similar,
areas with HEPA D areas if HEPA depending on slightly lower
– and associated not initially High centralised vs due to Uncertain
AHU upgrades proposed terminal and efficiencies of
facility size prospective
design

Slide 13 © PharmOut 2018

 Isolator backgrounds

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Upgrade of Possible change in $100Ks+ $10Ks+
certain isolator background Moderate depending on depending on Uncertain
backgrounds to selection complexity of scope of
Grade C facilty changes

Slide 14 © PharmOut 2018

Online monitoring for WFI

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
May require Compliance would 30-50K NA
retrofit of online be standard Moderate Uncertain
TOC. In rare configuration
cases retrofit for
conductivity

Slide 15 © PharmOut 2018

Increase in speciation requirements

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Higher level of identification events. Moderate $150K+ Moderate
May justify in-house speciation
equipment

Slide 16 © PharmOut 2018

 Focus on new technology

Compliance Requirements Current Non- Cost of Compliance Inspection

Compliance Level Priority
Legacy New Legacy New
Retrofitting of Implement new $?? $??
equipment and technology where Moderate Uncertain
process? practical (risk
assessment)

Slide 17 © PharmOut 2018

Final Thoughts

The current draft does not achieve the initial

expectation of “no adverse impact … with respect to
either resources or costs” Annex 1
Final Version
The final impact is unclear, given that the draft is not $ impact:
finalised, and there is no guidance on treatment of Read all
about it
legacy facilities
The extent to which financial implications will be
allowed to impact technology based decisions is
unclear
We should have some hope that there will be additional
clarity in the final document

Slide 18 © PharmOut 2018

Questions?

Ashley Isbel
Validation Services Manager/Lead Consultant

Ashley.isbel@pharmout.net

Slide 19 © PharmOut 2018