Parexel Webinar Presentation Deck

Regulatory reliance &
desk-top inspections

The new normal?

24 June 2020

Mark Birse
Vice President, Technical

Phil Crooker J.D.
Vice President, Technical

Viswanadh Kuppa
Senior Director, Business Development

Presenters EXPERIENCE

Mark Birse – 17 years at MHRA: Deputy Director Inspection, Enforcement & Standards Division & Head of
MHRA Inspectorate and Process Licensing
Phil Crooker
– Executive Bureau member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S)
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AREA EXPERTISE

– GMP inspections of manufacturers of investigational drugs, finished drug products, active
ingredients, excipients and packaging materials

– Regulatory risk-based inspection programs and approaches, including desk-based assessments
– Regulatory crisis management (e.g. H1N1/09 Pandemic, Heparin)

EXPERIENCE

– Regulatory counsel and acting team lead at FDA for compliance and enforcement.
– FDA policy development for case assessment, records in lieu of inspection,

delay/deny/limit/refuse inspections, mutual recognition and cooperative agreements.

AREA EXPERTISE

– Public health emergency procedures, medical countermeasures, and expedited programs –
CTAP, EUA, CGMP waivers, Fast Track Designation, BTD and PRIME

– Product lifecycle management, technology transfer and supply chain operations.
– Juris Doctor (J.D.), Purdue Global University and Admitted to the California Bar and federal court.
– Manufacturing compliance and enforcement

Why Remote Desktop cGMP Audits?

Global COVID-19 related travel restrictions and limited regulatory resources are
driving more health authority regulators to use desktop audits
FDA

FDASIA 706, records request in advance of, or in lieu of inspection under FD&C Act
Sec. 704(a)4
Risk Based Algorithm - Demonstration of cGMP compliance and positive
production/facility history may qualify companies for off-site inspection consideration
OMQ: “We’re doing what we’ve always done, are busy, and are adapting”

EMA

European Economic Area (EEA), GMP certificates and time-limited manufacturing and
import authorizations are automatically extended until the end of 2021
For new sites and facilities within and outside the EEA that have not been inspected or
where an inspection is required, a remote inspection may be carried out.

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How are regulators assessing facilities?

More virtual inspections - A tool at a time of crisis
Balancing risk

More likely to be desk-top if there was a previous onsite inspection

Limitations: facilities, instrument/equipment operation and staff behaviors hard to assess remotely

“Hybrid” inspections – combination of desktop and remote “virtual” audit.
Using Mutual Recognition Agreement (MRA), cooperative agreements and confidentiality
commitments with trusted allies.
Making risk-based facility classification decisions based on existing data.
Balancing safety of medicines vs availability and avoidance of shortages
Do you a have plan when a HA contacts you for a virtual inspection?

COVID-19 isn’t putting Regulators out of the compliance
business – Be ready for inspection alternatives

Read posts on desk-based inspections
and COVID-19 impact on our blog

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Wider impact

Agencies are ‘businesses’ too

Most shutting offices and home working – some could be out for rest of year
Increased staff pressures and reduced support for enquiries.

Application program goal dates appear to be largely intact so far

Case assessment timelines could shift.

Domestic inspections for some OK or will be first wave of restart

How does this balance with risk?

If companies change supply models, on-shoring, is there regulatory capacity to
respond?

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Knowledge Exchange
Regulators Sharing Inspection Outcomes

How do they ‘trust’ each other? What are they doing with information?

Formal recognition Often nothing – just a tick box

Trading blocks (EU / ASEAN) Trust in the system
MRAs
Frameworks EU countries have well established
Underpinned by audits – JAP/JRP systems for using MRAs
EUDRAGMDP database can be used
Less formal reliance Gap analysis against own systems
Support decision making for historical
PIC/S GMP Reliance initiative cases of non-compliance

Country A Reliance Country B More likely to maintaining status quo

Regulatory Manufacturing For FDA a much newer process.
Decision Data site

Inspection?
Full / Part / Desk-top / None

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What has Parexel observed so far...
Regulators

Postponed inspections (PAI for applications vs surveillance)
Document and Data requests by FDA with quick turnaround time for response
Reliance on MRA inspection outcomes (some)
Communications from FDA related to impact on submission review due to inspection delay
Domestic inspections are occurring onsite based on risk
Use of technology – cameras and videos, data sharing

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What has Parexel observed so far...
Industry

Firms need to protect staff, protect operations and protect patient supply
This is leading to increased operational pressures and staff stresses and fears
There has been a reduction in the level of quality oversight
Increase in the number of deviations and data integrity issues being raised
Companies are unprepared for remote inspections
Regulators will return and remember…… GMP and data integrity are not optional

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When regulators return

Inspectors will want to know

What happened at your facility
concerning quality during COVID-19?

Food and Drug Administration (FDA) World Health Organization (WHO)

Medicines and Healthcare products Regulatory Agency (MHRA)

European Medicines Agency Therapeutic Goods Administration (TGA)

Australian Government Department of Health

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When regulators return Data Integrity

Inspectors will want to know: Can you confirm that you have control?

Change Control Fewer staff on-site and more staff working from
home
How managed How you defined core roles
Lack of provision for maintaining a quality
Open and dynamic vs one offs and closed system and oversight during a pandemic
Wider considerations of changes made and any Access to documents and data often restricted
potential impact on quality Staff anxious and stressed
Pressures to maintain supply
Deviations

More? Less?
Review closer than before

Regulatory flexibilities

Have they been used?

How did you maintain control and quality?

Are you able to explain everything you have
done?

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Future operational state? – but fundamentals don’t change!

Within Regulators Global Harmonization
Hybrid – on-site / off-site – based on
risk, knowledge and complexity. Greater reliance on mutual recognition
and cooperative agreements.
Enhanced Real-time Communications
(WebEx/Zoom etc.) to accomplish Implementation of PIC/S
inspection goals inspection guidelines – ICH model.
User fee program for compliance –
Don’t expect “V” shaped trajectory for transparency, access and timelines.
return to past practices.
Cloud based data/dossier globally
Augmented regional inspection staffing available
FDA - much more frequent use of “706”
authorities and desk-top audits. Partnerships
Third Party Qualified – low risk drugs
Quality Metrics or Benchmarking and facilities (like device inspection
process?)
Modified risk-based site selection
model. Excipient CGMP model.

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Parexel’s remote
desktop cGXP audits

Preparing for regulatory off-site
compliance assessment

Making an informed evaluation of your needs

We can prepare you for a remote 5-point 1. Assessment of the operations
regulatory inspection and support assessment
your dialogue with regulators, Our experts will review your
both pre- and post-inspection process operations and assess your
company’s needs and end goals
5. Regulatory dialogue
2. Desktop review
4.Deliverables and onsite audit
We can assess products
Detailed reports and assessments that are in your pipeline or
which describe present cGMP gaps
and provides recommendations for are already approved
remediation, where appropriate. On-
site audits can be performed on an as 3. Videoconference
needed basis. and interviews

13 Using technology to meet your
needs and deliver quality

Parexel’s remote desktop cGMP audits and offerings

Expert compliance assessment Assessment of pipeline and Evaluation of corporate
of all six quality systems; approved products and policies and site
manufacturing strategy procedures against
quality, facilities and including, aseptic, biotech regulatory requirements
and non-sterile and industry best practices
equipment, production, manufacturing
laboratory controls, Regulatory requirements
material, packaging & labeling

Six-system evaluation Manufacturing strategy

Backed by 1000+ worldwide consultants including 80+
former regulators and inspectors

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For any Enquires reach us at

Minaj Kudche - Associate Director, Business Development
[email protected]
Souvik Majumder – Director, Business Development
[email protected]

Viswanadh Kuppa - Senior Director, Business Development
[email protected]

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Thank you