Regulatory update and landscape for ATMPs.

(Andrew Hopkins 17th March)

2

Scope

• MHRA and innovation

• Regulatory updates

• How do the GMPS apply to ATMPS

3

Organisational structure

Medicines and Healthcare Products Regulatory Agency

(The agency)

CPRD NIBSC MHRA

Devices

IE&S

Licensing

VRMM

Communications

Directorate

Finance & Procurement

Human Resources

Information Management

Policy

Corporate

4

Corporate Plan 2013-18

Five key themes set out the agency’s strategic direction:

1. The role of regulation and the regulator

2. Bringing innovation safely to market

3. Strengthening surveillance

4. Safe products and secure supply in globalised industries

5. Achieving excellence – a well-run, efficient and effective

organisation

5

Global influence

• Currently Chair of PIC/S

• Lead and input on a number of areas GMP

• Including a number of PICs guides

• Annex 1 joint working group

6

Research

Preclinical

Phase Clinical

Phases

MA

Commercial

supply

GMP, GDP, GPvPGLP GMP, GCP

Engagement E n g a g e m e n t

MHRA engagement across the product lifecycle

Innovation

Innovation

7

‘Bringing innovation and new products speedily and safely to

patients’

Ensure the Agency makes a full contribution to the cross-Whitehall growth

and innovation agenda – both through maximising existing initiatives and

identifying further initiatives where possible

Ensure effective and efficient implementation of EU legislation in line with

Agency and wider DH and Government objectives

Wide range of contact points within the MHRA

Innovation support – MHRA

8

Launched March 2013

• Encourage early dialogue with researchers and companies

• Help clarify regulatory requirements

Applicable to all of the MHRA product areas

Provide regulatory / informal advice or scientific advice

• Request at any stage of product development

• Irrespective of existing guidelines

More than 230 enquiries received to-date

MHRA: Innovation Office

9

For ATMPs / cell therapies / regenerative medicines

Launched in October 2014

Hosted by MHRA through the Innovation office website

A cross-regulatory Agency advice source

Innovation support – ‘One Stop Shop’

10

To encourage use of the IO/OSS – help provided to organisations to navigate regulatory processes

MMIP – development of case studies

11

Scope

• MHRA and innovation

• Regulatory updates

• How do the GMPS apply to ATMPS

12

Annex 1 update

History

• First issued in 1972

• Number of revisions since then 1996, 2003, 2005, 2007

and 2009, but not full revisions

• 2012 first proposal to revise

• Proposal Re-issued in 2014

• Concept paper agreed February 2015

13

Annex 1 update

History

• Joint working group between PIC/S and EMA

• Have agreed a new structure

• First full draft has been shared between the working group

• Original date for submitting to IWG and PIC/S committee

was October 2015

• New deadline agreed of Mid 2016

14

Key changes

• Restructured

• Introduction of the principles of QRM

• Focus on keeping the operator away from the product and

keeping up with new technologies

• Environmental and process monitoring

15

Key changes

Restructured

• New sections

• Scope

• PQS

• Utilities section

• Environmental and process monitoring

• More logical flow

• Hopefully easier to follow

16

Key changes

New sections

• Scope

• Widening to other areas of manufacture, ointments and creams,

biologicals?

• PQS

• Emphasising the elements of Chapter 1 for sterile manufacture

• Especially change control

• Investigations

• CAPA

17

Key changes

Introduction/re-enforcing of the principles of QRM, especially for

new processes and equipment

• Design

• Assess

• Procedure

• Assess

• Monitor

• Assess

18

Key changes

Introduction of the principles of QRM

• Often the assessment is weak!

• Start at the end and work back

• Need to get it right

19

Key changes

Keep operator

away from

product

20

Key changes

Keeping the operator away from product

• Use of current technologies (RABS/Isolators)

• Looking to support new technologies

• Single use/Disposable closed system

• Aseptic connectors

• Design part of QRM!!

21

Key changes

Environmental and process monitoring

• Bringing all monitoring together:

• Viable environmental monitoring

• Non viable monitoring

• Process simulations

22

Key changes

Environmental and process monitoring

• The tool box in its entirety!

23

Key changes

Environmental and process monitoring

• Monitoring part of QRM

• Re-enforcing the risk assessment for design of monitoring

• Know the process

• Know the facility

• Then monitoring can be appropriately designed.

24

Other GMP updates

Chapter 5

“5.10 At every stage of processing, products and materials

should be protected from microbial and other contamination.”

Lot of change around segregation of products, linked to cleaning

validation and the tox tool

25

Other GMP updatesChapter 5

“5.20 A Quality Risk Management process, which includes a potency

and toxicological evaluation, should be used to assess and control

the cross-contamination risks presented by the products

manufactured. Factors including; facility/equipment design and use,

personnel and material flow, microbiological controls, physico-

chemical characteristics of the active substance, process

characteristics, cleaning processes and analytical capabilities

relative to the relevant limits established from the evaluation of the

products should also be taken into account. The outcome of the

Quality Risk Management process should be the basis for

determining the necessity for and extent to which premises and

equipment should be dedicated to a particular product or product

family. “

26

Other GMP updatesChapter 5

“5.21 The outcome of the Quality Risk Management process should

be the basis for determining the extent of technical and

organisational measures required to control risks for cross-

contamination. These could include, but are not limited to, the

following:”

• Technical Measures

• Organisational Measures

27

Other GMP updatesChapter 5

“5.22 Measures to prevent cross-contamination and their

effectiveness should be reviewed periodically according to set

procedures.”

28

Other GMP updatesAnnex 15

• Links to chapter 3 and 5 changes

• No more retrospective change

• Changes in validation models

29

Other GMP updatesAnnex 15

“9.2. Where microbial testing of product is carried out, the method

should be validated to confirm that the product does not influence

the recovery of microorganisms.”

“9.3. Where microbial testing of surfaces in clean rooms is carried

out, validation should be performed on the test method to confirm

that sanitising agents do not influence the recovery of

microorganisms.”

30

31

“Non” GMP updates

GMP for ATMPs

• Legal requirement to have specific guidance

• Being led by the Commission

• Aim to produce guidance that is commensurate with risk

• Using a QRM approach

32

“Non” GMP updates

GMP for ATMPs

Challenges

• Short shelf life

• No antimicrobial activity

• May not have a second chance

• Fine balance!

• Innovation vs Patient safety

33

Scope

• MHRA and innovation

• Regulatory updates

• How do the GMPS apply to ATMPS

34

How do the GMPS apply to ATMPS

• Still need to protect the product

• Frequently need to protect the operator and the facility

• Still need to protect patient

• QRM key

• New technologies

• New Processes.

35

Thank you for listening

Any questions?

36

Contact

Andrew Hopkins

GMDP Inspector

andrew.hopkins@mhra.gsi.gov.uk

www.mhra.gov.uk

https://www.gov.uk/government/groups/mhra-innovation-office

37

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