Complementary Medicines Doreene Kohalmi Senior Inspector - - PowerPoint PPT Presentation

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Complementary Medicines Doreene Kohalmi Senior Inspector - - PowerPoint PPT Presentation

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Good Manufacturing Practices for Complementary Medicines Doreene Kohalmi Senior Inspector Manufacturing Quality Branch Monitoring and Compliance Division, TGA Complementary Medicines Australia - 2015 Quality Learning Seminar 3 June 2015

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Good Manufacturing Practices for Complementary Medicines

Doreene Kohalmi Senior Inspector Manufacturing Quality Branch Monitoring and Compliance Division, TGA Complementary Medicines Australia - 2015 Quality Learning Seminar 3 June 2015

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Overview

  • GMP clearance application process
  • TGA compliance risk framework
  • Major deficiencies commonly identified
  • Manufacturing quality challenges
  • TGA industry working group

Good Manufacturing Practices for Complementary Medicines 1

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Manufacturing Quality Branch GMP clearance application process

2 Good Manufacturing Practices for Complementary Medicines

Quality manufacturing

On-site inspections of manufacturers and compliance verifications (paper-based assessments) Australian and overseas manufacturers are assessed prior to supply

  • f goods and are then

regularly reviewed Inspections against the PIC/S Guide To Good Manufacturing Practice For Medicinal Products 15 January 2009 & other relevant requirements

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Inspections scheduling

Arrange inspection dates with:

  • Manufacturer
  • Sponsor

Plan inspection Conduct inspection

Close out inspection and assign A1, A2, A3

  • r U rating

Issue licence or certificate & clearance Is evidence from recognised regulator available? Australian sponsor supplies evidence Yes No

High level TGA manufacturer assessment process

Good Manufacturing Practices for Complementary Medicines

If evidence is acceptable GMP clearance issued

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TGA compliance risk framework

Good Manufacturing Practices for Complementary Medicines 4

Low compliance risk High compliance risk TGA’s approach to compliance

Help and support

  • Make ongoing

compliance easy

Inform and advise

  • Help to become

and stay compliant

Correct behaviour

  • Deter by detection

Enforce

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TGA compliance risk framework

Good Manufacturing Practices for Complementary Medicines 5

Low compliance risk High compliance risk

Committed to doing the right thing / Trying to do the right thing but don’t always succeed / Don’t want to comply but will if made to

Regulated entity – attitude to compliance

Voluntary compliance

  • Effective compliance

systems

  • Management is

compliance orientated

Accidental non- compliance

  • Ineffective and/or

developing compliance systems

  • Management

compliance orientated but lacks capability

Opportunistic non- compliance

  • Resistance to

compliance

  • Limited poor

compliance systems

  • Management not

compliance orientated

Intentional non- compliance

  • Deliberate non-

compliance

  • No compliance systems
  • Criminal intent
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Current MQB reinspection frequency based on risk

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Inspection frequency matrix - medicines

Re-inspection period in months Risk category Compliance rating Acceptable Unacceptable A1 A2 A3 High 24 18 12 Determined by Review Panel Medium 30 20 12 Low 36 24 12

Good Manufacturing Practices for Complementary Medicines

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Current MQB reinspection frequency based on risk

Compliance levels

A1 = Good

Few deficiencies of a relatively minor nature

A2 = Satisfactory

Few major deficiencies (x<6) and /or a large number of minor deficiencies and no critical.

A3 = Basic

A large number of major (5<x<11) and/or a large number of minor deficiencies and no critical.

Not rated = unacceptable

One or more critical and/or a large number of major deficiencies.

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Inspection frequency matrix - medicines Re-inspection period in months

Risk category Compliance rating

Acceptable Unacceptable A1 A2 A3

High

24 18 12 Determined by Review Panel

Medium

30 20 12

Low

36 24 12

Good Manufacturing Practices for Complementary Medicines

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Current MQB reinspection frequency based on risk

Product/process risk classifications

Medium risk

  • Non-sterile medicines,

including herbal, unless specified as high risk

Low risk

  • Minerals, vitamins, fish
  • ils and other

supplements

  • Sunscreens
  • Single step –

labelling/packaging; analysis/testing; release for supply and storage

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Inspection frequency matrix - medicines Re-inspection period in months

Risk category Compliance rating

Acceptable Unacceptable A1 A2 A3

High

24 18 12 Determined by Review Panel

Medium

30 20 12

Low

36 24 12

Good Manufacturing Practices for Complementary Medicines

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MQB reinspection frequency under consideration

Product/process risk classifications

Medium risk

  • Registered non-sterile

medicines, including registered herbal

Low risk

  • All listed medicines,

including listed herbal

  • Sunscreens
  • Single step –

labelling/packaging; analysis/testing; release for supply and storage

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Inspection frequency matrix - medicines Re-inspection period in months

Risk category

Compliance rating Acceptable Unacceptable A1 A2 A3

High

36 24 12 Determined by Review Panel

Medium

42 30 18

Low

48 36 24

Good Manufacturing Practices for Complementary Medicines

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Major deficiencies commonly identified by TGA

  • Quality management system (QMS)
  • Personnel
  • Premises and equipment
  • Documentation
  • Production
  • Quality Control
  • Storage

Good Manufacturing Practices for Complementary Medicines 10

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Major deficiencies commonly identified by TGA

  • Quality management system (QMS)

– Unsatisfactory deviation management , such as inadequate investigation and record keeping – Inadequate resourcing of quality management functions including product release – All product quality reviews not conducted and/or not all elements covered

Good Manufacturing Practices for Complementary Medicines 11

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Major deficiencies commonly identified by TGA

  • Personnel

– Inadequate training and skills assessment – Practices do not reflect documented procedures

Good Manufacturing Practices for Complementary Medicines 12

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Major deficiencies commonly identified by TGA

  • Documentation

– Inadequate manufacturing instructions – Inadequate records keeping – including batch records

Good Manufacturing Practices for Complementary Medicines 13

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Major deficiencies commonly identified by TGA

  • Production

– Processes not validated or inadequately validated – Revalidation not conducted routinely – Inadequate change control management – Inadequate design of facilities, equipment and procedural measures for the prevention of contamination and cross-contamination – Reprocessing/rework inadequately controlled

Good Manufacturing Practices for Complementary Medicines 14

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Major deficiencies commonly identified by TGA

  • Quality Control

– Test methods not validated or verified and/or validation incomplete – Testing inadequate – Records of testing incomplete and/or ineffective review arrangements

Good Manufacturing Practices for Complementary Medicines 15

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Major deficiencies commonly identified by TGA

  • Storage

– Inadequate controls and monitoring of storage conditions – Storage conditions not always as per label requirements

Good Manufacturing Practices for Complementary Medicines 16

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Manufacturing quality challenges

  • Control of the supply chain
  • Complex formulations
  • Complex manufacturing chains

Good Manufacturing Practices for Complementary Medicines 17

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Manufacturing quality challenges

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GMP

Deviations

Supply chain

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TGA – Industry Working Group on GMP

  • Membership:

– Accord – Active Pharmaceutical Ingredient Manufacturer’s Association of Australia – Australia New Zealand Industrial Gas Association – Australian Self Medication Industry – Complementary Medicines Australia – Generic Medicines Industry Australia – Medicines Australia

  • To prioritise and discuss issues of a regulatory and technical nature arising from current regulation and

propose solutions

  • Establish and oversight Technical Working Groups to develop:

– new, or review existing, guidelines – comments on draft PIC/S guidelines for tabling by TGA at PIC/S meetings – guidance documents

19 Good Manufacturing Practices for Complementary Medicines

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TGA – Industry Working Group on GMP

  • Technical guidance documents
  • Guidance on release for supply

– Part 1 published TGA website version 2.0 January 2015

  • Clarifies general requirements and responsibilities for undertaking release for supply (RFS)

and release for further processing (RFFP) – Part 2 close to publication

  • Includes specific examples of the manufacturing process chain and how RFS and RFFP work

in the specific examples cited

20 Good Manufacturing Practices for Complementary Medicines

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TGA – Industry Working Group on GMP

  • Guidance on release for supply – Part 2

– The specific examples included to-date include the following:

  • Release for supply from a secondary packaging site
  • Re-release of a product after minor further steps of manufacture
  • Stability conducted by a separate licensed manufacturer
  • Full product manufacture at one site followed by secondary packaging at another site and

returned to the original manufacturer for release for supply

  • Bulk packaging from 2 manufacturing sites

– Part 2 will be a live document that can have more relevant useful examples added as needed

21 Good Manufacturing Practices for Complementary Medicines

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References

  • Latest Trends In Manufacturing Quality – Enhancing the TGA Inspection Process

– Harry Rothenfluh PhD – Assistant Secretary Manufacturing Quality Branch – Presentation at ARCS Scientific Congress 5 May 2015 – http://www.tga.gov.au/presentation-latest-trends-manufacturing-quality

  • Regulatory Compliance Framework – 27 June 2013

– http://www.tga.gov.au/regulatory-compliance-framework

  • Inspection Frequency Matrix – Medicines and Blood , Tissue and Cellular Therapies

– http://www.tga.gov.au/manufacturer-inspections-risk-based-approach-frequency

  • Manufacturer Compliance History

– http://www.tga.gov.au/manufacturer-compliance-history

  • Manufacturer Inspections – Product/Process Risk Classifications

– http://www.tga.gov.au/manufacturer-inspections-productprocess-risk-classifications

Good Manufacturing Practices for Complementary Medicines 22

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References

  • Guidance on Release for Supply – Part 1

– 23 January 2015 – http://www.tga.gov.au/publication/guidance-release-supply

  • Technical Guidance on the Interpretation of Manufacturing Standards

– http://www.tga.gov.au/publication/technical-guidance-interpretation-manufacturing-standards

  • Australian Regulatory Guidelines Good Manufacturing Practice (GMP) Clearance for Overseas

Manufacturers

– 17th Edition - May 2011 – http://www.tga.gov.au/publication/gmp-clearance-overseas-manufacturers

Good Manufacturing Practices for Complementary Medicines 23

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