CIP Cycle Development:Manual to Automated CleaningTorben M. Andersen, McFlusion Inc

1

McFlusion Inc

CIP Cycle Development:Manual to Automated Cleaning

Integrating CIP Design, Recipe &

Cleaning Validation

For FDA Compliance and Optimized

2

For FDA Compliance and Optimized

Cleaning.

Agenda

Transition – From manual to automated cleaning

Feasibility Studies – On-site CIP recipe development

Examples – Equipment, report

3

Equipment – Practical examples

FDA Trends – Our experience

Conclusion – Do it right and avoid costly mistakes

Agenda

Transition – From manual to automated cleaning

Feasibility Studies – On-site CIP recipe development

Examples – Equipment, report

4

Equipment – Practical examples

FDA Trends – Our experience

Conclusion – Do it right and avoid costly mistakes

Making the Transition to Automated Cleaning:

These new challenges require groundwork studies and tests of cleaning procedures (manual or automated CIP).

1) Engineering and cleaning validation are synchronized.

2) A successful and validatable cleaning method and

Transition to Automated Cleaning

5

2) A successful and validatable cleaning method and approach are incorporated in conceptual and/or preliminary engineering design phases.

Typical Questions to be Addressed:

•How fast can we clean?

•What is the lowest possible USP water consumption?

•Can we clean without detergents?

•Can we make cost/benefit justifications for automated CIP?

•Can we guarantee the cleaning method?

Transition to Automated Cleaning

6

•Can we guarantee the cleaning method?

•How can we fulfill existing and/or upcoming validation acceptance criteria?

•How can we address cross-contamination issues?

•Why can’t we meet acceptance criteria for swabs (µg/cm2) with our existing CIP system?

Agenda

Transition – From manual to automated cleaning

Feasibility Studies – On-site CIP recipe development

Examples – Equipment, report

7

Equipment – Practical examples

FDA Trends – Our experience

Conclusion – Do it right and avoid costly mistakes

On-site Testing & CIP Recipe Development

•Commissioning & decommissioning in hours.

•On-site cleaning tests typically performed in 1 to 5 days.

Feasibility Studies

8

CIP Units for Testing

Feasibility Studies

9

•CIP Flow: 3 – 70 gallon/minute (10 - 265 liter/minute).•Pressure/Temperature: 10-1000 psi (1-70 bar)/30 - 95ºC•2 Detergents: 0 - 200 mS/cm or 0 - 10.00 kg•Time: Intermittent and continuous•Type: Single pass / re-circulation•Drying: Hot compressed or forced air

Spraying Units for Testing

Feasibility Studies

• Jet Head Spray Devices:

Toftejorg and GamaJet.• Rotating Spray Devices:

Rokon, SaniMidget and Lechler.• Static Spray Balls: 180º, 270º,

double set.• Accessories: wands, spears,

10

• Accessories: wands, spears, adapters, fittings.

• Prepared for a variety of pressure and flows.

Analytical Instruments

Examples

11

•Test for: Conductivity, pH, and TOC.•Test Types: Client’s preferred test types.•Development of SOPs for swabs, rinse water sampling.

On-site Testing & CIP Recipe Development

Process

•Analyze problems.

•Define goals.

•Define test method and acceptance

Feasibility Studies

12

•Define test method and acceptance criteria.

•Describe possible cleaning approaches.

On-site Testing & CIP Recipe Development

Feasibility Studies

Cleaning time

Coverages of surfaces

to be cleaned

13

Pressure and impactChemical type and

concentration

Temperature CIP Flow

On-site Testing & CIP Recipe Development

Feasibility Studies

1) Cleaning Feasibility Study.

2) Cleaning Feasibility Study Protocol.

14

3) Test Activities.

4) Cleaning Feasibility Report.

Valid Documentation following GTP & GDP

Off-site Tests Using Placebo Equipment

Feasibility Studies

•Simulation of cleaning on placebo production equipment with or without active product.

•Detergent simulations in laboratory settings on active ingredients to test product removal capabilities (e.g. PACE studies from Steris).

•Off-site tests minimize cost, production down time.

15

•Off-site tests minimize cost, production down time.

•Off-site tests cannot substitute on-site cleaning tests in actual production environment and/or equipment, which is expected to be applied for the final processes.

Agenda

Transition – From manual to automated cleaning

Feasibility Studies – On-site CIP recipe development

Examples – Equipment, report

16

Equipment – Practical examples

FDA Trends – Our experience

Conclusion – Do it right and avoid costly mistakes

CIP of Poly Vinyl Alcohols Mixer

Examples

Before

After

17

Only city/USP water used, no detergents.

Before

CIP of Coating Pan

Examples

After

18

Caustic wash, USP rinse, 10 min. cycle time.

Before

CIP of Coating Pan

Examples

AfterAfter

19

Caustic wash, USP rinse, 10 min. cycle time.

BeforeBefore

CIP of Fluid Beds

Examples

20

Automated CIP cut cleaning time 75%.

Examples

CIP of Fluid Beds

City water

consumption

cut 60%

21

USP water

consumption

cut 80%

Examples

Other Types of Equipment

We have performed tests on:

•750 liter bioreactors

•70 liter bioreactors

•Aseptic filling machines

22

•Aseptic filling machines

•Synthesis reactors and condensers

•Centrifuges

Agenda

Transition – From manual to automated cleaning

Feasibility Studies – On-site CIP recipe development

Examples – Equipment, report

23

Equipment – Practical examples

FDA Trends – Our experience

Conclusion – Do it right and avoid costly mistakes

Standard Modular Range of CIP Equipment

Equipment

•Unit program designed for full transition to

automatic cleaning with focus on practical

implementation and acceptable cost/benefit.

24

Standard Modular Range of CIP Equipment

Equipment

3 main levels for

•Performance

•Instrumentation

•Automation

•Documentation

25

•Documentation

•Qualification.

•Cost range: from around $25,000 into six figures.

Agenda

Transition – From manual to automated cleaning

Feasibility Studies – On-site CIP recipe development

Examples – Equipment, report

26

Equipment – Practical examples

FDA Trends – Our experience

Conclusion – Do it right and avoid costly mistakes

Increased FDA Focus on Cleaning-Related Issues:

1) Inadequate, inconsistent manual cleaning.

2) Inadequate scientifically-based cleaning cycle development rationale.

• Analytical methods

• Recovery studies

• “Worst-to-Clean” definitions in current cleaning

FDA Trends

27

• “Worst-to-Clean” definitions in current cleaning validation processes

3) Cleaning related issues in existing, validated (CIP ) processes.

4) Lack of consistency in CIP recipe cleaning methods on identical products within the same company.

Actions Addressing Cleaning-Related Issues:

1) Improve SOP’s, training and acceptance criteria for cleaning release or consider CIP cleaning for consistent adequate cleaning.

2) Develop validated analytical methods.Perform recovery studies, group equipment, define “hot spots” and “hard-to-clean” areas, and define and justify “worst-to-clean” equipment.

FDA Trends

28

clean” equipment.

3) Failure investigation reports with recommended solu tions.Groundwork / initial studies to provide guarantees that next validation will succeed and “survive.”

4) Investigate to generate documentation and justifica tionof current methods.

Agenda

Transition – From manual to automated cleaning

Feasibility Studies – On-site CIP recipe development

Examples – Equipment, report

29

Equipment – Practical examples

FDA Trends – Our experience

Conclusion – Do it right and avoid costly mistakes

Do It Right, Avoid Costly Mistakes

•Description of CIP recipe(s).

•Definition of possible use, type(s), and amount of detergents.

•Water usage for cleaning.

•Description of flow / pressure conditions.

Conclusion

30

•Description of flow / pressure conditions.

•Description of cleaning devices to be applied for cleaning.

•Establishment of acceptance criteria.

•Cost / benefit analyses covering possible solutions.

•Establishment of linked engineering design and validation planning.