cosmetic gmp implementation part 8

8/13/2019 Cosmetic GMP Implementation Part 8

http://slidepdf.com/reader/full/cosmetic-gmp-implementation-part-8 1/13



BEWARE of Biofilm Buildup

SOURCE: http://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074905.htm 164



Process Water System

Design Phase • Assemble cross-functional team

• Determine quality of feed water

• Determine required specifications

• Write protocols

Pre-validation • Calibration of instruments

• Validation of test methods

3



Purified Water System Design Considerations

• 316LSS material of

construction• Sanitary electro-polishing and

passivation

• Sanitary clamp fittings or orbitalwelds

• Lines sloped to drain 1/8 in/ft

• Recirculation loop 3-5ft/sec

• Sanitary pumps, Submicronfilters (0.2μm) on tanks andvents

• Use-point fittings or GMPvalves

• Sanitary diaphragm-type and

stem valves only. No ball, gate,plug, butterfly, globe or discvalves.

• Drains must have air-break toprevent back-siphoning

• Minimize dead-legs to 6D

• Control biofilm buildup(recirculation, 85oC,ozonation)

• No added substances

SOURCE: Manfredi, Joe, “Myths, Rumors, Fantasies about Water

System Design”, Pharmaceutical Technology CGMP Compliance 2006,

pp 28-38 4



Cationic column Anionic column

Hygienic pump

Outlets or storage.

Ozone generator

UV light

HCl NaOH

Eluates to

neutralization

plant

Air break to sewer

Drain line

from water softener

Watermust bekeptcirculatin

g

Typical deionizer schematic

1

2345

6

1

23

4

5

6

Return to deioniczer

Cartridge

filter 5 µm

Cartridge

filter 1 µm

Water for Pharmaceutical Use



Installation Qualification

• Assure that the system is installed per designcriteria

• Test water before and after each piece of

equipment in-line. Not just at point-of-use!

• Use that data to write your SOPs

(backflushing, regeneration, etc.)

• For example . . .

6



Qualification of Mixed Bed Deionizers

• Conductivity

• PSID (scaling)

• Run lengthgallonage

• Amount of

regenerate• Rinse water

gallonage

• Silica(channeling)

• Bacterial load

• Other (eg. Airquality)

Monitor feed water and effluent

Regeneration In-UseDilute Base

Anion

Cation

Air Dilute Acid To Waste Purified Process Water

Cation

&Anion

Mixed

Bed

Mixed bed regeneration requires backwashing for separate treatment with acid andbase. They are mixed with air before start-up. 7



Operation Qualification

• Is the system operating correctly? – Pumps at right pressure?

– Water flow correct?

• Continue to test feed water, sample ports andpoints-of-use

• Monitor system changes to validate the SOPs

8



Water Validation and the

Corporate Audit • Allow extra time to audit the water system

• Trained persons are needed to maintain the

water system• Must check for specifications and acceptance

criteria for each sampling point

9



10

Water for Process Use

• Designed, constructed andvalidated to prevent microbial

proliferation and assure quality

• SOPs for maintenance, cleaning &sanitization on frequent basis

• Monitor & test to assureconformance to chemical, physical

and microbiological specifications

• Sanitary sampling portsafter each component

• Check at point-of-use daily

• Record & document test results

• Alert & action limits

• Corrective action plan



Performance Qualification

• Test all sample ports for 30 consecutive days

(spring, summer, fall and winter)• Validation complete after one full year

• Trend analysis may help avoid having torevalidate

• Develop change control procedures• Establish acceptance criteria for each piece of

equipment

• Establish alert and action limits

• Develop corrective action plans• Confirm the action had the desired affect

11



Establish microbial quality control

using trend analysis



The Validation Timeline

cosmetic gmp implementation part 8

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