D2-7.1 - Pharmacopoeial Requirements Pharmaceutical Water

Day-2, Session -7.1Day-2, Session -7.1

““Pharmacopoeial requirements for Pharmacopoeial requirements for Pharmaceutical waterPharmaceutical water””

(35m)(35m)

Speaker -Speaker - Sumant Baukhandi, PhDSumant Baukhandi, PhD

Pharmacopoeial Requirements

†EP requirements†USP requirements†Key points†Monitoring†Control

†EP requirements†USP requirements†Key points†Monitoring†Control


EP – 3 Types of Waters:Purified Water - monographHigh Purified Water - monographWater for Injections - monograph

Potable Water – is not covered by a monograph, but must comply with the standards laid down by the competent authority


USP – 8 Types of Waters:1. Non-potable

2. Potable (drinkable) water

3. USP purified water

4. USP water for injection (WFI)

5. USP sterile water for injection

6. USP sterile water for inhalation

7. USP bacteriostatic water for injection

8. USP sterile water for irrigation

FPs as per USP


EP - Purified Water:PUW is used for preparation of medicinal products

other than those that require water which is sterile and / or apyrogenic

PUW which satisfies the test for endotoxins may be used in the manufacture of dialysis solutions

Prepared by distillation, by ion exchange or by any other suitable method


USP – Purified Water:PUW is used as an excipient in production

of non-parenteral preparations and in other pharmaceutical applications,

such as cleaning of certain equipment and non-parenteral product-contact components

PUW must meet the requirements for ionic and organic chemical purity and must be protected from microbial contamination


USP – Purified Water:PUW should be tested for Conductivity, TOC,

microbiological qualityFor the sake of purity comparison, the

analogous Stage 1 and 2 conductivity requirements for Purified Water at 25 0C are 1.3 µS/cm and 2.1 µS/cm, respectively

Feed is Drinking Water - This water may be purified using unit operations that include de-ionization, distillation, ion exchange, reverse osmosis, filtration, or other suitable purification procedures

Purified Water System Skid


EP – Highly Purified Water:HPW is intended for use in the preparation of

medicinal products where water of high biological quality is needed, except where WFI is used

Current production methods include double pass Reverse Osmosis coupled with other suitable techniques, such as ultra-filtration and (Electro)de-ionization

It meets the same quality standards as WFI but its production methods are considerably less reliable than the multiple distillation for WFI, and consequently not used as WFI


USP – Highly Purified Water:HPW is intended for use in the preparation of

medicinal products where water of high biological quality is needed, except where WFI is used

It uses materials that are highly efficient de-ionizers and that do not contribute copper ions or organics to the water, assuring a very high quality water.

It meets the same quality standards as WFI but its production methods are considerably less reliable than the multiple distillation for WFI, and consequently not used as WFI

Bioburden 10 CFU / 100 mL


USP – Highly Purified Water:It is water that is prepared by deionizing previously

distilled water, and then filtering it through a 0.45-µm rated membrane. This water must have an in-line conductivity of not greater than 0.15 µS/cm (6.67 Megohm-cm) at 25 0C

If the water of this purity contacts the atmosphere even briefly as it is being used or drawn from its purification system, its conductivity will immediately degrade, by as much as about 1.0 µS/cm, as atmospheric carbon dioxide dissolves in the water and equilibrates to bicarbonate ions


EP –Water for Injection:WFI is the water for preparation of medicines

for parenteral administration when water is used as a vehicle (WFI in bulk) and

for dissolving or diluting substances or preparations for parenteral administration before use (sterile WFI)

It complies with monograph of PUW with additional requirements for BET (0.25 IU of En/mL), conductivity & TOC

Multiple distillation is the only official method for WFI generation


USP –Water for Injection:WFI is used as an excipient in production of

parenteral and other preparations, where product endotoxin content must be controlled,and in other pharmaceutical applications, such as cleaning of certain equipment and parenteral product-

contact components It complies with all chemical requirements of

the monograph of PUW as well as an additional bacterial endotoxin specification Reference: USP <1231>


Validation The pharmacopoeias recommend validating the water

system, adequately Validation to include sampling from points identified as

critical Sampling methodology Testing methodology – Dilution plate or membrane

filtration – which is the method of choice Microbiological test media – nutrient / R2A agar Incubation conditions Evaluation

Pharmacopoeial RequirementsContamination Control The pharmacopoeias recommend adequate control of

microbial contamination Effective systems to minimize microbial pass &

propagation at different stages of treatment Effective storage, distribution, sanitization UV treatment – dose, exposure Ozone treatment Other technology requirements regarding – material of

construction, vent filters, welds quality, sanitary fittings, slopes, surface finish, dead legs, re-circulation loop, etc..

Periodic inspection of the system Change control management

Water System – Biofilms

• Major Concern is Bio-films:• Microbial settling & colonizing on pipe surfaces• Mainly Pseudomonas species• Surface pits provide cavities for initial settlers• Biofilms are a collection of micro-organisms surrounded by a matrix

(slime layer that they secrete), which forms on surfaces in contact with water

• Quorum sensing and chemical signaling• Microcolonies with extracellular matrix• Network of channels• Cells experience different environmental conditions• Multi-species

O2

Biofilm formation and growth

Biofilm

Given the heterogeneity of the environment, how is the bio-film community structured?

There is a strong relationship between the cell’s environment and its physiology and structure.

Science News

Biofilm formation

Nutrient levels decrease towards

the center

Variety of environmental niches

form

Biofilm formation and growth

Biofilm in Automated water systemsBiofilm in Automated water systems

The above figure shows that the surface irregularities in such a finish are large enough to harbor several layers of Pseudomonas aeruginosa

Pharmacopoeial RequirementsMonitoring The pharmacopoeias recommend adequate monitoring

program for water system This includes established written SOPs for sampling,

monitoring of water samples, periodically Scientific rationale Sampling plan – based on risks of contamination and

criticality of use - Sampling methodology Testing methodology – Dilution plate or membrane

filtration – which is the method of choice Microbiological test media – nutrient / R2A agar Incubation conditions


۩ References:

1. EMEA Guidance – Water for Pharmaceutical Purposes

2. EP

3. USP General Chapter <1231) - Water for Pharmaceutical Use

4. USFDA Guidance – High Purity Water (1993)

THANKS!

For inquiries please contact –Sumant Baukhandi, PhD

Director – Pharma Institute of GMPs,

Director – pharmaACCESS

7, Phase-1, Vasant Vihar,

Dehradun-246 006

Uttaranchal State, INDIA

Landphone: 91-135 276 3092

Cellphone: 91- 99970 10901

Email ID: [email protected] ; [email protected]

Website: www.pigmp.com

mailto:[email protected]







http://www.pigmp.com/



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D2-7.1 - Pharmacopoeial Requirements Pharmaceutical Water