d2-7.1 - pharmacopoeial requirements pharmaceutical water
TRANSCRIPT
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
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>
Pharmacopoeial Requirements
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
Pharmacopoeial Requirements
۩ 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