INTRODUCTION TO PHARMACEUTICAL CLEAN ROOM Presented by: Kiran Kumar M. Pharm First Sem.(Q.A.T.) Roll no. 634 Padm . Dr. D. Y. Patil Institute Of Pharmaceutical Sciences And Research Pimpri , Pune-18

Contents Purpose of clean protocol Introduction Classification Types of contamination Contamination sources Contamination control Clean room enviroment monitoring Conclusion Refrences

Purpose Of Clean Protocol Promote Successful Cleanroom Operations Ensure Safety in the Clean Environment Provide Operational Conditions that Meet Process & User Needs

What is a Clean room? A clean environment designed to reduce the contamination of processes and materials. This is accomplished by removing or reducing contamination sources. “Federal Standard 209E” defines a clean room as a room in which the concentration of airborne particles is controlled to specified limits. “British Standard” defines a clean room as a room with control of particulate contamination, constructed and used in such a way as to minimize the introduction, generation and retention of particles inside the room and in which the temperature, humidity, airflow patterns, air motion and pressure are controlled.

Principles of the Clean Environment Air is highly (HEPA) filtered (99.97% @ 0.3μm) Layout should minimize particle sources in filtered air stream Air flow should remove most particles generated by process Clean room

Classification Of Clean Room

ISO Standards

CLASSIFICATION OF AIR & MICRO-ORGANISM AS PER WHO GUIDELINES

CLASSIFICATION AS PER EU cGMP

Schedule M

Comparison of various grades described in various guidelines Sr. no U.S. Federal 209 E MHRA/TGA ISO Standards 1 Class 100 A & B 5 2 Class 10,000 C 7 3 Class 1,00,000 D 8

Types of Contamination Particulate Dust, skin, hair, makeup… Chemical Oil, grease, metal ions, perfume… Biological Bacteria, fungi, rodents??? Radiation Ultraviolet light…

Contamination Sources People ~75% Ventilation ~15% Room Structure ~5% Equipment ~5% Contamination Control Personnel Control Dress code Personal Hygiene Gowning Environmental Control Entrance and exit Materials and supplies Cleaning and maintenance Atmospheric (HVAC & Microbial monitoring)

Personal Hygiene Shower each day before entry Control Dermatitis & Dandruff Do not smoke before or after entry No chewing gum or tobacco No Cosmetics , Jewellery or wrist watches should be worn Leave all personal items in changing room (wallets,keys,comb etc.) Avoid coughing and sneezing if unavoidable leave the clean room Do not move vigorously(Brisk movements shed large particles from body movement)

Gowning Proper gowning order Hair cover Hood Shoe covers Coverall Gloves Face mask Safety Glasses Cotton garments shed fibers. Hence, not used Decron (polyster)

HVAC SYSTEM AIR HANDLING SYSTEM: Pressure differential between 2 area should be 0.05-0.1 inch water guage. Requirements – Temp should be 15-25 °C. Atleast 20 air changes should be there per hr. Cleanliness requirements i.e. class 100. Relative humidity 45-55 %.

HEPA & UEPA High efficiency particulate air (HEPA): They are box type depth filters used for air filtration. These filters are made up of glass fibers. Efficiency of HEPA filters are 99.97% against 0.3 μm particles. Testing for HEPA filters: Hot DOP test (efficiency testing), Cold DOP test (integrity testing) , Air flow resistance test Ultra low penetration air (ULPA): Most ULPA filters are replaceable extended media dry filters that have a minimum particle collection efficiency of 99.9997 % efficient for particles greater than or equal to 0.12-micron in size.

AIRFLOW DISTRIBUTION AND CONTROL Unidirectional:(sometimes referred as laminar flow) is an airflow pattern in which essentially the entire body of air within a confined area moves with uniform velocity and in single direction with generally parallel airstreams. Clean rooms; class 100 and below have unidirectional airflow pattern. Laminar air flow ----120 FPM Non-unidirectional: airflow is not unidirectional by having a varying velocity, multiple pass circulation or nonparallel flow direction. Conventional flow clean rooms (class 1000 & 10000) have non-unidirectional or mixed air flow patterns. Mixed patterns : combine some of each flow type.

Some specific requirements Entry & Exit Enter and exit quickly. Only one person may enter at a time. Each user must use their own access card. Pass from the gowning area to the clean area slowly to reduce migration of particles between areas. Restricted no. of people in aseptic area. Drug sensitivity tests should be carried out for employees working in critical area. Medical check-ups of people works in critical area should be more frequent than other employees. Some specific requirements

clean room environment monitoring Test Frequency Particle Monitoring in air--------------6 monthly HEPA Filter Integrity Testing---------Yearly Air Changes Rate Calculation-------6 Monthly Air Pressure Differentials--------------Daily Temperature and Humidity------------Daily Microbiological monitoring by---------Daily, and at decreased settle plates and / or swabs in frequency in other aseptic areas areas

Conclusion The main purpose of building a cleanroom suite is to provide a vital element in the assurance of product quality according to whole concept of good pharmaceutical manufacturing operation. The resultant facility should prevent contamination of the product, and should be seen to be doing so by the incorporation of effective monitoring devices.

references Current Good Manufacturing For pharmaceuticals; Manohar A. Potdar; Page no:70-73. Pharmaceutical Quality Assurance, Manohar A. Potdar , Nirali Prakashan; Page no:13.1-13.10 Comparison of Quality Requirements for Sterile Product Manufacture as Per Indian GMP and USFDA ;Yogita P, N Vishal Gupta, Natasha NS, Ashwini Nageen L, R Sudeendra Bhat; Research Journal of Pharmaceutical, Biological and Chemical Sciences; Jan 2012 volume 3(1): 225-236. www.fda.gov

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