VALIDATION OF BUNG PROCESSOR

Transcription

1 243 P a g e International Standard Serial Number (ISSN): International Journal of Universal Pharmacy and Bio Sciences 6(2): March-April 2017 INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND BIO SCIENCES IMPACT FACTOR 2.96*** ICV 6.16*** Pharmaceutical Sciences RESEARCH ARTICLE!!! VALIDATION OF BUNG PROCESSOR Shridhar.M*, M.P Gowrav, Gangadharappa.H.V Department of Pharmaceutics (Pharmaceutical Quality Assurance) Jagadguru Sri Shivarathhreeswara University, Sri Shivarathreeshwara Nagara, Mysuru Karnataka, India. KEYWORDS: Validation of autoclave, Vacuum leak test, Bowiedick test, Heat distribution test, Heat penetration test. For Correspondence: Shridhar.M* Address: Department of Pharmaceutics (Pharmaceutical Quality Assurance) Jagadguru Sri Shivarathhreeswara University, Sri Shivarathreeshwara Nagara, Mysuru Karnataka, India. ABSTRACT In accordance with GMP, each pharmaceutical company should identify what qualification work is required to prove that the critical aspects of their particular operation are controlled. The key elements of a qualification and validation programme of a company should be clearly defined and documented. Qualification is the integral part of GMP and there is no effective QA program without qualification. Now-a-days it is mandatory to incorporate qualification activity for any system in the manufacturing premises for all pharmaceutical industries. The purpose of this study is to initially develop the sterilization process parameter for the porous load articles then implement the sterilization process for the porous articles. The process development included qualification of equipment and the articles. The autoclave cum bung processor which is used for the cleaning and sterilizing rubber stoppers, garments and machine parts. Initially installation qualification was done followed by performing the qualification of the equipment by performing Vacuum leak test, Bowie dick test, heat distribution test and heat penetration test. The equipment passes all tests and hence the equipment is suitable for sterilization purpose as it meets the predetermined specification and quality attributes. Hence the autoclave cum bung processor is considered to be qualified.

2 244 P a g e International Standard Serial Number (ISSN): INTRODUCTION: An autoclave is a pressure chamber used to carry out industrial processes requiring elevated temperature and pressure different to ambient air pressure. Autoclaves are used in medical application to perform sterilization, and in the chemical industry to cure coatings, vulcanize rubber and for hydrothermal synthesis 1. Autoclave was invented by Charles Chamber land in The name comes from Greek autoself, and Latin clavis - key, a self- locking device 3. The standard temperature and pressure of an autoclave Processes conducted at high temperatures for short time periods are preferred over lower temperatures for longer times. Some standard temperatures/pressures employed are 115 C/10 psi, 121 C/ 15 psi, and 132 C/27psi. (psi=pounds per square inch). In universal autoclave, autoclaving generally involves heating in saturated steam under a pressure of approximately 15 psi, to achieve a chamber temperature of a least 121 C (250 F) but in other applications in industry, for example, other combinations of time and temperature are sometimes used. Please note that after loading and starting the autoclave, the processing time is measured after the autoclave reaches normal operating conditions of 121 C (250 F) and 15 psi pressure, not simply from the time you push the "on" button 4,5. There are four basic types of autoclaves. These types depend upon the method employed to remove air from the sterilization chamber: Downward displacement autoclaves, Positive pressure displacement autoclaves, Negative pressure displacement autoclaves and Triple vacuum autoclave. The downward displacement autoclave is also referred to as a gravity displacement unit. This is because of the method of air removal in the sterilization chamber. A pool of water in which an element is immersed, turns to steam when heated. As steam is lighter than air, it forces the air in the sterilization chamber downward and out through a drain hole. Once the temperature in the sterilization chamber is sufficient, the drain hole is closed automatically and the sterilization process begins. A positive pressure displacement autoclave is an improvement upon the design of a downward displacement unit. Steam is created in a second, separate chamber and held until the proper amount to displace all of the air in the sterilization chamber is accumulated. The steam is then released into the sterilization chamber in a pressurized blast, forcing the air out through the drain hole and starting the sterilization process. A negative pressure displacement autoclave is one of the most accurate types available. Once the sterilization chamber door is closed, a vacuum pump removes the air. Steam is created in a second, separate chamber. Once the air has been completely removed from the sterilization chamber, the

3 245 P a g e International Standard Serial Number (ISSN): steam is then released into the sterilization chamber in a pressurized blast much like that of a positive pressure displacement unit. A triple vacuum autoclave is set up in a similar fashion to a negative pressure displacement unit in that there is a vacuum pump to remove air from the sterilization chamber and steam is created in a second, separate chamber or unit. The process begins by the vacuum removing the air, then a pulse of steam. This is repeated three times, hence the name "triple vacuum" autoclave 6. The working process of autoclave Basically, steam enters the chamber jacket, passes through an operating valve and enters the rear of the chamber behind a baffle plate. It flows forward and down through the chamber and the load, exiting at the front bottom. A pressure regulator maintains jacket and chamber pressure at a minimum of 15 psi, the pressure required for steam to reach 121 C (250 F). Overpressure protection is provided by a safety valve. The conditions inside are thermostatically controlled so that heat (more steam) is applied until 121 C is achieved, at which time the timer starts, and the temperature is maintained for the selected time. Figure 1: The temperature profile for a saturated steam vented cycle of autoclave tₒ to t n is the time interval in the computation of the Fₒ value. F 1 to Fn areas represent the lethal dose provided to the material being treated. The shaded area under the curve obtained through summation of F 1 to F n values represents the total Fₒ value. In the heating phase, saturated steam is admitted into the chamber, displacing the cold air until the exposure temperature and corresponding saturated steam pressure are attained. In the exposure phase, the sterilizing temperature is maintained by saturated steam for the prescribed exposure time. The cooling phase can be achieved by slow exhaust (for containers filled with liquids) or fast exhaust (for goods required to be dry after sterilization). This phase is completed when the pressure reaches atmospheric pressure 7.

4 246 P a g e International Standard Serial Number (ISSN): Where F 0 = F 0 Value F 0 = Σ 10 (T-121)/z t T = Average Temperature z = Value which indicates relationship of lethality to temperature = 10 C (assumed) 121 C = Sterilization Temperature F 0 is defined as the number of equivalent minutes of steam sterilization at 121 C delivered to a load (product) D-value (decimal reduction value): it is time required at temperature T to reduce a specific microbial population by 90% or by a factor of 10 Z-value: it is the number of degrees of temperature change necessary to change the D-value by a factor of Industrial and scientific autoclaves Although best known as sterilizers, autoclaves can also be used to carry out all sorts of industrial processes and scientific experiments that work best at high-temperatures and pressures. Unlike sterilizing autoclaves, which usually circulate steam, industrial and scientific autoclaves may circulate other gases to encourage particular chemical reactions to take place. Industrial autoclaves are often used for "curing" materials. For example: Rubber can be vulcanized (heated, toughened, and hardened with sulfur) in an autoclave. Nylon (a plastic) can be made by "cooking" a concentrated salt solution in an autoclave to encourage what's called condensation polymerization. Some autoclaves combine elements of both sterilization and industrial manufacture. For example, natural cork (wooden) bottle stoppers have to be boiled and sterilized before they're suitable for use. Traditionally, that was done in large water tanks; now it's much more likely to be done on a large scale in computer-controlled, industrial autoclaves 9. Validation The documented evidence that the process, equipment, facilities or systems, operating within established parameters, can perform effectively and reproducibly giving results meeting predetermined specifications. Validation master plan Describes the areas of activities within which validation is to take place and provides an overview of the status of planning. It lists the areas, systems and projects being managed, defines the status of validation for each and gives a broad indication of when validation is to be completed. It is a

5 247 P a g e International Standard Serial Number (ISSN): general plan and would normally cover all equipment and processes. It should include all systems for which validation is planned. Validation plan Description of the validation activities, responsibilities and procedures. It describes specifically how the validation is to be done and details responsibilities if the validation team. Validation protocol Outlines the objectives of validation of a specific equipment, testing protocol including elements such as installation, operational and performance qualification and documentation. Within the laboratory there should a validation policy which is a strategy document that clearly defines what the validation process is and its purpose within the laboratory. The policy should make a commitment to maintaining critical processes and systems in a valid state and should mention applicable regulations, standards and guidelines that underpin the laboratory s approach to validation. The validation policy will specify what should be validated and how validation is executed as defined in the validation master plan. The validation master plan (VMP) is a quality management system document. It should be a controlled document, approved by senior laboratory management and regularly reviewed and, if necessary, revised in response to organizational and operational changes. The VMP should be based on and refer to the validation policy. The VMP should clarify Under what circumstances Who is responsible How the validation will be performed and documented How the validated state will be maintained through regular servicing and calibration and requalification. For large projects such as the implementation of a new laboratory information system or relocation of the laboratory to new facilities, it may be appropriate to have a project-specific VMP. The VMP will inform those working as part of the project team to ensure that the project delivers processes and systems that are in a validated state and fit for use. Also, it may be desirable for reasons of complexity to have separate VMPs covering different systems such as computer systems and automated test systems. A VMP should cover The organizational structure and responsibilities for validation activities Summary or list of equipment, facilities or systems to be validated and qualified How validation is planned and scheduled

6 248 P a g e International Standard Serial Number (ISSN): The formats for validation documentation Links to other relevant quality system processes (e.g.document control, training, equipment calibration and maintenance.) Validation process Each part of the validation process should be documented. There should be a written plan for performing each validation to specify who is responsible for managing and performing the various validation tasks such as production of validation protocols and approvals of validation documentation. Validation protocols should be written for each phase of the validation to include acceptance criteria. The validation plan and the validation protocols may be combined into a single document. The outcome of each phase of validation should be recorded and the overall conclusions, with a scientific assessment of any failures should be documented in a validation summary report. The validation records and summary report must be reviewed and approved before putting the system affected into use. Validation plan The plan should first identify: Validation protocol What is being validated Where the validation will take place Why the validation is taking place providing reference to any relevant change. The validation stages required Validation time-frames Overall management of the validation Performing the validation and recording the outcome A validation protocol is an integral element of the validation plan. The protocol describes: The qualification/validation phase (DQ, IQ, OQ, and PQ) That tests will be performed The objectives of the validation in terms of acceptance criteria for each test Records to be completed. What needs to be tested, how many tests to do and the acceptance criteria at each validation phase will be specific to each validation and must be founded on the scientific and technical basis of the processes and systems involved. It should be possible to establish the specific requirements by reference to the relevant risk assessments, URS, published standards, regulations & guidelines.

7 249 P a g e International Standard Serial Number (ISSN): Validation record proformas should be completed as part of the protocol and approved along with the protocol 10. THE DIFFERENT TESTS ARE FOLLOWS FOR VALIDATION OF AUTOCLAVE Vacuum leak test Status of equipment under validation Result analysis Table 1: Status of vacuum leak test 1 Equipment Auto clave cum bung processor 2 Make Machine fabric 3 Capacity 1215 liters 4 Acceptance criteria 123±2 C 5 Cycle time 121 C@ 10 min 6 Temperature range 121 C to 125 C 7 Pressure range 1.2 bar to 1.3 bar 8 Type of sensor used T type 9 Cycle name Vacuum leak test Table 2: Probes result of vacuum leak test Temperature [ C] Channel Min Max Average Std dev CH CH CH CH CH CH CH CH CH CH CH CH CH CH CH CH Pressure [bar] CH

8 250 P a g e International Standard Serial Number (ISSN): Table 3: Result of vacuum leak test 1 Test start time 10:48:06 2 Sterilization start time 10:52:51 3 Sterilization end time 11:02:51 4 Sterilization hold time 10 min 5 Standard sterilization cycle 123±2 C 6 Time at which first probe reached desired temperature 10:52:21 7 Time at which last probe reached desired temperature 10:52:51 8 Maximum temperature recorded C 9 Minimum temperature recorded C 10 Maximum pressure recorded bar 11 Minimum pressure recorded bar 12 Test end time 11:04:17 Bowie Dick test Status of equipment under validation Table 4: Status of Bowie Dick test 1 Equipment Autoclave cum bung processor 2 Make Machine fabric 3 Capacity 1215 liters 4 Acceptance criteria 123±2 C 5 Cycle time min 6 Temperature range 121 C to 125 C 7 Pressure range 1.2 bar to 1.3 bar 8 Type of sensor used T type 9 Cycle name Bowie dick test Result analysis

9 251 P a g e International Standard Serial Number (ISSN): Table 5: Probes result of Bowie Dick test Temperature [ C] Probes Min Max Average Std Dev P P P P P P P P P P P P P P P P Pressure [bar] P Table 6: Result of Bowie Dick test 1 Test start time 11:14:21 2 Sterilization start time 11:50:28 3 Sterilization end time 12:07:28 4 Sterilization hold time 17 min 5 Standard sterilization cycle 123±2 C 6 Time at which first probe reached desired temperature 11:49:58 7 Time at which last probe reached desired temperature 11:50:28 8 Maximum temperature recorded C 9 Minimum temperature recorded C 10 Maximum pressure recorded bar 11 Minimum pressure recorded bar 12 Test end time 12:11:59

10 252 P a g e International Standard Serial Number (ISSN): Graph 1 : Bowie Dick test graph Figure 2: Results of Bowie Dick test sheets Heat distribution study Status of equipment under validation: Table 7: Status of heat distribution test 1 Equipment Autoclave cum bung processor 2 Make Machine fabric 3 Capacity 1215 liters 4 Acceptance criteria 123±2 C 5 Cycle time min 6 Temperature range 121 C to 125 C 7 Pressure range 1.2 bar to 1.3 bar 8 Type of sensor used T type 9 Cycle name Without load

11 253 P a g e International Standard Serial Number (ISSN): Result analysis Table 8: Probes result of heat distribution test Temperature[ C] Channel Min Max Average Std dev CH CH CH CH CH CH CH CH CH CH CH CH CH CH CH CH Pressure [bar] CH Table 9: Result of heat distribution test 1 Test start time 14:36:06 2 Sterilization start time 14:58:28 3 Sterilization end time 15:29:28 4 Sterilization hold time 30 min 5 Standard sterilization cycle 123 c±2 C 6 Time at which first probe reached desired temperature 14:57:58 7 Time at which last probe reached desired temperature 14:58:28 8 Maximum temperature recorded C 9 Minimum temperature recorded C 10 Maximum pressure recorded 1.292bar 11 Minimum pressure recorded 1.201bar 12 Test end time 15:44:42

12 254 P a g e International Standard Serial Number (ISSN): Result analysis of biological indicator Table 10 : Biological indicator result of heat distribution study By steam at a temperature of 121 C and Sterilization method pressure of 1.2 bar Standard sterilization cycle Biological indicators used 30 minutes Self contained ampoules of Geobacillus stearothermophilus population 10 6 cfu/strip Incubation temperature 55±2 C S. No. Table 11: Observation of biological indicator Observation Position of biological indicator 24 hours 48 hours 1 P P P P P P P P P P P P P P P P Positive control = No growth + = Shows growth Figure 3: Results of chemical indicators for heat distribution test

13 255 P a g e International Standard Serial Number (ISSN): Graph 2: Heat distribution test graph Heat penetration study Status of equipment under validation Table 12: Status of heat penetration study (maximum load) 1 Equipment Auto clave cum bung processor 2 Make Machine fabric 3 Capacity 1215 liters 4 Acceptance criteria 123 ± 2 C 5 Cycle time min 6 Temperature range 121 C to 125 C 7 Pressure range 1.2 bar to 1.3 bar 8 Type of sensor used T type 9 Cycle name Rubber stopper maximum load (60000)

14 256 P a g e International Standard Serial Number (ISSN): Result analysis Table 13: Probes result of heat penetration study (maximum load) Temperature[ C] Channel Min Max Average Std dev CH CH CH CH CH CH CH CH CH CH CH CH CH CH CH CH Pressure [bar] CH Table 14: Result of heat penetration study (maximum load) 1 Test start time 11:57:14 2 Sterilization start time 16:47:50 3 Sterilization end time 17:17:50 4 Sterilization hold time 30 min 5 Standard sterilization cycle 123 C ± 2 C 6 Time at which first probe reached desired temperature 16:47:20 7 Time at which last probe reached desired temperature 16:47:50 8 Maximum temperature recorded C 9 Minimum temperature recorded C 10 Maximum pressure recorded bar 11 Minimum pressure recorded bar 12 Test end time 18:59:05

15 257 P a g e International Standard Serial Number (ISSN): Figure 4: Rubber bungs for heat penetration test (maximum load) Result analysis of biological indicator Table 15: Biological indicator result of heat penetration study (maximum) By steam at a temperature of 121 C and pressure Sterilization method of 1.2 bar Standard sterilization cycle 30 minutes Self contained ampoules of Geobacillus Biological indicators used stearothermophilus population 10 6 cfu/strip Incubation temperature 55±2 C Table 16: Observation of biological indicator S. No. Position of biological indicator Observation 24 hours 48 hours 1 P P P P P P P P P P P P P P P P Positive control = No growth + = Shows growth

16 258 P a g e International Standard Serial Number (ISSN): Figure 5: Results of chemical indicators for heat penetration study (maximum load) Graph 3: Heat penetration test (maximum load) graph CONCLUSION After conducting the Vacuum leak test, Bowie-dick test, Heat distribution test, Heat penetration test, the results are satisfied and results are captured in the above respective tables and hence it proves that equipment meets its acceptance criteria and equipment passes the above tests. REFERENCES: 1. Gupta NV, Shukshith KS. Qualification of Autoclave. Int J PharmTech Res. 2016;9(4): Fernbach E, Joubert, Roux E, Pasteur E, Strauss. Charles Chamberland, En collaboration arec Online etymology dictionary, available at

17 259 P a g e International Standard Serial Number (ISSN): Hugo WB. A brief history of heat and chemical preservation and disinfection. J Appl Bacteriol. 1991;71(1): Seymour SB. Disinfection, Sterilization and preservation, Lippincott Williams and Wilkins, 5 th ed Wark G. Types of autoclaves [Internet]. How. [cited 2016 Jan 25]. Available from: types autoclaves.html 7. Howard J. Operation of the autoclaves, available at 8. Ankur C. Microbiology sterilization, available at 9. Chrise W. How does an autoclave work, available at Allard S, Burgess G, Cuthbertson B, Elliott C, Haggas R, Jones J et.al., Guidelines for validation & qualification including Change Control, for hospital transfusion laboratories. 2014:1-24.