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Showing posts with label Media Fill Test Validation of Aseptic Process. Show all posts
Showing posts with label Media Fill Test Validation of Aseptic Process. Show all posts

Saturday, July 25, 2009

Media fill Test Assurance of Sterility of parantral dosage form Injectables

Assuring the sterility of injectables sterile dosage form is very critical and must .Each and every container produced in a batch of a parentral dosage form should be sterile, even it is not possible to test each and every containers of a batch of parentral dosage form for sterility ,but enough evidence can be produced to claim the product as a sterile.
Media fill test is a toll to ensure the integrity of the process , environment , machinery and facility.
Parentral dosage forms manufacturing facilities should adapt the concept of Quality by design in their process , machinery's and formulations.

Even FDA has given lot more stress on sterile dosage form in the guidelines issued to pharmaceutical industries.
There is much scope for development in this field .

Media fill make use of culture medias instead of actual products , this process is carried out to evaluate the process along with machinery's being used for manufacturing of sterile dosage form .
Small change in the process can give variable results in media fill test.

Media fill make use of a suitable microbiological media , in place of actual product .
This media is filled as that of actual product is being filled , by following exact steps , as that of actual product , starting from dispensing to compounding to sterilization , filtration , autoclaving and storage .

Media fill test or process is designed to evaluate following points in manufacturing of parantral dosage form

1.Facility and room design
2.Design of filling machine
3.Flow of the manufacturing process
4.Heating , ventilation , and air conditioning Design and validation.
5.Utility design and validation
6.Response to any deviation
7.Trends in environmental monitoring data.
8.Decontamination program (Contamination control ) cleaning and sensitization .
9.Process simulation
10.Personal training and Qualification.

Following key points should be considered for exact simulation of media fill run

1.Type of product being filled.
2.Batch size of product
3.Containers and closures
4.Fill volume
5.Filling line speed.
6.Personals (Operators, working shifts )
7.Filling line configuration
8.Sterile hold time.
9.Number of units being filled , actual production quantity simulation.
10.Acceptance criteria.
11.Run duration
13.Elements which affect assurance of sterility

Worst cases should also be considered to evaluate integrity of manufacturing process and its validation , worst cases should not be the worst , they should be , the cases which may occur while in regular process .

Selection of growth media for Media fill runSelection of growth media for media fill run is very critical , I will like you to read my earlier article where I have written about a case where media fail test results were failing where as actual product did not failed.
That was because of growth media ,
Never the less media should support the growth of wise range of microorganisms,
Including aerobic bacteria , anaerobic bacteria , yeasts , molds , fungi.

Microbial environment monitoring program results should be considered for selecting the range of media to support the growth of a particular organism.
FDA has recommended use of soybean casein digest media well known as Tryptone soya broth.
Due to risk of precontamination of such media , demand your suppliers required clarification and certification for “BSE free” Oxoid cold filterable Tryptone soya broth.

FDA guidance also make it clear that if the product is being filled in nitrogen environment , and anaerobic medium should be used , Example .Fluid thioglycollate .

1.Prefer a media which is presterilised by radiation for your media fill run.
2.Select a media which dissolves at ambient temperature.
3.Avoid medias with mycoplasma.
4.Media should be filterable , should not block the filters .This is very important , otherwise , the process could not be simulated.

Media fill Run Process

The process should be simulated , exactly at the same point as that of product the medium should be introduced to process , just as the product is filtered and used , media should be filtered and introduced in to line .

Perform the growth promotion test on media on conclusions drawn from incubation period of 14 days.
All the units that are incubated after filling should be inspected for any defect , as that of a regular product,
Document the quantities of rejection with reasons .
Incubation is done for 14 days at 20 to 35 °C + 2.5 °C
All units should be incubated in inverted position.for first 7 days and then in up right position for 7 days .
Microorganisms isolated in Environment monitoring program should also be picked up by Media fill run.

A case study where
Media fill run failed
Pharmaceutical Validation

Cleen Room Classification

Pharmaceutical Industry

Pharmaceutical Manufacturing

Clinical Trials

You will find detailed information about Injectable dosage form ,Manufacturing of Injections and sterile dosage form Standard operating procedure SOP for microbiology and aseptic techniques over this website search

This website is a Guide for pharmaceutical manufacturing , pharmacy students pharmacy colleges and pharmacists pharmaceutical companies in health care

Sunday, March 29, 2009

Midia fill run Validation Aseptic sterile dosage form manufacturing

Aseptic as well as terminal sterile production of Sterile dosage form .
21 CFR parts 210 & 211 states about current GMP requirements for biological products covered by 21 CFR 600-680. Sections 210.2(a) and 211.1(b) provide that where ever it is impossible to comply with the applicable regulations, the regulation specifically applicable to the drug product in question shall supercede the more general regulations. You need to factor 21 CFR 211.113(b) which states, " A appropriate written procedures, which are designed to prevent microbiological contamination's of drug products which are purporting to be sterile, should be established and followed. Such procedures should include validation of such sterilisation process."

Aseptic process of manufacturing of sterile pharmaceuticals is a process of manufacturing which involves transfer of a sterile drug in to a sterile container manually or automated procedure in a sterile and aseptic aria.

While other way in process of terminal sterilization , all containers are rendered sterile by dry heat sterilization or autoclaveing .

Media fill runs for sterile dosage form manufacturing validation 

Media fills is a process which simulates the risk of contamination which arises during the process of filling of sterile dosage form in both terminal sterilization as well as aseptic process, a sterilized placebo of a dosage form. Placebo should be chosen to be of similar flow & filling performance characteristics to the sterilized dosage form to mimics exactly with the normal conditions of the aseptic process of production, as most critical operation within aseptic manufacture is the aseptically filling stage. At the point of filling, sterile dosage form is at highest level of risk of contamination from environmental or air-borne microorganisms while it is being transferred from one container to other.
Media fill is a process simulation it should be done so that it simulates the exact routine production process, which includes steps in formulation, filtration and filling stages. This will vary in relation to the type of product to be filled, example .liquid or solid dosage forms, and all process simulation is a completely unique event .
The study should be performed using a microbiological growth media in place of a active medicament. it can be treated as a 'worst case' scenario as most of the pharmaceutical products do not support microbiological growth. Selection of medium in Midia fill run is based on its ability to integrate into the process at the earliest step and can be introduced in to the filling process by filtration. Growth promotion a characteristic has to allow recovery of a typical flora recovered from environmental monitoring programs. Many times microbiological media themselves become a a source of contamination so this can be avoided by media irradiation and can be presented either in the dehydrated format or as a ready to use broth.
latest culture media, are available in market which are specially made for media fill trials, possess certain characteristics which allows process simulations; they are irradiated so that they can be used for introduction into compounding areas, can be dissolve in cold water and we can have filtration performance.

Sterile dosage form may get contaminated by surface-to-surface transfer of microorganisms from personnel as well as the manufacturing equipment. Freedom from microorganism of such manufacturing equipment is very important factor. Effective cleaning and decontamination procedures are important aspects of aseptic manufacture. Aseptic manufacture brings a sterile dosage form and the finished presentations pre-sterilised product-contact components together without contaminating them. It is also essential for equipment to be maintained sterile in between clean-downs. Unprotected environments where contamination by air-borne microorganisms is inevitable. Hence aseptic filling equipment are placed in areas that are protected from the general contaminated environment ie clean rooms.
During midia fill run personnel, components, equipment, movement and services in and out of protected areas needs also to be controlled if the protective barriers are to be effective in preventing contamination. Necessary intrusions to be brought into the aseptic areas through some form of decontamination or sterilisation process, example, via a double-ended autoclave. Personnel should be gowned in sterilised clothing that prevent skin borne and hair borne micro organisms, respiratory and digestive activities from contaminating the aseptic area, the manufacturing equipment, or any component of the sterile preparation . Personnel should be trained for aseptic techniques of working in aseptic areas, a specific localized protection must be provided to a written procedure for aseptic operations and techniques should be provided to operators.
You will get detailed information about pharmaceuticals and pharmacy related to pharmaceuticals manufacturing over this blog about following topics
Quality management guide for pharmaceuticals
Quality Guide for pharmaceuticals
Quality assurance in pharmaceuticals Pharmaceuticals guide
Quality assurance for pharmaceuticals manufacturing
Pharmacy guide Sterile dosage form
c GMP for pharmaceuticals.
Sterile dosage form manufacturing and its requirements.

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