Sunday, February 28, 2016

Where should airflow velocity measurements be taken, with respect to a filling line or other aseptic processing areas?


Where should airflow velocity measurements be taken, with respect to a filling line or other aseptic processing areas?


📚Recommendation
Airflow velocity measurements should be taken at locations where meaningful and reproducible results can be obtained. This typically at a distance of 15-30 cm from the filter face.
Rationale for Recommendation
The primary reason for airflow velocity measurements in unidirectional airflow areas (e.g, area where products , product contact packaging components, and product contact surfaces are exposed) is to ensure adequate airflow to protect the materials from external airborne contamination and to verify continued compliance with qualified conditions. The adequacy of the environment can be determined, in part, from airflow velocity and air flow pattern studies, and from particulate matter monitoring (at the working position).
Accurate measurements can be taken ad changes over the detected when air flow velocity are evaluated at a predetermined distance from filter surface, which is sufficiently close to the filter surface to be reproducible to detect changes in the performance of the filter.
The airflow velocity depends on the design of the filling line, room design, and air-handling system. Once velocity is determined, it is important to ensure that the velocity stays within the specific parameters. Routine air velocity measurements should be taken at the same locations used during the initial airflow studies to ensure consistency.



Reference Guidance:
EudraLex; The Rules Governing Medicinal Products in the European Union
Volume 4; EU Guidelines to Good Manufacturing Practice; Medicinal Products for Human and Veterinary Use; Annex 1; Manufacture of Sterile Medicinal Products (corrected version)

Laminar air flow systems should provide a homogeneous air speed in a range of 0.36 – 0.54 m/s (guidance value) at the working position in open clean room applications. The maintenance of laminarity should be demonstrated and validated. A uni-directional air flow and lower velocities may be used in closed isolators and glove boxes.

Reference Guidance:
USFDA Sterile guidance document http://www.fda.gov/downloads/Drugs/.../Guidance/ucm070342.pdf (accessed o 09-08-2015)


A velocity of 0.45 meters/second (90 feet per minute) has generally been established, with a range of plus or minus 20 percent around the set point. Higher velocities may be appropriate in operations generating high levels of particulates.
It is important to conduct periodic monitoring of filter attributes such as uniformity of velocity across the filter (and relative to adjacent filters). Variations in velocity can cause turbulence that increases the possibility of contamination. Velocities of unidirectional air should be measured 6 inches from the filter face and at a defined distance proximal to the work surface for HEPA filters in the critical area.

Reference Guidance:
WHO 961 annex 6

The local zone for high-risk operations, e.g. filling and making aseptic connections. Normally such conditions are achieved by using a unidirectional airflow workstation. Unidirectional airflow systems should provide a homogeneous air speed of 0.36–0.54 m/s (guidance value) at a defined test position 15–30 cm below the terminal filter or air distributor system. The velocity at working level should not be less than 0.36 m/s.
The uniformity and effectiveness of the unidirectional airflow should be demonstrated by undertaking airflow visualization tests.

🏅Reference Guidance:
Schedule M

🏹For Grade A laminar air flow work stations, the air flow rate shall be 0.3 meter per second ± 20% (for vertical flows) and 0.45 meter per second ± 20% (for horizontal flows)
👉🏻swapnil✌🏻

Wednesday, February 24, 2016

Titration Problems

Titration Problems



Molarities of acidic and basic solutions are often used to convert back and forth between moles of solutes and volumes of their solutions, but how were the molarities of these solutions determined? This webpage describes a procedure called titration, which can be used to find the molarity of a solution of an acid or a base.

In titration, one solution (solution 1) is added to another solution (solution 2) until a chemical reaction between the components in the solutions has run to completion. Solution 1 is called the titrant, and we say that it is used to titrate solution 2. The completion of the reaction is usually shown by a change of color caused by a substance called an indicator.

A typical titration proceeds in the following way. A specific volume of the solution to be titrated (solution 2) is poured into an Erlenmeyer flask (Figure 1). For example, 25.00 mL of a nitric acid solution of unknown concentration might be added to a 250 mL Erlenmeyer flask.

A solution of a substance that reacts with the solute in solution 2 is added to a buret. (A buret is a laboratory instrument used to add measured volumes of solutions to other containers.) This solution in the buret, which has a known concentration, is the titrant. The buret is set up over the Erlenmeyer flask so the titrant can be added in a controlled manner to the solution to be titrated (Figure 1). For example, a 0.115 M NaOH solution might be added to a buret, which is set up over the Erlenmeyer flask containing the nitric acid solution.



Figure 1    Setup for a Typical Titration     In a typical titration, the titrant in the buret is added to the solution in the Erlenmeyer flask until the indicator changes color to show that the reaction is complete.

An indicator is added to the solution being titrated. The indicator is a substance that changes color when the reaction is complete. In our example, phenolphthalein, which is a commonly used acid‑base indicator, is added to the nitric acid solution in the Erlenmeyer flask. Phenolphthalein has two chemical forms. In acidic conditions, it is in the acid form, which is colorless. In basic conditions, an H+ ion is removed from each phenolphthalein molecule, converting it to its base form, which is red.

The titrant is slowly added to the solution being titrated until the indicator changes color, showing that the reaction is complete. This stage in the procedure is called the endpoint. In our example, the NaOH solution is slowly added from the buret until the mixture in the Erlenmeyer flask changes from colorless to red. The OH− ions in the NaOH solution react with the H3O+ ions in the HNO3 solution.

H3O+(aq)  +  OH−(aq)  →  H2O(l)

As long as there are excess H3O+ ions in the solution, the solution stays acidic, the phenolphthalein stays mostly in the acid form, and the solution is colorless. When enough NaOH solution is added to react with all of the H3O+ ions, the reaction is complete. When a small amount of extra NaOH solution is added, perhaps one drop, there will be an excess of hydroxide ions, OH−, in solution. These react with the phenolphthalein molecules, changing them from the acid form to the base form. Because the base form is red, the solution turns red, telling us that the reaction is complete (or just slightly beyond complete).

The volume of titrant added from the buret is measured. For our example, let's assume that 18.3 mL of 0.115 M NaOH has been added. The following setup shows how the molarity of the nitric acid solution can be calculated from this data.



                           = 0.0842 M HNO3

The first step the unit analysis thought-process is to clearly identify the units that you want. Molarity describes the number of moles of solute per liter of solution, so we start by placing moles of HNO3 over 1 L HNO3 solution.

Because molarity is a ratio of two units, we begin our calculation with a ratio of two units. Knowing that we want volume of HNO3 solution on the bottom when we are done, we place 25.00 mL HNO3 solution on the bottom at the start. We place 18.3 mL NaOH solution on the top of our ratio, giving us the ratio of two units overall that we want.

We convert milliliters of HNO3 solution to liters of HNO3 solution using the relationship between milliliters and liters. The last two conversion factors convert from amount of one substance in a chemical reaction (mL NaOH solution) to amount of another substance in the reaction (mol HNO3). Thus this is an equation stoichiometry problem that requires at its core the conversion of moles of NaOH to moles of HNO3 using the molar ratio for the reaction between them.

NaOH(aq)  +  HNO3(aq)  →  NaNO3(aq)  +  H2O(l)

In order to use the molar ratio to convert from moles of NaOH to moles of HNO3, we need to convert from volume of NaOH solution to moles of NaOH using the molarity as a conversion factor.



Sample Study Sheet: Acid-Base Titration Problems

Tip-off – You are given the volume of a solution of an acid or base (the titrant – solution 1) necessary to react completely with a given volume of solution being titrated (solution 2). You are also given the molarity of the titrant (solution 1). You are asked to calculate the molarity of solution 2.

General Procedure

Use the unit analysis process, with the following general format.



The first conversion factor is used only when you are not given liters of solution 2. (Because you are usually given milliliters, you may instead need to use a conversion factor that converts from milliliters to liters.)

The second conversion factor is used only when you are not given either milliliters or liters of solution 1. (You are usually given milliliters, so if your molarity conversion factor is in the form that includes "103 mL #1 soln", this conversion factor is not necessary.)

The coefficients in the final conversion factor come from the balanced equation for the reaction.

Complete the calculation in the usual way.



EXAMPLE:  Calculating Molarity from Titration Data

Titration reveals that 11.6 mL of 3.0 M sulfuric acid are required to neutralize the sodium hydroxide in 25.00 mL of NaOH solution. What is the molarity of the NaOH solution?

Solution:

H2SO4(aq)  +  2NaOH(aq)    →   2H2O(l)  +  Na2SO4(aq)



                                        =  2.8 M NaOH
👉🏻swapnil✌🏻

Tuesday, February 23, 2016

MICROBIAL LIMIT TEST

MICROBIAL LIMIT TEST PROCEDURE

1.0  Equipments Required

       LAF
       Filtration Assembly
       Sterile 0.45 micron membrane filter
       Sterile Pipettes – 1 ml and 10 ml

2.0  Material Required

       Sterile 0.1% w/v peptone 3 X 100 ml
       70% IPA solution
       Sample for testing
       SCDA and SCDA plates
       SDA and SDA plates
       SCDM 3 X 100 ml

3.0  Procedure:

3.1  Total Aerobic Microbial Count:

3.1.1  Collect the sample to be tested for microbial limit test as per sampling plan.
3.1.2  Use specified quantity of sample for each of the test specified in the individual monograph and pre-treat the sample as following method-
3.1.3  Water Soluble Product: Dissolve 10 gm or dilute 10 ml of sample, unless otherwise specified, in sterile 90 ml peptone water or buffered sodium chloride-peptone solution pH 7.0
3.1.4  Product Insoluble In Water: Suspend 10 gm or 10 ml sample, unless otherwise specified, in sterile 90 ml peptone water with 0.1% polysorbate 80 or buffered sodium chloride-peptone solution pH 7.0
3.1.5  Fatty Products: Homogenize 10 gm or 10 ml of the sample, unless otherwise specified, with 5 g of polysorbate 80. If necessary heat to not more than 40°C. Mix carefully while maintaining temperature on water bath. Add 85 ml of sterile peptone water or buffered sodium chloride-peptone solution pH 7.0

3.2  Examination of sample by Membrane Filtration Method:

3.2.1  Aseptically connect the rubber tube of sterile manifold to receiver tank and receiver tank rubber pipe tovacuum pump.
3.2.2  Using sterile smooth tip forceps, place a 47 mm diameter 0.45m sterile membrane filter on the center of the filter support screen. Without disturbing the filter, place the funnel on top of the filter holder base.
3.2.3  Separately transfer 10 ml of pretreated sample from step no. 3.1.3 to each two 90 ml of sterile 0.1% peptone water. Mix well and transfer the whole quantity of dilution to each of two membrane filters and filter immediately.
3.2.4  Wash both the membrane filter with each 3 x 100 ml of sterile 0.1% peptone water into the filtration funnel and filter under partial vacuum
3.2.5  After completion of filtration process, shut off the vacuum with the help of vacuum control key.
3.2.6  Transfer one of the membrane filters, intended for the enumeration of bacteria, to the surface of the plate containing SCDA and other, intended for the enumeration of fungi, to the surface of the plate of SDA.
3.2.7  For positive control carry out the same procedure in duplicate except for sample use 100 ml fluid A inoculated with 100 bacterial cells and another 100 ml fluid A is inoculated with c.albicans intended foridentification of total aerobic and fungal count respectively.
3.2.8  For negative control carry out the same procedure except for sample use 100 ml sterile 0.1% peptone water.
5.3.2.9  Incubate the plates for 5 days, unless a more reliable count is obtained in shorter time, at 30 to 35°C in the test of bacteria and 20 to 25°C in the test for fungi.
3.2.10  Count the number of colonies that are formed. Calculate the number of cfu per gram or per ml of the sample being examined.

3.3  Examination of sample Plate Count Method:

3.3.1  Use this method for fatty products and product insoluble in water.
3.3.2  Use 90 mm sterile petri plate. Take a four-petri plate and label two plates for bacteria and remaining two for fungi count. Transfer 1 ml quantity of each pretreated dilution sample solution to each of four petri plates.
3.3.3  Add 15 ml of sterile liquefied SCDA at not more than 45°C, in to two plates labeled for bacterial count.
3.3.4  Then add 15 ml of sterile liquefied SDA at not more than 45°C, into two plates labeled for fungal count.
3.3.5  Allow to solidify the plates at room temperature, invert and incubate at 30 to 35°C for 5 days and 20 to 25°C for 5 days respectively.
3.3.6  Count the number of colonies that are formed. Calculate the number of cfu per gram or per ml of the sample being examined.

3.4  Test For Specified Microorganisms:

3.5  For Membrane Filtration Method:

3.5.1  Follow the same procedure described under 3.2.1 to 3.2.5, transfer one of the membrane filter, intended for enrichment of E. coli and Salmonella to a tube containing 100 ml of sterile nutrient broth, and other membrane intended for enrichment of Pseudomonas aeruginosa and Staphylococcus aureus, to a tube containing 100 ml of sterile Soybean casein digest medium.
3.5.2  For positive control carry out the same filtration procedure in duplicate except for sample use 100 of peptone water inoculated with approx 100 cells of E. coli or Salmonella and another 100 ml of peptone water inoculate with Staph. aureus or Ps. aeruginosa and transfer the membrane to 100 ml of sterile nutrient broth and soyabean casein digest medium respectively.
3.5.3  For negative control carry out the same procedure except for sample use 100 ml of sterile peptone water for both the tubes.

3.6  For Plate count method (Direct Inoculation)

3.6.1  Use this method for Fatty products and Product insoluble in water.
3.6.2  Transfer separately 1 ml quantity of pretreated sample from step no. 3.1.4 and 3.1.5 to a tube containing 100 ml of sterile nutrient broth and soybean casein digest medium.
3.6.3  For positive control inoculate approx 10 to 100 cells of E. coli or salmonella into nutrient broth and Staph. aureus or Ps. aeruginosa in Soybean casein digest medium.
3.6.4  For Negative control inoculate 1 ml of sterile peptone water in both the medium.
3.6.5  Incubate all the tubes at 35 – 37°C for 18 to 24 hours.
3.6.6  Observe the tubes for growth, by means of turbidity. If the growth is present in sample tube and positive control tube and absent in negative control tube, proceed for further identification of specific microorganisms i.e. E. coliSalmonellaPs aeruginosa and Staphylococcus aureus.
3.6.7  If growth is not observed in sample tube and negative control tube and observed in positive control tube, need not proceed for further identification of specific microorganisms i.e. E. coliSalmonellaPs aeruginosa and Staphylococcus aureus.

3.7  Escherichia coli:

3.7.1  By means of inoculating loop, streak a portion from enrichment culture (obtained from nutrient broth of previous test) on the surface of MacConkeys agar plate.
3.7.2  Simultaneously carry out the positive control by streaking a growth of E. coli on the surface of MacConkeys agar plate. For negative control incubate the plate as it is without inoculation.
3.7.3  Invert and incubate all the plates at 35 to 37°C for 24 hours.
3.7.4  Upon examination, if none of the colonies are brick red in colour and have a surrounding zone of precipitated bile, the sample meets the requirements of the test for the absence of Escherichia coli.
3.7.5  If the colonies described above are found, transfer the suspect colonies individually to the surface ofLevine eosin-methylene blue agar medium.
3.7.6  Simultaneously carry out the positive control by streaking a growth of E. coli on the surface of MacConkeys agar plate. For negative control incubate the plate as it is without inoculation
3.7.7  Invert and incubate all the plates at 35 to 37°C for 24 hours
3.7.8  Upon examination, if none of the colonies exhibits both a characteristic metallic sheen under reflected light, the sample meets the requirements of the test for the absence of Escherichia coli

3.8  Salmonella:

3.8.1  Primary Test: Aseptically add 1.0 ml of the enrichment culture (obtained from nutrient broth of previous test) to each of two tubes containing (a) 10 ml of sterile Selenite F broth and (b) tetrathionate-bile-brilliant green broth and incubate at 35 to 37°C for 24 to 48 hours.
3.8.2  From each of these two cultures subculture on at least two of the following four agar media: Bismuth sulphite agar, Brilliant green agar, Deoxycholate-citrate agar and Xylose-lysine-deoxycholate agar.
3.8.3  Simultaneously carry out the positive control by streaking a loop full growth of Salmonella on surface of one of the above media, which is used for testing. For negative control incubate the agar plate without streaking or inoculation.
3.8.4  Invert and incubate all the plates at 35 to 37°C for 18 to 24 hours.
3.8.5  Upon examination, if none of the colonies confirms to the description given in Table-1, the sample meets the requirements of the test for the absence of the genus Salmonella.
3.8.6  If any colonies confirming to the description in Table-1, carry out the secondary test.
Table-1
Sr. No
Medium
Description of colony
1
Bismuth sulphite agar
Black or green
2
Brilliant Green Agar
Small, transparent and colorless, or opaque, pinkish or white (frequently surrounded by a pink or red zone)
3
Deoxycholate-citrate agar
Colorless, and opaque, with or without black center.
4
Xylose-lysine-deoxycholate agar
Red with or without black centers.
3.8.7  Secondary Test: Subculture any colonies showing the characteristics given in Table –1, in triple sugar-iron agar by first inoculating the surface of the slope and then making a stab culture with the same inoculating needle.
3.8.8  At the same time inoculate a tube of urea broth. Incubate at 36 to 38°C for 18 to 24 hours.
3.8.9  Upon examination, no evidence of tubes having alkaline (red) slant and acid (yellow) butt (with or without concomitant blackening of the butt from hydrogen sulfide production), the sample meets the requirements of the test for absence of genus salmonella.

3.9  Pseudomonas aeruginosa:

3.9.1  Streak a portion of the medium from soyabean casein digest medium (obtained from nutrient broth of previous test) on the surface of cetrimide agar medium,
3.9.2  Simultaneously carry out the positive control by streaking a loop full growth of Ps. aeruginosa on the surface of cetrimide agar. For negative control incubate the cetrimide agar plate without inoculation. Invert and incubate all the plates at 35 to 37°C for 18 to 24 hours.
3.9.3  If, upon examination, none of the plate contains colonies having the characteristic listed in Table-2 for the media used, the sample meets the requirements for freedom from Ps. aeruginosa.
3.9.4  If any colonies confirming to the description in table – 3 are produced, carry out the Oxidase and pigment test.
Table-2
Medium
Colony characteristic
Fluorescence in UV light
Oxidase
Gram stain
Cetrimide Agar
Generally greenish
Greenish
Positive
Negative rods
Pseudomonas agar for detection fluorescein
Generally colorless to yellowish
Yellowish
Positive
Negative rods
Pseudomonas agar for detection Pyocyanin
Generally greenish
Blue
Positive
Negative rods.

3.9.5  Pigment Test: Streak representative suspect colonies from the agar surface of cetrimide agar on the surface of pseudomonas agar medium for detection of fluorescein and pseudomonas agar medium for detection of Pyocyanin.
3.9.6  Cover and invert the inoculated plates and incubate at 33 to 37°C for not less than 3 days.
3.9.7  Examine the streaked surface area under UV light and determine whether colonies confirming to the description in Table-2.
3.9.8  Oxidase Test: If growth of suspect colonies occurs, place 2 or 3 drops of a freshly prepared 1% w/v solution of N, N, N1, N1-tetramethyl-4-phenylenediamine dihydrochloride on filter paper and smear with the suspected colony. If there is no development of a pink color, changing to purple, the sample meets the requirements of the test for absence of Pseudomonas aeruginosa.

3.10  Staphylococcus aureus:

3.10.1  Streak a portion of the medium from soyabean casein digest medium (obtained from nutrient broth of previous test) on the surface of one of the agar medium listed in Table-3
3.10.2  Simultaneously carry out the positive control by streaking a loop full growth of Staphylococcus aureus on the surface of agar medium. For negative control incubate the agar plate without inoculation.
3.10.3  Invert and incubate all the plates at 35 to 37°C for 18 to 24 hours
3.10.4  If, upon examination, none of the plate contains colonies having the characteristic listed in Table-3 for the media used, the sample meets the requirements for freedom from Staphylococcus aureus.
3.10.5  If any colonies confirming to the description in table – 3 are produced, carry out the coagulase test.
Table – 3
Sr. No
Selective Medium
Colony characteristic
Gram Stain
1
Vogel-Johnson agar
Black surrounded by yellow zones
Positive cocci in clusters
2
Mannitol-salt agar
Yellow colonies with yellow zones
Positive cocci in clusters
3
Baird-Parker agar
Black, shiny, surrounded by clear zone of 2 to 5 mm
Positive cocci in clusters
3.10.6  Coagulase Test: Transfer representative suspect colonies from the agar surface or any of the media listed in Table-3 to individual tubes, each containing 0.5 ml of mammalian, preferably rabbit or horse plasma with or without additives.
3.10.7  Incubate at 37°C and examine the tubes at 3 hours and subsequently at suitable intervals up to 24 hours.
3.10.8  If no coagulation in any degree is observed, the sample meets the requirements of the test for the absence of Staphylococcus aureus.

4.0  Precaution

4.1  Keep the hands clean and used strictly IPA rinsed hand gloves throughout the operations.
4.2  Run positive and negative control along with each test.
4.3  The microbial limit test must be carried out under LAF.
4.4  For pour plate method, if necessary dilute the sample in the sample solution to obtain 100 to 300 cfu.

5.0  Frequencies

       Batch wise

6.0  Abbreviation

       SOP : Standard Operating Procedure
       IPA : Isopropyl Alcohol
       LAF : Laminar Air Flow
       cfu : Colony forming unit
       SCDA : Soybean casein digest Agar
       SCDM : Soybean casein digest medium
       SDA : Sabouraud Dextrose Agar

Swapnil Bhardwaj

Wednesday, February 10, 2016

What is 'grand fathering'?

❓What is 'grand fathering'?
 
🅰"Grand fathering" simply means the possibility that the rule may not apply to any system in existence before the rule came into effect. Part 11 does not allow for grandfathering of legacy systems. Therefore, systems installed before August 20, 1997 must be made compliant or replaced.
👉🏻swapnil✌🏻

Principle of Sterilization

🌟pharma discussion🌟
PRINCIPLES OF STERILIZATION:

👉🏻MOIST HEAT STERILIZATION:
Moist heat sterilization is otherwise refered as steam sterilization under pressure.
Mechanism of killing of microorganisms:
Heat in the form of saturated steam under pressure is the most practical and dependable agent for sterilization. Bacterial death by moist heat sterilization is due to denaturation and coagulation of essential protein molecules (enzymes) and cell constituents.
Steam sterilization under pressure is carried out in an autoclave, which is an airtight, jacketed chamber designed to maintain a high pressure of saturated hot steam. Because the autoclave permits the attainment of high moist-heat temperatures and because heat exchange by steam is more rapid than by dry heat, this method of sterilization is more efficient than the dry-heat method. Sterilization of aqueous solutions, glassware, and rubber articles is best done by steam under pressure. This process is not suitable for sterilizing solutions of drugs that are thermolabile in nature.
Conditions to be followed for the moist heat sterilization according to The USP XXI and BP 1988 are given below:
* Pressure: 15 lb / square inch (psi)
* Temperature: 121 C
* Time: 15 minutes

👉🏻DRY HEAT STERILIZATION:
Mechanism of killing of microorganisms:
The vital constituents of cells such as proteins (enzymes) and nucleic acids are denatured by oxidation. The killing of microorganisms by heat is a function of the time-temperature combination. [1]
Dry heat is the simplest and most economical method of sterilization. This method requires higher temperatures and longer exposure times to achieve the same microbial-killing efficiency as compared with that of steam sterilization. A major problem associated with dry heat
sterilization is non uniform distribution of temperature. A fan is usually installed in the oven to overcome this problem, but unless the fan is properly baffled it may blow around powders that are to be sterilized. Furthermore, dry heat cannot be used with materials that are heat sensitive. It is mainly used for sterilization of glass and metal objects. It can also be used to sterilize thermostable powders and fatty substances.
Conditions to achieve complete sterilization by dry heat sterilization are as follows:
Cycles recommended as per BP 1988 are:
* A minimum of 180 C for not less than 30 minutes.
* A minimum of 170 C for not less than 1 hour.
* A minimum of 160 C for not less than 2 hours.

👉🏻RADIATION STERILIZATION:
Mechanism of killing of microorganisms:
The radiation employed for the sterilization may be ionizing or non ionizing radiation. Gamma and X-rays, having energies more than about 10eV, are called ionizing radiations because they have enough energy to knock electrons away from molecules and ionize them. These radiations create free hydrogen radicals, hydroxyl radicals and some peroxides which cause different kinds of intracellular damage. The less energetic ultraviolet radiation cannot ionize and it is absorbed and excites the electrons and rises them to higher energy states, thus finally destroying the cellular structure of the microorganism. When properly operated, the UV radiation technique can reduce the level of airborne bacterial contamination in a room by 90% within 30 min.
Pharmaceutical products are more resistant to degradation by ionizing radiation if they are in a powdered form than in a liquid form. Thermolabile drugs such as penicillin, streptomycin, thiamine, and riboflavin have been effectively sterilized by ionizing radiation. In hospitals, UV radiation is used to control the spread of infection during or after surgical procedures.

👉🏻CHEMICAL STERILIZATION: 
This process involves exposure of materials to sterilize gasses such as ethylene oxide, formaldehyde, glutaraldehyde , propylene oxide.
Gaseous sterilization is accomplished by exposure to a gas that kills microorganisms. The most commonly used gas for sterilization is ethylene oxide. Ethylene oxide acts by alkylation. Ethylene oxide is a cyclic ether that has flammable and explosive properties, especially when confined and mixed with oxygen. It is therefore often used in combination with inert gases such as carbon dioxide to avoid hazard. The effectiveness of ethylene oxide in the sterilization process depends on relative humidity, gas concentration, temperature, exposure time, and the extent of contamination. The normal working ranges for the relative humidity and ethylene oxide concentration are 30 to 60% and 500 to 1000 mg/l, respectively. At these ranges, the times required for complete sterilization are 2 to 5 h at 55 C. In practice, an exposure time of 6 h or more is normally used to provide a safety margin. Ethylene oxide sterilization is effective in sterilizing a wide variety of materials including surgical instruments and gloves, plastic syringes, disposable needles, tubing sets, and dialysis units. In addition, it is often used to sterilize thermolabile powdered drugs such as penicillins. However, some drugs, for example, thiamine, riboflavin, and streptomycin, lose potency when treated with ethylene oxide.
Phenol and phenolic compounds produces a variety of effects on the microorganisms. Based on their concentration they exert various effects like disruption of cells, precipitation of cell protein, inactivation of enzymes and lekage of aminoacids from the cells.
Other chemical agents include alcohols, halogens, heavy metals and their compounds, dyes, detergents, quaternary ammonium compounds and aldehydes etc.

👉🏻FILTRATION STERILIZATION:
This method is used for sterilizing thermolabile solutions, which will otherwise be degraded by other conventional heating methods. The drug solutions are passed through the sterile bacteria proof filter unit and subsequently transferring the product aseptically into the sterile containers which are then sealed. Depth and surface filtration are suitable for prefiltration of pharmaceutical products as they can retain large amounts of particles. To strerilize a product it is often necessary to combine several types of filtration to achieve removal of microorganuisms.
👉🏻swapnil✌🏻

Tuesday, February 9, 2016

What is GMP

GMP is that part of Quality Assurance which ensures that the products are consistently manufactured and controlled for the purpose of their intended use or as required by marketing authorization.
This covers all the matters related to the quality and repeatedly ensures that the quality of reliability which is reproducible. It is secured for all the time with an objective of serving the exact needs of the customer and also fulfills the requirements of regulatory agencies around the world.
GMP as per Guidelines
The MCA (UK) states
   GMP is that part of Quality Assurance which ensures that the products are consistently manufactured and controlled for the purpose of their intended use or as required by marketing authorization and product specification.
The MCC (South Africa) states
   GMP is that part of Quality Assurance which ensures that the products are consistently manufactured and controlled for the purpose of their intended use as per legal requirements, marketing authorization and product specification. It also adds that the GMP is thus concerned with both Production and Quality control matters.
Good Manufacturing practice is that part of Quality Assurance which ensures that the products are consistently produced and controlled to Quality Standards appropriate to their intended use and as required by marketing authorization.
GMP is aimed at eliminating inherent risks in any Pharmaceutical production. Such risks are Cross-Contamination (especially from unexpected contaminants) and mix-ups caused by e.g. false labels put on container.
Drugs and Cosmetics rules 1945 published as require by sections 12 and 33 of The Drugs and cosmetics Act 1940.
The Schedule M of the said act talks about Good Manufacturing practices and requirements of premises, plant and equipment for Pharmaceutical products.

Importance of heavy metal. Test

🌟pharma discussion🌟
❓ Water for pharmaceutical use shall be free heavy metals why ?
🅰 Heavy metals like lead and arsenic are highly cumulative neurotoxic metals, heavy metals are not eliminated out of our body easily like other drugs and molecules but heavy metals bind with proteins and tend to get accumulated in fatty tissues, nerve tissue is most likely to get damaged by heavy metals, heavy metal causes nervous tissue damage there for water must be free from heavy metals.
👉🏻swapnil✌🏻

Tips for resume

🔱Pharma discussion 🌟
😎क्या आपका रिज्यूम मोबाइल फ्रेंडली है , कैसे चैक करें ❓

👩🏻रिक्रूटर भी हम लोगो की तरह ही होते है , उनके पासहज़ारो काम होते है , उनका समय बहुत सारे कामों मेंबंटा होता है। आज जब मोबाइल बहुत विकसित (Hi -tech ) है तो , लोग अक्सर अपने बहुत सारे काममोबाइल पर ही करना पसंद करते है , जैसे ईमेल चेककरना और रिप्लाई करना , ऐसे ही वो आपका रिज्यूमभी मोबाइल पर चैक कर सकते है , पर क्या आपकारिज्यूम मोबाइल फ्रेंडली है , मतलब क्या वह मोबाइलपर भी कंप्यूटर की तरह ही देखा जा सकता है।

आमतौर पर लोग बहुत कम धैर्यवान होते है , और आज के बड़े जॉब मार्किट में हज़ारो कैंडिडेट उपलब्ध है , अगर आपका रिज्यूम मोबाइल पर सही से नहीं दीखता तो वो उसे छोड़ सकते है , और ये आपके लिए एक अच्छी जॉब गंवाने जैसा हो सकता है।

हम आपको कुछ ऐसी बातें बता रहे है जो आपको अपना रिज्यूम बनाते समय ध्यान में रखनी चाहिए।

👉🏻डाउनलोड करने में आसान हो :

कल्पना कीजिये रिक्रूटर ने आपका रिज्यूम डाउनलोड किया और वो डाउनलोड होने में बहुत अधिक समय ले , तो अगर वो आपके रिज्यूम को बिना देखे ही छोड़ दे तो इसमें कोई बड़ी बात नहीं , पर ये आपके लिए दुर्भाग्यपूर्ण हो सकता है। इसलिए अपने रिज्यूम में सिंपल फॉण्ट का इस्तेमाल करें , और बहुत ज्यादा कलर या इमेज का इस्तेमाल न करे , ये आपकी फाइल को हैवी बना देते है , और हमारे देश में जहाँ अभी इंटरनेट उतना विकसित नहीं है , तो रिज्यूम को डाउनलोड होने में दिक्कत आ सकती है

👉🏻महत्वपूर्ण बातों को हाईलाइट करें :

रिक्रूटर सबसे पहले आपके रिज्यूम को सामान्य नजर से देखता है  , और अगर उसे आपके रिज्यूम में कुछ विशेषता नजर आती है तब ही वो आपके रिज्यूम को

आगे पढता है या उसमे अपनी दिलचस्पी जाहिर करता है।  और अगर आपका रिज्यूम मोबाइल पर सही से देखा जा रहा है और उसमे वो विशेष बाते उसे पहली नजर में मिल जाती है जो उसे अपने कैंडिडेट में चाहिए , तो वो जरूर आपके रिज्यूम को इंटरव्यू के लिए चुनना चाहेगा।

👉🏻अपने महत्वपूर्ण लिंक्स को हाइपरलिंक करें :

आपको अपने प्रोफाइल से जुड़े महत्व पूर्ण लिंक्स को हाइपरलिंक करना चाहिए , जैसे आपका फ़ोन नंबर , ईमेल , और लिंक्ड इन  अकाउंट रिज्यूम में हाइपर लिंक किया होना चाहिए जिससे रिक्रूटर आसानी से आपके प्रोफाइल को चेक कर सके और जरुरत पड़ने पर बिना दिक्कत  आपको कांटेक्ट कर सके।

👉🏻पढ़ने में आसान हो :

आपके रिज्यूम का मोबाइल व्यू , एक न्यूज़ पेपर आर्टिकल की तरह होना चाहिए ,जिसमे आपके बारे में जानकारी दी जा रही है , जो आसानी से पढ़ा जा सके और इतने अच्छे ढंग से प्रस्तुत किया गया हो की वो पढ़ने वाले को लगे की इस रिज्यूम को पूरा देखा जाना चाहिए। इसलिए आपके रिज्यूम का पहला एक तिहाई हिस्सा बहुत महत्वपूर्ण है।  इस हिस्से में आपकी शैक्षिक योग्यता (Qualifications ) , आपकी स्किल (Skill ) आदि होनी चाहिए।  वाक्यों (sentences) को छोटा और स्पष्ट रखें। और महत्वपूर्ण चीज़ो को बुलेट्स बना कर लिखें।

😊और अंत में अगर आपने अपना रिज्यूम बनाते वक़्तइन सभी बातो को ध्यान में रखा है तो अपने रिज्यूमको एक बार , जितना सम्भव हो सके अलग अलगतरह मोबाइल , टेबलेट या आई फ़ोन में चैक कर लें।

👉🏻swapnil✌🏻

Force degradation

🌟pharma discussion🌟
❓Forced degradation(stress testing) and accelerated stability testing are same?
🅰. Forced degradation and stress testing are not same. Stress testing is likely to be carried out on a single batch of the drug substance. The testing should include the effect of temperatures (in 10°C increments (e.g., 50°C, 60°C) above that for accelerated testing), humidity (e.g., 75 percent relative humidity or greater) where appropriate, oxidation, and photolysis on the drug substance. The testing should also evaluate the susceptibility of the drug substance to hydrolysis across a wide range of pH values when in solution or suspension. Photo stability testing should be an integral part of stress testing.
👉🏻swapnil✌🏻

Monday, February 8, 2016

Dry Fogging in Pharma clean rooms

Minncare Dry Fog System increases efficacy for large pharma company

When other methods failed to meet their room disinfection standards, a large Midwest pharmaceutical plant selected the Minncare Dry Fog System from Mar Cor Purification, and it was up to the task.
With the advances and innovations in the medical industry, the need for microbiological clean environments has been ever-increasing. Room disinfection and clean environments go hand-in-hand, and many microbiology sensitive industries rely solely on their cleanrooms for production, research and development. With strict government regulations, customer liabilities and heavy competition a plant must have a quality disinfection process to continue innovating and producing.

The main reason was to eliminate formaldehyde and to have a faster process. Formaldye takes much longer to return to service because it is a hazardous chemical. The Midwest pharmaceutical plant was searching for a system that would increase automation, improve efficacy and achieve higher levels of reliability compared with its other systems; it decided to try critical area fogging and selected the Minncare Dry Fog System.
One DF system is capable of disinfecting rooms up to 35,000ft3. With droplet sizes of only 7.5µm, dry fogging droplets bounce off solid surfaces, eliminating excess condensation, the possibility of corrosion, and surface wetting, providing a cleaner, more thorough disinfection process than other fogging methods and manual spray-and-wipe.

The plant had already used two other disinfection procedures, H202 (hydrogen peroxide) and formaldehyde, but the methods left them unsatisfied. To see if the Minncare Dry Fog System was right for them, the plant conducted tests in the staging area for large parts and equipment about to be brought into the cleanroom, and also the active pharmaceutical ingredient production area – an area requiring exhaustive and thorough disinfection, which previously required the plant to be evacuated for days.

The plant found the Dry Fog process to be effective in these test areas and recommended moving forward with the use of the system throughout its cleanroom facilities
Swapnil Bhardwaj

What do you mean by linking e-records to e-signatures?

What do you mean by linking e-records to e-signatures?

  
Part 11 Sec. 11.70 states that electronic signatures and handwritten signatures executed to electronic records must be linked (i.e. verifiably bound) to their respective records to ensure that signatures could not be excised, copied, or otherwise transferred to falsify another electronic record. The agency does not, however, intend to mandate use of any particular 'linking' technology. FDA recognizes that, because it is relatively easy to copy an electronic signature to another electronic record and thus compromise or falsify that record, a technology-based link is necessary. The agency does not believe that procedural or administrative controls alone are sufficient to ensure that objective because such controls could be more easily circumvented than a straightforward technology based approach.

What is Grain direction

❓Grain direction
🅰Paper Grain Direction
Yes, just like wood, paper has a grain. The grain in paper comes from how the fibers of the paper are arranged. The fibers are typically parallel to each other across the sheet and knowing the grain direction is important when we go to fold the sheet of paper.

If we fold against the grain, then the fibers crack and we get an uneven or rough fold and the fold won’t be as clean or flat as we might want. Going parallel to the grain reduces the cracking and we get a smooth, flat fold.

☀How to determine the grain
With thinner papers it is harder to tell the grain direction, heavier papers are more obvious and easier to determine.

♨Three quick tests to check for grain direction

1) Tear Test – Take a sheet of paper and tear it horizontally and then vertically. One tear should have been straighter than the other. The tear that was straighter is parallel to the grain, the jagged tear is going across the grain.

2) Bend Test – Take a sheet of paper, bend the paper (don’t fold or crease it) horizontally and vertically. There will be less resistance in one direction than the other. The bend with less resistance is parallel to the grain.

3) Fingernail Test – Take a sheet of paper and using the fingernails of your thumb and middle finger pinch the paper and slide them across and then down the paper. One direction should produce a “wave”, the wave indicates that you went across the grain.

🌟Short or Long Grain
Papers can be referred to as short or long grain, this refers to the direction the grain is running. Is it running across the short dimension or the long dimension of the paper?

👉🏻Short Grain – The grain runs parallel to the short edge of the paper.

👉🏻Long Grain – The grain runs parallel to the long edge of the paper.

✌🏻A quick way to tell the grain direction is by reading the package the paper came in. The second number in the paper’s dimension indicates the grain. So if we have an 11×17 sheet of paper, the grain is running parallel to the 17-inch edge of the sheet and is referred to as Long Grain. If the paper is 17×11, then the grain is running parallel to the 11-inch edge of the paper and is referred to as Short Grain.

👉🏻Folding and Grain
You should always plan your folds to go with the grain of the paper. This is something our Job Planners do each time you submit a job. They figure out how to engineer your job and then they know which grain direction to order.

😊Sometimes you can have two folds, one that goes with the grain and one that goes across. We can minimize the problems of going across the grain by using a letterpress score. What we recommend is creating a die to score the cross grain folds. This literally bends the fibers of the paper in the direction we want to fold the paper and reduces the cracking we might get with a convention score and fold.

👉🏻swapnil✌🏻

What is the difference between QA & QC ?

What is the difference between QA & QC ?                             ✒Difference between Quality Assurance and Quality Control:


🔨 QA - Decision maker

💣QC - Service department

🔨 QA - Controls / more conscious about the hidden quality in the product.

💣QC - Checks the apparent quality of the product.

🔨 QA - has different tools like, in-process checks, validation, qualification, etc. and develops its own specifications (RM/PM/FG).

💣QC - single tool i.e. Specification & test methods which are already given by diff. pharmacopoeia (IP/EP/USP/etc).

🔨Quality Assurance is a part of quality management process which concentrates on providing confidence (assures) that quality requirements must be fulfilled.

💣Quality Control is a part of quality management process which concentrates on fulfilling the quality requirements.

🔨Quality Assurance is a set of activities for ensuring quality in the processes by which products are developed.

💣Quality Control is a set of activities for ensuring quality in product. The activities focus on identifying defects in the actual products produced.

🔨 Quality Assurance is the process of managing for quality;

💣Quality Control is used to verify the quality of the output.

🔨Quality Assurance develops the quality in the product.

💣Quality Control checks🔎 the Quality of the product.

🔨The goal🏫 of Quality Assurance is to prevent introducing defects in the PRODUCT which help to improve the development and testing processes.

💣The goal of Quality Control is to identify the defects in the PRODUCT after it is developed.

🔨QA is Pro-active means it identifies weaknesses in the processes.

💣QC is Reactive means it identifies the defects and also corrects the defects or bugs also.

🔨 QA - It does not involve executing the program or code.

💣QC - It always involves executing the program or code.

🔨 All peoples who are involved in the developing PRODUCT responsible for the quality assurance.

💣Testing team is responsible for Quality control.

🔨 Quality Assurance is process oriented.

💣Quality Control is product oriented.

🔨 Quality Assurance basically aims to prevention of defects to improve the quality.

💣Quality Control basically aims to detection of defects to improve the quality.

🔨QA - It identifies weakness in processes to improve them.

💣QC - It identifies defects to be fixed.

🔨 Verification is an example of Quality Assurance.

💣Validation/Testing is an example of Quality Control.

🔨QA - It is a staff function.

💣QC - It is a line function.

🔨 QA - It is done before Quality Control.

💣QC - It is done only after Quality Assurance activity is completed.

🔨Quality Assurance means Planning done for doing a process.

💣Quality Control Means Action has taken on the process by execute them.

🔨Quality Assurance dept. has more concerned about the impurity in the product rather than the purity.

💣Quality Control dept. has more concerned about the purity in the product.

🔨 Quality Assurance deals with the Quality of total yield quantity of the product.

💣Quality Control deals with the small sample quantity for checking the Quality of the product.