Sterilization Methods and the Design on Sterilization Process

What are pharmaceutical cleanrooms?

A controlled environment that protects pharmaceutical products from contamination and pollutants such as dust, airborne microbes, and aerosol particles -subject to FDA validation -focus on BOTH nonviable (inanimate) and viable (live) contamination -Use aggressive chemical and UV light cleaning on surfaces to maintain sterility

Equipment qualification

-qualification of sterilization equipment and its associated utility systems MUST be performed prior to beginning the performance -The reproducibility of sterilization cycles is largely dependent on controls, utilities, mechanics of sterilizer, and its ability to consistently operate according to expectations

Ionizing radiation

-used for commercial sterilization -must have good penetrating power, high sterilizing efficiency, little or no damage, and be efficient

Dry heat sterilization

-used for heat-stable and non-aqueous preparations, powders, containers -heat is carried from radiation, convention, and conduction -takes longer to sterilize for two reasons: 1. dry heat kills microorganisms by oxidative processes which are less efficient than hydrolytic mechanisms of steam 2. Dry air does not possess latent heat

Physical methods of sterility

1. Dry heat sterilization 2. Moist heat sterilization 3. Radiation Sterilization

Cultures used in sterility testing

1. Fluid thioglycollate is primarily suitable for the growth of anaerobic bacteria 2. Soybean casein digest medium (aka tryptone soy broth) is suitable for aerobic bacteria and fungi

Three main approaches to sterilization cycle development

1. Overkill 2. Bioburden/biological indicator (BB/BI) 3. Bioburden

General methods of sterility

1. Steam (heating in autoclave) 2. Dry heat (hot air oven) 3. Ionizing radiation 4. Ethylene Oxide 5. Filtration

Chemical methods of sterility

1. Sterilization by heating with bactericide 2. Gaseous Sterilizati6on

Benefits of good manufacturing hygiene resulting in low microbial levels

1. shorter autoclaving times -> reduced energy costs 2. Shorter heat exposure -> reduced degradation of active ingredient 3. fewer dead bacterial cells in the product -> reduced risk of injection failing the bacterial endotoxins test

Biological Indicators operate on the basis of ____.

Color change

(T/F) Gamma beams are faster than electron beams

False

(T/F) High energy elections require a radioactive source

False, they don't because they are generated electrically

(T/F) It's possible to guarantee or prove that an article is sterile.

False, you can only make a probability that it is sterile

Sterilization by radiation

Frequently used agents are infrared radiation, ultraviolet light, gamma radiation, and high-velocity electrons -Gamma radiation is rarely used for water-containing products

D value

The rate at which microorganisms are killed in a sterilization process is expressed as the D-value (decimal reduction time), which is the time required to reduce the population to 10% of its initial value -the lesser the D value, the more effective the sterilization because the microorganism was killed in a shorter amount of time -depends on 4 factors 1. Types of microbes: small microbes die faster than large ones 2. Composition of microbes: shape of bacteria, if they have a capsule 3. The surface on which the operation is done 4. Temperature: the higher the temperature, the higher the effectiveness

(T/F) Ionization causes free radical production and damage to DNA

True

(T/F) Steam sterilization is the most common and most reliable method to sterilize items

True

(T/F) Sterility is an absolute concept. There are no degrees of it; it's either sterile or it's not.

True

Gas sterilization

Two main agents are oxidizing and alkylating agents, can sterilize without damage

Bioburden/biological indicator approach

a method where incomplete destruction of a resistant biological indicator can be used to demonstrate the capability of the process to reliably destroy any bioburden

Bioburden approach

a method where multiple bioburden isolates from the material are evaluated for resistance to sterilization methods and utilized as biological indicators to demonstrate the lethality of the process

Z value

a parameter which indicates how killing rate is influenced by temperature -defined as the number of degrees in Celsius the temperature has to be increased to achieve a tenfold reduction in the D value. -the smaller the Z value, the greater the sensitivity of the microorganism toward the change in temperature

Overkill approach

a process where destruction of high concentration of resistant microorganism supports the elimination of bioburden that might be present in routine processing

Moist heat sterilization

heat and moisture kills microorganisms on objects and surfaces

Sterility Assurance Level

quoted as 10^6 (1 living organism per 1,000,000 items)

Inactivation factor

the inactivation factor quantifies the proportion or number of microorganisms killed by a sterilization process

F value

the time required to kill a specific population of bacteria at a specific or constant temperature -F values enable the killing effect of one autoclave cycle to be compared with another

Sterilization by filtration

useful in noticing small members of bacteria