ASEMINAR ON

VALIDATION OF SOLID DOSAGE FORMS

Babu Banarasi Das University, Lucknow

PRESENTED BY-Naincy GuptaM.PHARM (IInd Sem) PHARMACEUTICS

INTRODUCTIONSolid Dosage Forms- A substance having definite shape and

volume manufactured for the administration of active and/or inert

ingredient(s).

Solids include tablets, capsules, powders, granules and certain

suppositories.

Disadvantages of Solid Dosage Forms

1) Difficult to swallow.2) patients cannot swallow pills.3) Takes longer to absorb in the body.

Advantages of Solid Dosage Forms

1) More accurate dosing.2) Releases medication over a longer period of

time.

VALIDATION

DEFINITION - :

QUALITY ASSURANCE DEPT; API DEFINITION - VALIDATION Validation word derived from ‘valid’ which means “can be justified or defended”.

Validation is a systematic approach to identifying, measuring, evaluating ,documenting,& reevaluating a series of critical steps in manufacturing process that require control to ensure are producible final product.

Validation is an established documented evidence which provides high degree of assurance that a specific equipment, process,

method or system will consistently produce results meeting its predetermined specifications and quality characteristics”.

VALIDATION OF RAW MATERIALS

1) Validation begins with the raw materials, active pharmaceutical ingredients excipients.

2) Raw materials, major causes of product variation or deviation from specification.

3) Most uncontrollable component in the complete product/process validation scheme because morphology particle size/surface area not be completely defined this early.

It includes validation of both active ingredients& excipients.

Characteristics - particle size, surface area, color, density.

Chemical characteristics- water content residue on ignition & heavy metals.Variables: Flow, blend uniformity, granulation solution/binder uptake compressibility, lubricant efficiency.

Example1) Mg sterate (lubricant). Its action depends on particle size. 2) dyes (color) variation in material occur depending upon...a) Method of transportation chosen.b) Exposure of material to undesirable conditions (heat and humidity)

RAW MATERIALS & ITS IMPORTANCE

• Chemical characteristics : Drug impurities can affect the stability.

• Physical properties: Drug morphology, solubility & particle size/surface area may affects drug availability.

• The particle size, shape , and density can affect material flow and blend uniformity.

• The hygroscopic drug caring in handling the material and the reproducibility of the manufacturing process.

STEPS FOR RAW MATERIALS VALIDATION

1. Each raw material validated by testing at least 3 batches from primary & alternate supplier ; representing the ranges, both high and low.

2. Depending on the susceptibility aging, physical, chemical, and/or microbiological stability should be assessed.

3. If under acceptable range, especially for materials sensitive to small changes; then appropriate to use several lots of raw material with low and high ends of the specification.

4. The final step of raw material validation should involve an on-site inspection of the vendor’s to review the manufacturing operations, controlling & conforming to regulatory requirements.

ANALYTICAL METHOD OF VALIDATION

Prior to any validation program analytical criteria must be assessed are- Accuracy of method: true valuePrecision of method: estimate reproducibilitySpecificity: accurately measure a SPECIFIC analyte in the presence of other components.• out-of-day variation:• operator variation• instrument variation • laboratory variation

NEED OF ANALYTICAL METHODS VALIDATION

Analytical methods need to be validated, verified, or revalidated in the following instances -1) Before initial use in routine testing. 2) When transferred to another laboratory. 3) Whenever the conditions or method parameters

for which the method has been validated change (for example, an instrument with different characteristics or samples with a different matrix) and the change is outside the original scope of the method.

DEVELOPMENT OF ANALYTICAL METHOD

Cognizant of the laboratory conditions

development of analytical method

routinely run ensuring the validity & ruggedness

if less than optimum or if deficient

re- evaluation

method modified---- high accuracy , greater efficiency &

high reproducibility preferred if automated--- expertise training

CONTROL OF PROCESS VARIABLES

DefinationA process variable, is the current status of a process under control. The process variable is a dynamic feature of the process which may change rapidly.Accuate measurementvof process variable is important for the maintanance of accuracy in a process.

• An example of this would be the temperature of a furnace. The current temperature is called the process variable, while the desired temperature is known as the set-point.

Importance1) Measurement of process variables are

important in controlling a process.2) The process variable is a dynamic feature of the

process which may change rapidly. Accurate measurement of process variables is important for the maintenance of accuracy in a process.

3) There are four commonly measured variables which affect chemical and physical process: pressure, temperature, level and flow.

Process variables:Is for consistent production; by challenging a process during development to determine variables to becontrolled.(for as quality means & specification compliance) Steps in development of validation program- 1) Obtaining test data to determine the numerical range of each parameter. Example-Assess the tablet hardness over a series batches.

2) Establishings pecification limits from the test data derived for a given parameter.

3) Determine how well the specification limit Indicates that the process is under control.

4) Certify the eqipment operating condition.

Example- rpm,temp are within specification limits.

Process Validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products.It is an establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics.”

CONTROL OF PROCESS Validation

Defination

PARAMETERS FOR ESTIMATION OF PROCESS

VALIDATIONProcess validation is generally done with three consecutive batches. All the critical parameters were evaluated for fixing the optimum process parameters. Every processing step is validated for all the three batches and the results obtained must be present within the acceptance criteria, such that the product can be forwarded for the commercial production. All the problems that arise during validation are overcome and the product will be kept ready for the commercial batch production.

CHANGE CONTROL

• Must be a review procedure for validated processes• From time to time changes may be

necessary• Documented change control procedure

needed• changes do not require re-validation

• Written procedures should be in place to describe the actions to be taken if a change is proposed to a product component, process equipment, process environment, processing site, method of production or testing or any other change that may affect product quality or support system operations.

• All changes must be formally requested, documented and accepted by the validation team. The likely impact / risk of the change on the product must be assessed and the need for the extent of re-validation should be determined.

General view of process validation

Schematic diagram of processing steps and respective in-process variables during tablet

manufacture

CAUSE-AND-EFFECT OR "FISHBONE DIAGRAM

1)The"fishbone" diagram represents all possible relationships and interrelationships that may exist among the various process variables (possible causes) and the single response or product attribute (effect) affected during the manufacture of a tablet dosage form.

2) The central line of the cause and effect diagram is a composite of all the possible factors that may influence the

quality and consistency of dose uniformity of the tablet . 3) Branches off the central line represent the influence of the

six unit operations or process steps. 4)The principle process variables for each process step that can

cause or influence the final outcome are depicted as sub-branches off each of the six main branches.

BENEFITS

1) Helps determine root causes.2) Encourages group participation.3) Uses an orderly, easy-to-read format to diagram cause

and effect relationships.4) Indicates possible causes of variation.5) Increases knowledge of the process by helping

everyone to learn more about the factors at work and how they relate.

6) Identifies areas for collecting data.

GUIDELINES FOR PROCESS VALIDATION

SOLID DOSAGE FORMS (TABLETS): A) Tablet Composition: 1) Normal properties 2) Density 3) Particle size distribution4) Surface area 5) Flow properties 6) Moisture content7) solubility

• B) Process evaluation & selection 1) Blending operation2) Determine time of un mixing 3) Characteristics of blend

Bulk density Particle size distribution

4) Color uniformity

C) Wet granulation1)Evaluation of binder

Binder concentration Solubility in granulating solution

2)Evalution of mixed granulation3)Evalution of drying

D)Tablet compression 1)Appearance 2)Color quality 3)Powder flow 4)Speed of tablet machineE)Tablet coating 1)Evaluate coating procedure in different size pans 2)Coating speed 3)Amount of material required application

D) Equipment evaluation1) Blending equipment 2) Granulating equipment3) Tablet equipment4) Tablet coating

Check list of Validation and Control Documentation

Sr. No. Selection of cGMP Validation and control documentation

1 Introduction Establishing of QA & PV functions

2 Organization and personnel. Establishment and facility installation and qualification

3 Buildings and facilities Plant and facility installation qualificationMaintenance and sanitationMicrobial and pest control

4 Equipment Installation and qualification cleaning methods.

5 Air and water quality Water treatment and steam systems air, heat, and vacuum handling.

6 Control of raw material, in-process material, product

Incoming components Manufacturing non-sterile products

7 Production and process controls Process control systems (instruments and computers)

8 Packing and labeling controls Depyrogenation, sterile packing, filling, and closing.

9 Holding and distribution Facilities

10 Laboratory controls Analytical methods 11 Records and reports Computer systems 12 Returned and salvage drug products Batch processing

THANKING

YOU