VALIDATION OF RAW MATERIALS

Transcription

1 Seminar On VALIDATION OF RAW MATERIALS By S.Rajesh kumar M.Pharmacy I SEM Department of Industrial pharmacy University college of pharmaceutical sciences Kakatiya university

2 CONTENTS INTRODUCTION TO VALIDATION DEFINITION OF VALIDATION QUALITY ATTRIBUTES WHY TO VALIDATE WHEN TO VALIDATE DEFINITION OF RAW MATERIAL STEPS INVOLVED IN RAW MATERIAL VALIDATION CONCLUSION REFERENCES

3 VALIDATION Validation is the scientific study of a system To prove that the facility/system/equipment/method is consistently doing what it is supposed to do (i.e., that the process is under control). We want to make decisions based on good science and not hunches and assumptions! To determine the process variables and acceptable limits for these variables, and to set-up appropriate in-process controls. 1

4 FDA DEFINITION OF VALIDATION Validation is a process of demonstrating, through documented evidence, that a process, procedure, method, piece of equipment, or facility will consistently produce a product or result that meets predetermined specifications and quality attributes. 2

5 Quality Attributes Identity Safety Potency Purity Stability Efficacy 3

6 Why validate? It is required by the current good manufacturing practice(cgmp) regulations promulgated by the US FDA. It should be performed because it is in accord with good business judgment. 4

7 WHEN A PROCESS SHOULD BE VALIDATED The following model may be useful in determining whether or not a process should validated: A Is Process Output Verifiable YES B Is Verification Sufficient & Cost Effective YES C Verify & Control the Process NO NO D Validate E Redesign Product and/or Process 5

8 DEFINITION OF RAW MATERIAL RAW MATERIAL: It is a term used to denote starting materials, reagents and solvents intended for use in the production of intermediates or active pharmaceutical ingredient(api). 6

9 RAW MATERIAL VALIDATION Several steps are required to validate a raw material. They are as follows: (I) LIST ALL THE RAW MATERIALS NEEDED TO PREPARE A PRODUCT BATCH. The list should include the materials used in production and testing Active ingredients Excipients Processing aids Chemicals Official standards Laboratory materials 7

10 (II) IDENTIFY AT LEAST TWO SUPPLIERS FOR EACH RAW MATERIAL. After we have complete list of all raw materials needed, we must locate sources of these materials. It is always advisable to locate and validate at least two suppliers. EVALUATION FOR SELECTING A SUPPLIER: (1)Provide the raw material that we need (2)Must be capable of providing the grade that we want (3)Providing the quantity that we require (4)To provide increased quantities quickly (to evaluate the supplier s capacity) (5)Determine whether our supplier is a manufacturer or distributor? 8

11 (6) Cost of the raw material. (7) Reputation and reliability of the supplier. NOTE: He must use written standard operating procedures and establish proper raw material storage conditions and distribution procedures. Precautions Joint agreements Attention Investigation 9

12 (III) IF A SUPPLIER IS NEW, VISIT HIS FACILITY. It is important to establish a good relationship with a supplier. To meet representatives personally. Inspect his facility. 10

13 During the visit, it is also important to observe.. housekeeping and sanitation practiced The use of written procedures and logs proper segregation and batch identification The use of laboratory notebooks The size of the laboratory area and staff The use of up to date laboratory instrumentation production equipment. and 11

14 (IV) OBTAIN SAMPLES AND SUPPLIER S CERTIFICATES OF ANALYSIS To determine the characteristics of the raw material. The certificates of analysis and samples the extent of variation from lot to lot on specific tests. It is important to measure this variation between different lots from the same supplier and then the variation between suppliers. 12

15 (V) ESTABLISH SPECIFICATIONS FOR EACH RAW MATERIAL List of parameters. For each parameter listed, an acceptable, measurable range of activity should be established. Compendial raw materials And non- compendial raw materials 13

16 (VI) ESTABLISH TEST PROCEDURES. A test procedure must be established for each specification. For raw materials that are compendial, test procedures are denoted along with their respective specifications. For raw materials that are not listed in official compendia,we embark into methods development. This work calls on compendial methods that exist for similar compounds, which can be modified. It also calls for methods that are published literature. Documentation of so developed test procedures should be paid attention. 14

17 (VII) ESTABLISH SAMPLING PROCEDURES. Documentation of raw material sampling is developed. This procedure includes general requirements that may apply to any raw material received in the plant, such as The number of containers to sample(sample size). Method of sampling. Individual raw materials may have certain sampling requirements based on their stability and/or intended use. Before these individual sampling procedures are instituted in routine practice, they should be evaluated as part of process validation. 15

18 (VIII) ESTABLISH OPTIMUM STORAGE CONDITIONS Raw material containers must be handled and stored under prescribed conditions in order to protect their stability over the stated shelf life. The chemistry of each raw material should be reviewed and aspects concerning hygroscopity, sensitivity to light,sensitivity to high and low temperature extremes, ability to support microbial growth,reactivity with any container or closure system, and oxidising capability are checked. Once we have established the factors that critically affect a raw material, we can conduct stability studies that will indicate the optimum storage conditions and establish a shelf life for the raw material. 16

19 (IX) ESTABLISH SHELF LIFE Shelf life or expiry dating of a raw material is the time period within which it must be used. Some times we assign an expiry date that is shorter than our data indicate, so that we will always use fresh raw materials. The shelf life of a raw material is established by testing over time in the containers and closures to be used, after storage under the anticipated optimum conditions, and also under adverse conditions. 17

20 (X) CHALLENGE OF THE RAW MATERIALS. The last step required to validate a raw material is the operation in which the information that has been established concerning the raw material is challenged, to assure that is scientifically sound and meaningful. 18

21 CONCLUSION To build up quality in the final product a thorough control over each step of the process is required. This makes it essential to establish a documented evidence to be developed by thorough experimentation. So the raw materials are not an exception to this and they should be validated by opting an systematic approach. 19

22 REFERENCES Robert A. Nash, pharmaceutical process validation. Berry, I.R.,and Daniel harpaz, validation of active pharmaceutical ingredients. P.P.sharma, how to practice GMP S. Validation in API manufacturing plants.brussels:active pharmaceutical ingredients committee. Guide to Inspections Validation of Processes. Washington DC:use Food and Drug Administration. Validation of compendia Methods.The United States Pharmacopeia Convention,Inc.,

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