Process validation of capsule

1. Process Validation of
Capsules
Presented by: Arun Agarwal
(CSIR-JRF)
ID: 53253
Supervisor: Dr. Wahajuddin
(Principal scientist)
Division: Pharmaceutics and
pharmacokinetics

2. Validation
 The concept of validation was first proposed by two Food and Drug
Administration (FDA) officials, Ted Byers and Bud Loftus, in the mid
1970’s in order to improve the quality of pharmaceuticals.
 The prime focus of validation is on ensuring if the quality is built into
the system at every step, and not just tested for at the end.
 Validation is documented act of proving that any procedure, process,
equipment, material, activity or system actually leads to the expected
results.

3. Process validation
 USFDA defined process validation as,
“Establishing documented evidence which provides high degree of
assurance that a specific process will consistently produce a product
meeting its pre determined specifications and quality characteristics.”

4. Types of process validation
 Prospective process validation
 Prospective validation is carried out during the development stage by
means of a risk analysis of the production process, these are then
evaluated on the basis of past experience to determine whether they
might lead to critical situations.
 Concurrent process validation
 Concurrent validation is carried out during normal production. This
method is effective only if the development stage has resulted in a
proper understanding of the fundamentals of the process.
 The first three production-scale batches must be monitored as
comprehensively as possible.
 The nature and specifications of subsequent in-process and final tests
are based on the evaluation of the results of such monitoring.

5.  Retrospective process validation
 Retrospective validation involves the examination of past
experience of production on the assumption that composition,
procedures, and equipment remain unchanged; such experience
and the results of in-process and final control tests are then
evaluated.
 Revalidation
 Revalidation is needed to ensure that changes in the process
and/or in the process environment, whether intentional or
unintentional, do not adversely affect process characteristics and
product quality.

6. Importance of Process Validation
 Quality of product id assured
 Optimization of the process
 The cost of quality of product Is reduced
 The market recalls of product is minimized
 The process is under control and detail study is possible

7. Documents used in process validation
 Validation master plan
 The validation master plan provides an outlook of the overall validation
operation, its organizational structure, its content and planning.
 Validation protocol and report
 Validation protocol is a plan of actions stating how process validation will
be done, it specifies who will conduct the various tasks and defines the
testing parameters, sampling plans, testing methods and specifications.

8. A suggested scheme for the validation protocol and subsequent report
concerning a particular process is shown below:
 Purpose (the validation) and prerequisites
 Presentation of the entire process and sub-processes, flow diagram,
critical steps/risks.
 Validation protocol, approval.
 Installation qualification, drawings.
 Qualification protocol/report.
 Standard operating procedure (SOPs)
A Standard Operating Procedure is a document which describes
the regularly recurring operations to ensure that the operations
are carried out correctly (quality) and always in the same manner
(consistency).

9. Validation Process of Capsule

10. Validation steps
 Capsule composition
 Process evaluation and selection
 Encapsulation
 Equipment evaluation

11. Capsule composition
 Capsule shell
 Provide the reason for the presence of each ingredient In the capsule
formula.
 Justify the level and grade of each ingredient.
 Explain the selection of capsule size and shape
 Discuss the need for capsule identification (e.g. color or imprinting)
 Capsule shell content
 Establish the compatibility of capsule shell and his content.
 Determination of the hygroscopic nature of the material which could effect
the:
 Stability of the active ingredient
 Hardening of the material which decrease the dissolution rate
 Brittleness of the capsule shell

12. Process evaluation and selection
 The process to manufacture the contents of a hard gelatin
capsule is the same as a tablet.
 It may required only a blending step, such as a direct
compression tablet, or several unit operations, such as a wet
granulation tablet (e.g., mixing, wet milling, drying, dry
milling, and blending). In either case, the materials are then
encapsulated in a capsule shell.

13. Encapsulation
 Encapsulation is a critical step in the production of capsules, similar to the compression
step for tablet dosage forms.
 The materials may also need to be compressible in order to be dosed into the capsules;
however, they should also be easily disaggregated so not to adversely affect the
dissolution of the drug.
Factors to consider during encapsulation are:
1. Encapsulation type:
The type of encapsulation technique (e.g., auger, vacuum, dosator) required for the
formulation needs to be determined and justified.
Examples are:
 Auger: Capsugel Type B or Elanco No. 8
 Vacuum: Perry
 Vibratory: Osaka
 Dosing disk: H&K
 Dosator: MG2 or Zanasi
*The type of technique may be dependent on such factors as drug or formulation properties and equipment
availability.

14. 2. Encapsulation speed:
The formulation should be encapsulated at a wide range of speeds to determine the
operating range of the encapsulator. By examining the capsule weights, the adequacy
the material’s flow will be determined.
The following in-process tests should be examined during the encapsulation step:
 Appearance
 Capsule weight
 Disintegration
 Weight uniformity

15. Equipment evaluation
1. What is the encapsulation mechanism (e.g., auger, dosing disk, dosator)?
2. How many encapsulation stations does the encapsulator have?
3. What is the operating range of the unit?
4. What is the output range of the encapsulator (i.e., capsules per min)? Will the unit
meet the demands (sales forecast) for the product?
5. What kind of powder feeding capabilities does the equipment have(e.g., gravity- or
power-assisted)? Can this capability be altered or controlled?

16. 6. How long can the equipment operate without routine maintenance?
7. How long is the turn around time for complete cleaning? This downtime can be
significant and may affect the need for a multi-shift operation or additional
machines.
8. Does the equipment possess automated weight control capability?
9. Can the equipment perform a specialized function in addition to basic
encapsulation (e.g., tablet in capsules with excipient backfill)?
10. Is the unit capable of being contained to protect the operator and environment?

17. References
 Jeffrey S. Rudolph, R. J. S. (2003). Validation of Solid Dosage Forms.
Pharmaceutical Process Validation. A. A. W. Robert A. Nash, Marcel Dekker, Inc.
129: 198-229.
 https://apps.who.int/medicinedocs/en/d/Js5516e/16.6.html (Accessed on 2nd
October 2019).

18. Thank you!!