Process Validation

Question 1

FDA Process Validation Def

Answer 1

Collection and evaluation of data from process design to commercial production stage. Scientific evidence; consistently delivers quality product

Question 2

EMA Process Validation Def

Answer 2

Documented evidence that the process (operated in established parameters). Effectively and reproducibility to produce medicinal product to meet predetermined specifications and quality attributes

Question 3

Purpose of Process Validation

Answer 3

Confirms proper design of manufacturing process to ensure quality product (quality assurance, defect minimisation and reduces cost). Regulatory requirement: evidence for process control

Question 4

FDA Process Validation Stages

Answer 4

Process Design, Process qualification and Continued process validation

Question 5

FDA Process Design Outline

Answer 5

Commercial manufacturing based on knowlege gained through development and up-scale up activities

Question 6

FDA Process Qualification Outline

Answer 6

Evaluation of process design to determine if capable of reproducible commercial manufacturing. 2 parts: Facility Design & Qualification of Utilities and Process Performance Qualification

Question 7

FDA Continued Process Verification Outline

Answer 7

Ongoing assureance (in control) gained in execution of routine process

Question 8

EMA Equivalent to FDA’s Continued Process Verification

Answer 8

Ongoing Process Validation

Question 9

EMA Pharmacovigilance, FDA Equivalent

Answer 9

PPQ part 2 phase

Question 10

3 Stages of Product Lifecycle

Answer 10

Product & process dev, Commercial manufacture process and Process control maintenance

Question 11

Areas FDA & EMA Guidance

Answer 11

Drug product, Drug substance and Biologics for Human & Vetinary medicines

Question 12

3 Different Forms of Process Validation

Answer 12

Traditional, Continuous and Hybrid

Question 13

EMA Traditional Process Validation Outline

Answer 13

When pharmaceutical/process dev is concluded and scale up production scale prior to marketing. Manufacture number of consecutive batches at production scale under normal operating procedures

Question 14

Number of Batches Consideration

Answer 14

Process variability, Process complexity, Knowledge gained, Supportive Commercial scale data, Manufacturer overall experience

Question 15

Min batches for Traditional Process Validation

Answer 15

3 production batches (unless otherwise specified). 1 or 2 may suffice if enough data’s generated from piolet scale. Needed for critical manufacturing steps, conduct additional tests as necessary

Question 16

EMA Continuous Verification Outline (NOTE: Different from FDA’s)

Answer 16

Pre-approval eval for products developed by QbD approach to ensure adherence to control strategy and high assurance of product quaity. Enabled by Process Analytical Tech & Multivariate Statical Process Control

Question 17

How is EMA’s Continuous Verification Different from FDA’s

Answer 17

Continuos FDA = Ongoing EMA = Post-Approval. Continuos EMA = during approval

Question 18

EMA Continuous Process Validation Methods

Answer 18

At line (sample extracted from line, tested with equip in room and disposed), In line (probes on line, sample doesn’t need to be extracted), On line (sample extracted, tested in room & returned). Or QC labs

Question 19

EMA Hybrid Process Approach

Answer 19

Traditional and continuous verification at different steps of same process. Used for: Post-authorisation validation activities and Ongoing process verification

Question 20

Validation Considerations

Answer 20

Cover all manufacturing site, Bracketing approach (if eval different batch sizes, strengths & pack sizes), GMP Compliance, Data needs to be in dossier and accessible at manufacturing site at all times

Question 21

Process Validation Pre-Requisite

Answer 21

Pharmaceutical/process dev at commercial scale is concluded, Equipment & utiles qualifications concluded, Validated analytical test methods, Trained personnel and Approved process validation protocol

Question 22

Process Validation Protocol Outline

Answer 22

Specifies manufacturing; conditions, controls, testing & expected outcomes for process validation stages

Question 23

Process Validation Includes

Answer 23

Purpose, Scope, Pharmacovigilance background & overview, Manufacturing batch record, Study design (Lot number, Batch size, In-process controls), Acceptance criteria, Materials/methods/equipment list, Process validation plan and Approval Protocol

Question 24

Process Validation Report Outline

Answer 24

Pharmacovigilance conclusion. Discuss & cross-reference protocol, Data summary & analysis, Unexpected observation eval, Describe corrective actions & changes, Data clear conclusions, Quality unit review & approval