UNIT II PHARMACEUTICAL QUALITY SYSTEM

Question 1

• Effective quality management system for the pharmaceutical industry
• Comprehensive model based on ISO quality concepts
• Includes cGMP, complements ICH Q8 (Pharmaceutical Development) and ICH Q9 (Quality Risk Management).

Answer 1

ICH Q10-Pharmaceutical Quality System

Question 2

AREAS OF PHARMACEUTICAL QUALITY SYSTEM:

Answer 2

Quality Risk Management
Contamination/Cross Contamination
Good Documentation Practice
Good Quality Control Laboratory Practice
Self-inspection
Continuous Improvement

Question 3

A systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle

Answer 3

QUALITY RISK MANAGEMENT

Question 4

Risk Management Process:

Answer 4

1. Identify the Risks
2. Analyze the Risk
3. Evaluate or Rank the Risk
4. Treat the Risk
5. Monitor and Review the Risk

Question 5

CAUSE AND EFFECT METHOD Fishbone

Answer 5

Fishbone (Ishikawa) Diagram

Question 6

CONTAMINATION/CROSS CONTAMINATION PREVENTION

Answer 6

N/A

Question 7

An impurity or any substance or material that causes contamination or spoilage.

Answer 7

Contaminant

Question 8

The undesired introduction of impurities of a chemical or microbiological nature or of foreign matter, into or on to a starting material or intermediate during production, sampling, packaging, repacking, storage, and transport.

Answer 8

Contamination

Question 9

Contamination of a starting material, intermediate product, finished product with another starting material or a product.

Answer 9

Cross-Contamination

Question 10

SOURCES OF CONTAMINATION/CROSS
CONTAMINATION:

Answer 10

Microbial Contamination
1. Facility
- Flow of Personnel
- Materials
-HVAC
-Waste
2. Equipment
- Assembly Cleaning Sterilization
3. Process
- Open Vs. Closed
4. Materials
- Raw material Reusable resin & Membrane filter
5. Utilities
- Water Gases
6. Personnel

Question 11

SOURCES OF CONTAMINATION/CROSS
CONTAMINATION:

Answer 11

Premises and Design of Building
Equipment
People
Heating Ventilation and Air Conditioning (HVAC) System
Manufacturing
Clothing and Footwear

Question 12

Written procedures for a laboratories program.
They define how to carry out protocol specified activities.
Most often written in a chronological listing of action steps.
They are written to explain how the procedures are supposed to work.

Answer 12

Standard Operating Procedures (SOP)

Question 13

An approved instruction either in paper or electronic form which guides about how an activity shall be executed.

Answer 13

Documents

Question 14

provide evidence that activities have been performed or results have been achieved.
A_____ is often considered as document.
They always document the past.

Answer 14

Records

Question 15

What is Good Documentation Practice:
Documentation must be;

Answer 15

Accurate : true / precise, error free,
Concise: short & clear information that is understood by all
Legible: shall be readable, understandable.
Traceable: who recorded it, where, when and how
Contemporaneous: documented at the time activity done
Enduring: Long lasting and durable
Accessible: Easily available / retrievable

Shall be Complete & Authentic:

Question 16

Principles of GDP:

Answer 16

A document with original signatures should never be destroyed.
Never falsify information
Never do white-out and cover-over-tapes
Never obliterate information or record Never over-write a record.
Never use pencil - use permanent ink for writting
No spaces, lines or fields are to be left blank Never use symbols e.g ditto marks or arrows to indicate repetitive and consecutive entry

Question 17

Observations on Poor Documentation Practices

Answer 17

Missing signature and dates at the time of activity performed.
Non-uniform date and signature
Activity was performed & writing on one day and signed on another day.
Blank spaces
Illegible writing
Too many corrections
Write-overs, multiple line-through
“White-out” or other masking device
Error correction not signed/dated, and reason for the correction not written
Not traceable
Data integrity

Question 18

Benefits of GDP

Answer 18

Compliance to regulatory requirement- No observation / warning letters/Import Alert/ ban
Build confidence on System & practice
Correct, complete, current and consistent information Effectively meets customers and stakeholders’ requirements.
Ensure the traceability
Useful for review; investigation & CAPA
Solve complicated problems
Reduce or eliminate assumptions and second-guessing.
Eliminate the need to re-ask the same questions
Specify clear instructions to staff
Consistent quality, yield and performance of staff.

Question 19

GMP- Documentation Requirements

Answer 19

•Keep in mind, after the product is released and shipped to the customer, what remains behind is the Document.
Documentation/record is useful to us ONLY if it is 100% accurate.
So it is important for us to understand and follow the Good Record Practice.

Question 20

Why do people sometimes fail to document activities or events properly?

Answer 20

People don’t clearly understand what or when to document.
Procedures may not be completely understood or followed.
People aren’t always held accountable.
People will make mistakes.
People don’t always make corrections properly.
People do not relate records to auditing.
People don’t understand the legal role of documentation

Question 21

Record Keeping System
How do maintain the record?

Answer 21

Bound notebook pre-numbered
loose sheets (Pre-numbered, the printing have to be controlled and also the storage as control records)

Every register Forms shall have
- Format/control number/header
- Date of opening
- Date of closing
- Table of content where applicable

Question 22

Record Writing/Data Entry

Answer 22

Enter complete and accurate information at the time work is performed.
Enter signature or initials (according to procedure) When one or more person complete the task, all person must sign.
Never sign your name for performance of a job for work actually performed by someone else.
Limit the use of abbreviations and acronyms.
Use a non-water-soluble pen for writing on any official document.
Use Ball point pens of blue or black colored inks to make entries.
Don’t use pens like gel pens, ink pens for making entries.
Don’t use pens like red, green color ink.
Spaces and cells cannot be left “blank”!
When spaces or cells do not contain information, EACH must contain the appropriate “not applicable” entry. Or N/A
This rule applies to all product-related documents - electronic and written.
× Never use ditto
× Never use lines (with or without arrows) to show a continuation of values or entries in a column or row.
Corrections to written records must be made properly.
* NEVER mask the original entry.
* NEVER USE “correction” liquid, tape, or material.
Corrections to written records must be made properly.
X DO NOT USE “write overs” (Don’t turn a “6” or “9” into an “8”.)
X Never vary your initials or signature

Question 23

How to properly make corrections:
When an entry or calculation must be corrected, follow these steps:

*Draw a single line through the incorrect entry. *Enter correct information above or to the side of the incorrect entry.

•Write your initials and date of correction. Write justification if possible •When two people signed the original entry, and then another changes the entry, the second person must also sign for the change.

Answer 23

Draw a single line through the incorrect entry.
Enter correct information above or to the side of the incorrect entry.
Write your initials and date of correction. Write justification if possible
When two people signed the original entry, and then another changes the entry, the second person must also sign for the change.

Don’t deface the original entry!!!

Question 24

GDP Error Description

Answer 24

The following are the example of notations that may be used to describe error corrections.
Calculation error
Transposition
Illegible entry
Wrong entry

Clearly Record the Data

Question 25

Consequence of illegible writing:

Answer 25

Suppose this is a final product, and the specification is 27 29 is acceptable..
But what if it’s 24? Now what?
We might have to reject the entire experiment and redo. This consumes time and resources.
Avoid sloppy writing
Similarly try to write in Caps where possible

Question 26

Good Documentation Practice

Answer 26

Computer print outs taken on thermal paper or easily fading inks should be photocopied and maintained. Original shall be destroyed after verification
Use polyvinyl alcohol base gum or white glue for pasting of graphs etc.
Use clear transparent tape for mending (patch-up).

Question 27

Dont’s of Good Documentation Practice:

Answer 27

Don’t remove any pages or portions from a note book Don’t make any temporary entries in a bit of paper of hand
Preserve the notebooks intact. Do Not Use “Sticky” Notes.
Do Not Back-Date Or Post-Date.
Do Not Use Asterisks That May Cause Confusion (Such As Using The Same Asterisk For Different Footnotes). Do Not Transcribe Data.
Avoid Use of Unbound Laboratory Notebooks

Question 28

Recreating and Rewriting Records

Answer 28

Recreating or rewriting records should be avoided.
If necessary to do this;
- The supervisor and QA Approvals are required when recreating records.
- It is important to identify the recreated document as “rewrite” and to reference the sources of the information.
Records can be recreated only when:
1. The original record is illegible:
2. An incorrect form or document was used
3. The record is reparable
4. The original was in A format that would not keep (thermal paper strips)

Question 29

Good Documentation Practice

Answer 29

Lab record:
Enter enough details so the document can be understood in the future.
Documents should be signed and dated by the person who performed the test.
A reference to the identification of the sample. analysed should be included.

Question 30

Witnessed/Checked/ reviewed by:

Answer 30

The second check: When one person performs the task and the second person verifies that it has been performed correctly.
Double checking our work provides additional assurance that no mistakes were made.
The person who is the “verifier” must be clear as to what they are verifying by affixing their signature to the document.
- Examples: charging of raw materials; Monitoring critical parameters

Question 31

Good Documentation Practice

Answer 31

Reviewer:
-Must be verified by a second person
-Signature of the person verified
-Verify within a time frame
Review he documentation:
- PRS, Test record, material issue, Cleaning, records, calibration and equipment records, raw data, yield & Calculations etc.
Review of the original records when the records are complete / after complete analysis of a sample has been performed.
All raw data, all printed / electronic data
-Chromatogram, spectrum weight prints, This can be done on a sheet/record where all results have been summarized
If a notebook is no longer used and unused pages are remaining
-Draw a line across the first unused page
-Indicate “the remainder of the note book is not used”
-Sign with date

Question 32

Check the following during review:

Answer 32

Missing records and out-prints
Incomplete entries
Illegible corrections
Cross References
Deviations, if any investigation the impact on the product
Valid calibrations and service intervals of test equipment
Compliance with specifications, parameter ranges or acceptance criteria including tighter customer specifications

Question 33

Examples of deviations are:

Answer 33

Incorrect charging of raw materials.
Temperature, pressure, vacuum parameters outside defined limits.
Operating instructions not correctly followed.
Breakdown of equipment or failure of utilities.
Equipment out of calibration.
Records not adequately completed.
Temporary alteration to defined instructions
In Process Control Limits not achieved.
Extraneous contamination of API and intermediates
Any other unplanned event.

Question 34

Good Documentation Practice

Answer 34

Errors or mistakes are possible - person recording is human Correction, corrective action and preventive action
-List the documentation errors /mistakes/ deviation
-Classify and trend
-Train the persons
-Correction where possible
-Report the deviation to QA
-Investigation & root cause
-Understand issue & take CAPA

Question 35

Good Documentation Practice

Answer 35

Document Retention & Retrieval:

ICH Q7: 6 Documentation And Records 21CFR 211.180(d)… These records or copies….shall be subject to photocopying or other means of reproduction as part of such inspection.
Records that can be immediately retrieved from another location by computer or other electronic means shall be considered as meeting the requirements of this paragraph,”

Store the documents & records in secured place until retention period

Question 36

GDP Implementation:

Answer 36

Swear to record the actual information/data
Be honest
Strengthen the review Report the deviation
Train the operators or chemists on common/ identified mistakes or errors

Question 37

All this is achievable through

Answer 37

Positive attitude
Positive thoughts
Removal of mental blocks Open or willing to change
Understand the need of business
Destruction of Ego

Question 38

Good Documentation Practice

Answer 38

Summary
Documentation is a record of our product history.
GMP documents are legal documents & requirement. The “double check” (review) assures that our work is correct. All work should be documented at the time work is performed.
Correct the errors properly
Report the deviations if any and implement the CAPA
Train all the staffs on GDP and explain the consequences.

Question 39

The requirements of 21 CFR part 11 covers electronic records. 21 CFR part 11 compliance applies to both in-house developed computer systems, as well as commercial off-the-shelf software.

The 21 CFR part 11 requirements apply to software (both “open systems” and “closed systems”) used to implement any part of a quality system

Answer 39

21 CFR Part 11

(CODE OF FEDERAL REGULATIONS)

Question 40

You sent
The 21 CFR part 11 checklist includes, but is not limited to:

Answer 40

Document control - lifecycle management and review/approval workflow for standard operating procedures (SOPs), forms used in manufacturing, device history records, product labels, and other documents
Nonconformance, including corrective and preventive action (CAPA) management
Customer complaint management
Manufacturing equipment calibration and maintenance records
Device manufacturing records

Question 41

21 CFR Part 11
(CODE OF FEDERAL REGULATIONS) - CONCEPT

Answer 41

Any quality system records electronically stored and managed come under the FDA 21 CFR part 11 compliance umbrella.