the detail about ICH Q7 GMP for API

1. Guided by Dr.H.S Mahajan Sir (HOD Quality
Assurance & Pharmaceutics)
PRESENTED BY
Prashik s shimpi
M.Pharm First Year (IISEM)
DEPARTMENT OF QUALITY ASSURANCE
R.C. PATEL INSTITUTE OF PHARMACEUTICAL
EDUCATION & RESEARCH,SHIRPUR.
1

2. contents
 Introduction
 Members of ICH
 purpose of ICH
 ICH guidelines
 ICH Q7 guideline GMP for API
 Conclusion
 References
2

3. Introduction
 The complete name of ICH is the “International Conference
on Harmonisation of Technical Requirements for Registration
of Pharmaceuticals for Human use.
 ICH Established in 1990 between the European
Union,Japan,and united states.
 Commited to reducing duplication during research and
development of new drugs while safeguarding quality,safety
and efficacy .
3

4. ICH Members
Regulatory Agencies
 EMEA - European Union
 MHLW - Japan
 FDA - US
Trade Associations
 EFPIA - Europe
 JPMA - Japan
 PhRMA - US
4

5. Purpose of ICH
 Safe, effective and high quality medicines are
developed and registered in the most efficient and cost
effective manner.
 To Promote public health.
 Prevent unnecessary duplication of clinical test.
 Minimize the use of animal testing without
compromising safety and effectiveness.
 Identification eliminationof the need to duplicate studies
to meet different regulatory requirements.
5

6. ICH guidelines
 The ICH Topics are divided into four major categories and ICH Topic
Codes are assigned according to these categories.
Quality
Those relating to
chemical and
pharmaceutical
Quality
Assurance
(stabilitytesting,
impurity
testing,Analytical
validation .etc.)
Safety
Those relating
to in vitro & in
vivo pre
clinical studies
(Genotoxicity
testing,Toxicity
Testing.etc.)
Efficacy
Those relating to
clinical studies in
human subject
(Dose response
studies,Pharmaco
vigilance, Clinical
study reports
,Good clinical
practice.etc.)
Multidisciplinay
Those are cross
cutting topics
which do not fit
uniquely into one
of the QSE
(MedDRA,ESTRI
CTD.etc.)
6

7. Quality Guidelines
Q1A - Q1F Stability
Q2 Analytical Validation
Q3A - Q3D Impurities
Q4 - Q4B Pharmacopoeias
Q5A - Q5E Quality of Biotechnological Products
Q6A- Q6B Specifications
Q7 Good Manufacturing Practice
Q8 Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality System
Q11 Development and Manufacture of Drug
Substances.
Q12 Lifecycle management 7

8. ICH Q7 guideline GMP for API
 This guideline for GMP for API.
 This guideline establish (Dated 10 November 2000)
 GMP is that part of Quality assurance, which ensure that products
are consistently produce and controlled to the quality standards
appropriate to their intended use and as required by the marketing
authorisation.
 This document (Guide) is intended to provide guidance regarding
good manufacturing practice (GMP) for the manufacturing of active
pharmaceutical ingredients (APIs) under an appropriate system for
managing quality.
 In this Guide “manufacturing” is defined to include all operations of
receipt of materials, production, packaging, repackaging, labelling,
relabelling, quality control, release, storage and distribution of APIs
and the related controls. 8

9. Quality Management
 Quality should be the responsibility of all persons involved in
manufacturing.
 There should be a quality unit(s) that is independent of
production and that fulfills both quality assurance and
qualitycontrol responsibilities.
 QC Unit –
1. The quality unit(s) should be involved in all quality-related
matters.
2. Releasing or rejecting all APIs. Releasing or rejecting
intermediates for use outside the control of the manufacturing
company.
3. Establishing a system to release or reject raw materials,
intermediates, packaging, and labeling materials.
9

10. Cont…
 QA Unit –
1. Review & approve all quality related documents.
2. Review of batch production & quality control records.
3. Making sure that the premises and equipment are maintained and records
kept.
4. Reviewing & Approving validation protocols.
5. Making sure that production facilities are clean and, when appropriate,
disinfected.
• Internal Audits( Self Inspection) –
1. To verify compliance with the principles of GMP for APIs, regular internal
audits should be performed in accordance with an approved schedule.
 Product Quality Review-
 A review of adequacy of corrective actions.
 A review of any changes carried out to the processes or analytical methods;
 A review of all batches that failed to meet established specification(s). 10

11. Personnel
 A. Personnel Qualifications .
 B. Responsibilities.
 C. Personnel Hygiene-
1. Personnel should practice good sanitation and health
habits.
2. Personnel should avoid direct contact with intermediates
or APIs.
3. Smoking, eating, drinking, chewing and the storage of
food should be restricted.
11

12. Buildings & facilities
 A. Design & construction
 Buildings & facilities should have adequate space for
the orderly placement of equipment & material to
prevent mix ups & contamination.
 There should be defined areas or other control
systems for the following activities:
1. Receipt, identification, sampling, and quarantine of
incoming materials, pending release or rejection;
2. − Storage of released materials.
3. − Production operations.
4. − Packaging and labelling operations.
5. − Laboratory operations. 12

13. Cont…
 B.Utilities
 All utilities that could impact on product quality (e.g. steam,
gases, compressed air, and heating, ventilation and air
conditioning)
 C. Water
 Water used in the manufacture of APIs should be demonstrated
to be suitable for its intended use.
 Where water used in the process is treated by the manufacturer
to achieve a defined quality, the treatment process should be
validated and monitored with appropriate action limits.
 D.containment
 E.Lighting
 F. Sewage & Refuse
 G.Sanitation & Maintenance
13

14. Process Equipment
 A. Design & construction
 Equipment used in the manufacture of intermediates and APIs
should be of appropriate design and adequate size, and suitably
located for its intended use, cleaning, sanitization (where
appropriate), and maintenance.
 Production equipment should only be used within its qualified
operating range.
 B. Equipment Maintenance & Cleaning
 Schedules and procedures (including assignment of responsibility)
should be established for the preventative maintenance of
equipment.
 Inspection of equipment for cleanliness immediately before use .
 Assignment of responsibility for cleaning of equipment.
 A complete description of the methods and materials, including
dilution of cleaning agents used to clean equipment . 14

15. Cont…
 C. Calibration
 Control, weighing, measuring, monitoring and test
equipment that is critical for assuring the quality of
intermediates or APIs should be calibrated according to
written procedures and an established schedule.
 D. Computerized Systems
 GMP related computerized systems should be validated.
The depth and scope of validation depends on the
diversity, complexity and criticality of the computerized
application.
 Appropriate installation qualification and operational
qualification should demonstrate the suitability of
computer hardware and software to perform assigned
tasks.
15

16. DOCUMENTATION AND
RECORDS
 A. Documentation System and Specifications
 All documents related to the manufacture of intermediates
or APIs should be prepared, reviewed, approved and
distributed according to written procedures. Such
documents can be in paper or electronic form.
 All production, control, and distribution records should be
retained for at least 1 year after the expiry date of the batch.
For APIs with retest dates, records should be retained for at
least 3 years after the batch is completely distributed.
16

17. Cont…
 B. Equipment Cleaning and Use Record
 Records of major equipment use, cleaning, sanitization
and/or sterilization and maintenance should show the date,
time (if appropriate), product, and batch number.
 C. Records of Raw Materials, Intermediates,
API Labelling and Packaging Materials
 The name of the manufacturer, identity and quantity of each
shipment of each batch of raw materials, intermediates or
labelling and packaging materials for API's; the name of the
supplier; the supplier's control number(s), if known, or
other identification number; the number allocated on
receipt; and the date of receipt. 17

18. Cont…
 D. Master Production Instructions (Master
Production and Control Records )
 To ensure uniformity from batch to batch, master
production instructions for each intermediate and API
should be prepared, dated, and signed by one person and
independently checked, dated, and signed by a Q.A Unit.
 Master production instructions should
include:
 The name of the intermediate or API being manufactured
and an identifying document reference code.
 List of raw material & it’s quality characteristics.
 An accurate statement of the quantity or ratio of each
raw material or intermediate to be used.
18

19. Cont…
 E. Batch Production Records (Batch Production
and Control Records)
 Batch production records should be prepared for each intermediate and API
and should include complete information relating to the production and
control of each batch.
• Batch production record should include,
1) Name of API
2) Batch No.
3) Date
4) Identity of major equipment.
5) Specific identification of each batch
including weight, measures, &
batch no. of raw materials.
6) Signature of the person performing &
directly supervising the each critical
steps in the operation.
19

20. Cont…
 F. Laboratory Control Records
1) Description of samples received for testing which includes,
- Material name
- Batch No.
- Date of Sampling
- Quantity
- Date – the sample was received
for testing.
2) Reference to each test method.
3) Weight of sample used for each test.
4) A complete record of all raw data generated during each test with
graphs, charts & spectra from laboratory instrumentation.
5) Signature of the person who performed each test & the date on which
the tests were performed.
20

21. Material Management
A. General Controls There should be written procedures describing
the receipt, identification, quarantine, storage, handling, sampling, testing,
and approval or rejection of materials.
B.Receipt and Quarantine Upon receipt and before acceptance, each
container or grouping of containers of materials should be examined
visually.
C. Sampling and Testing of Incoming Production Materials .
D. Storage -Materials should be handled and stored in a manner to
prevent de.gradation, contamination, and cross-contamination.
E. Re-evaluation -Materials should be re-evaluated as appropriate to
determine their suitability for use (e.g., after prolonged storage or exposure
to heat or humidity).
21

22. PRODUCTION AND IN-
PROCESS CONTROLS
 A. Production Operations
 B. Time Limits
 C. In-process Sampling and Controls
 D. Blending Batches of Intermediates or APIs
 Contamination Control -Residual materials can be
carried over into successive batches of the same
intermediate or API if there is adequate control.
22

23. PACKAGING AND IDENTIFICATION
LABELLING OF APIs AND
INTERMEDIATES
 There should be written procedures describing the receipt,
identification, quarantine, sampling, examination and/or testing
and release, and handling of packaging and labeling materials.
 Records should be maintained for each shipment of labels and
packaging materials showing receipt, examination, or testing,
and whether accepted or rejected.
Packaging Materials Containers should provide adequate
protection against deterioration or contamination of the
intermediate or API that may occur during transportation and
recommended storage. Containers should be clean and, where
indicated by the nature of the intermediate or API, sanitized to
ensure that they are suitable for their intended use.
 Label Issuance and Control. 23

24. STORAGE AND
DISTRIBUTION
 Warehousing Procedures -Facilities should be
available for the storage of all materials under appropriate
conditions (e.g. controlled temperature and humidity when
necessary.
 Distribution Procedures -1)APIs and intermediates
should only be released for distribution to third parties
after have been released by the quality unit.
2)APIs and intermediates should be transported in a
manner that does not adversely affect their quality.
3) Special transport or storage conditions for an API.
24

25. LABORATORY CONTROLS
 A.General Controls
 B. Testing of Intermediates and APIs -An impurity
profile describing the identified and unidentified
impurities present in a typical batch produced by a
specific controlled production process should normally be
established for each API.
 C. Validation of Analytical Procedures .
 D. Certificates of Analysis -Authentic Certificates of
Analysis should be issued for each batch of intermediate
or API on request.
25

26. Cont…
 E. Stability Monitoring of APIs -A documented, on-going
testing program should be designed to monitor the stability
characteristics of APIs, and the results should be used to
confirm appropriate storage conditions and retest or expiry
dates.
 F. Expiry and Retest Dating -When an intermediate is
intended to be transferred outside the control of the
manufacturer’s material management system and an expiry or
retest date is assigned, supporting stability information should
be available (e.g. published data, test results)
 G. Reserve/Retention Samples -purpose of potential future
evaluation of the quality of batches of API.
26

27. Validation
 A documented programme, which provides a high degree of
assurance that a specific process will consistently produce, a
product meeting its pre- determined specifications and
quality attributes.
 A.Validation Policy
 The company's overall policy, intentions, and approach to
validation, including the validation of production processes,
cleaning procedures, analytical methods, in-process control
test procedures, computerized systems, and persons
responsible for design, review, approval and documentation
of each validation phase, should be documented.
27

28. Cont…
 B. Qualification- Design Qualification (DQ): documented
verification that the proposed design of the facilities, equipment,
or systems is suitable for the intended purpose.
 Installation Qualification (IQ): documented verification that
the equipment or systems, as installed or modified, comply with
the approved design, the manufacturer’s recommendations
and/or user requirements.
 Operational Qualification (OQ): documented verification that
the equipment or systems, as installed or modified, perform as
intended throughout the anticipated operating ranges.
 Performance Qualification (PQ): documented verification that
the equipment and ancillary systems, as connected together, can
perform effectively and reproducibly based on the approved
process method and specifications. 28

29. Cont…
 C. Process Validation Process Validation (PV) is the
documented evidence that the process, operated within
established parameters, can perform effectively and
reproducibly to produce an intermediate or API meeting its
predetermined specifications and quality attributes .
 Types of process validation
1) Prospective validation :-
• Prospective validation should normally be performed
for all API processes.
• Prospective validation performed on an API process
should be completed before the commercial distribution of
the final drug product manufactured from that API. 29

30. 2) Concurrent Validation :-
Concurrent validation is a subset of prospective validation and
is conducted with the intention of ultimately distributing
product manufactured during the validation study.and which
becomes the I.P.Q.C tests.
3) Retrospective Validation :-
Process validation should confirm that the impurity profile for
each API is within the limits specified.an establishing
documented evidence that a system does what if purpose to
do based on a review and analysis of historical data and
information obtained during production of clinical or
marketable product.
30

31. Cont…
 D.Cleaning Validation- Cleaning procedures should normally
be validated. In general, cleaning validation should be directed
to situations or process steps where contamination or carryover
of materials poses the greatest risk to API quality.
 E. Validation of Analytical Methods-Methods should be
validated to include consideration of characteristics included
within the ICH guidelines on validation of analytical methods.
The degree of analytical validation performed should reflect the
purpose of the analysis and the stage of the API production
process.
31

32. Cont…
 Rejection and reuse of materials
 Complaints and recalls
 Contract manufacturer
 Agents, brokers, traders, Distributors, repackers and
Relabellers
 Specific guidance for APIS manufactured by cell/culture
/fermentation
 APIS for use in clinical trials
32

33. conclusion
 ICH Q7 is very important in maintaining quality
of the API.
 API manufacturer can improve output of the
manufacturing process.
 Helps to enhance productivity as well as
effectiveness of the manufacturing process.
 ICH Q7 ensures less batch to batch variations and
less chances of recalls.
 Following this guideline can also help during
regulatory inspections. 33

34. References
 Good manufacturing practice guide for active
pharmaceutical ingredients Q7,current step 4 version
dated 10 November 2000.
 Q7 Good Manufacturing Practice Guidance for Active
Pharmaceutical Ingredients Guidance for Industry
September 2016.
 Kuchekar B.S., Khadatare A.M., Itkar S.C., Forensic
Pharmacy, Nirali Publication, page no.16.16 to 16.25
 www.ich.org (official ICH Web site)
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