ICH GMP GUIDELINES Q7

ICH Q7A means the good manufacturing practice guidance for active pharmaceutical ingredients developed under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.

1. ICH GMP GUIDELINES Q7 BY- PROF . VEDANSHU MALVIYA P.R. POTE PATIL COLLAGE OF PHARMACY, AMARAVATI.

2. C o n t e n t Introduction Members of ICH P u r p o s e o f I C H I C H g u i d e li n e s I C H Q 7 g u i d e l i n e G M P f o r A P I Conclusion References

3. Introduction The complete name of ICH is the "International Conference on Harmonisation of Technical Requirements for Registration of P h a r m a c e u t i c a l s f o r H u m a n u s e . ICH Established in 1990 between the European Union, Japan, and united states. Committed to reducing duplication during research and development of new drugs while safeguarding quality, safety and efficacy.

4. Purpose of ICH Safe, effective and high quality medicines are developed and registered in the most efficient and cost effective manner. T o P r o m o t e p u b li c h e a l t h . Prevent unnecessary duplication of clinical test. Minimize the use of animal testing without compromising safety and effectiveness. Identification elimination of the need to duplicate studies to meet different regulatory requirements.

5. I C H G u i d e li n e s The ICH Topics are divided into four major categories and ICH Topic Codes are assigned according to these categories.

6. I C H Q 7 G u i d e l i n e s G M P f o r A P I 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 authorization. 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, relabeling, quality control, release, storage and distribution of APIs and the related controls.

7. 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 quality control responsibilities. Q C U N I T : The quality unit(s) should be involved in all quality-related matters. Releasing or rejecting all APIs. Releasing or rejecting intermediates for use outside the control of the manufacturing company. Establishing a system to release or reject raw materials, intermediates, packaging, and labeling materials.

8. C o n t … Q A U n i t – Review & approve all quality related documents. Review of batch production & quality control records. Making sure that the premises and equipment are maintained and records kept. R e v i e w i n g & A pp r o v i n g v a l i d a t i o n p r o t o c o l s . Making sure that production facilities are clean and, when appropriate, disinfected. I n t e r n a l A u d i t s ( S e l f I n s p e c t i o n ) – 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).

9. Personnel Personnel Qualifications Responsibilities Personnel Hygiene – Personnel should practice good sanitation and health habits. Personnel should avoid direct contact with intermediates or APIs. Smoking, eating, drinking, chewing and the storage of food should be restricted

10. B u il d i n g s & F a c ili t i e s D e s i g n & C o n s tr u c t i o n Buildings & facilities should have adequate space for the orderly placement of equipment & material top prevent mix ups & contamination. There should be defined areas or other control systems for the following activities: Receipt, identification, sampling, and quarantine of incoming materials, pending release or rejection; Storage of released materials. P r od u c t i o n o p e r a t i o n s . P a c k a g i n g a n d l a b e l l i n g o p e r a t i o n s . L a b o r a t o r y o p e r a t i o n s .

11. Utilities All utilities that could impact on product quality (e.g. steam, gases, compressed air, and heating, ventilation and air conditioning) 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. Containment Lighting S e w a g e & R e f u s e S a n i t a t i o n & M a i n t e n a n c e

12. Process Equipment D e s i g n & C o n s t r u c t i o n 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. E q u i p m e n t M a i n t e n a n c e & C l e a n i n g 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.

13. 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. 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 t o p e r f o r m a s s i g n ed t a s k s .

14. D o c u m e n t a t i o n & R e c o r d s D o c u m e n t a t i o n S y s t e m a n d S p e c i f i c a t i o n s 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.

15. 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. R e c o r d s o f R a w M a t e r i a l s , I n t e r m e d i a t e s , A P I L a b e lli n g a n d P a c k a g i n g 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 A P I ' s ; t h e n a m e o f t h e s u pp l i e r ; t h e s u p p l i e r ' s c o n t r o l n u m b e r ( s ) , i f k n o w n , o r o t h e r identification number; the number allocated on receipt; and the date of receipt.

16. Batch Production Records (Batch Productionand 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, N a m e o f A P I B a t c h N o . Date I d e n t i t y o f m a j o r e q u i p m e n t . Specific identification of each batch including weight, measures, & batch no. of raw materials. Signature of the person performing &directly supervising the each critical steps in the operation.

17. Laboratory Control Records Description of samples received for testing which includes, M a t e r i a l n a m e Batch No. D a t e o f S a m p li n g Quantity D a t e - t h e s a m p l e w a s r e c e i v e d f o r t e s t i n g . 2 ) R e f e r e n c e t o e a c h t e s t m e t h o d . 3 ) W e i g h t o f s a m p l e u s e d f o r e a c h t e s t . A complete record of all raw data generated during each test with graphs, c h a r t s & s p e c t r a f r o m l a b o r a t o r y i n s t r u m e n t a t i o n . Signature of the person who performed each test & the date on which the t e s t s w e r e p e r f o r m e d .

18. M a t e r i a l M a n a g e m e n t General Controls: There should be written procedures describing the receipt, identification, quarantine, storage, handling, sampling, testing and a p p r o v a l o r e j e c t i o n o f m a t e r i a l s . Receipt and Quarantine: Upon receipt and before acceptance, each container or grouping of containers of materials should be examined visually. Sampling and Testing of Incoming Production Materials. Storage: Materials should be handled and stored in a manner to prevent degradation, contamination, and cross-contamination. 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).

19. P r o d u c t i o n & I n p r o c c e s s C o n t r o l s Production Operations T i m e L i m i t s I-process Sampling and Controls Blending Batches of Intermediates or APls Contamination Control -Residual materials can be carried over into successive batches of the same intermediate or API if there is adequate control.

20. STORAGE AND DISTRIBUTION Warehousing Procedures - Facilities should be available for the storage of all materials under appropriate conditions (e.g. controlled temperature a n d hu m i d i t y w h e n n e c e ss a r y . Distribution Procedures -1 )APIs and intermediates should only be released for distribution to third parties after have been released by the quality unit. APIs and intermediates should be transported in a manner that does not a d v e rs e l y a f f e c t t h e i r q u a li t y . Special transport or storage conditions for an API.

21. 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.

22. 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 I n g r e d i e n t s G u i d a n c e f o r I n d u s t r y S e p t e m b e r 20 1 6 . 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)

23. THANK YOU…….!