ICH Q7A GMP Guidance For API

1. ICH Q7A GMP Guidance For API Good Documentation Practices

2. Why Documentation is required..? • To define the method and control • To prevent errors from spoken communication Click for Example

3. This section covers • Documentation System and Specifications • Equipment Cleaning and Use Record • Records of Raw Materials, Intermediates, API Labeling and Packaging Materials • Master Production Instructions • Batch Production Records (BPR) • Laboratory Control Records • Batch Record Review

4. Good Documentation “Good Documentation” can achieve by continuous practice, like habit.

5. Documentation and Records What is Document? What is Record?

6. Documentation and Records Document: • Document provides a guidance / direction for performing work, making decision which effects the quality of the product. Ex: SOP’s, Spec & MOA, protocols ……etc. Record: • Record is evidence that a quality system action is performed Ex: Registers, records, reports…..etc.

7. Documentation and Records This section covers a large amount of guidance. Most of it is NOT NEW….. Basic Requirements for documentation • All the documents should be numbered for traceability • Reproduced document should be clear & legible • As soon as a document is superseded, the copies of the earlier version must be retrieve and destroyed

8. 6.1 Doc’ System and Specifications Just what is needed for a document ? • Review, approval and distribution of documents • Revision history • Record retention

9. 6.1 Doc’ System and Specifications • Review, approval and distribution of documents All documents related to the manufacture of intermediates or APIs should be prepared, reviewed, approved and distributed according to written procedures

10. 6.1 Doc’ System and Specifications • Revision History • If any changes were made in the approved document, we should have the revision history to trace out the changes made in the previous document.

11. 6.1 Doc’ System and Specifications • Record retention • Of production, control and distribution records • At least 1 year after expiry date • For APIs with retest date - at least 3 years after complete distribution of the batch

12. 6.1 Doc’ System and Specifications Documents to be stored for life time • Technology transfer document • DMF • Validations (Process & method)/Qualifications • Impurity profile • Degradation studies • Stress studies • Stability data • Product specifications • BPR’s submitted in DMF’s • Annual review reports • Complaints • Vendor qualification documents • Obsolete documents • Training records……etc

13. 6.1 Doc’ System and Specifications Record retention • Records may be retained as originals or true copies (accurate reproductions) • Originals or copies should be available at the establishment where the activity occurred • Prompt retrieval from another location by electronic or other means is acceptable

14. 6.1 Doc’ System and Specifications Record retention……cont. • If reduction techniques (microfilm) or electronic records are used, suitable retrieval equipment and means to produce hard copy should be readily available

15. 6.1 Doc’ System and Specifications Entries in records should • Use proper units of measure( ºC, Kg, Lt…etc) • Be indelible (incapable of being removed, erased or washed away) • Made in spaces provided • Made directly after performing the activity • Use blue / Black bal pen only. • Post it notes scrap pieces of papers are not to be used for recording data. • Ditto marks and arrows are not acceptable

16. Entries in records should…… • It shall be the responsibility of the personnel making use of the documents to see that the documents are maintained properly without being subject to any sort of damage • If an entire page or section or a cell is intended to be left blank in the BPR, Work books, Logbooks, Equipment log books, Inward registers and other reports a diagonal line is to be placed through the page or section or cell and written ‘NA’ with signature & date • All the entries shall be made as and when the operation is being completed • Use of ear brackets with one signature & date to indicate verification of several operations can be done • In the batch production records and inward registers, date column need not be filled each and every time. Writing the date in first row of each and every page is adequate. In addition, whenever the date changes at 00.00 hours the first entry shall also have the new date entered.

17. Click for Example Corrections • Overwriting or erasing or blocking of data shall not be done • Errors and overwriting shall be corrected with a single line cross out, then initialled and dated • Correction fluids shall never be used Note:All corrections arising based on review of the document to be done with current date only

18. 6.1 Doc’ System and Specifications Electronic signatures (if used) should be • Authenticated • Secure

19. 6.2 Equip Cleaning and Use Record • Records of major equipment • use • cleaning • sanitization and/or sterilization (if performed) • maintenance

20. Equip Cleaning and Use Record . . . • Should include • Date (DD/MM/YY or DD-MM-YY) • Note: Effective date can written as • DD-MM-YYYY Ex: 27-04-2009 • Time ( in 24 hrs pattern, if appropriate) • Product • Batch number • Person performing cleaning and maintenance & reviewer signature.

21. Equip Cleaning and Use Record . . . Dedicated equipment • Records of cleaning, maintenance and use can be part of batch record or maintained separately

22. 6.3 Records of Materials For raw materials, intermediates, API packaging and labeling • Name of manufacturer • Identity and quantity of each shipment of each batch • Date of receipt • Batch No.

23. Clarification of terms • Master Production Instruction • master recipe or SOP • Batch Production Record • record of actual batch produced

24. 6.4 Master Formulae • Name of intermediate or API being manufactured • Identifying document reference code • The procedure shall start with general instruction. • Synthetic scheme and process flow along with equipment details. • Holding time study for wet/ dry material • Complete list of raw materials and intermediates • Accurate statement of the quantity or ratio of each material to be used (including unit of measure) • Major production equipment to be used • Special notations or precautions • The conditions in which API/ Intermediate shall be stored, type of packing materials used and the labelling .

25. 6.4 Master Formulae Detailed production instructions • Sequences to be followed • Ranges of process parameters • Sampling instructions • In-process controls with acceptance criteria • Time limits • Expected yield Note: The finished product label should be attached with the master formulae

26. 6.5 Batch Production Records • Should be prepared for each intermediate and API • Should include complete information relating to production and control of the batch

27. 6.5 Batch Production Records Prior to issuing for use • Checked that it is the correct version and a legible accurate reproduction of the master • Numbered with a unique batch or id number, dated and signed

28. Dates • Times when appropriate • Identity of major equipment • Specific information for each material used • weights or amount • batch or id number Note that in continuous production, the product code, date and time can serve as the unique identifier until final number is allocated 6.5 Batch Production Records Documentation of completion of each significant step should include

29. 6.5 Batch Production Records Documentation of completion of each significant step should include • Any deviation / Incident noted • In-process or lab test results • Actual yield • Description of packaging • Representative label (Ex: Blending BPR)

30. 6.5 Batch Production Records Documentation of completion of each significant step should include • Investigation (if appropriate) • critical deviations should be investigated • investigation should extend to other batches that may be associated • Results of release testing

31. 6.6 Lab Control Records • Complete data from all tests conducted • Description of sample • material name or source • batch number or other distinctive code • date taken • quantity and date received for testing (where appropriate) • Reference to test method used • Weight or measure of sample used

32. 6.6 Lab Control Records • Data on preparation and testing of • reference standards • reagents • standard solutions • Complete record of raw data generated in addition to graphs, charts, and spectra (Chromatograms). • Record of calculations including • units of measure • conversion factors • equivalency factors

33. 6.6 Lab Control Records • Statement of test results and comparison with acceptance criteria • Signature of person who performed each test • Date the test was performed • Date and signature of person reviewing for • accuracy • completeness • compliance with established standards

34. Complete Lab Records • Any modification to an analytical method shall be followed as per change control procedure. • Calibration of lab instruments • Stability testing on APIs • Out of specification (OOS) investigations

35. Complete Lab Records • Review of batch production record and lab control records before batch is released or distributed • according to written procedure • any deviations, investigations or OOS should be included in this review non-critical process steps also to be • reviewed by qualified production personnel • following procedures approved by quality assurance and the investigation details to be documented.

36. Release Authority • Quality Assurance is responsible for releasing or rejecting all APIs (2.2) Records to be maintained: • Packing records. • Dispatch Records • Customer specifications & MOA….etc

37. Any Doubts …..?

38. Thanks for your attention.