Skipping test For raw material and packaging material

Dears
I wat to SOP For Skipping test for Raw material and packaging material

Reduced testing/skip testing
(Taken from Pharma Tech journal- Approaches to Reduced Sampling and Testing for Starting Materials
December 2, 2019)

The term “reduced testing” describes the practice whereby, after receipt of the starting material, not all parameters of the specification are tested. Only a reduced number of parameters are tested, while the other parameters are taken from the certificate of analysis from the manufacturer. This is an established approach in the pharmaceutical industry that requires an established system for the qualification of suppliers (34–37). The DIN ISO 2959-3 from the International Organization for Standardization (ISO) describes the statistical requirements for establishing this approach (38).

According to ICH Q6, reduced testing should not be established before the market authorization is granted (39). The prerequisite for reduced testing is an audited and qualified manufacturer that has been assessed and classified (34, 35, 36).

Some requirements in circumstances where reduced testing is permitted or minimum requirements are applicable can be found in different guidelines. According to chapter 5 of the EU-GMP guide, the manufacturer should have appropriate experience with the material (8). ICH Q7 requires full testing on at least three batches (10). Health Canada also recommends testing the first three batches of the starting material and repeating this procedure whenever the manufacturing process has changed (20). Some authors suggest testing the first 30–40 batches in full analysis (37).

The manufacturer of the medicinal product should establish the frequency for full testing. The accepted differences between the internally generated analytical results and the results of the supplier certificate of analysis should be defined, before the results are compared (35).

It is industry practice that at each starting material undergoes a full testing on an annual basis. According to Health Canada, it is permitted to do a rotational full testing if one manufacturer supplies more than one starting material. For example, if a manufacturer supplies three starting materials, it is possible to perform a full test on only one of the starting materials each year. At least every five years, a full testing of each starting material should be performed (20).

If the testing of the drug product manufacturer identifies a discrepancy in comparison with the starting material manufacturer, an investigation should be done first by the drug or medicinal product manufacturer and if he/she does not find the root cause, the investigation should be extended to the supplier/manufacturer of the starting material. Until completion of the measures, the certificate of analysis of the manufacturer should not be accepted (8).

Skip or periodic testing means that neither the manufacturer of the starting material, nor the pharmaceutical company test a certain parameter (37). If a pharmaceutical company wants to establish skip or periodic testing for a registered specification parameter, this approach must be submitted to the authorities (40, 41). In general, according to FDA, a required criteria cannot be not measured without a surrogate test (42). But for certain parameters (e.g., heavy metals or residual solvents), USP allows excipient manufacturers to perform skip testing, if validated processes are in place. This approach is also applicable for non-monographed excipients. However, full testing is required annually, and certain parameters, such as identity and strength, must be tested every time. The applied testing frequency of each parameter must be shown on the certificate of analysis (43).

In the end, it is the responsibility of the pharmaceutical manufacturer to verify if all necessary parameters have been tested. It is recommended to audit the suppliers and to verify the results from the manufacturer with results from in-house testing (43).

Discussion

As described in the previous sections, there are different options to reduce the sampling and testing of starting material. The market authorization holder has the ultimate responsibility to ensure the quality of the starting material, but the viewpoints of the different authorities could help to derive a strategy.

Sampling generally requires identity testing of each container. Reduced sampling is possible, but requires additional work to justify it. Independently, if the sampling for the full analysis is created from the samples of the identity testing or separately, a general square root +1 sampling plan might be too simple. A risk-based sampling plan is recommended.

The identity testing of only mixed samples is possible under certain circumstances. The method used must be suitable to identify potential mix-ups even in mixed samples. In combination with a spectroscopic method, such as Raman or NIR, it is possible to perform the monographed or the approved methods on mixed samples.

The analysis for the full testing requires a representative and homogeneous mixed sample. The preparation of the mixed sample should be described in detail, especially the number of samples that are permitted to be combined in one sample.

A full testing of all parameters at every goods receipt is not required. Results from the manufacturer’s certificate of analyses can be used. However, it should be defined when it is permitted to move from full testing to reduced testing, at which frequency the full testing is repeated, and under which circumstances it is necessary to move back to full testing.

References

  1. European Commission, Chapter 1, “Pharmaceutical Quality System,” EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use , (EC, 31 Jan 2013).
  2. U. Holzgrabe et. al., Deutsche Apotheker Zeitung , No. 26, pp 57 (2003).
  3. FDA, Guidance for Industry, Testing of Glycerin for Diethylene Glycol (Rockville, MD, May 2007).
  4. S. Belz, R. Endler, and T. Gumz, Deutsche Apotheker Zeitung , No. 38, pp 62 (2011).
  5. European Commission, Chapter 6 “Quality Control”, EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use (EC, 1 Oct. 2014).
  6. L. Torbeck, Pharmaceutical Technology , 36 (4) (2012).
  7. A. Frank, PharmInd , No. 1, pp 68-75 (2011).
  8. European Commission, Chapter 5, “Production”, EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice
    for Medicinal Products for Human and Veterinary Use (EC, 1 March. 2015).
  9. European Commission, “Sampling of Starting and Packaging Materials,” EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use , Annex 8.
  10. ICH, Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients , Step 4 version (ICH, 2000).
  11. EC, EudraLex Volume 4 , Glossary (EC, 31 Jan 2013).
  12. ICH, Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities) , Step 4 version (ICH, 2012)
  13. US Code of Federal Regulations, Title 21, Food and Drugs (U.S. Government Publishing Office, Washington, DC), Part 210.3, pp. 157-158, 1 April. 2019.
  14. Inspektorate–Swissmedic, “Anforderungen an die gebindeweise Garantierung der Identität von Ausgangsstoffen,” Vers. 4.0, 8 August 2018.
  15. US Code of Federal Regulations , Title 21, Food and Drugs (U.S. Government Publishing Office, Washington, DC), Part 211.84, pp. 164-165, 1 April 2019.
  16. US, Code of Federal Regulations , Title 21, Food and Drugs (U.S. Government Publishing Office, Washington, DC), Part 211.160(b), p. 172, Apr. 1. 2019.
  17. FDA, “How does FDA interpret the regulations (21 CFR part 211) regarding the establishment of expiry dating for chemicals, reagents, solutions, and solvents?,” Question in Questions and Answers on Current Good Manufacturing Practices-Control of Components and Drug Product Containers and Closures ,” (FDA, 28 August 2018.
  18. USP, General Chapter <1097>, “Bulk Powder Sampling Procedures”, USP 42–NF 37 , pp. 7599-7611 (USP, 3 June 2019).
  19. EMA, Guidance on Good Manufacturing Practice and Good Distribution Practice: Questions and Answers
    www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-manufacturing-practice/guidance-good-manufacturing-practice-good-distribution-practice-questions-answers#eu-gmp-guide-annexes:-supplementary-requirements:-annex-8:-sampling-of-starting-and-packaging-materials:-use-of-near-infrared-(nir)-technology-for-container-wise-identity-testing-section.
  20. Health Canada, “Raw material testing,” Good Manufacturing Practices Guide for Drug Products (GUI-0001), pp. 32 – 41, 28 February 2018.
  21. Australian Government Department of Health Therapeutic Goods Administration, Sampling and Testing for Listed and Complementary Medicines–Technical Guidance on the Interpretation of the PIC/S Guide to GMP, Version 2.0 (January 2019).
  22. WHO, WHO Technical Report Series, “Annex 4 WHO Guidelines for Sampling of Pharmaceutical Products and Related Materials,” No. 929, 2005.
  23. Health Canada, Good Manufacturing Practices Guide for Drug Products (GUI-0001) , Appendix B–Questions and Answers “Raw material testing”, pp. 127–131, 28 February 2018.
  24. EDQM, “1. General Notices”, pp. 3 - 10 European Pharmacopoeia 10.0 (EDQM, July 2019).
  25. M. Blanco et al, Analyst , 123, 135R–150R (1998).
  26. EDQM, “2.2.40. Near-infrared Spectroscopy,” European Pharmacopoeia 10.0, pp. 70-75 (EDQM, July 2019).
  27. EDQM, “2.2.48. Raman Spectroscopy,” European Pharmacopoeia 10.0, pp. 92-94 (EDQM, July 2019).
  28. USP, General Chapter <1119>, “Near-infrared Spectroscopy,” USP 42-NF 37 , pp. 7724-7730 (USP, 3 June 2019).
  29. USP, General Chapter <1120>, “Raman Spectroscopy,” USP 42 - NF 37 , pp. 7731-7737 (USP, 3 June 2019).
  30. EMA, Guidance on Good Manufacturing Practice and Good Distribution Practice: Questions and Answers , “EU GMP guide annexes: Supplementary requirements: Annex 8: Sampling of starting and packaging materials: Use of near-infrared (NIR) technology for container-wise identity testing.”
  31. EMEA, “Note for Guidance on the Use of Near Infrared Spectroscopy by the Pharmaceutical Industry and the Data Requirements for New Submissions and Variations,” August 2003.
  32. EMA, Guideline on the Use of Near Infrared Spectroscopy by the Pharmaceutical Industry and the Data Requirements for New Submissions and Variations (EMA, 27 Jan. 2014).
  33. HK Srivastava, S. Wolfgang, J.D. Rodriguez, Anal Chim Acta , 914, pp. 91–99 (31 March 2016).
  34. European Commission, EudraLex Volume 4, “Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use, Part II: Basic Requirements for Active Substances used as Starting Materials” (EC, 13 August 2014).
  35. P. Lienbacher, M. Karner, PharmInd , No. 3, pp. 364-369 (2016).
  36. P. Lienbacher, M. Karner, Pharmaceutical Technology , Volume 2017, Supplement, Issue 1, pp s32-s37 (2017).
  37. UR Mallu et al, Pharm Anal Acta, 5, 2, (2014).
  38. ISO, “ISO 2859-3:2005-Sampling procedures for inspection by attributes-Part 3: Skip-lot sampling procedures,” May 2005.
  39. ICH, Q6A Specifications: Test Procedures and Accepatance Criteria For New Drug Substances And New Drug Products: Chemical Substances , Step 5 version, (ICH, 6 October 1999).
  40. “Guidelines on the details of the various categories of variations”, Official Journal of the European Union , C 223/1, 2 August 2013.
  41. FDA, Guidance for Industry Changes to an Approved NDA or ANDA, Rev. 1 (Rockville, MD, April 2004).
  42. B. Carlin, Pharmaceutical Technology , Volume 31, Issue 9 (2007).
  43. USP, General Chapter <1080>, “Bulk Pharmaceutical Excipients–Certificate of Analysis”, pp. 7527 - 7534, USP 42-NF37 , (USP, 3 June 2019).
2 Likes