12.01.2015 |

LOGFILE No. 01/2015 - GMP-Outlook 2015

GMP-Outlook 2015: What to expect in the world of GMP?

by Thomas Peither

Your job is to implement the upcoming changes in the world of GMP in your procedures and daily business. We have identified the most important topics that have already been finalised or are in discussion for 2015. Again in this year we can follow the quote from Heraclitus who wrote approx. in 500 BC:

"There is nothing permanent except change."

Quality requirements in drug manufacturing have been changing for years and will continue to change in 2015. Regulators dominate this discussion and have already published some finalised regulations. The updates were discussed in some recent conferences, and we have analysed some additional sources to compile the most important changes for you in this article.

European GMP requirements in the EU Guide to GMP

Changes regarding the EU Guide to GMP and regarding additional GMP/GDP will be as follows:

Already adopted and published documents:

  • Chapter 3 Premises and Equipment (coming into operation 1 March 2015)
  • Chapter 5 Production (coming into operation 1 March 2015)
  • Chapter 8 Complaints and Product Recall (coming into operation 1 March 2015)
  • Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (EMA/CHMP/CVMP/ SWP/169430/2012) (coming into operation 1 June 2015)

Draft documents:

  • Annex 15 Qualification and Validation
  • Annex 16 Certification by a Qualified Person and Batch Release
  • EMA-Guidelines on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use
  • EMA-Guidelines on the principles of good distribution practices for active substances for medicinal products for human use

Additional documents for which revision is planned:

  • Annex 1 Manufacture of Sterile Medicinal Products (in cooperation with PIC/S)
  • Annex 13 Manufacture of Investigational Medicinal Products (due to the new EU Regulation on clinical trials on medicinal products for human use)
  • Annex 17 Parametric Release (Publication of first draft was originally foreseen in 2014.)

Cross-Contamination
The subject of cross-contamination will be dealt with in 2015 on the basis of new requirements laid down in Chapters 3, 5 and the new EMA guideline. Also Annex 15 will take up this topic. Especially the toxicological assessment presents a new challenge to many companies, and expertise has to be built up in this area.

Supplier Assessments
The supply chain implies a high quality and safety risk for drug manufacturing today. In times of globalisation the supply chain has to be managed and controlled. With professional supplier assessments this risk can be reduced. For that reason supplier assessments are an important element to improve the supply chain and to make it more transparent. The purchaser has to know the risks in the supply chain and has to implement procedures to decrease these risks. This is also a requirement of the new Chapter 5 of the EU GMP Guide.

Qualification
We do not exactly know when Annex 15 of the EU Guide to GMP will be finalised. We expect publication in the first quarter of 2015. You do not need to worry about that, if you have qualified your equipment and facilities at the state-of-the-art level. Annex 15 adapts to the approaches performed in practice. We will deliver further analysis after publication of the final version.

Process Validation
International harmonisation is one of the engines driving the process validation approach laid down in the upcoming Annex 15. No short-term changes are necessary for most drug manufacturers. But nevertheless this topic demonstrates that procedures have to be continuously improved to stay up-to-date and to be GMP conform.

Cleaning Validation
This will be an open discussion point until the final version of Annex 15 becomes available. Presumably there will be a change in the visual clean criterion. It will probably no longer be allowable for this acceptance criterion alone to be used.

US-FDA: Harmonization & Quality Oversight

US-FDA usually publishes its guidance agenda in early February. The work programme of 2014 has still the following open points:

  • Contract Manufacturing Arrangements for Drugs: Quality Agreements
  • GXP Consideration for Outsourced IT (Cloud Computing) Systems in Medical Product Manufacturing and Clinical Study Environments
  • Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice (current version from 2006)
  • The following Guidance for Industry is available as draft, but still not finalised:
  • Interim Good Manufacturing Practice for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug and Cosmetic Act

Quality Oversight
FDA is continuously claiming the quality oversight principle through inspections. Quality oversight means implementing quality unit functions that have the oversight over all processes. This also means to supervising and releasing quality control data by quality assurance. You will have to establish adequate responsibilities in the near future to fulfil these requirements.

Harmonisation
It can be observed that global guidances have a great impact on the development of new and revised EMA and FDA regulations. The goal of new documents is mostly not to create new requirements, but rather to encourage industry to implement adequate quality procedures and to harmonise regulations. Regulatory bodies want to develop adequate frameworks. Quality should be orientated towards critical processes in manufacturing and not be implemented only to follow regulatory requirements. Procedures must be reasonable and not driven only by regulatory documents. Today it is important to take the lifecycle model, risk and knowledge management into account. The ICH guidelines raised these principles in the international discussion, and mean-while they have been referenced in every new international guidance.

New ICH -Guideline on Lifecycle Management is in planning

A lot of changes in the EU Guide to GMP and the US-FDA guidelines are being triggered by the principles laid down in ICH guidelines. We expect that this will also happen in the future. ICH announced that they are developing a new guideline ICH Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management. ICH will publish a first draft in 2016. We will observe the ICH activities and keep you informed.

Conclusion

We could copy our conclusion in the outlook for the year 2014. The medium-term concepts have not changed and it will be everyone's duty to cover the following tasks:

  • Establish and improve your (quality) risk management in your company
  • Improve your process understanding and try to share the knowledge with a lot of employees
  • Try to describe and document the processes following science-based knowledge
  • Improve your quality oversight in your organisation with clear responsibility descriptions and transparency
  • Improve the understanding of the complete supply chain and ensure efficient monitoring and control of the supply chain partners


2015 is again a year with a lot of challenges for all parties. Regulatory bodies, pharmaceutical industry and suppliers have a great chance to improve quality procedures. You can stay up-to-date with our newsletter LOGFILE and knowledge data base GMP MANUAL.

References

20. GMP-Conference 3.- 4.12.2014, Darmstadt, PTS Training Service 

PDA/FDA Joint Regulatory Conference 2014, 8.-10. September 2014, Washington DC Original
Versions of Chapters 3, 5, 8 and Annex 15 und 16 of the EU Guide to GMP are included in the GMP MANUAL, Maas & Peither, www.gmp-publishing.com 

Internet links to the final versions of the EU Guide to GMP documents (Chapters 3, 5, 6 and 8):
http://ec.europa.eu/health/files/eudralex/vol-4/2014-08_gmp_chap3.pdf 
http://ec.europa.eu/health/files/eudralex/vol-4/2014-08_gmp_chap5.pdf 
http://ec.europa.eu/health/files/eudralex/vol-4/2014-08_gmp_chap8.pdf 

EMA-Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/11/WC500177735.pdf 

Annex 15 (draft): http://ec.europa.eu/health/files/gmp/2014-02_pc_draft_gmp_annex.pdf 
Annex 16 (draft): http://ec.europa.eu/health/files/eudralex/vol-4/pdfs-en/v4_anx16_2013_rev.pdf 

EMA Guidelines on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use (draft): 
http://ec.europa.eu/health/files/gmp/2013-02_guidelines_excipients_cons.pdf 

EMA Guidelines on the principles of good distribution practices for active substances for medicinal products for human use (draft): 
http://ec.europa.eu/health/files/gmp/2013-02_gdp_for_api_cons.pdf 

Interim Good Manufacturing Practice for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug and Cosmetic Act: 
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm377050.pdf 

Final Concept Paper Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management: 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q12/Q12_Final_Concept_Paper_July_2014.pdf

Author:

Thomas Peither
Editor in Chief
Maas & Peihter AG, Schopfheim, Germany
Email: thomas.peither@gmp-publishing.com

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