[Stability Testing related News – vol.15]

◆ Managing CAPA and Investigation Processes still in the Focus of Inspectorates (19-Nov-14 ECA)

  Deviations and CAPA remain hot topics in inspections. The inspectorates’ summaries of their observations show that things do not always work as desired. Recently, the U.K. authority MHRA (Medicines and Healthcare Products Regulatory Agency) published its Top Ten Deficiency Categories. The report “GMP Inspection Deficiencies 2013” covers 630 inspections performed in 2013. According to the report, “deficiencies relating to ‘Quality Systems’ are by far the most prevalent observed during inspections”.

The most common deficiencies during the time frame considered are listed below:

1. Investigation of anomalies
2. Quality management
3. Investigation of anomalies – CAPA
4. Contamination, chemical/physical (or potential for)
4. Supplier and contractor audit
6. Quality management – change control
7. Documentation – procedures/PSF/TAs
7. Personnel issues – training
9. Design and maintenance of equipment
9. Documentation – manufacturing
9. Finished product testing – chemical

As in the previous year, the investigation of anomalies is again at the top of the list. Observations concerning CAPA issues already follow on the third position.

What are the reasons for this? The MHRA published a set of frequently asked questions (FAQs) concerning Quality Risk Management (QRM) already in 2010. The questions and the relevant answers give a good overview and useful tips on how EU inspectorates inspect QRM elements in relation to the ICH Guidelines Q9 and Q10 and how they intend to enforce them. The British authority has emphasised particularly that all inspectorates will include QRM processes in the future, since they are required in chapter 1 of the EU-GMP Guide (Part 1). This includes the handling of complaints, the management of deviations and CAPA.

Taking a closer view at the examples of the defect area findings it becomes obvious that root cause analysis, impact assessment and associated actions are still challenging for many companies.

 

◆ New USP Proposals on “Supply Chain Integrity” (26-Nov-14 ECA)

  An interesting article of the USP on the future USP chapters for supply chain integrity and security can be found in the Pharmacopoeial Forum 40(2).

Supply Chain Integrity and Security (SCIS) is defined as a set of procedures and technologies which are used to ensure visibility and traceability of products within the supply chain.

This aims to protect end consumers against counterfeit products. The ultimate aim is to detect falsified products and prevent them from entering the supply chain and thus the market.

The risks may include:

• Adulteration of the material or product
• Misbranded products containing unlabeled ingredients 
• Expired products that are relabeled and sold to end-users
• Materials or products meant for destruction
• Materials and products that are not effectively recalled 

Among the risks involved in the supply chain security is mainly theft of products during storage and/ or transportation which frequently occurs in the practice.

At the end of this guideline, you can find an appendix listing the definition of various terms like:

• Adulteration – storage of a material “under insanitary conditions”, non GMP-compliant conditions which may have an influence on the quality of the product.
• Counterfeit Drugs
• Diversion – “The unlawful redirection of pharmaceutical products […] to legal and illegal markets”
• Economically motivated adulteration – Production of fraudulent products with the intention to make an economic gain.

More information about the new Chapter <1083.4> can be found on the USP website of the Pharmacopeial Forum (PF).

 

◆ DSCSA Implementation:Product Tracing Requirements – Compliance Policy (24-Dec-14 FDA)

  DSCSA (Drug Supply Chain Security Act) take effect for manufacturers, wholesale distributors, and repackagers on January 1, 2015.

This act sets forth new definitions and requirements related to product tracingcertain prescription drugs as they are distributed within the United States.

This system will enhance FDA’s ability to help protect U.S. consumers by improving detection and removal of potentially dangerous products from the pharmaceutical distribution supply chain.

To minimize possible disruptions in the distribution of prescription drugs in the United States, FDA does not intend to take action against trading partners who do not, prior to May 1, 2015.

 

◆ Guideline “ICH Q3D – Elemental Impurities” published as Step 4 Document! (12-Jan-15 ECA)

  On 19 December 2014, the Guideline “ICH Q3D – Elemental Impurities” was released on the ICH website – nearly one year and a half after the publication of the draft (Step 2b document) on 5 August 2013. The Expert Working Group (EWG) in charge of the guideline has taken more time to find an agreement and a consensus because of the several comments given by diverse associations on the guideline and the final determination of the “permitted daily exposure” (PDE) for the different metals.

Compared to the draft guideline from August 2013, most of the limits have changed: more stringent PDE values apply for 17 out of the 24 elements! 

This guideline constitutes a milestone in the risk assessment and analysis of new medicinal products that have not yet been authorised. It is partly complex and will pose a considerable challenge to the chemical and pharmaceutical industry – particularly of already authorised medicinal products. A transposition period of 3 years has been granted for the application of the requirements set in the guideline. (Last sentence in Chapter 2 Scope: “Application of Q3D to existing products is not expected prior to 36 months after publication of the guideline by ICH”.).